Venkatesan Renugopalakrishnan, Northeastern University
Pulickel Ajayan, Rice University
Catherine Klapperich, Boston University
Dorian Liepmann, University of California, Berkeley
Anarghya Innovations and Technology Private Limited
MilliporeSigma (Sigma-Aldrich Materials Science)
Thermo Fisher Scientific
BM06.01: Keynote Session
A. Paul Alivisatos
Monday AM, November 27, 2017
Sheraton, 2nd Floor, Back Bay B
7:00 AM - BM06.01.01
Imaging of Nanocrystals and Nanocrystal-DNA Assemblies in the Graphene Liquid Cell
A. Paul Alivisatos 1 Show Abstract
1 , Lawrence Berkeley National Laboratory, Berkeley, California, United States
We have developed a graphene liquid cell for the transmission electron microscope, in which a thin specimen of liquid, ~100nm in thickness, is encapsulated by two windows of graphene. In this cell we can observe motions and dynamics of nanocrystals, DNA directed nanocrystal assemblies, and protein shells and capsids. We are able to observe the growth of colloidal nanocrystals, as well as the structure of individual nanocrystals at a high level of detail.
7:45 AM - BM06.01.02
Engineering the Nanoparticle Corona for Sensors at New Biological Interfaces
Michael Strano 1 Show Abstract
1 , Massachusetts Institute of Technology, Cambridge, Massachusetts, United States
Our lab at MIT has been interested in how the nanoparticle corona – the region of adsorbed molecules surrounding the particle surface - can be engineered for molecular recognition. We have recently introduced a method we call CoPhMoRe or Corona Phase Molecular Recognition1 for discovering synthetic, heteropolymer corona phases that form molecular recognition sites at the nanoparticle interface, selected from a heteropolymer library. We show that certain synthetic heteropolymers, once constrained onto a single-walled carbon nanotube by chemical adsorption, also form a new corona phase that exhibits highly selective recognition for specifc molecules. We have a growing list of biomolecules that we can detect using this approach including riboavin, L-thyroxine, dopamine, nitric oxide, sugar alcohols, estradiol, as well as proteins such as fibrinogen. The results have signifiicant potential in light of the fact that nanoparticles such as single walled carbon nanotubes can be interfaced to biological systems at the sub-cellular level, with unprecedented sensitivity. Several recent demonstrates indicate that spatial and temporal information on cellular chemical signaling can be obtained using arrays of such sensors. Other examples including sensor tattoos for mice, stable for more than 400 days in-vivo, will be shown. Lastly, I will highlight recent advances to control the traffcking and localization of nanoparticle systems in living plants using a mechanism that we call Lipid Exchange Envelope Penetration (LEEP). We demonstrate a living plant, interfaced with multiple nanoparticle types that can detect explosives, ATP and dopamine within or from outside the plant, and communicate this information to a user’s cell phone. Engineering the nanoparticle corona in this way offers significant potential to translate sensor technology to previously inaccessible environments.
8:30 AM - BM06.01.03
All-Solution, All-Nanocrystal Based Wearable Temperature Sensors for Effective Strain Decoupling
Hyungmok Joh 1 , Woo Seok Lee 1 , Seung-Wook Lee 2 , Haneun Kim 1 , Min Su Kang 1 , Mingi Seong 1 , Soong Ju Oh 1 Show Abstract
1 Materials Science and Engineering, Korea University, Seoul Korea (the Republic of), 2 Semiconductor Systems Engineering, Korea University, Seoul Korea (the Republic of)
A facile, yet unconventional method to decouple external strain effects is introduced to realize flexible, wearable sensors fabricated by all-solution, all-nanocrystal processes. Metallic charge transport behavior is achieved through inorganic ligand exchange of Ag nanocrystals (NCs) with tetrabutylammonium bromide (TBAB), and hopping charge transport is also achieved through organic ligands. The TBAB-treated Ag NC thin films exhibit linear resistance change when there is a difference in temperature or strain as a result of metallic charge transport. The electrode part as well as the sensor part are composed of the same material, Ag NCs, which is made possible from the low resistivity of inorganic ligand-treated Ag NC thin films. By integrating metallic Ag NC thin film temperature sensors on both the top and bottom side of the neutral mechanical plane and by using the different charge transport mechanisms, we effectively decouple the strain effects from positive and negative strain. The remaining factor to affect the resistance of the sensor is the temperature change, leading to precise measurement of temperature. Our strategy provides a low cost, simple, single-material method to fabricate temperature sensors without the need for any complicated sensor designs. We expect our sensors could be utilized in various fields such as healthcare monitoring, environmental control and disease diagnosis.
8:45 AM - BM06.01.04
Carbon Based Nanohybrid Thin Films as Novel Bioanalytical Sensing Platform
Samira Bagheri 1 , Amin TermehYousefi 1 Show Abstract
1 , Tufts University, Medford, Massachusetts, United States
Carbon-based electrodes, for electrochemical and electroanalytical sensor applications, are more suitable than other metal and metal oxide-based electrodes, because of wide potential window and a relatively low background noise level, which is very important as regards the electrochemical detection. Recently, carbon materials including carbon nanotubes, graphene/graphene quantum dots and carbon dots have been developed and employed as electrode materials. Electrochemical biosensors are responsible for quantification of analytes for medical diagnostics applications. They are considered as a promising means to investigate the content of a biological sample owing to the direct exchange of a biological process to an electronic output signal. In this research work, three dimensional graphene nanostructure has been applied to electroanalysis because of its extremely wide potential window and stability. Novel characteristics of nanocarbon materials attracted much attention for fabrication of numerous electrochemical biosensors with developed analytical capacities. The developed facile and easy electrochemical method for analtytes detection using modified glassy carbon electrode, which may open up new horizons in the production of cost-effective and sensitive biosensors.
BM06.02: Advancing Frontiers of 2D Nanomaterials I
Monday AM, November 27, 2017
Sheraton, 2nd Floor, Back Bay B
9:30 AM - *BM06.02.01
Fluorographene Sensing Platform
Tharangattu Narayanan Narayanan 1 Show Abstract
1 , Tata Institute of Fundamental Research Hyderabad, Houston, Texas, United States
Fluorination of graphene resulting to the conversion of sp2 carbon to sp3 is found to be bringing many fascinating attributes to the graphene honeycomb lattice.1-3 The presence of C-F bond in graphene can vary the surface wetting properties, magnetic nature, electronic conductivity, dielectric strength, and heterogeneous charge transfer characteristics of graphene. Here these attributes are proposed for the development of fluorographene based small molecules' sensors. Large area catalyst free single step growth for fluorogrpahene oxide is established and these atomically thin films are functionalized and further used for small molecule sensor development. Density functional theory based studies are conducted to study the selective interactions of various molecules with graphene and fluorographene, and wetting studies of these molecules with graphene unravel the possibilities of the development of patterned sensor devices with graphene/fluorographene. Electronic and electrochemical sensing platforms are realized with fluorographene and the results will be discussed.
1. Fluorographene: Synthesis and Sensing Applications, T. N. Narayanan, Ravi K. Biroju, and V. Renugopalakrishnan, Journal of Materials Research DOI: 10.1557/jmr.2017.135 (2017).
2. Fluorographene based Ultrasensitive Ammonia Sensor, Kiran K. Tadi, Shubhadeep Pal, T. N. Narayanan, Scientific Reports 6, 25221 DOI: 10.1038/srep25221 (2016).
3. Atomic Layers in Electrochemical Biosensing Applications – Graphene and Beyond, O. V. Manila, A. Alwarappan, and T. N. Narayanan,Current Organic Chemistry 19 (12), 1163-1175 (2015).
4. Defluorination of fluorographene Oxide via Solvent Interactions, Kiran K. Tadi, Santosh Kumar Bikkarolla, Kapil Bhorkar, Shubhadeep Pal, Narayan Kunchur, Indulekha N, Sruthi Radhakrishnan, Ravi Kumar Biroju, and T. N. Narayanan, Particle & Particle Systems Characterization 1600346 (1-7) (2017).
5. Fluorinated graphene oxide; a new multimodal material for biological applications, Rebeca Romero-Aburto, T. N. Narayanan, Yutaka Nagaok, Takashi Hasumura, Trevor M. Mitcham, Takahiro Fukuda, Paris J. Cox, Richard R. Bouchard, T. Maekawa, D. Sakthi Kumar, Suzy V. Torti, Sendurai A. Mani, Pulickel M. Ajayan, Advanced Materials, 25, 5632-5637 (2013).
6. The First-Magnetic-Nanoparticle-Free Carbon-Based Contrast Agent of Magnetic-Resonance Imaging-Fluorinated Graphene Oxide” by Y. H. Hu. Small (2014) 10 (8) 1451-1452.
7. Synthesis of fluorinated graphene oxide and its amphiphobic properties, T.N. Narayanan, A. Mathkar, Lawrence Alemany, GuanhuiGao, Paris Cox, Patrick Nguyen, Patritia Chang, Rebecca Romero-Aburto, Sendurai Mani, and P.M. Ajayan, Particle & Particle Systems Characterization, 30, 266-272 (2013).
10:00 AM - BM06.02.02
Superior Volatile Organic Compound Sensing Properties of Monolayer and Multilayers Black Phosphorus
Pengfei Ou 1 , Jun Song 1 Show Abstract
1 , McGill University, Montreal, Quebec, Canada
The unique structure and outstanding properties of black phosphorus (BP) in its monolayer and multilayers form promise numerous possibilities in device applications, attracting significant attention to this two-dimensional (2D) material. In the present work, the performance of monolayer and bilayer BP in sensing volatile organic compounds (VOCs, including ethanol, propionaldehyde, acetone, toluene, and hexane) has been systematically evaluated using first-principles density functional theory (DFT). Our results show that VOCs act as charge acceptors, and physically adsorb on the surface of monolayer BP, much strongly compared to MoS2 and graphene. The density of states (DOS) reveals that the adsorption does not significantly alter the valence and conduction bands. Compressive (tensile) strain is found to generally increase (decrease) the adsorption energy, for both monolayer and bilayer BP. We further calculated the current-voltage (I-V) characteristics using the non-equilibrium Green’s function (NEGF) formalism, and the adsorption of VOCs is found to induce a marked change in the I-V characteristics. Our results suggest that black phosphorus be a compelling candidate in sensing application for VOCs.
10:15 AM - BM06.02.03
Electrospun Nanofiber Induced Controlled Wrinkle Formation in Graphene Oxide Using LB Technique
Neha Chauhan 1 , Vivekanandan Palaninathan 1 , Toru Maekawa 1 , Sakthi Kumar 1 Show Abstract
1 , Toyo University, Kawagoe, Saitama Japan
Graphene has shown immense potential from electronics to biomedical applications due to the unique combination of properties. Apart from its planar 2D structure, surface corrugations on graphene have gained significant attention as it can lead to mechanical instability such as wrinkling, crumpling or rippling that can modify its inherent properties. Graphenic wrinkles have high accessible surface area and rapid electron transfer which affects a range of features like optical, mechanical, electrical structure, transfer properties and electrochemical properties . Various techniques including thermal expansion, chemical modification, wedging transfer, capillary compression, substrate stretching and ‘shrink films’ processes have been explored to create topological features. However, highly oriented and controlled wrinkled graphene oxide (GO) patterns on selective areas of any substrate at large scale has remained one of the critical physical attributes. This can amend its electronic structure, transport properties and even modify the chemical distribution which has a huge potential to serve many applications.
Here, we have developed a new versatile and novel approach to control the wrinkle formation in GO. Highly aligned PLGA electrospun nanofibers have been used as a supporting matrix to assist wrinkle formation and Langmuir-Blodgett (LB) technique is used to deposit monolayer GO sheets . Several parameters such as GO concentration, solution volume, surface pressure (SP), substrate hydrophilicity and dipping process have been regulated to achieve controlled orientation and wrinkle formation in GO. The effectiveness of this strategy is investigated by SEM, EDS, TEM, AFM, contact angle and XPS analysis. Our strategy provides a new tactic to control the wrinkle formation and orientation of GO sheets with ease and efficient scalable production. This can greatly benefit foldable/stretchable graphene-based sensors, ‘energy conversation and storage’, photovoltaic devices, supercapacitors, batteries, organic light-emitting diodes, photodetectors, fuel cells, nanogenerators and even for culturing cells. As a proof of concept, we have used this substrate to create a conducive environment to culture aligned array of neuronal cells.
1. Shikai Deng, et al. Wrinkled, rippled and crumpled graphene- an overview of formation mechanism, electronic properties, and applications. Materials Today, 2015, 19 (4), 197–212.
2. Neha Chauhan, et al. N2-Plasma-Assisted One-Step Alignment and Patterning of Graphene Oxide on a SiO2/Si Substrate Via the Langmuir– Blodgett Technique Adv. Mat. Interfaces, 2015, 2(5), 1-11.
10:30 AM - BM06.02.04
Ratiometric Temperature Mapping of Living Tissues Using Ultra-Conformable Polymer Nanosheets Loading Thermo-Sensitive Dyes
Toshinori Fujie 1 2 , Takuya Miyagawa 3 , Ferdinandus Ferdinandus 4 , Vo Doan Tat Thang 4 , Hirotaka Sato 4 , Shinji Takeoka 3 Show Abstract
1 Waseda Institute for Advanced Study, Waseda University, Tokyo Japan, 2 PRESTO, Japan Science and Technology Agency, Saitama Japan, 3 Graduate School of Advanced Science and Engineering, Waseda University, Tokyo Japan, 4 School of Mechanical & Aerospace Engineering, Nanyang Technological University, Singapore Singapore
To investigate hierarchical system of biology among cells, tissues and organs, there have been ongoing efforts for the development of bio-imaging tools. Such tools should be harmonized with the physical and mechanical property of living organisms. Herein, we report a micro-thermography of temperature mapping system with high spatial resolution, which was established with thermo-sensitive luminescent molecules (Eu-tris (dinaphthoylmethane)-bis-trioctylphosphine oxide: EuDT) embedded in a polymeric ultra-thin film (referred to as nanosheet). Owing to the ultra-thin structure of a hundreds-of-nm thickness, the nanosheet thermosensor conformed to the surface of muscle tissue in small flight insects (i.e., Dicronorrhina derbyana beetle), and mapped out their temperature shift of muscular activity. We then prepared a thermosensor consisting of bilayered nanosheets loading thermo-sensitive and insensitive dyes (EuDT and Rhodamine 800, respectively). In this way, the bilayered luminescent nanosheet allowed for the ratiometric thermometry, which eliminates undesired luminescence-intensity-shift due to focal drift or animal’s z-axis displacement. The ratiometric imaging successfully showed the desired intensity-shift due to the temperature shift of the living muscle. We also, for the first time, achieved video-filming of temperature-shift distribution of the living muscle tissue from rest to active states in chronological order. Interestingly, the video revealed heterogeneous thermogenesis from different muscle fibers in the same body, prior to the active state called as “pre-flight preparation” or “escape mode” in beetle behavior. In fact, the normalized luminescent ratio in different muscle fibers was calculated to be the different temperature shifts; 5.0 oC up in dorso ventral muscle (DVM) and 3.3 oC up in dorsal longitudinal muscle (DLM), respectively. Therefore, the nanosheet thermosensor is a useful bioimaging tool for in vivo micro-thermography, which will lead to the understanding of microscopic heat production and/or transfer in living cells, tissues and organisms with high spatial resolution.
10:45 AM - BM06.02.05
Wearable, Wireless Eye Therapy Devices Using Red Light-Emitting Diodes on 3D Surfaces
Young-Geun Park 1 , Byeong Wan An 1 , Jang-Ung Park 1 Show Abstract
1 , Ulsan National Institute of Science and Technology, Ulsan Korea (the Republic of)
The studies of wearable light emitting devices have been applied to virtual reality, a head-mounted display, or augmented reality display such as Google glass. As a further effect of light emitting devices above displays, lights have a therapeutic effect on the eye, especially in red to near infrared (between 600 to 1100 nm) range of wavelength. There are eye therapies using light, but the current phototherapy devices have bulk and rigid shapes, thus it is hard to provide continuous and personalized treatment in human eyes.
Herein, we present new approaches for fabricating light therapy devices on three-dimensional structures for an eye, one is glasses type device using a red organic light-emitting diode (OLED) and the other is contact lens type device using a red inorganic light emitting diode (ILED). First, OLED is formed on the nonplanar shaped glasses lens by electrohydrodynamic jet printing. The printing process overcomes the challenges in conventional OLED fabrication processes confined to two-dimensional substrates and the failure by constant strain. Conformally printed OLED has no strain on the glasses lens and has a wavelength of 652 nm peak, and transmittance of 54.8% at 550 nm for see-through wearable eye therapy. The device is wirelessly controlled by Bluetooth module and battery. The therapeutic effect of red OLED glasses is also in vitro tested for targeting the macular eye degeneration. Red OLED is proved to have a positive effect on the eye cell viability. Second, ILED device is also fabricated on the soft contact lens. A wireless-powered circuit which includes an antenna, diode, capacitor and a single ILED pixel which emits red light (620 nm wavelength) is embedded in contact lens and wirelessly functioned by AC powered transmitting antenna. ILED pixel is located not to interrupt the visibility but the light reaches inside the eye and the device can suggest a wearable platform of light therapy for the eye. ILED lens device was worn on the rabbit’s eye and operated in wireless condition without heat dissipation. These results provide platforms of wearable eye phototherapy devices.
BM06.03: Advancing Frontiers of 2D Nanomaterials II
Tharangattu Narayanan Narayanan
Monday PM, November 27, 2017
Sheraton, 2nd Floor, Back Bay B
12:30 PM - *BM06.03.01
Electronic and Vibrational Properties of Silicene Studied by STM Tip-Enhanced Raman Spectroscopy
Shaoxiang Sheng 1 , Kehui Wu 1 Show Abstract
1 , Institute of Physics, Chinese Academy of Sciences, Beijing China
Combining ultrahigh sensitivity, spatial resolution and capability of resolving chemical information, tip-enhanced Raman spectroscopy (TERS) is a powerful tool to study molecules or nanoscale objects. Here we demonstrate that TERS, based on a low temperature scanning tunneling microscopy (LT-STM), can also be a powerful tool in studying two-dimensional (2D) materials. We have achieved an unprecedented 109 Raman signal enhancement combined with a 0.5 nm spatial resolution, using silicene on Ag(111) as a prototypical 2D material system. By the selective TERS enhancement on vertical Raman modes, we were able to identify the origination of Raman modes in silicene, which has remained unclear so far. Monolayer silicene phases, which are different only in the bucking direction of the Si-Si bonds, can be identified by TERS. The debating issue on the origination of the Raman modes from monolayer silicene are clarified combining TERS and first principles calculations. Furthermore, we have also investigated the vibrational proprties of silicene nanoribbons, and revealed interesting local structural features in these atomic chains. This method will hopefully be extended to the study on various emerging two-dimensional materials.
1:00 PM - *BM06.03.02
Novel Topological Quantum States in Silicene, Germanene and Stanene
Yugui Yao 1 Show Abstract
1 , School of Physics, Beijing Institute of Technology, Beijing China
Silicene, germanene and stanene, analogies of graphene, have attracted increasing attention during the past few years. They share most of the outstanding electronic properties of planar graphene (e.g., the ‘‘Dirac cone”, high Fermi velocity and carrier mobility). However, due to the low buckled geometry, silicene, germanene and stanene has several prominent advantages: (1) a much stronger spin–orbit coupling, which may lead to a realization of quantum spin Hall effect in the experimentally accessible temperature, (2) a better tunability of the band gap, which is necessary for an effective field effect transistor (FET) operating at room temperature, (3) an easier valley polarization and more suitability for valleytronics study. In this talk, I will introduce some novel quantum states especially topological properties in these two-dimensional materials, such as quantum spin Hall effect, quantum anomalous Hall effect, quantum valley Hall Effect, topological superconductivity [1-4].
Key Words：Silicene, Graphene, Stanene, topological insulator, topological superconductor, QSHE, QAHE
 Cheng-Cheng Liu, Wanxiang Feng, and Yugui Yao, “Quantum Spin Hall Effect in Silicene and Two-Dimensional Germanium”, Phys. Rev. Lett. 107, 076802 (2011); Cheng-Cheng Liu, Hua Jiang, and Yugui Yao, “Low-energy effective Hamiltonian involving spin-orbit coupling in silicene and two-dimensional germanium and tin”, Phys. Rev. B 84, 195430 (2011); Hao-Ran chang, Jianhui Zhou, Hui Zhang, and Yugui Yao, “Probing the topological phase transition via density oscillations in silicene and germanene”, Phys. Rev. B 89, 201411(R) (2014); Maoyuan Wang, Liping Liu, Cheng-Cheng Liu, and Yugui Yao, “van der Waals heterostructures of germanene, stanene, and silicene with hexagonal boron nitride and their topological domain walls” Phys. Rev. B 93, 155412, (2016).
 Hui Pan, Zhenshan Li, Cheng-Cheng Liu, Guobao Zhu, Zhenhua Qiao, and Yugui Yao, “Valley-Polarized Quantum Anomalous-Hall Effects in Silicene”, Phys. Rev. Lett. 112, 106802 (2014); Hui Pan, Xin Li, Hua Jiang, Yugui Yao, and Shengyuan A Yang, Valley-polarized quantum anomalous Hall phase and disorder-induced valley-filtered chiral edge channels, Phys. Rev. B 91, 045404 (2015).
 Wenhui Wan, Yanfeng Ge, Fan Yang, and Yugui Yao, “Phonon-mediated Superconductivity in Silicene”, EPL 104, 36001 (2013); Lida Zhang, Fan Yang, and Yugui Yao, “Topological Superconductivity in Doped Silicene”, Sci. Rep. 5 08203 (2015); “Itinerant ferromagnetism and p+ip' superconductivity in doped bilayer silicene”, Phys. Rev B 92, 104504 (2015); Feng Liu, Cheng-Cheng Liu, Kehui Wu, Fan Yang, and Yugui Yao, “d+id' Chiral Superconductivity in Bilayer Silicene”, Phys. Rev. Lett. 111, 066804 (2013).
