Aleksandr Noy, Lawrence Livermore National Laboratory and University of California Merced
Nurit Ashkenasy, Ben Gurion University of the Negev
Christopher F. Blanford, University of Manchester
Arash Takshi, University of South Florida
Symposium Support Aldrich Materials Science
Asylum Research, an Oxford Instruments Company
Journal of Materials Science
Journal of the Royal Society Interface
SS2: Bioelectronics with Nanowires, Carbon Nanotube and FET Devices
Tuesday PM, April 02, 2013
Westin, 2nd Floor, Metropolitan Ballroom I
2:30 AM - SS2.01
Microfluidic-encapsulated Carbon Nanotube Field Effect Transistors for the Detection and Monitoring of Protein/DNA Interactions
David D Ordinario 1 Mary Nora Dickson 1 Anthony Burke 1 Jonah Jocson 1 Alon A Gorodetsky 1
1University of California - Irvine Irvine USAShow Abstract
Carbon nanotube field effect transistors (CNT FETs) are promising nanoscale tools for the electrical detection of biomolecular analytes. However, typical CNT FET-based sensors are difficult to modify with biomolecular recognition elements in high yield and exhibit poor sensitivity in complex biological media. We will discuss a strategy for the fabrication of massively parallel, independently-addressable CNT FETs encapsulated within a microfluidic housing. This housing enables the reliable modification of hundreds of CNT FETs with biomolecular recognition elements, allows for rapid delivery of arbitrary analytes to the independent devices, and minimizes complications associated with biofouling. We have applied this platform for the fully electrical monitoring of protein/DNA interactions. Our findings hold broad implications for the development of integrated, fully electrical sensing platforms.
2:45 AM - SS2.02
Electrical Biomolecule Detection Using Nanopatterned Silicon via Self-assembled Block Copolymer Lithography
Chang Kyu Jeong 1 Hyeong Min Jin 1 Jae-Hyuk Ahn 3 Tae Jung Park 2 Hyeon Gyun Yoo 1 Min Koo 1 Yang-Kyu Choi 3 Sang Ouk Kim 1 Keon Jae Lee 1
1Korea Advanced Institute of Science and Technology (KAIST) Daejeon Republic of Korea2Korea Advanced Institute of Science and Technology (KAIST) Daejeon Republic of Korea3Korea Advanced Institute of Science and Technology (KAIST) Daejeon Republic of KoreaShow Abstract
Nanostructures in a field-effect transistor (FET) have been regarded as potential use in high performance biosensor. The high sensitivity is enabled by the nano-dimensional channel, which is comparable to the Debye screening length (~7 nm) and the size of biomolecules. Block copolymer (BCP) lithography, a nanopatterning technology that exploits macromolecular self-assembly, is a potential candidate to overcome the intrinsic resolution problems of conventional photolithography.
Herein, we suggest the electrical biomolecule detection using Si nanostructure by BCP lithography. The polystyrene-block-poly(methyl methacrylate) (PS-b-PMMA) thin films with hexagonal cylinder nanopattern are employed as templates for single step dry etching to realize the large-area Si nanomesh structure of sub-20 nm-scale features. The resultant nanomesh electrical channel modified with biotinylation successfully detects two type proteins of streptavidin and avidin down to nanoscale molarity (~1 nM). The nanopattern comparable to charge screening length and the large-area of three-dimensional gate effect at silicon nano-channel enable the biosensor to demonstrate the excellent sensitivity and stability. A simulation is also conducted to confirm the nanopatterning effect on electrical biomolecule detection. This straightforward nanofabrication combining the elaborate self-assembly principle with one-step process offers a high throughput manufacturing way to nanoelectronics for clinical lab-on-a-chip application and biomolecular kinetics studies.
This research is submitted to Advanced Materials.