 Zhao et.al., “Rise of silicene: A competitive 2D material”, Prog. Mater. Sci. 83, 24 (2016).
1:30 PM - BM06.03.03
Fluorographene Based Ammonia Sensor
Shubhadeep Pal 1 , Tharangattu Narayanan Narayanan 1 Show Abstract
1 , TIFR Centre for Interdisciplinary Sciences, Hyderabad India
Exposure of ammonia can cause irritation to human respiratory system, skin, eyes etc. and a long exposure can lead to pulmonary odema. This can further leads to kidney problems or ulcers caused by Helicobacter pyloribacterial stomach infection. Even an ammonia test can deliver information about the liver functioning status. Ammonia sensing can also help to predict Reye syndrome which damage liver and brain. Presently various sensing platforms are existing for ammonia: metal oxide based sensors, catalytic ammonia sensors, conducting polymer based ammonia sensors, optical and spectrometric ammonia detection, gas permeable membranes based selective detection techniques etc. are the most frequently used techniques. But these methods lack the synergy of selective, sensitive, cost effective, and fast detection platform. A clinical ammonia sensor demands the above mentioned features along with a limit of detection value (LOD) of ~ 50 ppb within a response time of a few minutes. Existing selective optical methods are inadequate for the development of a portable point of care (POCs) ammonia sensors where limited sample needs to be detected using economically viable routes. The principle involved in the present ammonia sensor is strong and selective interaction of fluorographene (5wt% fluorine doped graphene) and ammonia. Here our interest lies on ammonia (NH3(gaseous phase)) and ammonium ion (NH4+(Liquid phase)) sensing with fluorine (F) doped graphene. Density functional theory based calculations show that electrostatic interactions between highly electronegative fluorine in fluorographene and hydrogen in ammonia form a strong interaction through hydrogen bonding. Further low surface energy of fluorographene makes it as hydrophobic leading to the devoid of other hydrogen bonding interactions. Thus this leads us a platform for selective ammonia/ammonium sensing at sub-pico molar level. This has been demonstrated with an impedance ammonia sensor using fluorographene modified screen printed electrode. Hence fluorographene brings a selective, highly sensitive, cost-effective and fast detection platform for ammonia/ ammonium.
1. Fluorographene based Ultrasensitive Ammonia Sensor, Kiran K. Tadi, Shubhadeep Pal, and T. N. Narayanan, Scientific Reports 6, 25221, doi: 10.1038/srep25221 (2016).
1:45 PM -
2:30 PM - *BM06.03.05
Extraordinary Light-Matter Interactions in Phosphorene
Yuerui Lu 1 Show Abstract
1 , Australian National University, Canberra, Australian Capital Territory, Australia
Phosphorene has recently gained tremendous interest in the current decade, specifically, black phosphorus monolayer, a unique 2D material, investigation of which has led towards the creation of new scientific discoveries for future optoelectronic sensor devices. Beyond the success of graphene and other 2D layered materials research over the past decades, the increased interest towards this new emerging single-element structured material is because of its layer dependent 0.3-2.0 eV bandgap modulation range which is also the bandgap modulation range of single- and few-layered Graphene and Transition Metal Dichalcogenides (TMDs). Besides that, phosphorene allows strong light-matter interactions at resonance because of its unique physical structure and outstanding electrical and optical properties. I would like to show the extraordinary light-matter interactions in phosphorene. Phosphorene owns quasi-1D excitons in a 2D system. We are able to precisely engineer the 0D-like excitons in air-stable monolayer phosphorene, which provides a unique platform to investigate the fundamental phenomena in the ideal 2D-1D-0D hybrid system. Finally, I will briefly highlight the potential biomedical applications of phosphorene.
Monday PM, November 27, 2017
Sheraton, 2nd Floor, Back Bay B
3:00 PM - *BM06.04.01
Point of Care Device for Renal Biomarkers
Joseph Bonventre 1 Show Abstract
1 Division of Renal Medicine, Brigham and Women's Hospital, Boston, Massachusetts, United States
The classical methods of assessing renal function, by measurement of serum blood urea nitrogen (BUN) and serum creatinine, are insensitive and nonspecific especially in the setting of acute kidney injury (AKI) or failure (ARF). The overall goal of these studies is to: Develop a point of care device that could measure urine and plasma Kidney Injury Molecule-1 (KIM-1), a sensitve and specific marker of proximal tubule injury, to drive physician decision making and improve patient outcomes. KIM-1 is a type 1 transmembrane protein that is not detectable in normal kidney tissue but is expressed at very high levels in dedifferentiated proximal tubule epithelial cells in human and rodent kidneys after ischemic or toxic injury. It is also a sensitive indicator of baseline kidney disease which is often clinically silent. A soluble form of cleaved KIM-1 can be detected in the blood and urine of patients with AKI and chronic kidney disease (CKD). Currently urinary or plasma KIM-1 measurements are performed using plate ELISA assays or microsphere-based Luminex xMAP technology that requires 3-4 hours of assay time and is dependent on a large analyzer. This approach greatly limits the use of the marker and its utility to make important decisions that are time sensitive in the care of the patient, including in the in-patient setting. A sampling of clinical utility of point of care measurement of KIM-1 include:
1)Early diagnosis of acute kidney injury (AKI) in the hospitalized patient. It is very important to avoid AKI given the very high morbidity and mortality associated with this diagnosis. Early detection of kidney proximal tubule injury will enable the physician to modify fluid management and doses of drugs that have nephrotoxic complications; 2)Monitoring of drug therapy for early signs of toxicity. This applies to both approved drugs but also drugs in development, especially when the drug has been implicated in nephrotoxicity; 3)Prediction of patients with diabetics who have high risk of progression of chronic kidney disease to end stage disease which will necessitate dialysis or transplantation. Diabetes is the leading cause of end stage kidney disease for which therapies (dialysis and transplantation) costs the US about 44 billion dollars per year. Blood levels of KIM-1 have been found to predict progression of diabetic kidney disease to end stage disease requiring dialysis or transplantation; 4)Diagnosis of early kidney injury associated with exposure to environmental toxins. We recently reported that urinary KIM-1 levels were associated with serum levels of chromium and arsenic in 83 children in northern Mexico. Worldwide it has been estimated that one-third of disease burden among children is related to preventable environmental risk factors.
3:30 PM - *BM06.04.02
Biomarkers of Human Diseases
Ramasamy Paulmurugan 1 , Dorian Liepmann 2 , Venkatesan Renugopalakrishnan 3 4 Show Abstract
1 Department of Radiology, Stanford School of Medicine, Canary Center at Stanford for Cancer Early Detection, Palo Alto, California, United States, 2 Department of Mechanical Engineering, University of California, Berkeley, Berekely, California, United States, 3 , Children's Hospital, Harvard Medical School, Boston, Massachusetts, United States, 4 Department of Chemistry and Chemical Biology, Northeastern University, Boston, Massachusetts, United States
Biomarkers are small and macromolecules present in bodily fluid that indicate disease initiation, progression, and response to treatment, and guide for disease prognosis, diagnosis, and drug response non-invasively from a small volume of blood or other bodily fluids. Ideally, if a biomarker is available from peripheral sources it reduces the costs and minimizes the potential complications associated with the collection of samples. Even this will be much more promising if the biomarker quantifications are combined with devices or methods that can quantify the biomarkers level with high sensitivity and specificity. Currently, most of the biomarkers used for disease diagnosis are either proteins or small molecule chemicals present in the peripheral blood, urine or cerebrospinal fluid (CSF). In the present ‘genomic era’ nucleic acid based diagnosis are under preparations and clinical evaluations for developing next-generation high sensitive kits for disease diagnosis. Small regulatory RNA (microRNAs) based diagnostics are also a promising approach once a clear pattern for each disease has been established. Currently this approach is limited since there is no complete list of microRNAs presence in a cell that has been established. Other important biomarkers, still poorly exploited, are epigenetic post-translational modifications in proteins such as methylation, sumoylation, neddylation, and acetylation. Especially these changes in histone proteins are considered highly promising since these post-translational modifications are highly organized and changes to this pattern in general alter cellular homeostasis and lead for pathogenesis. But establishing a method to accurately measure the changes within transcriptionally active euchromatin versus silenced heterochromatin regions need tremendous optimization, but a promising area to consider as it is more accurate than any other transient biomarkers that are available to date. Overall focus of this review talk will be to highlight current status of biomarker discovery research, methods available for diagnosis, and improvements and futuristic approaches needed in this research area.
Venkatesan Renugopalakrishnan, Northeastern University
Pulickel Ajayan, Rice University
Catherine Klapperich, Boston University
Dorian Liepmann, University of California, Berkeley
Anarghya Innovations and Technology Private Limited
MilliporeSigma (Sigma-Aldrich Materials Science)
Thermo Fisher Scientific
BM06.05: 2D Nanomaterials in Oncology
Tuesday AM, November 28, 2017
Sheraton, 2nd Floor, Back Bay B
7:00 AM - BM06.05.00
Biomimetic Carbon Nanotube Gas Sensor
Yen Ngo 1 , Michael Brothers 1 , Ahmad Islam 2 , Grant Slusher 1 , Kathy Fullerton 1 , Jennifer Martin 1 , Benji Maruyama 2 , Claude Grigsby 1 , Rajesh Naik 1 , Steve Kim 1 Show Abstract
1 711th Human Performance Wing, Air Force Research Laboratory, Wpafb, Ohio, United States, 2 Materials & Manufacturing Directorate, Air Force Research Laboratory, WPAFB, Ohio, United States
Air Force interest in wearable sensors for continuous force protection and human performance monitoring using physiological signs, cognitive biomarker, and chemical/biochemical volatile/nonvolatile molecules requires sensors with high sensitivity, selectivity or specificity, and energy-efficiency that are not yet available in commercial off the shelf sensors. Moreover, the number of potential gaseous targets that indicate the human physiological and cognitive states are constantly emerging from the biomarker discovery studies. Thus, the development of sensor technology faces challenges in meeting up with this explosively growing numbers of targets. Increasing the affinity or specificity of the Chemical Recognition Elements (CREs) will benefit the sensor response to the target with greater signal to noise ratio enabling significant reduction in sensor training time and non-specific interferences from various levels of other chemicals. Based on nature’s olfactory receptor-like concept, we demonstrate how a bioinspired CRE acts as the “sensing material” which can selectively bind to the target chemical. The CRE’s influence on enhancing the sensitivity and selectivity of a carbon nanotube (CNT) based electronic sensor is discussed in this paper. The selectivity of this biomimetic sensor platform is demonstrated by the parallel-testing with a commercial gas sensor. The overall sensor performance is planned to be tested in a custom built chemical chamber equipped with chemical composition, flow, and pressure regulators simulating an operation-relevant condition. This research can ultimately achieve the USAF sensing capabilities for monitoring pilot breathing air as well as protecting the health and performance of the Airman.
7:15 AM - *BM06.05.01
High Sensitive Biosensors for MicroRNA Quantitation—A Clinical Perspective
Ramasamy Paulmurugan 1 , Rammohan Devulapally 1 , Pulickel Ajayan 2 , Dorian Liepmann 3 , Venkatesan Renugopalakrishnan 4 5 Show Abstract
1 , Stanford University, Palo Alto, California, United States, 2 Material Science and NanoEngineering, Rice University, Houston, Texas, United States, 3 Mechanical Engineering, University of California, Berkeley, California, United States, 4 Children’s Hospital, Harvard Medical School, Boston, Massachusetts, United States, 5 Department of Chemistry and Chemical Biology, Northeastern University, Boston, Massachusetts, United States
MicroRNAs (miRNAs) are small regulatory molecules tightly control the expression of genes involved in various cellular pathways. The expressions of microRNAs are dysregulated in cells at various pathological conditions. Because of their extensive functional involvement in many cellular processes, under both normal and pathological conditions, they are potentially considered as biomarkers in disease diagnosis and therapeutic targets in drug development. MiRNAs are single stranded, evolutionarily conserved non-coding RNAs of 18 to 22 nucleotides in length, spliced from hair-pin loop transcripts of pre-miRNAs of ∼60 to 80 nucleotides. MiRNAs are coded by approximately 1% of genome in many species, and approximately 3% in human genome. MicroRNAs are constantly released from cells in to blood circulation as a protein-RNA complex; hence they are stable in the blood for longer times compare to other freely circulating biomolecules. Because miRNAs expression is dysregulated in various pathological conditions including cancer, and the secreted miRNAs are very stable in the blood circulation, precise quantitative profiling of pathologically associated miRNAs in the blood can serve as biomarkers to diagnose diseases at the early stage, and also can serve as markers in evaluating treatment response of diseases to therapeutic interventions. Hence, development of high sensitive, simple, and rapid quantitative detection system for multiple miRNAs in a single device would profile the pattern of circulating microRNAs in the blood and can be used for early diagnosis to reveal pathological conditions. Especially, developing a multiplex miRNA detection system using a high sensitive single layer graphene biosensor based on Field effect transistor (FET) electrical impedance spectroscopy (EIS) would be sensitive and easy to translate for routine clinical diagnosis as Point-of-care (POC) devices. The sensor composed of a single monolayer of graphene designed with microfluidic device to quantify multiple microRNAs in a single device and also with thermal regulatory mechanism to denature and hybridize isolated microRNAs from the samples would be desirable. The development of high sensitive sensor based on graphene in combination with FET-EIS readout could accuratively quantify the panel of microRNAs associated with a particular disease in a single device along with internal controls. This strategy could significantly change the current clinical management of patients with different diseases including cancer.
7:45 AM - BM06.05.02
Glycan-Stimulation Enables Purification of Prostate Cancer Circulating Tumor Cells on PEDOT NanoVelcro Chips for RNA Biomarker Detection
Chun-Hao Luo 1 , Mo-Yuan Shen 1 , Jie-Fu Chen 2 , Hsian-Rong Tseng 3 , Edwin Posadas 2 , Hsiao-hua Yu 1 Show Abstract
1 , Academia Sinica, Taipei City Taiwan, 2 , Cedars-Sinai Medical Center, Los Angeles, California, United States, 3 Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, California, United States
A glycan-stimulated and poly(3,4-ethylene-dioxythiophene)s (PEDOT)-based nanomaterial platform is fabricated to purify circulating tumor cells (CTCs) from blood samples of prostate cancer (PCa) patients. This new platform, phenylboronic acid (PBA)-grafted PEDOT NanoVelcro, combines the three-dimensional PEDOT nanosubstrate, which greatly enhances CTC capturing efficiency, with a poly(EDOT-PBA-co-EDOT-EG3) interfacial layer, which not only provides high specificity for CTC capture upon antibody conjugation but also enables competitive binding of sorbitol to gently release the captured cells. CTCs purified by this PEDOT NanoVelcro chip provide well-preserved RNA transcripts for the analysis of the expression level of several PCa-specific RNA biomarkers, which may provide clinical insights into the disease.
8:00 AM - BM06.05.03
Metallic Nanoislands on Graphene for Cellular Electrophysiology and Post-Radiation Monitoring for Head and Neck Cancer Patients
Darren Lipomi 1 Show Abstract
1 , University of California, San Diego, La Jolla, California, United States
This paper describes a type of mechanical sensor based on metallic nanoislands supported by single-layer graphene. These composite films transduce strain information using one of two mechanisms. In the first mechanism, modulation in conductivity is produced by widening of the gaps between nanoislands upon strain. This piezoresistive mechanism is sensitive to strains as small as 0.001% and as large as 10% when placed on elastomeric substrates. In the second mechanism, the metallic nanoislands are treated with an alkane thiol whose sensitivity to surface-enhanced Raman scattering (SERS) can be modulated by strain. That is, strain causes adjacent nanoislands to separate, which attenuates the electric field between nanoislands. This attenuation reduces the scattering of the molecules adsorbed to the surface—which we have nicknamed the “piezoplasmonic” mechanism. We have used these films to measure the contractions of cardiomyocytes using the piezoresistive mechanism and to stimulate (electrically) and measure the contractions of myoblast cells using the piezoplasmonic mechanism. Such sensors can also be bonded to medical adhesives to for physiological measurements. In this context, we combined piezoresistive strain sensing with surface electromyography (EMG) to measure swallowing activity of head and neck cancer patients after radiation therapy. Such patients must adhere to rigorous swallowing exercises following radiation or risk developing swallowing dysfunction. When combined with a machine learning algorithm, it is possible to use EMG and graphene/nanoisland films to monitor swallowing activity and adherence to the exercise protocol.
8:15 AM - *BM06.05.04
Nanomaterial Based Non-Invasive Biosensors for Cancer Detection
Bansi Malhotra 1 Show Abstract
1 , Delhi Technological University, New Delhi India
Biosensors are known to offer many advantages such as flexibility, increased assay speed, automation, reduced costs of diagnostic testing , capability for multi-target analyses and automation for clinical diagnostics applications1-4. These interesting bioelectronic devices have the potential to facilitate state-of-the-art molecular analysis that can be carried out without requiring a state-of-the-art laboratory. Biosensor is an electronic device that can be used to detect a desired biological analyte by converting a biochemical reaction via a transducer into an electrical signal.1,2 Biosensors for cancer detection have recently aroused much interest.
Oncologists currently heavily rely on a few biomarkers and histological characterization of tumors. Some of the molecular signatures include protein profiles, changes in gene expression, genetic and epigenetic signatures and post-translational modification of proteins. These molecular signatures provide new opportunities for development of biosensors for cancer detection. Biosensors have enormous potential to contribute to the evolution of new molecular diagnostic techniques for patients suffering with cancerous diseases. In this context, nanostructured metal oxides have recently been found to play an important role towards the fabrication of a biosensor for cancer detection. I will talk about some of the recent results obtained in our laboratories relating to the fabrication and application of nanosrtuctured metal oxide (zirconia) based non-invasive biosensors for oral cancer detection.2-4
Recent advances in carbon based nanosystems for cancer theranostics,Shine Augustine,,Jay Singh, Manish Srivastava, Monica Sharma, Asmita Das and Bansi D. Malhotra ,Biomaterials Science,2017,5,901
Biofunctionalized Nanostructured Zirconia for Biomedical Application: A Smart Approach for Oral Cancer Detection,2015 , Suveen Kumar, S. Kumar, Sachchidanand Tiwari, S. Srivastava, M. Srivastava, B.K.Yadav, S.Kumar, T.T.Tran, A.K.Dewan, A.Mulchandani,J. G. Sharma,S.Maji and Bansi Dhar Malhotra,Advanced Science ,2015, Volume 2,1500048
Nanostructured Zirconia Decorated Reduced Graphene Oxide Based Efficient Biosensing Platform for Non-invasive Oral Cancer Detection, Suveen Kumar, Jai Gopal Sharma, Sagar Maji and Bansi Dhar Malhotra, Biosensors & Bioelectronics,2015(78, 497-504
Highly Sensitive Protein Functionalized Nanostructured Hafnium Oxide Based Biosensing Platform for Non-invasive Oral Cancer Detection,Suveen Kumar, S Kumar, S Tiwari, S Augustine,Shine Srivastava, BK Yadav, B.D. Malhotra,Sensors & Actuators B 2016,235, 1-10
8:45 AM - BM06.05.05
Heat Induced Chemotherapy Delivery Systems for Colorectal Cancer Treatment
Hale Arca 1 , Nicole Levi-Polyachenko 1 Show Abstract
1 , Wake Forest Medical Center, Winston Salem, North Carolina, United States
A biodegradable elastomeric polyester, poly (1,8-octanediol co-citric acid) (POC) has been previously investigated for its potential in tissue engineering since it is a biocompatible and compressible material with surface affinity to various cell types. In the current study, POC has been used as a drug delivery vehicle after being synthesized by covalent coupling of non-toxic monomers, 1,8-octanediol to citric acid by polycondensation reactions, then cross-linking by heat to form a hydrogel network. The biggest advantages of the POC are the simple synthesis without a catalyst or cross-linking agent and, controllable crosslinking to tailor the elasticity and biodegradability by hydrolysis of ester linkages in physiological conditions.
The controlled delivery of chemotherapeutics has the potential to expose higher concentrations of pharmaceuticals over longer periods of time to cancer cells while minimizing systemic toxicity. Therefore we designed a polymeric system with oxaliplatin that can generate mild hyperthermia for colorectal cancer treatment. Rising temperatures increases the drug penetration and, cancer cells are more sensitive to mild hyperthermia than healthy cells. Therefore adding a heating component to a drug delivery system can be very beneficial for cancer treatment. To achieve the goal, donor–acceptor conjugated polymer nanoparticles (NPs) based on poly[4,4-bis(2-ethylhexyl)-cyclopenta[2,1-b;3,4-b’]dithiophene-2,6-diyl-alt-2,1,3-benzoselenadiazole-4,7-diyl] (PCPDTBSe) were prepared with Pluronic F127, a stabilizing agent. PCPDTBSe is a conductive polymer and used as the thermal component of the formulation that absorbs near infrared (NIR, 800nm) light then emits heat to release the drug at a higher rate and generate mild hyperthermia (temperatures up to 45°C). The conjugated polymers can form stable NPs in aqueous media, non-toxic until stimulated by NIR light and can generate repeatable heating cycles. Encapsulating PCPDTBSe NPs and chemotherapy drug oxaliplatin for their incorporation to POC polymer matrix increases the release rate of the drug as a result of the heating cycles. Thus, the polymer-based combination therapy can be useful in the future for clinical applications to generate heat by external stimulation and has potential for prolonged drug release as the polymer decomposes.
9:30 AM - *BM06.05.06
Application of Theranostics Materials against Cancer
Sakthi Kumar 1 Show Abstract
1 Bio Nano Electronics Research Center, Graduate School of Interdisciplinary New Science, Toyo University, Saitama Japan
Nanomaterials are finding more applications in the biomedical field as imaging materials and drug delivery vehicle to carry drugs to target site etc. New drugs and medical devices developed due to the fusion of bio and nanoscience could target and remove the cancer cells without making any collateral damage to healthy tissues.