3:00 AM - SS2.03
Silicon Nanowire Bioelectronics with Photoactivated Proton Pump Proteins
Mangesh Bangar 1 Ramya Tunuguntla 1 2 Kyunghoon Kim 1 3 Jia Geng 1 4 Costas Grigoropoulos 3 Jim DeYoreo 1 Caroline Ajo-Franklin 1 Aleksandr Noy 1 4 5
1Molecular Foundry at Lawrence Berkeley National Laboratory Berkeley USA2UC, Davis Davis USA3UC, Berkeley Berkeley USA4UC, Merced Merced USA5Lawrence Livermore National Laboratory Livermore USAShow Abstract
Membrane proteins, which enable some of the most important cellular functions, represent one of the key components of bioelectronics device architectures. Silicon nanowire devices represent a versatile and promising platform for integration of these protein functionality into biolectronic systems. The exquisite sensitivity of the doped nanowire conductance to the surface environment allows efficient electronic monitoring of the surface environment and gives us the ability to connect membrane protein functionality to the electronic readout. We describe the use of template self-assembly to build nanowire field-effect transistor-based bioelectronic devices and our efforts to incorporate photoactivated protein pump functionality into them. We will also focus on the challenges that are encountered during the formation of these structures, and will discuss strategies for overcoming these challenges and for improving device performance.
3:15 AM - SS2.04
Design, Fabrication and Functionalization of Nanostructured Electrodes for Integrated Sensors
Muhammad Mujeeb-U-Rahman 1 Axel Scherer 1
1Caltech Pasadena USAShow Abstract
Electrodes are the ubiquitous interface between electronic and biological systems. Micro/nano scale patterned electrodes provide enhanced performance by changing the diffusion profile and the reaction and charge transport phenomenon near the electrode surface. In this talk, we will discuss the optimum design for these electrodes for different sensing applications. Specifically, we will compare the effect of electrode material, surface structuring (macro, micro or nano), surface film quality and inter-electrode spacing for integrated sensors. We will show some example designs for electrodes optimized for sensing biochemical target analyte in blood (e.g. glucose) and for sensing DNA hybridization. We will also show that a hybrid of top-down and bottom-up approaches towards nanofabrication of such electrodes provide very fine control on their properties like sensitivity and dynamic range. This talk will also focus on the use of chemically cross-linked hydrogels and electrically polymerized materials for in-situ functionalization of these electrodes for biochemical sensing. These materials can be patterned to provide very thin but stable layers to provide the sensitivity and specificity required for many sensing applications. We will also show that the combination of our hybrid fabrication techniques with hydrogel/Polymer based in-situ functionalization provides a very useful fabrication methodology for completely integrated sensors. Also, incorporation of metal particles (micro or nano based upon application) in the functionalization matrix form a pseudo sol-gel that enhances the sensor performance and results in stable devices for long periods of time. This is very important for extending the useful lifetime of implantable devices and minimizes the need of recalibrating these devices often. We have used this technique to design nano- structured sensors for Microelectronics based systems. We will show the details of one such fully integrated system including on-chip circuitry, power generation, data communication and electrochemical sensing sub-systems.
3:30 AM - *SS2.05
Advances in Epidermal Electronics
John Rogers 1
1University of Illinois Urbana USAShow Abstract
Materials, mechanics designs and manufacturing systems are now available for electronic systems that achieve thicknesses, effective elastic moduli, bending stiffnesses and areal mass densities matched to the epidermis. Laminating such ‘epidermal&’ electronic devices onto the skin leads to conformal contact, and adequate adhesion based on van der Waals interactions alone, in a manner that is mechanically invisible to the user. In this talk, we describe recent advances in this type of technology, with an emphasis on materials that enable (1) direct printing of the electronics onto the skin, (2) bonding and encapsulation for robust, long-term wearability, (3) advanced sensors, ranging from temperature detectors with ~mK precision to hydration monitors with the ability for multiplexed spatial mapping and (4) human/machine interfaces, including examples in real-time control of helicopter drones via electromyography.
4:30 AM - SS2.06
Complementary H+-FETs with Acid and Base Doped Protonic Semiconductors
Yingxin Deng 1 Jungho Jin 1 Erik Josberger 2 Marco Rolandi 1
1University of Washington Seattle USA2University of Washington Seattle USAShow Abstract
Man made devices rely on electronic currents to exchange information. In biological systems, ionic and protonic currents are used instead. Artificial devices capable of controlling and monitoring these currents may provide an appealing biotic-abiotic interface. We have developed a polysaccharide (maleic chitosan) based H+-FET with protons as majority charge carriers. Protons hop along the hydrogen bonded water (proton wire) present along the polysaccharide following the Grotthus mechanism. According to this mechanism, OH- (proton holes) are also charge carriers. In our H+-FET, the maleic group in the maleic chitosan backbone acts as a dopant and donates protons into the proton wire. I will present OH- -FET devices made with chitin derivatives with base groups (piperidine). These bases act as proton acceptors and create OH- in the proton wire. These devices show gate dependence of the source-drain current consistent with negative charge carriers. Further, I will discuss H+-OH- junction devices in parallel to p-n junction devices and prospects for complimentary protonics.
4:45 AM - SS2.07
Gold Nanoparticle Decorated Organic Field-effect Transistors for Selective, In Situ Biodetection
Mallory L. Hammock 1 Oren Knopfmacher 1 Zhenan Bao 1
1Stanford University Stanford USAShow Abstract
Organic field-effect transistors (OFETs) are unique platforms for the detection of chemical and biomolecular species. Such sensors are able to directly transduce an analyte-binding event into an electrical signal, making them highly desirable for sensing platforms requiring a digital readout. In particular, the detection of biologically relevant molecules lends itself to this detection platform because of the inherent charge associated with many biomolecules, which can be detected by the OFET. Additionally, OFETs are more biocompatible than their inorganic counterparts, facilitating their use as biosensors. OFET sensor applications have historically been restricted to the detection of small molecules in the vapor phase, due to the incompatibility of many organic semiconductors with water. Our group first demonstrated the real-time detection of several small molecules in aqueous media using a water-stable organic semiconductor. These sensors were capable of low-voltage operation due to the incorporation of an ultrathin polymer dielectric layer, and were shown to be highly stable operating in aqueous conditions. In many early OFET sensors, the active layer itself displayed a serendipitous sensitivity to a number of small-moleucle analytes. However, while the limit of detection of these sensors has been demonstrated down to the part-per-billion (ppb) level, they suffer from a lack of true selectivity, making their response to a mixture of analytes quite complex. In order to define sensitivity for a particular molecule of interest, a receptor group must necessarily be integrated into the device&’s architecture, preferably by a method that does not damage the OFET itself. We recently developed a novel OFET sensor platform that is capable of stable operation in an aqueous environment while also allowing for the selective detection of a user-defined analyte. Sensitivity for the targeted analyte is engineered by virtue of the ordered array of AuNPs that decorates the OFET&’s surface. This highly versatile platform is compatible with a large number of available, thiolated receptor groups that can be used to functionalize the AuNPs through the well-known gold-thiol (Au-S) linkage. We have previously used this platform to demonstrate the highly selective detection of Hg(II) in solution. We have now expanded the sensing capabilities of this platform to biodetection, and have demonstrated the selective detection of thrombin with high sensitivity. Additionally, using this model protein, we systematically investigated the effect of varying the ionic strength of the buffer, the average center-to-center distance between the receptor sites, and the pH of the buffer in order to form a more comprehensive picture of biodetection with OFETs. Using these parameters, we are able to tune the limit of detection of our devices in order to match the particular application for which they will be used.
5:00 AM - SS2.08
Single Molecule Transport through the Carbon Nanotubes Incorporated in Liposomes
Jia Geng 1 2 Kyunghoon Kim 2 3 Costas Grigoropoulos 3 Caroline Ajo-Franklin 2 Aleksandr Noy 1 2 4
1University of California Merced Merced USA2The Molecular Foundry at Lawrence Berkeley National Laboratory Berkeley USA3University of California Berkeley Berkeley USA4Lawrence Livermore National Laboratory Livermore USAShow Abstract
Molecular control over mass transport has been an elusive goal in many scientific fields. Biological systems have developed protein ion channels that manage mass transport with a level of sophistication that is unmatched by inorganic analogs. Efforts to develop nanopores that approach the transport efficiency of biological molecules often run into fabrication or synthesis difficulties. An alternative approach could rely on unique properties of nanomaterials to provide alternative transport system scaffolding. Simulations have showed the potential of carbon nanotubes to work as extremely efficient nanofluidic channels due to their inherently smooth hydrophobic pore walls. While studies using macroscopic nanotube membranes and long individual nanotube pipe devices have shown evidence of fast transport, little is known about the transport in nanotube-based systems that approximate biological channels more closely. We present our initial results on preparation of nanotube-based membrane nanopores, their assembly into biological membranes, and single-channel transport measurements in these assemblies.