We have developed a nano system in which we have used dual drugs paclitaxel and suramin; paclitaxel to act as the drug against cancer and suramin to act against angiogenesis. For efficient targeting, we have utilized triple targeting moieties folate, TEM7 and CD31. We found that the developed nanoformulation worked very well and selectively destroyed cancer cells. The imaging moiety incorporated to the nanosystem helped us to image the cancer cells too.
We have also developed nanomaterials and biomaterials having applications in the field of nano drug delivery as well as in biotechnology.
10:00 AM - BM06.05.07
Serum miRNA Signature for the Detection of Clinically Significant Prostate Cancer
Ali Alhasan 1 2 , Chad Mirkin 2 Show Abstract
1 , King Abdulaziz City for Science and Technology, Riyadh Saudi Arabia, 2 , Northwestern University, Evanston, Illinois, United States
We report the identification of a molecular signature using the Scano-miR profiling platform based on the differential expression of circulating microRNAs (miRNA, miR) in serum samples specific to patients with very high-risk (VHR) prostate cancer (PCa). Five miRNA PCa biomarkers (miR-200c, miR-605, miR-135a*, miR-433, and miR-106a) were identified as useful for differentiating indolent and aggressive forms of PCa. All patients with VHR PCa in the study had elevated serum levels of miR-200c. Circulating miR-433, which was differentially expressed in patients with VHR versus low-risk (LR) forms of PCa, was not detectable by quantitative real-time PCR in samples from healthy volunteers. In blind studies, the five miRNA PCa biomarkers were able to differentiate patients with VHR PCas from those with LR forms as well as healthy individuals with at least 89% accuracy. Biological pathway analysis showed the predictive capability of these miRNA biomarkers for the diagnosis and prognosis of VHR aggressive PCa.
10:15 AM - *BM06.05.08
Design, Fabrication and Characteristics of Novel Theranostics for Cancer
Qingwen Guan 1 , Min Wang 1 Show Abstract
1 Department of Mechanical Engineering, The University of Hong Kong, Hong Kong Hong Kong
Despite the considerable advances in the biomedical field, cancer still remains a major cause for human deaths. The distinctive structural and functional features of nanomaterials have led to their increasing applications as anti-cancer nanotechnologies for diagnosis, imaging, and therapy. Developing and utilizing theranostics, which integrate diagnostic and therapeutic moieties in a single, nano-sized physical entity to perform detection, imaging and treatment functions, are revolutionizing cancer oncology. To achieve multiple functions, different types of nanostructures can be integrated into a single nanodevice in which each individual component performs its function and moreover new synergistic effects may be generated. The design of theranostics strongly depends on the targeted multiple functions as well as their final application. In general, there are two approaches to incorporate a diagnostic or therapeutic agent in a nanoparticle: it is stuck to the surface of a solid nanoparticle (noble metal, metal oxide, silica, carbon nanotube, quantum dot, etc.), or it is encapsulated in a (porous) nanostructure (polymer, mesoporous silica, micelle, liposome, etc.). Therefore, hybrid, dumbbell, core-satellite, core-shell, yolk-shell, and Janus structured nanoparticles are investigated for new theranostics. There are two strategies to fabricate multifunctional nanoparticles. The first, molecular functionalization, involves attaching antibodies, peptide proteins, dyes, etc. to pre-synthesized nanoparticles. The other strategy opts for integrating different types of nanocomponents into a single nanoparticle through one-spot synthesis. Due to their unique optical properties together with biocompatibility and facile synthesis, gold nanoparticles are excellent substrates for constructing novel theranostics. They can scatter light with extraordinary efficiency, thereby providing sufficient contrast in biomedical imaging. Their surface plasmon resonance effect empowers them for surface enhanced Raman scattering (SERS) detection with high sensitivity. In our research, using gold nanorods, highly branched gold nanoparticles and gold-silver hybrids, different types of multifunctional theranostics with different structures and core functions were designed and fabricated and their performance in cancer targeting, imaging and treatment was investigated. This presentation will present our investigations on theranostics based on metal-polymer nanoparticles, metal-mesoporous silica core-shell nanoparticles, metal-silica shell-metal satellite nanoparticles, metal-hollow silica yolk-shell nanoparticles, silica-metal core-metal satellite nanoparticles, etc. Anticancer drugs or plasmids could be encapsulated in polymer shell or mesoporous silica. Photothermal therapy, chemotherapy, gene therapy and combined therapy could be achieved by these theranostics.
10:45 AM - BM06.05.09
Development of a Novel Chemotherapeutic rGO Decorated ZnS:Mn QDs Nanoplatform for Breast Cancer Cell
Daysi Diaz-Diestra 1 2 4 , Bibek Thapa 1 3 , Juan Beltran-Huarac 3 4 , Brad Weiner 1 2 , Gerardo Morell 1 3 Show Abstract
1 Molecular Sciences Research Center, University of Puerto Rico, San Juan, Puerto Rico, United States, 2 Department of Chemistry, University of Puerto Rico, San Juan, Puerto Rico, United States, 4 Laboratory of Environmental Health Nanosciences, Center for Nanotechnology and Nanotoxicology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, United States, 3 Department of Physics, University of Puerto Rico, San Juan, Puerto Rico, United States
Cancer is one of the leading causes of death worldwide, the poor specificity and systemic side effects of the available therapies contribute to the low recovery prognosis for many patients. To circumvent these difficulties, novel therapies based on nanomaterials have being proposed. In this regard, reduced Graphene Oxide (rGO), has emerged as a novel nano-carrier for drugs, genes, and other therapeutic agents showing remarkable results. Quantum dots (QDs) have being integrated in rGO based nanoplatform for imaging and therapy purposes. Nevertheless, in most of the systems so far reported, the QDs used are highly cytotoxic. In this study, we have developed a drug delivery/ imaging nano-platform (NP) based on rGO/ZnS:Mn QDs to deliver DOX into MDA-MB 231 ( breast cancer cells). Mn doped ZnS QDs have being extensively used in different biomedical applications due to its unique optical properties as well its high biocompatibility. The loading content and encapsulation efficiency of NP toward Dox were 35% and 90% respectively. A detailed study of the effects of dispersion methods used for the preparation of the NP suspensions for cytotoxic studies was performed. It was observed that high energy sonication methods can dramatically altered the nanoparticles bio-compatibility probably caused by the NP surface disruptions. Confocal microscopy images further show the suitability of this NP as nanoprobe for imaging cancerous cells and confirm its high selectivity and efficiency (release of the loaded drug in the targeted cell’s nucleus). This piece of research represents a step forward in the development of novel drug delivery nanoplatforms.
BM06.06: Advancing Frontiers of 2D Nanomaterials III
Tuesday PM, November 28, 2017
Sheraton, 2nd Floor, Back Bay B
1:00 PM - *BM06.06.01
Low-Cost Sensors for Point-of-Care Bioanalysis Using Paper-Based Microfluidic Devices
Charles Mace 1 , Syrena Fernandes 1 , Jessica Brooks 1 , Keith Baillargeon 1 Show Abstract
1 , Tufts University, Medford, Massachusetts, United States
There are many situations in which measurements must be made outside of a laboratory setting or in the field. Access to technology that enables these measurements without sacrificing analytical performance is therefore necessary. This capability often requires the successful integration of sample preparation, liquid handling, and signal transduction within a single device, which may come at a significant expense to the user. However, a limited number of options exist for scenarios when the cost of a device is just as critical of a criterion as its performance. Paper-based microfluidic devices have the capacity to enable these critical features and fulfill many requirements of an ideal analytical platform for use in limited-resource settings: they are inexpensive, disposable, deliverable, and operationally simple. In this seminar, we will discuss our efforts towards the design and fabrication of a general, paper-based microfluidic device architecture that can be used to support the development of point-of-care immunoassays. We will describe how the material properties of paper (e.g., pore size, porosity, and surface area) influence the performance of an assay. Finally, we will demonstrate how simple chemical methods and nanomaterials can be used to improve the sensitivity of a measurement.
1:30 PM - BM06.06.03
Graphene and Graphene Quantum Dots (GQDs) Based Multiplexed Electrochemiluminescence (ECL) Biosensor for Point-of-Care Detection of Pathogens
Anup Kale 1 , Vedashree Sirdeshmukh 1 , Harshika Apte 2 Show Abstract
1 , College of Engineering Pune (COEP), Pune India, 2 School of Biotechnology and Bioinformatics, DY Patil University, Navi Mumbai, Pune, Maharashtra, India
The detection and prevention of water-borne and hospital-borne bacterial infections in time is a challenging task. Millions of people suffer due to the bacterial infections worldwide underlying the immediate need for developing a sensitive, rapid and facile diagnostic tool. The detection of multiple analytes simultaneously is at the core of developing next-generation diagnostic tools. The integration of nanotechnology with biomedicine and diagnostics has revolutionized the field and opened up new opportunities for better treatment and prognosis. Developing biosensors with nanoprobes and nano-transducer mediaters using the surface, electronic and electrocatalytic properties can lead to improved and multiplexed tools for pathogen detection. The Electrochemiluminescence (ECL) is one of the highly promising electrochemical techniques that offer high specificity and high sensitivity. Exploring nanomaterial based luminophores as ECL emitters has been a driving force in recent times for enhanced bioanalysis. Graphene based materials including Graphene Quantum Dots (GQDs) due to their inherent versatile properties are at the forefront of developing next-generation diagnostic tools.
Here in, we report on a sensing platform that can lead to a Point-Of-Care diagnostic tool for bacterial infections. We have selected E. coli and S. aureus as model organisms developed on-chip multiplexed ECL detection assay. In order to achieve higher sensitivity, we synthesized functionalized reduced Graphene Oxide/gold (rGO-AuNP) nanocomposites and GQDs studied their significance over traditional electrodes and ECL probes respectively. The electron microscopy revealed the uniform distribution of gold nanoparticles on rGO templates. It was a 3 step detection method. The Screen Printed Electrodes (SCE) were modified with rGO-AuNP nanocomposites for ECL based detection. Furthermore, pathogen specific (E. coli and S. aureus) antibody conjugated GQD440, GQD550 and GQD660 were used as ECL probes with co-reactants. The assay was optimized for GO-AuNP nanocomposites as a sensing and transuding platform and GQDs as ECL probes. The underlying mechanism with stability, specificity, signal amplification parameters and enhancing photo induced electron transfer were studied in detail. The results show that rapid detection of pathogens less than 1 CFU/mL in real samples is possible. This smart ECL nano-biosensor can be a significant contribution in the direction of Point-Of-Care diagnosis.
1:45 PM - BM06.06.04
Photoluminescent-Based Nanosensor for Sensitive Detection of Biomolecules
Rehab Amin 1 2 Show Abstract
1 , National Institute of Laser Enhanced Sciences, Cairo University, Giza Egypt, 2 , Egypt Nanotechnology Center, Cairo University, El-Sheikh Zayed Campus Egypt
Nanotechnology is promising in the field of optical sensors due to the unique size-dependent optical properties of nanoparticles. The large surface area of nanomaterials enables attachment of a large number of target molecules. Our recent Nano research in the field of biosensing will be presented.
Polymer-based nanomaterials; in particularly polyaniline nanoparticles have attracted growing attention due to its stability. Polyaniline nanosensor was developed and applied to detect glucose molecules optically using microplate assay. Results showed that the developed nanomaterials are a promising rapid and sensitive glucose sensor.
Quantum dots have received great attention in sensing and recognizing biomolecules due to their good luminescence quality and surface functionalization.
Recently, our group developed cadmium telluride quantum dots capped with thioglycolic acid as a fluorometric Cytochrome c (Cyt c) nanosensor. The prepared nanosensor could be used for the quantification of different concentrations of Cyt c ranging from 0.5 - 2.5 μM.
Although considerable technological success has been achieved in this field of Bio-Nano research, the environmental concerns of nanotechnology remain a great challenge. We successfully biosynthesized nanomaterials; in a clean, non-toxic and ecologically sound manner.
In conclusion, BioNano Research should gain considerable attention to understanding the properties of nanomaterials and their interactions for considerate applications.
2:30 PM - *BM06.06.05
Design of Hierarchical Biomaterials Based on Protein, Graphene and Other Building Blocks
Markus Buehler 1 , David Kaplan 1 , Shengjie Ling 1 , Zhao Qin 1 Show Abstract
1 , Massachusetts Institute of Technology, Cambridge, Massachusetts, United States
Spiders and silkworms are outstanding material masters in nature, and those and related organisms can serve as a powerful material platform to integrate synthetic and naturally occurring building blocks. Indeed, spiders and silkworms design and spin silk fibers with unrivaled mechanical properties by utilizing a simple, green and water-based approach. Whereas a variety of artificial spinning methods have been pursued, the preparation of regenerated silk fibers (RSFs) that retain the advantages of natural silks in terms of structural hierarchy and mechanical properties remains challenging. Inspired by the anisotropic liquid crystal and dry spinning features from the natural process, here we report a new bioinspired approach to spin RSFs. First, we develop a novel nematic silk microfibril solution, highly viscous and stable, by partially dissolving silk fibers into microfibrils. This solution maintains the hierarchical structures in natural silks and serves as spinning dope. It is then spun into RSFs by direct extrusion, offering a new route to generate polymorphic and hierarchical RSFs with physical properties beyond natural fiber construction, because no complicated coagulation and post-processing steps are required. The materials maintain the structural hierarchy and mechanical properties of natural silks, including a modulus of 11±4 GPa, even higher than natural spider silk. It can further be functionalized with a conductive silk/carbon nanotube coating, responsive to changes in humidity and temperature. We conclude the presentation by reviewing recent work on generating a new class of 2D materials that build on concepts of nacre's design principles, combined with proteins found in mussel threads.
3:00 PM - BM06.06.06
Electrochemical Gas Sensor to Diagnose Alzheimer’s Disease through Exhaled Breath
Shadi Emam 1 , Nian-Xiang Sun 1 Show Abstract
1 Electrical Engineering, Northeastern University, Boston, Massachusetts, United States
Researchers were always trying to find a method to diagnose Alzheimer’s disease (AD) at its earliest stage since when it is diagnosed; some tissues of the brain have already been damaged. Volatile organic compounds (VOCs) profile in exhaled breath reflects the metabolic changes, organ failure, or neuronal dysfunction, are reliable for diagnosis even at the very onset of disease. In this paper, an electrochemical gas sensor that can sense Butylated Hydroxytoluene (BHT) was fabricated and tested. BHT was among the chemicals found in the exhaled breath of AD patients. The three-layer sensor composed of the glassy carbon electrode (GCE), graphene-Prussian Blue (GR-PB), and molecular imprinting polymer (MIP) respectively from bottom to top. Molecular imprinting technology is self-assembly between target analytes and material precursors to create a molecular “lock and key” architecture. The developed sensor has been tested over 5-100 part per million (ppm) and 0.02-1 part per billion (ppb) level of concentration while the sensor resistance has been monitored. The limit of detection was 20 part per trillion (ppt). The sensor displayed high selectivity, excellent sensitivity and good reproducibility for the determination of BHT.
3:15 PM - BM06.06.07
Design and Implementation of Highly Versatile Peptide-Probe Modular Molecular Constructs for Bionanosensing with Single-Layer FETs
Richard Lee 1 , Dmitriy Khatayevich 1 , David Starkebaum 1 , Carolyn Gresswell 1 , Yuhei Hayamizu 2 , William Grady 3 , Mehmet Sarikaya 1 Show Abstract
1 GEMSEC, Materials Science and Engineering, University of Washington, Seattle, Washington, United States, 2 Organic and Polymeric Materials, Tokyo Institute of Technology, Tokyo, Meguro, Japan, 3 Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States
Biosensor platforms show promise for early diagnosis of many types of cancers. A key challenge in designing biosensors, however, is achieving high detection sensitivity without compromising target selectivity. Field effect transistors based on 2D solids offer enhanced sensitivity due to their atomically thin characteristics. Still, such biosensors must possess several critical attributes to detect ultra-low target concentrations within a bodily fluid: (1) Probes must be securely immobilized onto the 2D-layer substrate; (2) Optimal molecular packing of the probe must be controlled for efficient target capture; (3) Non-specific adsorption of molecules other than the target must be prevented; (4) Non-covalent attachment of the probe onto the surface is favored to avoid causing surface defects which would otherwise affect sensing properties. Achieving these attributes presents several major obstacles. Herein we developed a biosensor platform that addresses these challenges, and sets the foundation for further development of a versatile cancer diagnostic device. Here we use a mixed-monolayer of two graphene-binding peptides. One immobilizes probes onto the sensing surface and the other confers anti-fouling properties that mitigate non-specific protein adsorption. The probe immobilizing peptide is a modular chimeric construct and can be easily modified to detect various targets within complex biological mixtures. We show that specific biomarkers implicated in pancreatic cancer (CEA and CA19-9) were selectively detected in 10-8 g/mL range against a background of 3% fetal bovine serum. Additionally, the modular design was used to target microRNA biomarkers – with the eventual goal of collecting expression profiles for clinical diagnosis and prognosis of various diseases. Probe immobilization was characterized using surface plasmon resonance (SPR) analysis and confirms proper assembly of the chimeric construct (i.e., immobilized graphene-binding peptide displaying the probe). Raman spectroscopy was used to confirm biofunctionalization of the graphene surface, probe immobilization, and bio-recognition of the miRNA target. UV photoelectron spectroscopy (UPS) reveals hole-doping of graphene by the immobilizing peptide, and shows a change in work function before and after probe immobilization. Finally, targets were detected in physiologically-relevant pH and osmotic conditions using fluids that mimic the urine, plasma, serum and saliva milieu. In conclusion, we have developed a biosensing strategy for flexible target sensing of biomolecules which provides effective passivation of the sensing surface for highly-specific detection. The research was supported by NSF-MGI (Materials Genome Initiative) Program through DMR-1629071 and by the Amazon-Catalyst program through UW/CoMotion.
3:30 PM - *BM06.06.08
Graphene Nano-Electrodes for DNA Sequencing
Jan Mol 1 Show Abstract
1 Materials, University of Oxford, Oxford United Kingdom
Nanoscale biosensor technology has attracted considerable attention with its promise of revolutionizing techniques ranging from biological interfaces to rapid pathogen detection to enabling DNA data storage. Many approaches, such as nanopore sequencing, have been explored and are already achieving tremendous success, however new sensing modalities and architectures are emerging that are envisioned for the next generation of ever more capable biosensors. In recent years rapid advances have been made and many architectures have been put forward for novel approaches to biomolecular sensing using nanoelectronics, including the advent of tunnel junctions as a sensing platform. With high accuracy, sensitivity, and affordability these sensors are predicted to drive a shift to personalized medicine and rapid diagnostics in real time anywhere in the world.
Due to graphene’s remarkable properties, such as atomic thinness, high conductivity, and chemical stability in both air and liquid, it has attracted considerable attention for applications in biosensing. The ability to synthesize graphene via scalable methods and pattern it with nanoscale precision make graphene ideally suitable as the active component in biomolecular sensors. Graphene nanogaps offer the potential to probe analytes electronically at the atomic-scale with single-molecule sensitivity and high time resolution through recognition tunneling. We have developed a feedback-controlled electroburning technique that provides a mechanism to controllably and consistently produce a high yield of nanogaps with the desired nanoscale dimensions. Previously, we have demonstrated the application of feedback-controlled electroburnt nanogaps for single-molecule devices and single-electron transistors. Here we will present the progress towards developing graphene nano-electrodes for biomolecular sensing, with a specific focus on DNA sequencing.
Venkatesan Renugopalakrishnan, Northeastern University
Pulickel Ajayan, Rice University
Catherine Klapperich, Boston University
Dorian Liepmann, University of California, Berkeley
Anarghya Innovations and Technology Private Limited
MilliporeSigma (Sigma-Aldrich Materials Science)
Thermo Fisher Scientific
Wednesday AM, November 29, 2017
Sheraton, 2nd Floor, Back Bay B
7:00 AM - *BM06.07.01
Current Status of Therapeutic Diabetes Technology
Yogish Kudva 1 Show Abstract
1 , Mayo Clinic, Rochester, Minnesota, United States
The maturation of diabetes related devices and technologies has transformed the therapy of diabetes mellitus especially type 1 diabetes mellitus (T1D). T1D is characterized by high unpredictable glucose variability and thus requires a continuous glucose monitor (CGM) for optimal management. CGM technology has matured in the last 20 years enabling development of automated insulin delivery. An automated insulin delivery system based on CGM is now available in the US for clinical practice since March 2017. At this, 4 pivotal studies are in various stages of planning and initiation in the US and Western Europe. Data from these studies will be submitted to the FDA for clinical approval of such systems starting in 2019. Recent studies of automated insulin delivery and clinical trials mentioned above will be discussed. CGM is used by a minority of patients with diabetes. Even among patients with T1D, use of CGM and thus automated insulin delivery is limited. Reasons and upcoming solutions for this will be discussed. Finally, the landscape for the next 5-10 years for the field will be reviewed.
7:30 AM - *BM06.07.02
Graphene-Based Biosensors for Medicine and Research
Kiana Aran 1 2 , Pulickel Ajayan 3 , Venkatesan Renugopalakrishnan 4 5 , Dorian Liepmann 2 Show Abstract
1 School of Applied Life Sciences, Keck Graduate Institute, Claremont University Consortium, Claremont, California, United States, 2 Department of Bioengineering, University of California, Berkeley, Berkeley, California, United States, 3 Department of Materials Science and Nanotechnology, Rice University, Houston, Texas, United States, 4 , Children’s Hospital, Harvard Medical School, Center for Life Sciences, Boston, Massachusetts, United States, 5 Department of Chemistry and Center for Renewable Energy Technology, Northeastern University, Boston, Massachusetts, United States
Graphene based materials have been making a profound impact in biosensing applications due to their capability to adsorb a variety of biomolecules, which make them ideal materials for constructing biosensors. For example, a graphene-based field-effect transistor (FET) can easily detect individual molecules on its surface and is a reliable and highly sensitive candidate for recognizing biomarkers in biological fluids. In addition, integration of graphene into plastic-based microfluidic systems could make it possible to use standard manufacturing methods to create innovative multiplexed devices with improved biosensing technologies that are easy-to-use yet powerful. Development and initial results of hybrid plastic microfluidic devices with integrated graphene-protein biosensor chips for multiple diagnostic and research applications will be presented. For example, the performance of a graphene-based sensor in terms of sensitivity, precision, and accuracy designed for continuous glucose monitoring will be presented. The system uses a glucose oxidase-functionalized graphene, housed in a plastic microfluidic system, to transduce enzymatic binding of glucose into electrical signals that can be read and processed by a stand-alone system. Several chemistry steps are employed to functionalize the graphene chips and reduce non-specific binding, thus these sensors perform well in complex media such as whole blood, blood serum and cell growth media. In addition, by combining microfluidic technologies for sample distribution with graphene-based detection, digital biosensors with multianalyte detection capabilities can be created.
8:00 AM - BM06.07.03
In Vitro Optical Detection of Glycated Hemoglobin to Evaluate Glycemic State in Diabetic Patients
Sanghamitra Mandal 1 , Omar Manasreh 1 Show Abstract
1 Electrical Engineering, University of Arkansas, Fayetteville, Arkansas, United States
Glycated hemoglobin (HbA1c) level in blood is indicated as a percentage, and is based on the attachment of glucose molecules to the hemoglobin in red blood cells. The HbA1c level is highly correlated with risk factors of cardiovascular diseases, especially in obesity, hypertension and dyslipidemia amongst individuals without Diabetes Mellitus. A lyophilized reference control consisting of human blood based solutions is used as an in-vitro diagnostic control that is composed of a buffered bacteriostatic and fungi-static human blood matrix. The absorbance of diluted HbA1c is recorded using the Varian Cary 500 Scan UV-Vis-NIR spectrophotometer for a wavelength ranging from 200 - 1000 nm. Prominent absorbance peaks at 542 nm and 577 nm are noticed for diluted HbA1c concentrations ranging from 4 – 14 percentage. Since the absorbance peaks falls within the green color range of the visible light spectrum, a green light emitting device is used as the light source in the optical sensor instrumentation design. The intensity of the green light is measured using a photo-transistor after it passes through the diluted HbA1c samples. The photo-transistor output voltage changes depending upon the intensity of light photons passing through the samples. The photo-transistor voltage as a function of HbA1c percentage concentration shows an exponentially decaying curve. The equation parameters obtained from the regression analysis is then used to calculate the concentration depending upon the photo-transistor output voltage data. Since, the absorbance of HbA1c increases with concentration, the transmitted light decreases. Therefore, it is inferred that the absorbance and the voltage recorded by the photo-transistor are inversely related. The optical sensor is calibrated to different HbA1c percentage levels by measuring the output voltage of the photo-transistor. The percentage of unknown HbA1c solution is then predicted based on this calibration curve between output voltage and HbA1c percentage concentration.
8:15 AM - BM06.07.04
Self-Powered Ultrasensitive Glucose Sensor with Graphene Multiple Heterojunctions
Cheng-Han Chang 1 , Hsin Chen 1 , Yu-Ming Liao 1 , Hung-I Lin 1 , Yuan-Fu Huang 1 , Shih-Yao Lin 1 , Wei-Ju Lin 1 , Han-Yi Chou 2 3 , Yang-Fang Chen 1 Show Abstract
1 Department of Physics, National Taiwan University, Taipei Taiwan, 2 Graduate Institute of Oral Biology, School of Dentistry, College of Medicine, National Taiwan University, Taipei Taiwan, 3 Center for Biotechnology, National Taiwan University, Taipei Taiwan
A highly sensitive glucose biosensor based on graphene/ZnO/p-Si heterojunctions is demonstrated. Its sensing mechanism makes use of the large variation in the Fermi energy of graphene upon direct electron transfer of glucose oxidase at the presence of glucose molecules, with a film of ZnO acting as a sieve layer to block the carriers from transferring into the underlying semiconductor layer, resulting in a superb detection sensitivity. Through measurements of the current-voltage characteristics and time dependence of the changed current, this unique structure responds to glucose concentrations from as low as 0.1 pM to 100 μM range, which outperforms the best value ever reported by more than three orders of magnitude. Furthermore, we demonstrate the self-powered capability of this newly designed biosensor at room light illumination level, without compromising its sensitivity and dynamic range of detection. Altogether, this device presents with an excellent performance that surpasses all current glucose detection devices used in medical control, representing a novel possibility for easy and painless monitoring of blood glucose for patients with diabetes mellitus.
A biosensor based on vertically stacked graphene based multiple heterojunction has been designed, fabricated, and demonstrated. It shows an extremely high sensitivity, a wide range covering from 0.1 pM to 100 μM, and ultrafast response in the order of ms. Quite remarkably, the sensitivity sets the highest value ever reported, which exceed the best reported devices by more than three orders of magnitude. In addition, this newly developed biosensor exhibits a unique feature of high performance even under room light illumination without an external bias. All these outstanding characteristics are very useful for the next generation of advanced biosensors. Especially, the extremely high sensitivity may be able to lead to the development of non-invasive biosensors, and the self-powered capability is beneficial for the creation of handy, convenient, wearable, and green devices.
This work was supported by the Ministry of Science and Technology and the Ministry of Education of the Republic of China.
8:30 AM - *BM06.07.05
Molecular Engineering of Field-Effect Transistor Biosensors Based on 2D Nanomaterials
Junhong Chen 1 Show Abstract
1 , Univ of Wisconsin-Milwaukee, Milwaukee, Wisconsin, United States
Rapid, accurate, and low-cost detection of various biological species is an unmet need in many cases. For example, the Ebola virus transmits a highly contagious, frequently fatal human disease for which there is no specific antiviral treatment. Therefore, rapid, accurate, and early diagnosis of Ebola virus disease (EVD) is critical to public health containment efforts, particularly in developing countries where resources are few and EVD is endemic. Two-dimensional (2D) nanomaterials, such as graphene-based nanomaterials and black phosphorous nanosheets, have attracted significant attention in the field of biosensors because of their excellent electronic properties and large specific surface areas. This talk will unveil a powerful approach to real-time biosensors through molecular engineering of 2D nanomaterials in a field-effect transistor platform. The working principle of the biosensor is that the conductivity of 2D nanomaterial channel (usually measured in resistance) changes upon binding of biological species to molecular probes anchored on the nanomaterial surface. As such, the presence and the concentration of analytes, such as Ebola virus, bacteria, and proteins, can be determined by measuring the sensor resistance change. The platform technology allows for real-time detection of a wide range of biological species with superior sensitivity and selectivity.
BM06.08: Biosensors I
Wednesday AM, November 29, 2017
Sheraton, 2nd Floor, Back Bay B
9:30 AM - *BM06.08.01
Graphene Quantum Capacitance Biosensors
Steven Koester 1 Show Abstract
1 Department of Electrical and Computer Engineering, University of Minnesota Twin Cities, Minneapolis, Minnesota, United States
Graphene has the potential to form the basis of a powerful sensing platform due to its unique combination of properties, including high surface sensitivity, chemical stability, mechanical strength, and biocompatibility. However, nearly all sensor concepts based upon graphene are based upon simple resistive sensing, which can limit the range of applications suitable for these devices, including for many biological sensing applications where wire leads can be cumbersome or impractical. In this work, I describe a sensor concept that utilizes the quantum capacitance in graphene to create capacitive sensors, which can either be probed directly or used to form a passive sensor that can be interrogated wirelessly. Our group has developed a robust, high-yield fabrication process for graphene varactors and we have demonstrated devices with capacitance tuning ratios as high as 1.8-to-1, with excellent uniformity and yield. We have also performed a comprehensive study of disorder and variability in these devices and have performed extensive studies to understand the parasitic effect of water vapor on the sensor performance. Finally, I will show progress toward utilization of graphene varactors for a wide variety of biological sensing applications, with an emphasis on glucose and acetone sensors for treatment of diabetes.
10:00 AM - *BM06.08.02
Electrical Biosensing Based on Graphene Nanogap Electrode
Trupti Terse-Thakoor 1 , Pankaj Ramnani 2 , Claudia Villarreal 3 , Dong Yan 4 , Thien-Toan Tran 1 , Tung Pham 2 3 , Ashok Mulchandani 2 3 Show Abstract
1 Department of Bioengineering, University of California, Riverside, Riverside, California, United States, 2 Department of Chemical and Environmental Engineering, University of California, Riverside, Riverside, California, United States, 3 Department of Materials Science and Engineering, University of California, Riverside, Riverside, California, United States, 4 Center for Nano-Engineering (CNSE), University of California, Riverside, Riverside, California, United States
An electrical biosensor platform for highly sensitive detection of biomolecular interaction using a nanogap electrode is reported. A highly conductive single-layer graphene has been used as an electrode material. A novel, facile, inexpensive and reproducible method for fabrication of the nanogap electrode was employed. The nanogap was functionalized with biomolecules possessing high affinity for target analyte using a suitable chemistry. Affinity interaction of target analyte across the gap was detected based on the change in the conductance. Significant change in conductance was observed due to a narrower gap size and superior conductivity of the electrode material. The selectivity and sensitivity of the biosensor in detecting known concentration of target analyte was studied. The detection capability of this biosensor can be tuned down to the single to few molecules. Proposed biosensor platform can be used for any detection based on biomolecules affinity interaction such as for antigen-antibody or chemo selective interaction with full potential to be used as portable point of use biosensor.
10:30 AM - BM06.08.03
A Glucose Biosensor Based on Direct Electrochemistry of Glucose Oxidase Immobilized on Titanium Carbide Material (MXene)
Yu Zhao 1 , Lijia Pan 1 Show Abstract
1 , Nanjing University, Nanjing China
With the development of modern analytical chemistry and the advent of the direct electron transfer, people are more inclined to study the direct electrochemistry of enzymes. Direct electron transfer is a more intuitive and simple electrocatalysis. Compared with the first and second generations, direct electron transfer does not require a relay body, but through direct electronic exchange to complete the catalytic cycle. However, because of the properties of the enzyme itself, it is very easy to lose its activity and stability on conventional electrodes, so there are many defects in the sensors fabricated by ordinary methods. So, a material that can maintain the activity and stability of the enzyme is critical.
MXene is a new type of 2D nano material. Throughout the view of the organ-like structure, a large number of the Ti3C2 nano-layers with a large surface area point toward the closing end of the organ-like one, which is available for enzyme entrapment. The enzyme is adsorbed by surface functional groups of the nano-layers and funnelled toward the interior of the nano-layers that can become immobilized on the inner surfaces of the organ-like structure. In this study, a novel biosensor for glucose was prepared by immobilizing glucose oxidase (GOx) on MXene (Ti3C2) modified electrode. The MXene substrate accelerated the electron transfer from electrode surface to the immobilized GOx, leading to the direct electrochemistry of GOx. The biofunctional surface showed good biocompatibility, excellent electron-conductive network and large surface-to-volume ratio, which were characterized
by scanning electron microscopy, contact angle and electrochemical impedance technique. The direct electron transfer of immobilized GOx led to stable amperometric biosensing for glucose with a linear range from 0.1 to 2 mM and exhibit superb anti-interference performance. These results indicated that MXene are good candidate material for construction of the third-generation enzyme biosensors based on the direct electrochemistry of immobilized enzymes.
10:45 AM - BM06.08.04
A Tunable Surface Charge-Bias Zwitterionic Biointerface toward Controlling Blood Compatibility
Tsung-Yu Li 1 , Ta-Chung Liu 1 , San-Yuan Chen 1 Show Abstract
1 , National Chiao Tung University, Hsinchu Taiwan
To our knowledge, the studies of the charge bias of hydrogel interfaces on blood compatibility are rare. In this work, we have designed an electroresponsive zwitterionic hydrogel, describing a tunable blood compatibility as a function of surface charge-bias, essential to the design of blood-contacting devices. This newly-design hydrogel was synthesized by co-polymerization with zwitterionic poly(sulfobetaine methacrylate) (polySBMA) and [2-(methacryloyloxy)ethyl] trimethylammonium (TMA) via atomic free-radical polymerization, also in-situ conjugated with conductive poly(3,4-ethylenedioxythiophene) (PEDOT) chains. The neutral zwitterionic SBMA is negatively charged by TMA adding, and the surface charge-bias are well tuned through PEDOT chains being partially oxidized (conducted) alone the SBMA backbones by giving various potentials. The control of surface charge-bias ranging from -50 mV to 50 mV of zeta potential highly regulates the zwitterionic nonfouling nature to resist/adsorption of the coagulant of human plasma, platelet adhesion, leukocyte and the hemolysis of red blood cells. XPS and FTIR analysis proved the polymerization of SBMA-co-TMA and the existence of benzene ring, depending on the initial monomer ratios. Flow cytometer characterized the resist/adsorption of blood cells under different potentials. The neutral interfaces are blood-inert only if they present a high surface and bulk hydrophilicity. To sum up, this novel electroresponsive material hold promise as gel coating for biomedical devices or biomaterials.
BM06.09: Biosensors II
Wednesday PM, November 29, 2017
Sheraton, 2nd Floor, Back Bay B
12:30 PM - *BM06.09.01
Nano-Enabling Electrochemical Sensors for Life Sciences Applications
Paul Galvin 1 Show Abstract
1 , Tyndall National Institute, Cork Ireland
Electrochemical sensing systems are advancing into a wide range of new applications, moving from the traditional lab environment into disposable devices and systems, enabling real-time continuous monitoring of complex media. This transition presents numerous challenges ranging from issues such as sensitivity and dynamic range, to auto-calibration and antifouling, to enabling multiparameter analyte and biomarker detection from an array of nanosensors within a miniaturized form factor. New materials are required not only to address these challenges, but also to facilitate new manufacturing processes for integrated electrochemical systems. This paper examines the recent advances in the instrumentation, sensor architectures and sensor materials in the context of developing the next generation of nano-enabled electrochemical sensors for life sciences applications, and identifies the most promising solutions based on selected well established application exemplars.
The combination of emerging sensing platforms and electronic instrumentation promises not only to address those sensitivity issues, but to enable complete sensing solutions. These whole systems will need to provide multiparameter sensing within low cost miniaturized form factors, compatible with integration on wearable technologies, surgical tools, minimally invasive implantable devices and inline process analytical monitoring. Extended shelf-life stability and auto-calibration will be critical for most applications, but will be especially challenging in the case of biochemical sensors, particularly those involving enzymes as part of their sensing modality. Power consumption and power management will also be critical success factors for enabling autonomous electrochemical sensor systems to capture the right data at the right time; this will require intelligent control systems that adapt measurement protocols based on embedded software analysis of the data collected, appropriately managing the delicate balance between energy expenditure incurred by data communication with subsequent data processing in the cloud, versus local processing (with more limiting processing power) which could reduce the required frequency of data communication. With the development of high-volume low-cost miniaturized integrated circuits compatible with integration at or near the sensor, and in some cases as a single solid state device including the sensor, it is increasingly possible to integrate high sensitivity multiparameter nanosensor arrays with embedded signal processing electronics (to minimize issues with data quality between the sensor and the electronics) into autonomous miniaturised sensing systems for wearable and implantable biomedical devices, for process monitoring in the food and drinks, pharma and biopharma sectors, as well for continuous monitoring for security and environment applications.
1:00 PM - BM06.09.02
Nanomolar Detection of Lung Metabolites in Exhaled Breath Condensate Using Reduced Graphene Oxide Sensor—A Study of the Effects of Sample Matrix and Storage Conditions
Azam Gholizadeh 1 , Sakshi Sardar 1 , Kathleen Black 1 , Clifford Weisel 1 , Robert Laumbach 1 , Howard Kipen 1 , Andrew Gow 1 , Mehdi Javanmard 1 Show Abstract
1 , Rutgers, The State University of New Jersey, Piscataway, New Jersey, United States
Inflammation in the respiratory system can be non-invasively monitored by measuring biomarkers in exhaled breath condensate. Among the many molecules detected in exhaled breath condensate (EBC), nitrite and nitrate, are the stable end products of metabolism of nitric oxide. Increasing amounts of these have been found to be related to the level of inflammation in the respiratory systems. Several methods such as Griess reaction, photoluminescence, mass spectroscopy have been used to detect the quantity of nitrite in EBC samples. All of these methods have high sensitivity. However, they require pretreatment and are not portable. Recently our group reported an electrochemical graphene based sensor that can detect nitrite in EBC. This sensor can easily be portable however, needs further optimization to achieve detection in the nano-molar range. Moreover, standardization of new methods for clinical application is needed. Especially in EBC samples, the source of variation can be related to the technique of sample collection, processing, and analysis.
The aim of presented work is two-fold. We seek to improve the sensitivity of analysis and study stability of nitrite during storage. Moreover, as with electrical detection, the conductivity and nature of matrix are very important, these parameters have been studied with variation of electrolytes and EIS.
For monitoring these parameters, reduced graphene oxide modified screen printed electrode were used. Working electrodes were spin coated with graphene oxide and reduced electrochemically. Then, oxidative nitrite was detected with differential pulse voltammetry. The uniformity and reduction level of graphene oxide was studied using SEM and Raman spectroscopy. Also the effect of the matrix has been studied in different electrolytes. EBC blanks obtained from R-tube and EcoScreen have been used as the basic matrix to have most similar electrolyte to EBC samples for comparison of results with standard electrolytes.
In addition, the case study of fresh real EBC samples have been performed. Our sensor successfully distinguished between patients and blank samples with detection limit as low as nanomolar without any pretreatment. Results show this sensor can detect nitrite as low as 250 nM with high sensitivity. In addition, storage causes a decrease in the amount of nitrite to 80 percent, likely due to freezing. This study demonstrates the improvement in accuracy obtained from real-time measurement of nitrite in EBC.
1:15 PM - BM06.09.03
Synthesis of Pt and Pd Nanoparticles-Decorated In2O3 Heap-of-Straw-Like Nanostructures and Their Gas Sensing Properties in Exhaled Breath at Room-Temperature
Yu-Shan Hsu 1 , Kuan-Wei Chen 1 , Ying-Hao Pai 1 , Chun-Hua Chen 1 Show Abstract
1 , Department of Materials Science and Engineering, National Chiao Tung University, Hsinchu Taiwan
In this work, we synthesized a series of promising Pt or Pd nanoparticles functionalized In2O3 heap-of-straw-like nanostructures for sensing sub-ppm CO and acetone (C3H6O) at room temperature. Noninvasive illness detection via human breath analysis has become a new branch of medical diagnostics since it performs more efficiently, safely, and is easier to be used anywhere in comparison with the typical blood test. For instance, the acetone concentration in exhaled breath of diabetes is much higher than that of healthy people (~0.39 to 1.09 ppm) and the CO concentration of people who smoke a pack of cigarettes per day is ~20 ppm where a nonsmoker is only ~0−8 ppm. Obviously, the sensing limitation of specific gases is extremely essential for breath gas sensor. To achieve the required sensing performance, a series of novel highly-porous heap-of-straw-like In2O3 nanostructures which act as the base sensing material were successfully synthesized through hydrolysis of InCl3 in NaBH4 aqueous solution at room temperature with the subsequent heat treatments. For further decreasing the detection limits, increasing the sensitivity and responding rates, and more importantly, lowering the operating temperature, Pt or Pd nanoparticles were uniformly deposited to form a distinct Pd or Pt nanoparticles decorated In2O3 nanostructures. It was found that the present hybrid nanostructures could successfully and effectively detect sub-ppm level of CO and C3H6O gases at a relatively low temperature, evidently indicating their great potential for breath diagnostics.
2:30 PM - *BM06.09.04
Low Cost Lab-on-a-Chip System for Pathogen and Nutrient Monitoring in Precision Agriculture Applications
V Ramgopal Rao 1 Show Abstract
1 , Indian Institute of Technology Delhi, Delhi India
A low cost lab-on-a-chip (LOC) system which is simple and reliable is required for monitoring nutrients and pathogens of soil. Optimal amount of fertilizers and early diagnosis of pathogens can save the crop and increase the productivity and reduce ground water contamination. Our work demonstrates a complete LOC system based on a highly sensitive piezoresistive cantilever platform for agricultural applications. The microcantilever based sensor systems have the advantages of being robust, small, low power and have low fabrication costs because of batch processing which enables large-scale deployment.
Three different platforms based on both silicon and polymer technologies have been demonstrated. Silicon oxide/nitride microcantilever platform with polysilicon as a piezoresistive layer was fabricated using bulk micromachining. Later a novel low cost fabrication process for piezoresistive silicon nitride cantilever and polymer as an anchor based on SPARED (Spin-Pattern-Anchor-RElease-Device) MEMS process using surface micro-machining was developed. In this method, all layers were deposited by a low temperature Hot-Wire CVD (HWCVD) process. This method allows use of alternate materials and where silicon wafer is not consumed. This process has the advantages of polymer processing with the stability of silicon nitride.. The characterization of the device shows a spring constant of 0.9 N/m, gauge factor of 22 and resonant frequency of 22.5 KHz. We have also demonstrated a simple and cost effective process for fabricating polyethylene terephthalate (PET) cantilever-based sensor platforms with piezoresistive transduction. Silanized Graphene nanoplatelet/carbon black (GNP/CB) composite piezoresistive layer is coated on to the PET structural layer using a novel single step method. No specialized clean room facility or lithography tools are needed for this process. LASER was used to cut the devices from a PET sheet. The characterizations of the device showed the gauge factor to be ≈750 and the electrical sensitivity of 11 ppm/nm. This platform works well both in aqueous and vapor phase.
These platforms were then used to demonstrate the sensing of macronutrients (NKP) and plant pathogen Ralstonia solanacearum (RS). A novel single step protocol was used to functionalize antibodies on the surface of microcantilever surface for detection of pathogens. Similarly for NPK detections, ion-selective membranes are created on the surface of microcantilevers with ionophores embedded in Polyvinylchloride-Dioctylsebacate (PVC-DOS) polymer matrix. An LOC consists of an array of 4 piezoresistive microcantilevers with reference devices and test devices. Test devices are functionalized with the ionophores which will selectively bind to the soil nutrients that will result in a change of resistance which will be measured by the highly sensitive electronics.
3:00 PM - *BM06.09.05
The Science and Technology of 2D Crystals
Francesco Bonaccorso 1 Show Abstract
1 , Istituto Italiano di Tecnologia, Genova Italy
New materials and processes1 can improve the performance of existing devices or enable new ones,1-5 with the added values to be environmentally friendly. In this context, graphene and other inorganic 2D crystals are emerging as promising materials,1-7 with the opportunity to enable new products/devices.1 However, a fundamental requirement for the application of 2D crystals in areas ranging from flexible electronics and sensing to energy storage and conversion relies on the development of industrially scalable, reliable, inexpensive production processes.2 Moreover, the synthesis strategies should provide a balance between ease of fabrication, based on environmentally benign processes, and final material quality with on-demand properties.
Solution-processing2,6 offers a simple and cost-effective pathway to fabricate various 2D crystal-based (opto)electronic and photonic devices, presenting huge integration flexibility compared to conventional methods. Here, I will present an overview of graphene and other 2D crystals for flexible and printed (opto)electronic and biomedical applications, starting from solution processing of the raw bulk materials,2 the fabrication of large area electrodes3 for neuro-interfacing applications and their integration in prosthetic devices.7-10
1) A. C. Ferrari, F. Bonaccorso, et al., Nanoscale, 7, 4598 (2015).
2) F. Bonaccorso, et al., Materials Today, 15, 564, (2012).
3) F. Bonaccorso, et. al., Nature Photonics 4, 611, (2010).
4) F. Bonaccorso, Z. Sun, Opt. Mater. Express 4, 63 (2014).
5) G. Fiori, et al., Nature Nanotech 9, 768, (2014).
6) F. Bonaccorso, et. al., Adv. Mater. 28, 6136 (2016).
7) F. Bonaccorso, et. al., Science, 347, 1246501 (2015).
8) P. Cataldi, et al., Adv. Electr. Mater. 1600245 (2016).
9) A. Fabbro, et al., ACS Nano 10, 615 (2016).
10) J. Sha, et al., ACS Nano, 7, 8857 (2013).
3:30 PM - BM06.09.06
ZnO Nanostructures Based Flexible FET for Immuno-Sensing Applications
Syed Pasha 1 , Fahmida Alam 1 , Pandiaraj Manickam 1 , Nezih Pala 1 , Shekhar Bhansali 1 Show Abstract
1 Electrical and Computer Engineering, Florida International University, Miami, Florida, United States
Zinc oxide (ZnO) nanostructures serve as an ideal substrate for binding bio-recognition molecules viz., antibodies, aptamers, enzymes, microorganisms etc. Biocompatibility, ease of deposition and low cost makes it an ideal material for application to biosensing. The binding of biomolecules to ZnO is facilitated by the difference in the isoelectric points of the bioreceptor molecules (~5) and ZnO (~9). Using this strategy, construction of a back-gated bio-functionalized field effect transistors (FETs) is proposed here for linker-free and label-free detection of biomarkers. ZnO thin film/nanostructure based FETs were fabricated on both rigid (Si/glass) and flexible (PET) substrates. Fabrication of the above-said devices involves a five mask photolithography process. The ZnO gate sensing films were deposited using sputtering and sonochemical method. The deposited thin films were characterized using SEM, XRD and Raman spectroscopy. Electrical properties of sputter deposited ZnO layer and sonochemically deposited ZnO back-gated FET devices were measured using semiconductor parameter analyzer. The surface of the ZnO nanostructures was functionalized with cortisol-specific antibodies without any linker molecules for label-free detection of cortisol. Cortisol, the stress hormone is chosen as a model biomarker because of its importance in health related disorders.
3:45 PM - BM06.09.07
Direct Visualization of Graphene FET Biosensor Operation at the Nanoscale with Picomolar (pM) Sensitivity for Neuropeptide Y Using In Operando TEM
Ahmad Islam 1 , Li Xing 1 , Ming-Siao Hsiao 1 , Nicholas Bedford 1 , Rhett Martineau 1 , Yen Ngo 1 , Steve Kim 1 , Lawrence Drummy 1 Show Abstract
1 , Air Force Research Laboratory, Wright Patterson AFB, Ohio, United States
Graphene-based field effect transistor (GFET) sensors have been broadly applied in detection of biological macromolecules, such as RNA, DNA, peptides, and small toxic compounds. Here we show that the GFET sensor functionalized with a peptide is capable of detecting sub-10 picomolar (pM) levels of Neuropeptide Y (NPY), a 36-amino acid peptide, as molecular biomarker in artificial perspiration (AP). NPY is one of the abundant proteins within brain, and it is involved in regulation of important biological and pathophysiological functions such as food uptake, energy homeostasis, circadian rhythm and cognition. While synthesized in brain, excreted NPY was reported at sweat at a range of 0.8 – 2.9 pM in the perspiration obtained from normal healthy individuals and at a range of 14.2 – 73.2 pM in the perspiration from major depressive disorder patients.
We fabricated the graphene sensor specific for NPY by using a 12 amino acid NPY specific-binding peptide (N3 peptide) as the recognition element, which is identified using phage display. To fabricate these sensors, monolayer graphene was grown using chemical vapor deposition on a Cu film and then transferred to a liquid electrochemical TEM chip using low molecular weight PMMA and wet chemical etching of Cu using Fe(NO3)3 solution. Acetone wash and heat treatment was used to wash-off PMMA after transfer. The surface of graphene was then functionalized with N3 and the NPY-N3 interaction was examined using an image-corrected FEI Titan microscope and a liquid electrochemical cell. NPY is translated from mRNA as pre-pro-peptide of 97 amino acids before its ultimate cleavage into NPY peptide. The NPY pre-pro-peptide with a GST-tag assembles into a micelle-like structure of 20 nm in solution containing three-copies of GST-NPY dimer, as it was determined with Liquid Cell (LC)-TEM, cryo-electron microscopy and single particle reconstruction. GST-NPY micelles were able to freely move until binding onto graphene, confirming the existence of dynamic environment inside the liquid cell. The LC-TEM results on the structure and dynamic motion of tethered recombinant NPY reveals the interaction motif of the BRE on graphene. With optimization of the BRE based on in-situ characterization results, GFETs capable of selective NPY sensing with sub-10 pM sensitivity in AP were demonstrated.
Venkatesan Renugopalakrishnan, Northeastern University
Pulickel Ajayan, Rice University
Catherine Klapperich, Boston University
Dorian Liepmann, University of California, Berkeley
Anarghya Innovations and Technology Private Limited
MilliporeSigma (Sigma-Aldrich Materials Science)
Thermo Fisher Scientific
BM06.10: Biosensors III
Thursday AM, November 30, 2017
Sheraton, 2nd Floor, Back Bay B
7:00 AM - *BM06.10.01
2D Graphene Circuits for Electrically-Stimulating Transdifferentiation of Mesenchymal Stem Cells to Schwann Cells for Peripheral Nerve Regeneration
Surya Mallapragada 1 2 , Metin Uz 1 , Suprem Das 1 , Donald Sakaguchi 1 , Jonathan Claussen 1 Show Abstract
1 , Iowa State University, Ames, Iowa, United States, 2 DMSE, Ames Laboratory, Ames, Iowa, United States
Over 200,000 peripheral nerve repair surgeries are carried out each year, The current gold standard for treatment involves autografts, which suffer from significant drawbacks such as partial denervation at the donor site. A promising alternative involves degradable conduits seeded with Schwann cells to provide physical guidance and to secrete neurotrophic factors to facilitate peripheral nerve regeneration. However, due to the difficulties in obtaining Schwann cells for this treatment, we have developed a 2D graphene inkjet printed circuit to electrically stimulate readily-accessible bone marrow-derived mesenchymal stem cells and transdifferentiate them to Schwann cell-like phenotypes. An interdigitated electrode of the graphene-based substrate was inkjet-printed on a polyimide surface using a pulsed-laser annealing route. The pulsed laser process helped increase the electrical conductivity of the inkjet printed graphene by three orders of magnitude. We have demonstrated enhanced secretion of nerve growth factor (NGF) from the transdifferentiated cells as opposed to the undifferentiated MSCs. In addition, we have genetically engineered these MSCs to hyper-secrete brain-derived neurotrophic factor (BDNF). These BDNF-secreting cells have also been successfully transdifferentiated to Schwann cell-like phenotypes using solely electrical stimulation. The growth factor secretion is one of the key elements in facilitating peripheral nerve regeneration. This is the first time that transdifferentiation of MSCs to Schwann-cells have been successfully achieved solely with electrical stimulation. This approach allows us to potentially have spatial control over stem cell differentiation on substrates by spatially varying the electric fields and stimulation conditions on the substrates.
7:30 AM - BM06.10.02
A Nano-Surface Coatings Promotes Endothelization for Intracranial Stents
Junjie Zhao 1 , Jun Pang 1 , Krystal Gayle 1 , Janice Tsui 2 , Brian Cousins 1 Show Abstract
1 Division of Surgery and Interventional Science, University College London, London United Kingdom, 2 , Royal Free NHS Foundation Trust Hospital, London United Kingdom
Stroke is a major cause of disability and death worldwide. The role of intracranial stents (ICS) is essential in stroke management, but current ICS display unwanted side effects resulting in thrombosis and chronic inflammation followed by in situ re-stenosis.1 Surface modification strategies are now in demand to improve tissue interactions at the neurovascular interface. Several studies highlight that nanotopography can influence the cellular response.2 The aim of this study is to develop a reproducible surface topography on the nanometre scale as a more convenient and economic process for post modification of ICS.
We have developed a simple approach via the deposition of tri-block co-polymers, which endure phase separation to generate nano-scale surface features. Scanning electron microscopy (SEM) and atomic force microscopy (AFM) were applied to study the nanotopography and mean surface roughness (Ra) on polymer coated substrates. Human umbilical vein endothelium cells (HUVECs) between passage 3-6 were seeded on different samples in 24-well TCP at 50,000 cells/ml and cultured at 37°C in 5%CO2/95% humidified air over 10 d. Metabolic activity (MTT) and cell proliferation (total DNA) data was obtained at d 1, 7 and 10 to monitor cell activity and proliferation (n=12). All samples were fixed in 4% (w/v) glutaraldehyde and dehydrated in 100% (w/v) ethanol for morphological analysis and immunofluorescent staining for functional biomarkers.
RESULTS & DISCUSSION
SEM and AFM confirmed the presence of a uniform layer of tri-block co-polymers as nano-islands with respect to size and distribution. HUVECs cultured on nano-islands show increased cell activity, growth and proliferation when compared with uncoated controls (P<0.01). SEM revealed HUVECs cultured on control substrates (flat) had elongated phenotypes with lamellipodia and filopodial protrusions. HUVECs cultured on nano-islands show distinctive cell morphology with predominantly spread phenotypes, which appeared larger with an increase in number, density and the width of the filopodial protrusions. Immunofluorescent staining of HUVECs on nano-islands revealed a greater surface coverage and faster proliferation with some cells aligning to the nanofeatures displaying functional biomarkers, e.g. von Willebrand Factor (vWF).
We have developed a simple procedure to create random distribution array of nanostructures by phase separation. HUVECs demonstrate enhanced cell activity, growth and proliferation over 10 days. Cell morphological analysis of HUVECs revealed a distinctive cell response with the presence of functional biomarkers indicative of normal EC function. This procedure can be applied directly on to Nitinol™ and other biomaterial substrates to promote in-situ endothelisation and would be an ideal post modification for ICS.
1. Nguyen A, et al. Physics-Condensed Matter. 2016;28
2. Dalby M, et al. Biomaterials. 2006;27:2980-2987
7:45 AM - *BM06.10.03
Microengineered Hydrogels for Tissue Engineering and Surgical Applications
Nasim Annabi 1 2 3 Show Abstract
1 Department of Chemical Engineering, Northeastern University, Boston, Massachusetts, United States, 2 Biomaterials Innovation Research Center, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Cambridge, Massachusetts, United States, 3 Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States
Tissue engineering is an interdisciplinary field aimed at maintaining, restoring and enhancing the normal function of organs and tissues through the use of live cells, and by incorporating concepts from engineering, biological sciences and medicine. One of the central themes in the field of tissue engineering is the development of tissue constructs that mimic the three-dimensional (3D) architecture of native tissues. To date, tissue engineering has been successfully implemented in the engineering of several types of tissues including bone, cartilage, and vascular systems. Despite the significant progress in this field, many challenges still remain, which hinder the development of fully functional tissue constructs. Micro- and nanoscale technologies have been shown to hold great potential to address the current challenges in tissue engineering. These technologies have immensely benefited the fields of experimental biology and medicine, and have allowed the design of complex biomaterials that can be used for cell-based studies. Our research is focused on merging micro/nanofabrication techniques with advanced biomaterials for tissue engineering applications. Our group has been actively involved in engineering novel cell-laden elastomeric biomaterials with unique physical properties by using recombinant protein technologies. We use these elastomers as 3D matrices for various soft tissue engineering applications. In addition, we utilize them as elastic substrates loaded with smart nanocarries for engineering flexible electronics for on demand release of drugs and other biomolecules. Our work encompasses a wide range of scientific subjects, from materials science to biology. In this presentation, I will outline our work in the development of microscale hydrogels to modulate cell-microenvironment interactions for tissue engineering and drug delivery applications. I will also highlight some of the clinical applications of our engineered biomaterials.
8:15 AM - BM06.10.04
Immuno and DNA-Based Nanosensors Applied to the Rapid Detection of Infectious Diseases
Henrique Faria 1 , Nirton Vieira 1 , Juliana Bernardi 1 , Valtencir Zucolotto 1 Show Abstract
1 , University of Sao Paulo, Sao Carlos Brazil
The manipulation of nanomaterials in conjunction with specific biomolecules has been a crucial step in the development of novel bioconjugates for application in medical areas, for both, diagnosis and therapy. Nanobiosensors, in particular, have found applications as point-of-care diagnostic systems, in which an immobilized biorecognition layer containing for example, antibodies or ssDNA sequences is used to detect specific infectious diseases biomarkers in a simple and rapid manner. Among some concerning infectious diseases, those caused by Zika and Dengue virus are of special interest in many developing countries. Zika virus, in particular, has caused thousands of infections and generating high costs for the Health System. In addition to the symptoms caused to the patient, congenital Zika infection has become a major concern due to its association with microcephaly. The possibility of recognizing cases of zika in pregnants, on the onset of symptoms, is of great relevance. Here we show that upon an appropriate design of the biorecognition platforms, efficient immuno or genosensors can be efficiently applied to the detection of Zika and Dengue virus. The immunosensors comprised anti-NS1 antibodies immobilized on gold electrodes. Detection of the specific NS1 protein (a common Dengue biomarker) at concentrations as low as 0.25 ug mL-1 was carried out using the Field-Effect Transistor (FET) concept. Typical genosensors are based on the use of sensing electrodes containing immobilized DNA probes capable of hybridizing with specific target DNA sequences. Genetic sequences of primers and complementary capture probes were designed based on the analysis of the virus genomes. Electrical and/or electrochemical impedance spectroscopy (EIS) showed that the biosensors are selective for zika or dengue with a detection limit of 9.86 ± 0.89 nmol L-1. The biosensors showed selectivity for zika and dengue in the DNA assays, and therefore are promising for preventive nanomedicine applications.
8:30 AM - BM06.10.05
In Situ Sensing and Removal of Silver Nanoparticles via a Core-Shell Nano-Fibrous PVA/PAni Substrate Decorated with Fe3O4
Akshay Seshadri 1 , Olivia Brissette 1 , Hani Naguib 1 Show Abstract
1 , University of Toronto, Toronto, Ontario, Canada
Akshay Seshadri, Olivia Brissette and Hani E. Naguib,*
Department of Mechanical and Industrial Engineering, University of Toronto, Canada
Department of Materials Science and Engineering, University of Toronto, Canada
Institute of Biomaterials and Biomedical Engineering, University of Toronto, Canada
5 Kings College Road., Toronto, Ontario, Canada, M5S3G8
Anthropogenic silver nanoparticles (AgNPs) have become increasingly common as an antimicrobial agent in numerous modern-day consumer products, including toys, apparel, cosmetics, and medical equipment. However, disposal and degradation of these products have led to AgNPs entering aquatic environments in potentially toxic concentrations. Studies conducted on zebrafish have shown that AgNP concentrations of 5 μg/mL result in respiratory damage in growing embryos while concentrations of 50 μg/mL lead to death. While additional studies are presently being conducted to explore the impact of AgNPs on other aquatic organisms, assessments of toxicology have shown the ability of AgNPs to adsorb onto biomolecules and disturb functionality in enzymes, proteins, and DNA. With this hazard to aquatic life becoming more prominent as time progresses, a need for AgNP cleanup arises. In this study, we have fabricated a composite mat capable of in-situ AgNP removal in aquatic environments. Polyaniline (PAni) is polymerized onto an electrospun polyvinyl alcohol (PVA) mat, resulting in high AgNP selectivity and adsorption onto the mat due to the amine groups in PAni and the hydrophilicity of PVA. Attraction and aggregation of AgNPs is further increased by decorating the mat surface with iron(II,III) oxide nanoparticles (Fe3O4 NPs), which possess magnetic properties. Application of the PVA/PAni/Fe3O4 (PPF) mat in a 50 μg/mL AgNP-distilled water solution shows removal of nearly 100% of the AgNPs with sufficient exposure time and agitation of the mat. Cyclic voltammetry on the PPF mat after adsorption of the AgNPs showed an additional peak due to the redox reaction pertaining to AgNPs and Ag ions. This peak increased in magnitude with higher loadings of AgNPs on the PPF mat, enabling a form of AgNP sensing. This functionality in sensing and removal of AgNPs will be valuable in safeguarding aquatic environments and tackling pollution control stemming from nanotechnology and modern-day consumer waste.
8:45 AM - BM06.10.06
Towards Recognition Tunnelling Based DNA Sequencing with Graphene Nanogaps
Jacob Swett 1 , Pawel Puczkarski 1 , Xinya Bian 1 , Jan Mol 1 Show Abstract
1 Department of Materials, University of Oxford, Oxford United Kingdom
Here we report on the fabrication progress and initial data from a solid-state single-molecule graphene nanogap based biomolecular sensing architecture for DNA sequencing. The device which utilizes a nanometer-scale gap fabricated via feedback-controlled electroburning senses analytes via a mechanism termed recognition tunnelling. Briefly, the device is fabricated on a suspended SiN/Si architecture with metal electrodes fabricated via electron beam lithography and thermal evaporation. Apertures in the SiN, allowing for the translocation of DNA, are fabricated via focused ion beam milling and the graphene nanogaps are formed via a combination of electron beam lithography and feedback-controlled electroburning. The graphene is passivated via a dielectric coating with a co-aligned aperture, resulting in a single translocation pathway through the device. The architecture, which requires aligned <10nm features in multiple layers, is characterized with SEM, AFM, and S/TEM. Initial recognition tunnelling data from analytes will be presented.
10:00 AM - BM06.10.08
bFGF Delivery for the iPSC Expansion by Control Physiochemical Properties of Graphene Oxide Sheets
Jiwoong Heo 1 , Junjira Tanum 1 , Sohyeon Park 1 , Jinkee Hong 1 Show Abstract
1 , Chung-Ang University, Seoul Korea (the Republic of)
Graphene oxide (GO) is well known atomically thin two-dimensional nanosheet that has been used in various applications due to its unique physicochemical properties such as high conductivity, durability, low cytotoxicity, large surface area, impermeability and mechanical stabilities. Furthermore, presence of oxygen-containing functional groups provides reaction site for functionalization. Cytotoxicity of GO has been widely reported, however, growth factor delivery efficiency according to sheet size of GO is still not clearly understood. Growth factor such as fibroblast growth factor basic (bFGF) can be noncovalently attached onto the GO sheets by electrostatic interaction and hydrogen bonding and assist proliferation of human dermal fibroblast (HDF) as well as induced pluripotent stem cells(iPSC). In this research, we investigated how the sheet size and shape of GO would influence loading efficiency and proliferation of HDF cell & iPSC. We separated GO suspensions varying the lateral size from mixed GO suspension by ultrasonication and centrifugal method. The cytotoxicity, surface morphologies and bFGF delivery efficiency of GO sheets were analyzed.
10:15 AM - BM06.10.09
Urine-Resistant Nanocoatings on Elastomeric Substrates for Achieving a Reliable Long-Term Artificial Bladder
Angelo Cadorna 1 , Veronica Iacovacci 1 , Tommaso Mazzocchi 1 , Novello Pinzi 2 , Arianna Menciassi 1 , Leonardo Ricotti 1 Show Abstract
1 , The BioRobotics Institute, Pontedera Italy, 2 Urology Department, University of Siena, Siena Italy
Radical cystectomy due to tumors or traumas can be surgically addressed through ureterocutaneostomy and eterotopic/orthotopic neobladder reconstruction. These solutions are normally associated with a reduced patient’s quality of life, high rates of re-operation, electrolyte disturbances and risks of developing carcinomas. The development of a fully artificial bladder substitute is highly desirable. However, devices able to both expand/contract and to resist to urine in the long-term are not available, at present.
In this framework, we propose an artificial bladder featured by variable volume, high biocompatibility and high resistance to urine. To this purpose, a smart elastomeric structure made of polydimethylsiloxane has been devised. The system is able to change its internal volume without implying a stretching of the constitutive material, thus avoiding the formation of cracks on its inner surface.
The resistance to urine is guaranteed by providing the internal layer of the device with a 2D nanostructured coating, ensuring high resistance to encrustation. To this aim, we targeted: (i) low surface energy, to reduce surface wettability and avoid the adhesion of bacteria and incrustations; (ii) chemical inertia, to reduce chemical bonds between the coating and the substances dissolved in the urine; (iii) high density and firmness, to reduce the availability of contact-points for anchoring stones onto the device surface; (iv) low friction coefficient and low roughness, to avoid stones adhesion.
Four promising coatings were identified and compared. They were based on Diamond-Like-Carbon (DLC), Nano-Crystalline-Diamond (NCD), nanostructured Molybdenum disulphide (MoS2) and nanostructured Tungsten disulphide (WS2). DLC is a thermodynamically meta-stable state of carbon, in which diamond-like (sp3-hybridized) and graphite-like (sp2-hybridized) bonding coexist. It was prepared by plasma-enhanced chemical vapour deposition (CVD). NCD films are thin continuous layers of nanometer-sized diamond crystallites; they were also synthesized by CVD. MoS2 is an inorganic compound featured by a layered structure, in which a plane of molybdenum atoms is sandwiched by planes of sulphide ions. MoS2 coatings were produced by nanoparticle self-assembly, resulting in atomically smooth surfaces featured by high stability in water. WS2 forms dark grey hexagonal crystals with a layered structure in its bulk form. WS2 coatings were also produced by nanoparticle self-assembly.
Such nanocoatings were produced on top of elastomeric substrates, tested for long-term stability and compared in terms of ability to prevent encrustations. To this aim they were exposed to both sterile and non-sterile urine and characterized at different time-points, through optical profilometry, scanning electron microscope and Energy-dispersive X-ray spectroscopy analyses.
10:30 AM - BM06.10.10
Graphene-Based Anti-Microbials and Nanocomposites
Rigoberto Advincula 1 Show Abstract
1 , Case Western Reserve University, Cleveland, Ohio, United States
The large interest in graphene-based materials and other carbon-based polymorphs and nanomaterials are far reaching and now encompasses biomedical applications. The industrial scale and possibility of applying these to advanced manufacturing and commercial application have resulted in high throughput synthesis and lower costs. There is primary interest on their electrical and thermal conductivity properties. However, other applications are based on their ability to form very stable colloidal complexes and nanocomposites. This talk will focus on the class of graphene (G) and graphene oxide (GO) nanomaterials that have been prepared with high loading in polymer matrices and ultrathin films to result in anti-microbial properties. We describe the preparation of very stable dispersions that can be used for colloidal templating and nanopatterning, anti-corrosion-superhydrophobic coatings, and more importantly as anti-microbial agents. The preparation of these GO dispersions and nanocomposite coatings have been shown to be efficient in killing gram positive and gram negative bacteria such as E. Coli and B. Subtilis, as against mammalian fibroblast cells, they are shown to be relatively non-toxic. It is believed that some of this properties are related to: 1) free-radical oxygen species that may be generated by the nanoparticles, 2) platelet shape, size, and orientation, and 3) incompatibility of the basal plane orientation of the GO with biofilm growth through quorum sensing disruption. Interestingly, by preparation of colloidal particle dispersions that can be stabilized at liquid-liquid and air-liquid interfaces, functional Janus-type nanoparticles have been reported.
10:45 AM - BM06.10.11
Dramatic Enhancement of Fluorescence in Bioassays via a Lighting-Up Plasmonic Skin
Jingyi Luan 1 , Srikanth Singamaneni 1 Show Abstract
1 , Washington University in St. Louis, St Louis, Missouri, United States
Owing to the recent developments in nanotechnology, tremendous advances and innovations have been demonstrated in biosensing for disease diagnosis. However, their incompatibility with the clinical-based medical care device, infrastructure as well as the laboratory settings hindered the wide deployment of nanotechnology based analytical innovations to real-world applications. Here, we report a universal, facile, and innovative "add-on" method that can significantly enhance the fluorescent signal of the bioassays by using a plasmonic skin, with a localized surface plasmon resonance wavelength matching the excitation of the fluorescent dye of the existing bioassays. Compared to the innate fluorescent signal of the bioassay, implementation of a plasmonic film offered 20- to 50- times higher fluorescence intensity, which enables protein assays with a detection limit of fM concentrations and an increased dynamic range. We showed that the plasmon enhanced fluorescent assay allows the detection of KIM1, an early biomarker of acute kidney injury (AKI), to as low as 0.5 pM, which is one order magnitude lower than existing commercial bioassay like ELISA. We also demonstrate the plasmonic skin based fluorescent enhancement of multiplexed protein microarray with 8 AKI biomarkers in patient samples. We expect this technique to be highly promising in the real-world application due to its simplicity, ease-of-operation and universality that can be directly attached to the current fluorescent base bioassay.
BM06.11: Biosensors IV
Thursday PM, November 30, 2017
Sheraton, 2nd Floor, Back Bay B
12:30 PM - BM06.11.01
Nanoparticles-Grafted Functionalized Graphene Coated with Nanostructured Polyaniline Layered Nanocomposites for High-Performance Biosensors
Sanju Gupta 1 , Romney Meek 1 Show Abstract
1 , Western Kentucky University, Bowling Green, Kentucky, United States
The challenge remains to develop (chemical, electrochemical and biological) sensors from nanocomposites with broader electrical conductivity, molecular sensitivity and specificity. We report on the design and synthesis of scalable, metal nanoparticles-grafted functionalized graphene overcoat with nanostructured polyaniline nanocomposites and elucidate their high-performance as advanced biosensors. The versatility of the nanocomposite performance was corroborated by altering the size, areal density and morphology of electrodeposited gold and silver nanoparticles (NPs) on the nitrogenated functionalized graphene (NFG) as well as changing the density of the electropolymerized polyaniline (PANi) onto NFG. Among different NPs, gold (Au) and silver (Ag) NPs are strategically selected owing to their higher electrical conductivity, facile synthesis, easier processability and scalability. The critical modification of these architectures (NFG/Ag or AuNP/PANi) on fluorinated tin oxide electrodes increased the conductivity of the electrodes significantly and reduced the charge transfer resistance dramatically while investigating electrochemical properties. The high-performance biosensing application was demonstrated for the detection of ascorbic acid (AA) over electroactive components interfering species commonly found in blood serum samples and real samples, with enhanced electrical conductivity, sensitivity and a range of detection in-turn determining limit of detection. These nanocomposites are also applicable for potential applications in electrocatalysis, energy storage and conversion systems as well as enriching biofuel cell development. This work is supported in parts by NSF-MRI, KY NSF EPSCoR and KY NASA EPSCoR Grants.
12:45 PM - BM06.11.02
Label-Free Detection of Influenza Virus Using Biomimetic Nanopillar-Based Biosensor
Wang Sik Lee 1 2 , Taejoon Kang 1 2 , Jinyoung Jeong 1 2 Show Abstract
1 Hazards Monitoring Bionano Research Center, Korea Research Institute of Bioscience & Biotechnology, Daejeon Korea (the Republic of), 2 Department of Nanobiotechnology, University of Science and Technology, Daejeon Korea (the Republic of)
The influenza virus cause global pandemics every year. Precise diagnosis is therefore required to prevent spreading of the disease. The detection of influenza viruses has been developed using immunodiagnostic methods. However, it has problems which are time-consuming and specialized process. In this study, peptide-functionalized nanopillar based optical biosensor was fabricated for label-free detection of influenza virus. Spin on glass based nanopillar was prepared by nanoimprint lithography. A sialic acid-mimic peptide (SA-peptide), which specifically bind to hemagglutinin on surface of influenza virus, was successfully immobilized on nanopillar via polymerized dopamine as a biomimetic adhesive. Change in reflectance of the nanopillar biosensor allows monitoring of influenza virus. Our study demonstrated that 2-D nanostructure, integrated with SA-peptide, is used for detection of virus by optical spectroscopy. It revealed that influenza virus was detectable from 103 PFU (Plaque forming unit) by measuring reflectance spectra. Biomimetic modification of nanopillar and SA-peptide has potential as an alternative immunodiagnostic method for detection of influenza virus.
1:00 PM - BM06.11.03
Enhanced Sensitivity of Flexible Nanocrystal Based Strain Gauges Achieved by Metal-Insulator Heterostructure Design for Wearable Sensor Applications
Woo Seok Lee 1 , Seung-Wook Lee 2 , Hyungmok Joh 1 , Mingi Seong 1 , Haneun Kim 1 , Soong Ju Oh 1 Show Abstract
1 Materials Science and Engineering, Korea University, Seoul Korea (the Republic of), 2 Semiconductor Systems Engineering, Korea University, Seoul Korea (the Republic of)
We demonstrate all nanocrystal (NC) and solution based high performance wearable strain sensors. We incorporate insulating artificial atoms of quantum dot NCs into metallic Au NC thin film matrix to design metal-insulator heterostructures for resistive strain gauge layers, engineering the charge transport behavior and enhancing the sensitivity. We adopt nanocrack formation by applying high pre-strain in order to further increase the sensitivity, leading to the gauge factor up to 5,000, which is the highest sensitivity among NC based strain gauge sensors. The structural, chemical, optical, electrical and electromechanical properties of these NC thin films are investigated. We explore temperature dependent analysis to investigate the charge transport behavior in our heterostructures of metal-insulator artificial atoms. Percolation theory is adopted to clarify the origin of the enhanced sensitivity. Finally, we fabricate solution processed multi-array sensors that effectively detect the motion of each finger joint, the pulse on the wrist, and the vibration of vocal cords, providing a pathway to designing low cost and high performance electronic skins.
1:15 PM - BM06.11.04
Electrochemical Immunosensor for the Detection of S100B as Complementary Input in Traumatic Brain Injury Classification and Prognosis
Alexander Rodriguez 1 , Eliana Cervera 1 , Pedro Villalba 1 Show Abstract
1 Departamento de Medicina, Universidad del Norte, Barranquilla Colombia
Severity of head trauma is classified using the Glasgow coma scale (GCS), a qualitative instrument that measures the level of consciousness of a person. Literature has shown that GCS has limited capabilities to identify non-visible neuroinflammation processes; allowing a gap for underestimation of the true severity and, in many cases delaying the application of proper treatment. In this work, we develop a quick yet reliable method for detecting and quantifying s100b, a calcium binding protein that is the most frequently studied peripheral biomarker for blood-brain barrier disruption. Our approach consists of an electrochemical biosensor with a nanodiamond enhanced polymeric matrix as working electrode (ND-Pani). The working electrode surface was functionalized following crosslinking methods using (3-Aminopropyl)trimethoxysilane and Glutaraldehyde as binding molecules with the lysine amino-terminal groups of highly specific monoclonal antibodies. The changes in the electrochemical signal before and after the functionalization process were study using both DC and AC experiments to understand the mass transfer behavior of the complete biosensor. Response of the biosensor to the antigen was recorded using impedance spectroscopy experiments with a potassium ferrocyanide in potassium chloride solution as supporting electrolyte. Our results showed the characteristic semicircle behavior at the high frequency range associated to the redox probe of the electrolyte; also, the Warburg line has been observed at the low frequency range. The polarization resistance (Rp) of the Nyquist plots was study as the concentration increases; here it is observed a proportional correlation between the two variables, going from a relatively small Rp at the bare biosensor to a higher Rp when 1ng/mL was added to the supporting solution. A total of three different concentrations were tested, and results were plotted as the average of three independent measurements. Biosensor selectivity and robustness was tested using the s100b functionalized biosensor against neuronal nitric oxide synthase (nNOS) with no statistical relevant distortion.
1:30 PM - BM06.11.05
Bacterial Cellulose Based Anti-Fouling Composites for Healthcare and Food Packaging Applications
Shivakalyani Adepu 1 , Mudrika Khandelwal 1 Show Abstract
1 , Indian Institute of Technology, Hyderabad India
Background: Anti-microbial composites based on silver nanoparticles(AgNPs) are essential to prevent biofouling as AgNPs suffer least anti-microbial resistance. Amongst various substrates, bacterial cellulose (BC), has gained attention because of nanofibrous, microporous nature as the nano-sized pores restrict the growth, prevent aggregation and aids in sustained release of nanoparticles.
Objective: Aim of the current study is to synthesize broad spectrum antimicrobial AgBC composites containing minimal amount of silver with small particle size and narrow size distribution.
Methodology: Three variations of AgBC composites and AgNP colloid have been produced using sodium borohydride (NaBH4) reduction method by varying the molar ratios of AgNO3 to NaBH4 to vary the AgNPs dimension. XRD, TEM and SEM-EDS analysis was carried out. In vitro anti-microbial activity of colloid and composites was tested by disc diffusion method and broth diffusion method. Rotten food stuff derived mixed microbial culture was used as inoculum for food borne infections. Microbial strains most commonly responsible for blood stream infections, namely, P.aeruginosa, S.aureus, K. pneumonia, Bacillus sp., E.coli, K.aerogenes, were used as inoculum for nosocomial infections. Shelf life assessment study of food stuff was performed for 30 days at room temperature on commercially available polythene bag (PE), micro porous polypropylene bag (PP) and AgBC.
Results and Discussion: FCC structure of AgNPs was evidenced from XRD and crystallite size was found to decrease with increase in NaBH4 concentration. AgNPs attached to BC microfibrils with good spatial distribution were evidenced from SEM analysis. Atomic weight percent of Ag in AgBC was found to be 1.06 %. AgNPs dimension was found to be <10 nm in case of AgBC and >25nm in case of colloid, both synthesized with same reducing agent concentration. AgBC having <2% (W/W) of Ag exhibited 99.9% antimicrobial activity which was sustained up to 72h. This is attributed to the smaller particle size and sustained release of AgNPs from BC matrix. On the other hand, only 90% activity was observed with colloid due to aggregate formation. Composites displayed superior antimicrobial activity than colloid with equivalent amount of silver. In shelf life assessment study, food stuff was protected from microbial spoilage for 30 days when stored in AgBC, whereas spoilage was noticed within 15 days for food stuff stored in regular polythene bag. Moreover, AgBC exhibited superior anti-bacterial activity against nosocomial infection causing strains.
Conclusion: AgBC composite having <2% Ag can be used as a lining of regular food packaging material to preserve food till 30days. Toxicity due to high amount of silver can be prevented with these composites and can be safely used in other healthcare applications such as wound dressing, lining for ventilators, catheters, hospital bed lining, Surgical apparels and so on.
1:45 PM - BM06.11.06
Loss of Phospholipid Membrane Integrity Induced by Two-Dimensional Nanomaterials
Ines Zucker 1 , Jay Werber 1 , Menachem Elimelech 1 Show Abstract
1 Chemical and Environmental Engineering, Yale University, New Haven, Connecticut, United States
Two-dimensional (2D) nanomaterials have become a major focus for numerous applications, owing to their exceptional physical, mechanical, and electrical properties. However, the specific properties that make them so attractive also result in potential risks for the environment and human health. Environmental impacts, particularly interaction with living cells, have been studied for the carbon-based 2D nanomaterials, graphene and graphene oxide (GO), while very little data exist on other 2D compounds. Specifically, the interaction of 2D nanomaterials of different chemical composition with lipid bilayers has an important role in subsequent biological effects. Hence, there is a need to assess and compare the safety concerns associated with emerging 2D nanomaterials.
Five emerging 2D nanomaterials, including graphene oxide (GO), reduced graphene oxide (rGO), molybdenum disulfide (MoS2), copper oxide (CuO), and iron oxide (α-Fe2O3) were synthesized and comprehensively characterized to study their physical properties such as size, morphology, surface area, surface charge, and hydrophilicity. We quantitatively assessed the disruption of a phospholipid bilayer membrane (i.e., lipid vesicles) induced by 2D nanomaterials using a dye-leakage assay.
Dye leakage from the vesicle inner solution, which indicates loss of membrane integrity, was observed for GO, rGO, and MoS2 nanosheets, but not for CuO and α-Fe2O3, suggesting that chemical composition plays an important role during membrane–nanosheet interactions. Induced-aggregation was demonstrated for GO and rGO while physically interacting with lipid vesicles. In contrast, induced-stabilization was observed for MoS2 nanosheets when mixed with lipid vesicles, suggesting that the aggregation mechanism differed between the 2D nanomaterials. No loss of membrane integrity was observed under high oxidative stress, indicating that a physical mechanism rather than chemical oxidation induces lipid membrane disruption. Furthermore, the extent of physical interaction with GO was dependent on total surface area, not edge length, consistent with a physical lipid-extraction mechanism. Overall, lessons learned in the study provide meaningful insight into nanosheet effects on living cells.
2:30 PM - BM06.11.07
Bioactive Electrospun Cellulosic Nanofibers from Bacteria for Tissue Engineering and Regenerative Medicine
Vivekanandan Palaninathan 1 , Sreejith Raveendran 1 , Ankit Rochani 1 , Neha Chauhan 1 , Yasushi Sakamoto 2 , Toru Maekawa 1 , Sakthi Kumar 1 Show Abstract
1 Bio-Nano Electronics Research Centre, Toyo University, Kawagoe, Saitama, Japan, 2 Biomedical Research Centre, Division of Analytical Science, Saitama Medical University, Saitama Japan
Cellulosic materials have been of tremendous importance to mankind since its discovery due to its superior properties and abundance in nature. Recently, an increase in demand for alternate green materials has rekindled the interest for cellulosic materials. Bacterial cellulose was functionalized with sulfate groups through acetosulfation to gain solubility in aqueous media, which provides access to several applications . The cell viability, antioxidant and hemocompatibility assays have verified the highly biocompatible and antioxidant characteristics of Bacterial Cellulose Sulfate (BCS) in both in vitro and ex vivo conditions. From the in vitro and ex vivo studies it was evident that BCS has immense potential, which encouraged us to fabricate their nanoscale fibers that can be utilized in several applications such as wound healing, tissue engineering and regenerative medicine. Further, the cellulosic nanofiber networks with irregular fiber morphologies that were lost as a result of acetosulfation process were recreated via electrospinning process as uniform ultrafine nanofiber networks. Pure BCS failed to produce nanofibers due to poor spinability of its solution, hence novel BCS-PVA nanofibers were fabricated by simple electrospinning route to engineer ultrafine nanoscale fibers. The biological evaluation of the fabricated BCS/PVA nanofiber scaffolds was done using L929 mouse fibroblast cells, which confirmed that these nanofibers are excellent matrices for cell adhesion, proliferation and have remarkable properties suitable for various biomedical and tissue engineering applications.
1. Vivekanandan et al., Acetosulfation of bacterial cellulose: An unexplored promising incipient candidate for highly transparent thin film. MaterialsExpress, 2014; 4: 415-421.
2:45 PM - BM06.11.08
Nanoporous Atomically Thin Graphene Membranes for De-Salting and Dialysis Applications
Piran Ravichandran Kidambi 1 , Doojoon Jang 1 , Juan-Carlos Idrobo 2 , Michael Boutilier 1 , Jing Kong 1 , Luda Wang 1 , Rohit Karnik 1 Show Abstract
1 , Massachusetts Institute of Technology, Cambridge, Massachusetts, United States, 2 , Oak Ridge National Laboratory, Oak Ridge, Tennessee, United States
Dialysis is a ubiquitous separation process in biotechnology, biochemical processing and biological research. State-of-the-art dialysis membranes comprise of a relatively thick polymer layer with tortuous pores and suffer from low rates of diffusion leading to extremely long process times (often several days) and poor selectivity, especially in the 0-1000 Da molecular weight cutoff range.
Graphene and other atomically thin materials offer a fundamentally new approach to control mass transport at the nanoscale and allow new possibilities in membrane technology. The atomic thickness combined with excellent mechanical strength, chemical stability and the ability to sustain selective, nanometre-scale pores, allows for the realization of tailored nanoporous atomically thin membrane offering high permeance, high selectivity and high chemical resistance.
Here, we report on the fabrication of large-area (cm2) nanoporous atomically thin membranes (NATMs) by transferring graphene synthesized using scalable chemical vapor deposition (CVD) to polycarbonate track-etched (PCTE) supports. After sealing defects introduced during transfer/handling by interfacial polymerization, a facile oxygen plasma etch is used to create size-selective pores (≤1nm) in CVD graphene. We demonstrate size-selective separation and de-salting of small model molecules (~200-1355 Da) and proteins (~14000 Da), with ~1-2 orders of magnitude increase in permeance compared to state-of-the-art commercial membranes. Rapid diffusion and size-selectivity in NATMs offers transformative opportunities in purification of drugs, removal of residual reactants, biochemical analytics, medical diagnostics, therapeutics, and nano-bio separations.
Kidambi et al. Advanced Materials (2017)
Kidambi et al. Advanced Materials (2017)
Kidambi et al. Nanoscale (2017)
O’Hern et al. Nano Letters (2015)
3:00 PM - BM06.11.09
Preparation and Characterization of Layered Nano Carriers by the Self-Assembly Reaction of Carboxylic Acids and Metal Hydroxide
Mizuki Wada 1 , Hideyuki Tagaya 1 Show Abstract
1 Graduate School of Science and Engineering, Yamagata University, Yamagata Japan
Nowadays, much research has been carried out on the preparation of organic and inorganic composites organized at the nano level of organic and inorganic molecules. Such nano composites offer useful new properties as nano carriers that possess both characteristics of organic and inorganic compounds compared to conventional materials as functional compounds with high possibilities. Especially, the layered nano composite can be expected to have the functionality of the layer space, and it is expected to be applied in a wide range of fields from the life science material to the mechanical and electronic materials as the next generation industrial infrastructure technology. We have found that layered nano composite could be obtained by the self-assembly reaction of metal hydroxide with various organic compounds.
In this study reactions of metal hydroxide such as zinc hydroxide and calcium hydroxide with the di- and mono- carboxylic acids were investigated to obtain new nano carriers. In the self-assembly reaction, there are no restrictions of bulkiness of organic compounds fundamentally. In typical experiments, appropriate amount of carboxylic acids were dissolved in distilled water and acetonitrile. Metal hydroxide was mixed with the above solution under air atmosphere and stirred at 60oC for 5h. After the filtration and washing with distilled water, the samples were dried under vacuum at room temperature. The resulting powders were characterized by powder XRD, TG, SEM, and TEM in which clear layered structure was confirmed.
3:15 PM - BM06.11.10
A Novel Cantilever Based Technique to Characterize the Microscopic Strain in 2D Materials
Rajul Patkar 1 , V Ramgopal Rao 2 Show Abstract
1 , IIT Bombay, Mumbai India, 2 Director, IIT Delhi, Delhi, Delhi, India
There has been a lot of research on new materials and their composites for various applications. Material with high gauge factor will be ideal for piezoresistive cantilever devices. There is a need for a simple platform to characterize new materials instantly. In this work, we have demonstrated a novel polymeric device which can be used as a platform to analyze any new strain sensitive material which can be either drop casted, sputtered or evaporated onto the device. Alternately, these devices can also be used as a sensor. Fabrication of these devices is extremely simple and involves just three lithography steps. Sacrificial layer of silicon oxide is grown on a RCA clean substrate which will be removed at the end to release the devices. Structural layer of microcantilever is formed by patterning SU8-2005 on the sacrificial layer. Metal deposition and etching is done on the structural layer to form inter digited electrode (IDE) and contact pads. An anchor of SU8-2100 is patterned and sacrificial layer removed to release the devices. The final device is 5 µm thick cantilever with gold IDE structure and anchored to polymer. These devices are now ready to characterize any material for its strain sensitivity. The advantage is that one can characterize different materials for their deflection sensitivity and gauge factor instantly without going through fabrication process. The spring constant of the device was 2 N/m which was determined by nanoindenter. Two composites of SU8/carbon-black/graphene-glycidol and other graphene/SU8-glycidol composite were characterized using this platform. The composite was then drop casted on the IDE structure on the cantilever surface and the deflection sensitivity measurement was carried out by deflecting the tip of micro cantilever with a pre-calibrated micromanipulator needle and simultaneously measuring the voltage and current. The deflection sensitivity of the graphene composite was 90 ppm nm-1. This device can also be used as a sensor. Once the device is fabricated, piezo layer can be deposited on IDE structures. The electrical contacts can be made to measure the change in resistance or capacitance. The device can be passivated by evaporating either parylene, hot wire chemical vapor deposition (HWCVD) silicon nitride or by spraying Teflon. The advantage of such a device is reduced complexity in fabrication and improved sensitivity compared to plain IDE structures because of additional change in resistance due to deflection of cantilever beam. This process also avoids the damage of piezo layer during wet etching of sacrificial layer. The extreme simple process of fabrication makes this device a reliable low cost platform for sensing and characterization.
3:30 PM - *BM06.11.11
Noise Resistant Nanoscale Deflectometry for DNA Sequencing
Alex Smolyanitsky 1 , Boris Yakobson 2 , Michael Zwolak 3 , Daniel Gruss 4 Show Abstract
1 , Applied Chemicals and Materials Division, National Institute of Standards and Technology, Boulder, Colorado, United States, 2 Department of Materials Science and NanoEngineering, Rice University, Houston, Texas, United States, 3 Center for Nanoscale Science and Technology, National Institute of Standards and Technology, Gaithersburg, Maryland, United States, 4 Maryland Nanocenter, University of Maryland, College Park, Maryland, United States
Nanoscale molecular sensors show significant promise in revolutionizing healthcare, from sensing minute concentrations of chemicals in the bloodstream to enabling fast and accurate low-cost DNA sequencing. Before such sensors become truly technologically relevant, numerous challenges must be addressed, from achieving robust selectivity in realistic operational environments to developing noise-resistant readout schemes. In particular, a great number of biophysical applications require room-temperature operational conditions, which presents thermal noise in measured signals as a crucial obstacle in sensor design and operation.
We present an overview of the nanoelectromechanical system (NEMS)-based transducers (or deflectometers) for ultrafast DNA sequencing. The general approach is based on utilizing Watson-Crick base pairing, combined with the capacity of atomically thin membranes to deflect temporarily in response to sub-nanonewton forces. These forces arise from breaking hydrogen bonds, selectively formed between a suspended functionalized nanoribbon in an aqueous environment and a translocating DNA strand. By combining detailed electron transport calculations with atomistic room-temperature molecular dynamics simulations and theoretical considerations, we demonstrate thermal noise-resistant approaches to converting the resulting nanoribbon deflection into a robustly measurable electrical signal.
In an approach suitable for various electrically conductive or semiconductive atomically thin membranes, a nanoscale flat-plate capacitor-based motion sensor is presented. A molybdenum disulfide (MoS2) nanoribbon-based capacitive sensor  is discussed as an example. The transient capacitive current is demonstrated to require only low-pass filtering of the current signal, yielding an overall “raw” (single-measurement) read accuracy of 70-90% at the single base resolution and the rate of 70 million bases per second. Naturally, such a sensor is subject to parasitic ionic conduction, which “smears” the useful signal. We thus present analytical estimates of the detection limits imposed by this effect, thereby determining the maximum ion concentration allowed in the device-containing aqueous solution.
An alternative method relying on the electronic properties of graphene nanoribbons (GNRs) [2-4], devoid of the parasitic effects of ionic currents, is presented. By directly sampling all thermal fluctuations of the suspended GNR, we demonstrate that the corresponding charge carrier transmission peak is close to the Voigt profile, commonly observed in liquid/gas-phase spectroscopy. Although this profile itself is not experimentally measurable in this case, its analysis readily leads to determining GNR bias range, such that the resulting measurable current via GNR (in the 10-100 nA range) is modified by as high as 10 % when the GNR is deflected out of plane by a subnanonewton force. Finally, we present analytical estimates of the resulting GNR-based transducer’s sensitivity and its corresponding “processing bandwidth,” which provide clear insight into optimizing sensor performance in room-temperature conditions.
1. Smolyanitsky, A.; Yakobson, B. I.; Wassenaar, T. A.; Paulechka, E.; Kroenlein, K., A Mos2-Based Capacitive Displacement Sensor for DNA Sequencing. ACS Nano 2016, 10, 9009-9016.
2. Paulechka, E.; Wassenaar, T. A.; Kroenlein, K.; Kazakov, A.; Smolyanitsky, A., Nucleobase-Functionalized Graphene Nanoribbons for Accurate High-Speed DNA Sequencing. Nanoscale 2016, 8, 1861-1867.
3. Gruss, D.; Smolyanitsky, A.; Zwolak, M., Graphene Deflectometry for Sensing Molecular and Ionic Processes at the Nanoscale. in preparation 2017.
4. Gruss, D.; Smolyanitsky, A.; Zwolak, M., Communication: Relaxation-Limited Electronic Currents in Extended Reservoir Simulations. The Journal of Chemical Physics 2017, 147, 141102.
BM06.12: Poster Session
Thursday PM, November 30, 2017
Hynes, Level 1, Hall B
7:00 PM - BM06.12.01
Antibody-Based Biosensor Platforms for the Rapid Melatonin Hormone Detection
Lais Brazaca 1 , Camila Bramorski 1 , Juliana Bernardi 1 , Sanseray Machado 2 , Regina Markus 2 , Bruno Janegitz 3 , Valtencir Zucolotto 1 Show Abstract
1 , Nanomedicine and Nanotoxicology Group/University of Sao Paulo, Sao Carlos Brazil, 2 , Univesity of Sao Paulo, Sao Paulo Brazil, 3 , Federal University of Sao Carlos, Araras Brazil
Melatonin is a hormone mainly produced by the pineal gland, which may also be synthesized by defense cells under inflammatory conditions. Abnormal circulating levels of this hormone have been related to several diseases such as type 2 diabetes, Alzheimer’s disease and some types of cancer. Melatonin has been exclusively quantified by ELISA and radioimmunoassays, and despite the sensitivity and low detection limits exhibited by this method, it requires specific reagents and equipment, restricting the tests to few patients. To overcome such limitations, we present an electrochemical immunobiosensor for the simple and rapid melatonin quantification. Indium tin oxide (ITO) platforms were modified by the crosslinkers (3-Aminopropyl)triethoxysilane (APTES), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC), N-hydroxysuccinimide (NHS) for further anti-melatonin antibodies immobilization using the self-assembled monolayers technique. The biosensors devices displayed a linear response for melatonin in the range from 0.75 to 7.5 µmol/L using Electrochemical Impedance Spectroscopy (R2=0.989) and Cyclic Voltammetry (R2=0.953) as detection methods. The biosensors presented a good stability and reproducibility (3.45% and 2.87% for EIS and VC, respectively, n=3), exhibiting adequate responses even after 30 days of assembly. We expect the developed devices can contribute to the medical area, allowing precise and cost-effective detection and quantification of melatonin.
7:00 PM - BM06.12.02
Control of Antibacterial Activity of Gold-Coated Silver Nanoplates by Laser Irradiation
Kaung Kyaw 1 2 , Hiroaki Ichimaru 1 , Mitsuhiro Terakawa 3 , Yuta Miyazawa 4 , Daigou Mizoguchi 4 , Masayuki Tsushida 5 , Takuro Niidome 1 Show Abstract
1 Faculty of Advanced Science and Technology, Kumamoto University, Kumamoto Japan, 2 Department of Chemical Engineering, Yangon Technological University, Yangon Myanmar, 3 Department of Electronics and Electrical Engineering, Keio University, Yokohama Japan, 4 , Dai Nippon Toryo Co., Ltd., Otawara Japan, 5 Faculty of Engineering, Kumamoto University, Kumamoto Japan
It has been known that silver ions released by silver nanoparticles have bactericidal effect against a wide spectrum of bacteria. Silver ions, with adsorbed oxygen on the surface, silver ions can induce redox reactions on the membrane transport proteins of bacteria thereby deactivating them. Silver ions are also capable of impairing the energy transfer mechanism of bacteria during respiration process. However, it is important for silver nanoparticles to maintain their size and shape as we have encountered aggregations of silver nanoplates within a few hours after being dispersed in LB medium resulting in the loss of optical properties and especially their antibacterial activity. Then, we found that coating of silver nanoplates with gold layers increased their dispersion stability but reduced the antibacterial activity. In this study, we employed anisotropic silver nanoplates coated with gold as an antibacterial material. Since their shape can be changed to spherical structure by pulsed laser irradiation, we examined the change in their antimicrobial activity after the irradiation.
We prepared silver nanoplates coated with layers of gold atom on their surfaces. It showed extinction band at 630 nm. After pulsed laser irradiation (the second harmonics (532 nm) of a Q-switched Nd:YAG laser at repetition rate of 10 Hz. Irradiation time was 1 minute with the laser energy of 25 mJ/pulse), the shape changed to spherical form with an extinction band at 420 nm. As a result of energy dispersive X-ray spectroscopy (EDX), ratio of silver and gold before pulsed laser irradiation was about 22:1. However, ratio was changed to about 4.5:1 after the pulsed laser irradiation. It would be due to that by irradiating pulsed laser to Ag@Au NPLs, gold was melted and generated some defects. From them, internal silver atoms were released as ions. After the laser irradiation, increase of antibacterial activity was observed and it collated to the release of silver ion from the nanoparticles.
Pulsed laser irradiation could be used as a triggering mechanism to switch on the antibacterial effect. It can be concluded that gold-coated silver nanoplates can be considered as nanodevices capable of controlling the antibacterial activity by pulsed laser irradiation.
7:00 PM - BM06.12.03
Antibacterial Selenium Nanoparticle Coatings for Field Hospitals
James Moxley 1 Show Abstract
1 , Northeastern University, Boston, Massachusetts, United States
While advancing antibacterial resistance has recently come to demonstrate a looming threat to the health-care infrastructure of developed nations, many areas throughout the developing world still suffer persistently high mortality rates from commonly treatable bacterial strains. Humanitarian efforts in these regions, primarily seen today in the form of non-governmental organizational (NGO) outreach as well as peace-keeping military operations, are significantly strained by an incapability to reproducibly produce and maintain sterile conditions in the field. Injured personnel are often required to be rapidly transported out of the region in order to receive safe medical treatment, incurring large financial costs while demonstrating severe risks to the individuals in the process. In order to address this issue, antibacterial selenium nanoparticulate coatings were prepared for application in rapidly constructed field hospitals operating in diverse environments. These coatings have demonstrated antibacterial properties when applied to wall paneling suspended in various bacterial cultures. Ongoing work includes determining the effects of local weather (principally, heat and humidity) and transportation (principally, vibrational and shock disturbances) conditions on the persistence of applied coatings. New means of rapid, on-site administration of antibacterial nanoparticulate coatings, onto both medical instrumentation and house-keeping materials, are also currently under development.
7:00 PM - BM06.12.04
Preparation of Layered Nano-Composite by the Reaction of Ca(OH)2 with Carboxylic Acid as the Molecular Recognition Host
Yusuke Edamatsu 1 , Kobayashi Junichi 1 , Hideyuki Tagaya 1 Show Abstract
1 , Graduate School of Science and Engineering, Yamagata University, Yonezwa,Yamagata Japan
Recently, the study on the preparation of organic-inorganic composite organized at nano level has been carried out actively. Organic-inorganic nano-hybrids are characterized by having both organic and inorganic properties and layered structures are expected to have the ability to recognize molecules and incorporate differentially between the layers.
We have already succeeded to construct organic-inorganic composites with the layered structure at the nano level by self-organizing reaction of metal hydroxide and organic substances and have made clear their properties.
They are functional materials in which organic compounds and inorganic compounds are regularly arranged between the layers by ionic bonding. Layered structure can be modified and they can intercalate variable organic substances that are difficult to insert in usual host layers.
In this study, layered calcium hydroxide was reacted with calboxylic acids having different number of carbons, and characterized by TG, SEM, TEM and XRD. The results showed that as the number of carbons became larger, the interlayer distance increased. In fact, the interlayer distance of the composite was 29.5 Å when inserting decanoic acid, whereas it was 48.2 Å when stearic acid. The interlayer distance was in proportion to the number of carbons. It was also found that calboxylic acid having hydroxyl group and high bulkiness was incorporated into the layered calcium hydroxide.
Calcium doesn’t affect the human body, and layered calcium hydroxide may be possible to intercalate even bulkier substances such as very long chain calboxylic acids. It is well known that they are playing important roles in the body. Moreover, we can suggest that the control of interlayer spacing is easy. And besides, compounds in which a calboxylic acid having a hydroxyl group is inserted may distinguish only a polar substance from the mixture. So it has a great potential as a useful layered composite material with high added value.
7:00 PM - BM06.12.05
Bioconjugated Graphene Quantum Dot Nanoprobes for In Vivo and In Vitro Imaging
Ankarao Kalluri 1 , Devon Leighton 1 , Isaac Macwan 1 , Prabir Patra 1 Show Abstract
1 , University of Bridgeport, Bridgeport, Connecticut, United States
Bioconjugated graphene quantum dots (GQDs), which are edge functionalized nanometer-sized graphene pieces, are considered as one of the most promising and emerging bioactive fluorescent labels in biology and medicine. Due to the luminescence stability, biocompatibility, nanosecond lifetime, low toxicity, and high-water solubility, these GQDs are demonstrated to be excellent nanoprobes for sensing, immunoassay and bioimaging applications. Here, we report the conjugates of GQD-succinimidyl esters and GQD-maleimide probes, synthesized by coupling with carboxylate GQDs. These conjugates react with lysine or cysteine residues of a protein or any other molecules, which have the potential to be a new class of luminescent labels for evaluating biomolecular signatures on intact cells and tissue specimens. This carboxylated edge functionalized GQDs were synthesized by acid treatment and chemical exfoliation of carbon fibers. The formed GQDs exhibited a variety of color emissions depending on the reaction conditions such as temperature. Then, the GQDs were further reacted with N-hydroxy succinimide (NHS) and N-(2-amino ethyl) maleimide to form GQD-succinimidyl ester and GQD-maleimide functionalized probes respectively. The bioconjugated GQDs have broad excitation spectra, narrow emission spectra, long fluorescence time, negligible photo-bleaching, and are able to conjugate with proteins and peptides through their functional groups. Morphological analysis was done using TEM, AFM, and SEM. Furthermore, UV-Visible, fluorimetry and FT-IR analyses were performed on the synthesized probes to study their optical and chemical properties. Due to their low cytotoxicity and excellent biocompatibility, the bioconjugated GQDs have the potential to be used as an eco-friendly material in biolabeling and bioimaging processes. These properties are extremely promising for applications such as improving the sensitivity and multiplexing capabilities of molecular histopathology and disease diagnosis. The use of multicolor GQD nanoprobes in cell biology studies of proteins and peptides immunohistochemistry are considered to be the most important and clinically relevant applications.
7:00 PM - BM06.12.06
Efficient Coverage of ZnO Nanoparticles on Cotton Fibres for Antibacterial Finishing Using a Rapid and Low Cost In Situ Synthesis
Raquel Borda d' Água 1 , Rita Branquinho 1 , Maria Duarte 2 , Elisabete Maurício 3 , Ana Fernando 2 , Rodrigo Martins 1 , Elvira Fortunato 1 Show Abstract
1 Materials Science Department (DCM), CENIMAT/I3N, FCT-NOVA Faculdade de Ciências e Tecnologia (FCT) da Universidade NOVA de Lisboa and CEMOP/UNINOVA, Caparica, Portugal, Caparica Portugal, 2 Department of Sciences and Technology of Biomass, FCT-NOVA Faculdade de Ciências e Tecnologia (FCT) da Universidade NOVA de Lisboa, Caparica, Portugal, Caparica Portugal, 3 , CBIOS/Universidade Lusófona and Elisa Câmara, Lda, dermocosmética, Lisboa, Portugal, Lisboa Portugal
Textiles are known to be suitable for microorganism growth under ideal conditions, specially bacteria and fungi, due to their porous texture. Microbial colonization of fabrics causes a series of undesirable effects not only on the textile material, but also on the user himself. Therefore, the development of new and improved fabrics finishes that can prevent the growth and spread of microorganisms in these types of materials is crucial. In this study, antibacterial fabrics were produced by combining the bactericidal properties of zinc oxide nanoparticles (ZnONPs) with the high absorbency properties of the cotton fibres. The development of these fabrics was performed by sol-gel technology through an in situ synthesis of ZnONPs on cotton fibres. This technology associated to the in situ synthesis promoted the formation of a uniform and dense adsorption of the nanoparticles both inside and on the surface of fabric fibres. The antimicrobial activity of the functionalized fabrics was tested by the agar diffusion method and by the absorption method according to ISO 20743: 2013 standard, in the Escherichia coli ATCC8739, Pseudomonas aeruginosa ATCC9027, Staphylococcus aureus ATCC6538 and RN4220, methicillin resistant Staphylococcus aureus ATCC33591 (MRSA), Enterococcus faecalis ATCC29212, Staphylococcus epidermidis ATCC1228 and Propionibacterium acnes ATCC6919. Antibacterial assays, showed that ZnONPs coated fabrics exhibited antibacterial effect against P. acnes, S. aureus and S. epidermidis. Finally, tests conducted with hydrogen peroxide suggested the involvement of reactive oxygen species, namely the involvement of hydrogen peroxide, in the antibacterial activity of zinc oxide nanoparticles. Therefore, synthesised nanoparticles showed great potential to be used as coatings for medical, cosmetic or sports fabrics.
7:00 PM - BM06.12.07
Electronic Tongue System Based on an Array of Conducting Polymers and MoS2 for the Classification of Bisphenol A Based on Neural Networks Approach
Wania Christinelli 1 , Murilo Facure 1 2 , Flavio Shimizu 3 , Ricardo Cerri 4 , Osvaldo Oliveira Jr. 3 , Daniel Correa 1 2 , Luiz Henrique Mattoso 1 Show Abstract
1 Nanotechnology National Laboratory for Agriculture (LNNA), Embrapa Instrumentation, Sao Carlos, Sao Paulo, Brazil, 2 Center for Exact Sciences and Technology, Federal University of São Carlos, Sao Carlos, Sao Paulo, Brazil, 3 Sao Carlos Institute of Physics, University of Sao Paulo, Sao Carlos, Sao Paulo, Brazil, 4 Department of Computer Science, Federal University of São Carlos, Sao Carlos, Sao Paulo, Brazil
In the last few decades, many pollutants have shown adversal effects on the endocrine system of human beings and other mamals. Bisphenol A (BPA) is one of the most important chemicals globally synthesized in high volume, which is used in a wide variety of food-storage or packaging materials. BPA is a potent endocrine-disrupting compound (EDC) and its toxicity has gained attention in the literature. In this sense, the control of contamination by BPA is an important concern, and the development of chemical sensors have been pursed to detect this pollutant. Sensors produced using nanostructured hybrid materials have become an indispensable tool in the evaluation of contaminants, since they present high sensitivity to any compositional variation in the medium. Among the available technologies, the electronic tongue, which is a device formed by a set of distinct sensing units, have proved to be quite adequate for the detection of extremely low amounts of contaminants in liquids. In this work, we describe a microfluidic sensor, in which nanostructured films were deposited in interdigitated electrodes by the layer-by-layer (LbL) technique. The device is formed by 7 sensing units composed by poly (o-methoxy aniline), POMA, as the cationic layer and either poly(3-thiophene acetic acid), PTAA and Molybdenum disulfide (MoS2) as the anionic layer. Multidimensional projection techniques implemented in PEx-Sensors software were used to analyze the impedance data to distinguish between different solutions. The results collected with the e-tongue were treated using PEx-Sensors software using the multidimensional projection techniques such as IDMAP (Interactive Document Map), Principal Component Analysis (PCA) and Sammon’s mapping to analyze the resistance data. The main results showed the sensor presented high sensitivity and selectivity towards BPA detection. In addition, the collected sensor data was used as a training set for an Artificial Neural Network (ANN), in order to model the above problem as a classification task. The used ANN is composed of an input layer with 358 neurons, one hidden layer with 187 neurons, and one output layer with 16 neurons. The input layer is connected with the input data, and each of the 16 output neurons represents one of the 16 classes to be learned in the problem, which are BPA and endocrine contaminants in different concentrations. The experimental procedure was performed using the stratified 10-fold cross-validation strategy. The results for ANN was capable to correctly classify 95% of the input patterns indicating the potential of the methodology employed.
The authors would like to thank to financial support given by CNPq (402287/2013-4), FAPESP, SISNANO/MCTI, FINEP and Embrapa AgroNano research network.
7:00 PM - BM06.12.08
Partially Reduced Graphene Oxide's Augmentation of Enzyme Activity
Roshan Reddy 1 , Nicolas Williams 1 , Jerry Reyes 1 , Rebecca Isseroff 1 2 , Clement Marmorat 2 , Marcia Simon 3 , Fan Yang 2 , Stephen Walker 3 , Miriam Rafailovich 2 Show Abstract
1 , Lawrence High School, Cedarhurst, New York, United States, 2 , Stony Brook University, Stony Brook, New York, United States, 3 , Stony Brook School of Dental Medicine, Stony Brook, New York, United States
This research incorporated graphene oxide (GO) and partially reduced graphene oxide (pRGO) into dissolved gelatin which was then crosslinked with microbial transglutaminase (MTG). Rheological measurements indicated that the crosslinking time was reduced by a factor of two when pRGO was added to the gelatin/deionized (DI) water solutions, whereas gelatin dissolved in GO solution increased the time needed to crosslink by 33%. Addition of pRGO also increased the elastic modulus of the gelatin. pRGO appeared to enhance the rate of cleavage of the tissue from tissue culture plastic substrates when trypsin was added to the media, making it easier to remove the tissue for purposes of passage or cell counting. Staphylococcus aureus, when plated onto gelatin/DI water, gelatin/GO solution, and gelatin/pRGO solution, showed evidence of bacterial growth in all three types of gelatins but only the pRGO cultures showed a wide ring of surface depression around the inoculation site, suggesting pRGO activation of bacterial gelatinase. These findings indicate that pRGO may have an effect on enzymatic activity. Further studies are in progress.
7:00 PM - BM06.12.09
All Nanocrystal-Based and Solution-Processed Wearable Pressure Sensor for Sensing a Wide Range of Pressure
Haneun Kim 1 , Seung-Wook Lee 2 , Hyungmok Joh 1 , Mingi Seong 1 , Woo Seok Lee 1 , Min Su Kang 1 , Soong Ju Oh 1 Show Abstract
1 Materials Science and Engineering, Korea University, Seoul Korea (the Republic of), 2 Semiconductor Systems Engineering, Korea University, Seoul Korea (the Republic of)
Highly sensitive and flexible pressure sensors are of great interest in various applications, such as wearable devices, for human healthcare monitoring system, etc. However, recently developed pressure sensors are fabricated by expensive technique with time consuming, high temperature or vacuum based process, which also limits the realization of flexible devices. In this study, we designed a pressure sensor with metal/insulator hybrid nanostructures through lithography-free and all-solution-based process. Pseudo-pyramid-like hybrid structures are achieved by using insulating silver nanocrystals (NCs) and metallic nanocrystals to enhance the pressure sensitivity. We demonstrate that our hybrid structure pressure sensor shows enhanced sensitivity a factor of 155.4kPa-1 with wider range of pressure sensing regime. The origin of enhanced sensitivity was examined using conductive atomic force microscopy, combined with Chemical, optical, electronic, and electromechanical characterization. Interface engineering and chemical treatment are investigated to fabricate these hybrid structures on top of polydimethylsiloxane (PDMS) substrates to increase the mechanical stability. Finally, we designed and fabricated a multi array pressure sensor by an all-solution process, which showed higher pressure and spatial sensitivity compared to the sensing capability of human skin. Our promising fabrication methods provide a pathway to fabricate low-cost, high-performance and multifunctional sensors to be used in artificial skin.
7:00 PM - BM06.12.10
Gold Nanoparticles Assembled on Multilayer Graphene Sheets for Surface Enhanced Raman Spectroscopy of Glucose
Zafar Iqbal 1 , Laila Al-qarni 1 Show Abstract
1 Chemistry & Environmental Science, New Jersey Inst of Technology, Newark, New Jersey, United States
The small normal Raman cross-section of glucose is considered a major issue for its detection by surface enhanced Raman spectroscopy (SERS) for medical applications, such as blood glucose level monitoring of diabetic patients and evaluation of patients with other a since glucose is a marker for many human diseases. In this work, we report the use of commercial multilayer graphene sheets as substrates on which gold nanoparticles are chemically assembled by citrate reduction. The results show that these substrates are capable of providing SERS enhancement factors up to 1010 with a detection limit to 10-8 M in aqueous solutions of glucose. The SERS performance on graphene substrates are many orders of magnitude higher compared with results on gold coated chemically etched Klarite® silicon substrates. The glucose spectra over a wide range of concentrations in the 400-1500 cm-1 fingerprint region were recorded with a Thermo Scientific DXR Raman microspectrometer using 785 nm laser wavelength, 10 mW laser power and a 50x microscope objective. The intensity of the 1340 cm-1 line of glucose in particular varied linearly with glucose concentration and can be used as a calibration for samples of unknown concentrations. Chemometric methods were used to provide improved spectra at very low concentrations. The role of fractional charge transfer effects from the graphene substrate to glucose that could provide secondary enhancement of the spectra will also be evaluated .
 S. Chattopadhyay, M-S. Li, P. K. Roy, C. T. Wu, Analyst, 2015,140, 3935–3941.
7:00 PM - BM06.12.12
Characterization of a Nanopharmaceutical
Farah Mahmoud 2 1 , Tyler Feger 2 1 , B. Ellen Scanley 1 , Christine Broadbridge 3 4 5 , Todd Schwendemann 2 1 Show Abstract
2 Physics, Southern Connecticut State University, New Haven, Connecticut, United States, 1 CSCU Center for Nanotechnology, Southern Connecticut State University, New Haven, Connecticut, United States, 3 School of Graduate Studies, Research, and Innovation, Southern Connecticut State University, New Haven, Connecticut, United States, 4 Center for Research on Interface Structures and Phenomena, Yale and Southern Connecticut State University, New Haven, Connecticut, United States, 5 Office for STEM Innovation and Leadership, Southern Connecticut State University, New Haven, Connecticut, United States
Nanoscale pharmaceuticals represent a new area of care in medicine. However, one of the major hurtles in nanopharmaceuticals is FDA approval. To get FDA approval there is extensive characterization required. Previous work has focused on preparing nanoscale pharmaceutical samples that can be examine using traditional nanocharacterization techniques. The consistency of these nanoscale pharmaceuticals have been seen using Transmission Electron Microscopy (TEM). However, due to the nature of TEM the electrons interact very little with lighter elements and only the heavier elements are see. This artifact of TEM leads to uncertainly in imaging of encapsulated materials. The nanopharmaceuticals investigated here are enclosed in a sugar coating which is invisible to the TEM. Therefore, the work presented here is characterizing the nanoparticles sucrose layer that has been coated with Bismuth making the outer shell visible by TEM. The size and shape of the nanoparticles are examined, as well as comparing the sizes to the unstained nanoparticles. By subtracting the imaged sizes of the stained vs. unstained particle an estimate of the thickness of the sugar coating is made.
7:00 PM - BM06.12.13
Nanofibrous Paper Chemiresistors with Functionalized Nanoparticles towards Structurally-Tunable Sensing Interfaces
Shan Yan 1 , Chirag Soni 1 , Cameron Ghazvini 1 , Ross Hernandez 1 , Xin Liu 2 , Ning Kang 1 , Jack Lombardi 3 , Jin Luo 1 , Benjamin Hsiao 4 , Mark D. Poliks 3 , Ivan Gitsov 2 , Chuan-Jian Zhong 1 Show Abstract
1 Chemistry, State University of New York at Binghamton, Binghamton, New York, United States, 2 Chemistry, SUNY-ESF, Syracuse, New York, United States, 3 System Science and Industrial Engineering, SUNY-Binghamton, Binghamton, New York, United States, 4 Chemistry, Stony Brook University, Stony Brook, New York, United States
Abstract: Wearable biosensors show increasing potential for monitoring human performances and health conditions, but major challenges for their wide-spread applications include low sensitivity, limited biocompatibility, and high cost of materials. Here we report a novel flexible membrane-type composite scaffold derived from multi-layered nanofibrous paper as a low-cost and biocompatible matrix and functionalized nanoparticles, e.g., dendronized gold nanoparticles, as a chemically sensitive interfacial structure with tunable sizes and shapes to enable structural diversity and molecular sensitivity. Key elements to the novelty include the immobilization of poly(ether-ester) dendrons with oligoethylene glycol spacers on gold nanoparticles and the combination of hydrogen bonding and van der Waals interactions between partially interpenetrating dendrons leading to tunable interparticle interaction and spacing. The unique vapor, breath and sweat response characteristics have demonstrated an intriguing set of examples in embedding functionalized nanoparticles in nanofibrous membrane papers as a promising nanomaterials for construction of highly-tunable sensing interfaces of wearable biosensors.
7:00 PM - BM06.12.14
3D Nanowire Array/Nanoparticle Hybrid Structure as Electrochemical Biosensors for Antibiotic Detection
Zhiyang Li 1 , Victor Sarpong 1 , Zhiyong Gu 1 Show Abstract
1 , Univ of Massachusetts-Lowell, Lowell, Massachusetts, United States
Over the years, there have been global issues with bacterial resistance due to overprescription and overusage of antibiotics such as penicillin, and traces of various antibiotics have been detected in food and grocery products. Monitoring and regulation of antibiotics are impacted by detection techniques such as HPLC and ELISA that use expensive and complex instrumentation and require highly skilled personnel, making monitoring and controlling antibiotic usage difficult, time consuming and expensive. Therefore, it is necessary to develop a rapid, cost effective, highly sensitive and portable device for antibiotic detection. In this project, we developed an electrochemical biosensor based on Pt nanowire array (PtNWA)/Au nanoparticles (AuNPs) hybrid structure. First, the PtNWA/AuNPs structure was synthesized by electrodeposition within anodic aluminum oxide (AAO) membrane and electroless plating. Then, thioctic acid (TA) was applied to form a monolayer onto the surface of PtNWA/AuNPs electrode. After that, with the help of 1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) and N-hydroxysuccinimide (NHS) crosslinking agents, Penicillinase enzyme (PCNase) was successfully immobilized on the surface of the nanoparticles. Field Emission Scanning Electron Microscopy (FESEM) and Energy Dispersive Spectroscopy (EDS) were used to characterize the structure, morphology, and elemental composition of the prepared 3D vertical array. Electrochemical characterizations including Cyclic Voltammetry (CV) and Electrochemical Impedance Spectroscopy (EIS) were performed with a three electrode system. Due to the extremely large surface area of 3D PtNWA/AuNPs, a significantly high density of PCNase was immobilized, which resulted in a high sensitivity towards penicillin detection. Furthermore, the absence of Nafion layer results in a better repeatability and durability. Overall, this antibiotic biosensor based on novel 3D hybrid structure provides a promising platform for cheaper, quicker and easier antibiotic detection requirements.
7:00 PM - BM06.12.15
Targeted Delivery System Using Multi-pH Responsive Coaxial Nanofibers for Various Healthcare Applications
Daewoo Han 1 , Andrew Steckl 1 , Ashkan Tirgar 1 Show Abstract
1 Nanoelectronics Laboratory, Electrical Engineering and Computer Science, University of Cincinnati, Cincinnati, Ohio, United States
Local drug delivery targeted to specific organs can take advantage of different pH levels present in the targeted organs. Up until the 1950s, the release time and location could not be controlled in oral medications. This problem was solved by Röhm & Haas who developed the Eudragit polymers. The first commercial Eudragit product introduced in 1953 was soluble in basic conditions, which can protect pharmaceutical ingredients in the highly acidic environment of the stomach. Eudragit polymers were then developed that are dissolved within different physiological pH ranges to release drugs in targeted organs, such as stomach (pH 1-5), duodenum (pH > 5.5), jejunum (pH 6-7), and ileum (pH > 7). Eudragit L 100 (EL100) and Eudragit S 100 (ES100) are anionic copolymers derived from methacrylic acid and methyl methacrylate in the ratio of 1:1 and 1:2, designed to dissolve in pH > 6 or pH > 7, respectively. Eudragit E 100 is a cationic copolymer derived from dimethylaminoethyl methacrylate, butyl methacrylate, and methyl methacrylate with 2:1:1 composition, designed to dissolve in acidic fluids.
Very recently, nanostructured Eudragit polymers have emerged that can provide an extremely sensitive pH response with a faster dissolution rate than in bulk form. Recent reports demonstrated versatile properties of electrospun Eudragit fibers compared with other type of nanostructures, such as micro/nanoparticles. However, they only provide a single pH response using one specific Eudragit polymer. Multi-pH responses from one carrier system will provide very novel and fascinating options for various applications.
Using coaxial electrospinning, we have produced core-sheath fibers using different Eudragit materials with controlled multi-pH responses. Coaxial fibers with Eudragit L 100 (EL100) core and Eudragit S 100 (ES100) sheath give controlled release kinetics of core material at pH 6 based on the sheath thickness, which is controlled by the flow rate ratio of source polymer solutions. The thinnest sheath (~ 140 nm) provides much quicker release ~ 67 % within 4 hr compared to the thickest sheath (~ 250 nm) which provides the least core release ~ 5 %. Simply switching core and sheath material altered the multi-pH responses drastically. For coaxial fibers with ES100 core and EL100 sheath, while core release rate is similar, the sheath release rate becomes lower as the sheath layer becomes thicker. For example, thickest sheath (~ 200 nm) provides core and sheath release ratio of 1:1.7, while the thickest sheath (~ 120 nm) shows only a ratio of 1:2.5. At pH 5, all coaxial Eudragit fibers show no meaningful release from either core or sheath, while both core and sheath layers are completely dissolved at pH 7. Furthermore, extremely high surface area in the porous network of nanofibers provides much faster (> 30 times) response to external pH changes than that of equivalent cast films.
7:00 PM - BM06.12.18
Enhanced Cellular Morphology and Adhesion on Transition Metal Dichalcogenide Surfaces
Anthony Palumbo 1 , Shichen Fu 1 , Robert Chang 1 , Eui-Hyeok Yang 1 Show Abstract
1 , Stevens Institute of Technology, Hoboken, New Jersey, United States
Transition metal dichalcogenides (TMDs), such as WS2 and MoS2, have been widely explored as two-dimensional (2D) semiconducting nanomaterials with unique electronic, mechanical, and catalytic properties. Significant work has been performed to integrate these unique properties of TMDs towards biomedical applications, including drug delivery, therapeutics, biosensors and bio-imaging. Although cytotoxicity studies have been performed on TMDs, cell-substrate interactions of TMDs are not well-understood and require further study to illuminate the influence of TMDs on biological cell adhesion. In this work, WS2 and MoS2 are grown via chemical vapor deposition (CVD) on SiO2 substrates and seeded with human fibroblast cells. Cell culture is similarly performed on TMDs transferred onto additional substrates commonly employed in biomedical applications (i.e., PDMS). TMD-free control samples are used to compare the effects of TMD presence on the adherence of fibroblast cells. After 24 hours of culturing, the cell-substrate interactions are probed using a methyl violet staining. To perform dimensional metrology and analysis, optical microscope images are collected. Image processing using thresholding and noise filtering algorithms enables individual cell bodies to be segmented. Specifically, cellular morphometric features (cell area, eccentricity) are computed from the segmented cell outlines. Upon determination of the corresponding mean and standard deviation values, unpaired t-tests are performed on the mean values of cell area and eccentricity, whereas F-tests are performed on the variances. It is observed that the presence of TMDs improves the cellular adhesion. Cells adhering on TMD-free control samples are significantly smaller and more eccentric than those in the presence of TMDs, confirming this observation. Furthermore, cell morphology is determined to be more elongated on MoS2 than WS2. Whereas no statistical significance exists for the mean cell area between MoS2 and WS2, statistical significance is determined for their variances, indicating a significantly larger range of cell areas for WS2. Future experiments include cell culturing on patterned TMDs grown in controlled arrays. TMD patterns at predefined locations are created via photolithography on a SiO2 substrate with subsequent lift-off, followed by physical vapor deposition (PVD) of MoO3 or WO3 prior to CVD growth. Thus, ongoing work entails quantitatively analyzing cell-substrate interactions between biological cells and TMDs in relation to differing TMD area of coverage, layers, and porosity. Determination of changes in morphometric features will reveal the causal relationship between the measured TMD substrate properties and cell adhesion.
7:00 PM - BM06.12.19
Piezoelectric Mitochondria-Based Biosensor and Microfluidic Device for Investigations of Ion Dynamics
Magdalena Stobiecka 1 , Slawomir Jakiela 1 Show Abstract
1 Department of Biophysics, Warsaw University of Life Sciences, Warsaw Poland
Dysfunctional mitochondria appear to be involved in many diseases, such as neurodegenerative diseases, cancer, diabetes, inflammation, through their role in respiration, reactive oxygen species (ROS) generation, and energy production. In this work, we have designed and tested a mitochondria-based piezosensor to assess its utility as a powerful mass-sensing sensor to determine the ion dynamics and investigate the effects of ionophore valinomycin on potassium ion transfer rate. Mitochondria were embedded in polypyrrole films on gold electrode. The effects of hypertonic, hypotonic and isotonic solutions influencing the ion dynamics and swelling/shrinking of mitochondria have been analyzed using nanogravimetric technique as well as the microfluidic technique of hydrodynamic resistance measurements for an aqueous solution droplet, containing mitochondria, moving in a continuous oil phase.
Acknowledgements: This research was partially supported by funding provided by the Grant Opus No. 2014/15/B/ST4/04955 awarded by the National Science Center.
7:00 PM - BM06.12.21
Development of FRET Biosensor Based on Aptamer/Functionalized Graphene for Ultrasensitive Detection of Bisphenol A and Discrimination from Analogues
Sanju Gupta 1 , Rebecca Wood 1 Show Abstract
1 , Western Kentucky University, Bowling Green, Kentucky, United States
We report an ultrasensitive, effective and efficient platform for small molecule bisphenol A (BPA) detection based on Förster resonance energy transfer (FRET) between functionalized graphene (graphene oxide; GO and reduced GO; rGO) as acceptor and fluorescently tagged BPA specific aptamer (5’-FAM-tagged single-stranded DNA; FAM-ssDNA) as donor design. Due to noncovalent assembly and specific adsorption, fluorescent quenching of FAM probe takes place due to good overlap between FAM emission and the GO (and rGO) absorption spectrum. On addition of BPA analyte, the aptamer preferentially bounds to BPA, forming FAM-ssDNA–aptamer–BPA complexes, the FRET is disrupted possibly by switching its configuration or re-hybridization preventing aptamer from molecular adsorption on or away from GO or rGO surface and the fluorescence signal is restored (turn-on’ bioassay). This method relies upon competitive interaction between two hydroxyphenyl groups of BPA and “cytosine-cytosine” mismatches in ssDNA. The intensity of optical fluorescence signal was changed in linear proportion to BPA concentration ranging 50 pg/mL - 100 ng/mL, with low limit of detection £ 10 pg/mL. The sensitivity and specificity of biosensor toward BPA was demonstrated via several BP, BPB, BPC, DES analogues. The developed aptasensor assay is successfully implemented for real water (tap, bottled and river) samples and recovery rate is between 96.0% and 104% indicative of higher accuracy. These remarkable findings are attributed to interplay of large surface area and topologically interconnectedness provided by functional moieties in graphene scaffolds thus favorable interaction with FAM-ssDNA. This strategy can be extended to detection of other molecules by simply substituting the aptamer. We acknolwedge KY NSF EPSCoR and internal FUSE Grants from WKU Resaerch Foundation.
7:00 PM - BM06.12.22
Partial Thermal Reduction of Graphene Oxide for Use in Biosensor Applications
Stavros Chatzandroulis 1 , Myrto-Kyriaki Filippidou 1 , Evangelia Tegou 1 , Panagiota Petrou 2 Show Abstract
1 Institute of Nanoscience and Nanotechnology, NCSR "Demokritos", Athens Greece, 2 Institute of Nuclear & Radiological Sciences & Technology, Energy & Safety , NCSR "Demokritos", Athens Greece
The development of label-free protein detection protocols is expected to expand the application of biosensors to different aspects of human life. In this work, the immobilization of proteins towards the fabrication of a reduced graphene oxide (GO) biosensor is investigated. Mild thermal treatment is used to progressively reduce GO drop-casted on a SiO2substrate, after its hydrophilization and functionalization. As a result of the reduction, the graphene sp2 lattice of GO is gradually restored and its electrical conductivity is enhanced. At the same time, Fourier-transform infrared spectroscopic investigations suggest that GO retains functional groups during the course of the reduction, thus facilitating the immobilization of proteins on its surface.
Biotinylated Bovine Serum Albumin (b-BSA) is used as a model molecule in protein immobilization experiments. b-BSA was immobilized on GO drop-casted on APTES functionalized SiO2 substrates and heated for 1 h at 90oC, 120oC, 150oC, 180oC and 200oC. The immobilization of b-BSA was confirmed by inspecting the GO drops under a fluorescence microscope after reaction with the fluorescently labeled streptavidin. The signal obtained from GO drops coated by BSA instead of b-BSA was used to determine non-specific binding. Immobilization was successful for all cases. However, for 90oC heating, the fluorescence intensity was significantly higher than all other temperatures tested. Moreover, the intensity progressively decreases for higher temperature treatments concurrently with the decrease of the hydroxyl groups originally present in GO. This, in turn, suggests that the hydroxyl functionalities, present on the surface and the edges of the GO, contribute to a more effective immobilization of b-BSA.
Following successful immobilization of b-BSA on GO and RGO a simple and easy to implement sensor was constructed. Silver paint conductive adhesive was used to contact the GO drops by first drawing silver paint electrodes on a functionalized SiO2 substrate. Between the electrodes a GO drop was casted and heated to finalize the device. To determine the right heating temperature, one has to take into account that although best immobilization results of b-BSA were achieved for low temperatures (90°C and 120°C) the resultant conductivity of GO is low. Thus, in order to achieve both protein immobilization and a conductive state, temperatures higher than 150°C are required. I-V measurements were next conducted after each of the following steps: a) thermal treatment of GO, b) b-BSA immobilization, c) immersion in blocking solution, and d) incubation in streptavidin. The I-V slope was found to change following each of the above steps. On the other hand, in the blank sample no significant resistance change was observed after the introduction of the BSA blocking solution. These findings thus demonstrate the ability of the sensor to detect the immobilization of biotin on GO as well as the biotin-streptavidin interaction.