5:15 AM - SS2.09
Neurotransmitters Sensing Using Organic Electrochemical Transistors
Loig Kergoat 1 Daniel Simon 1 Magnus Berggren 1
1Linkamp;#246;pings Universitet Norrkamp;#246;ping SwedenShow Abstract
According to the World Health Organization, approximately 1 in every 100 of the world&’s 6.5 billion inhabitants suffers from epilepsy, Parkinson&’s disease, dementia, or some other neurological disease. These diseases are the result of an abnormal amount of chemical messengers called neurotransmitters, which are released from neurons. Accurate and specific measurements of these molecules can help in the diagnosis of pathologies. Biosensing with electrical readout has developed into a well established field in recent years. The technique relies on the electrochemical oxidation or reduction of the analyte or a product of an enzymatic reaction with it. Perhaps the most widely known and commercialized of such devices are the glucose sensors used in many of today&’s blood glucose monitoring units. Similar enzyme-based techniques have been developed to monitor neurotransmitters such as glutamate (Glu), acetylcholine (ACh), and other molecules possessing appropriate corresponding enzymes. Conducting polymers have been widely used for electrochemical biosensors. Recently, organic electrochemical transistors (OECTs) have been demonstrated as useful tools for biosensing. The detection principle is similar to that of classical electrochemical biosensors with a slight difference: OECTs rely on a similar method of detection as traditional electrochemical sensors, but are based on a three-electrode configuration rather than one or two electrodes. An electrical current passing through an organic electronic material between two of the electrodes (the “source” and “drain”) is modulated by electrochemical changes in the third “gate” electrode, resulting in an amplification of the signal and thus significantly higher sensitivity. Furthermore, OECTs can benefit from the various advantages of organic electronic devices, such as biocompatibility and low-cost production on flexible substrates. OECT-based sensors have already been demonstrated for glucose sensing. We focused our work on developing sensitive and selective neurotransmitters sensors using OECTs made of the benchmark conducting polymer, PEDOT:PSS. The detection of glutamate, acetylcholine and dopamine is investigated.
 H. Nakamura, I. Karube. Anal Bioanal Chem 377, 446-468 (2003).
 D.A. Bernards et al. Journal of Materials Chemistry 18, 116-120 (2007).
SS3: Poster Session: Bioelectronics
Tuesday PM, April 02, 2013
Marriott Marquis, Yerba Buena Level, Salons 7-8-9
9:00 AM - SS3.02
Specific Sensing Using a Bionanoelectronic Nose
Michael Daniel Aldridge 1 Kevin C. Daly 1 David Lederman 2 Cerasela Dinu 3 Letha Sooter 4
1West Virginia University Morgantown USA2West Virginia University Morgantown USA3West Virginia University Morgantown USA4West Virginia University Morgantown USAShow Abstract
We are currently fabricating an electronic nose platform which incorporates DNA aptamers (sensing elements) on a field effect transistor (transducing element).1 In theory, this approach will allow for the design of the sensor for any molecular target, because the method for producing DNA aptamers2 allows for the tailoring of binding affinity and specificity to a selected target of interest. The completed prototype will be capable of detecting cadaverine (1,5-diaminopentane) in the vapor phase.
Two types of semiconductors will be tested for the FET transduction element of the sensor: aluminum-doped zinc oxide thin film (n-type) and single walled carbon nanotubes (SWNT, p-type). The Al-ZnO thin films are grown by RF magnetron sputtering, and the SWNTs are purified and cut with acid to known length distributions. Aptamers will be attached directly to the semiconductor of the FET, and the conformational change associated with target binding will cause a displacement of the negative charges on the DNA relative to the transducer. This displacement will act as an effective top gate, and will provide the change necessary for detection.
As a first step towards assembly of a complete prototype we have characterized the grown ZnO films, using Hall measurements, AFM and XRD. We show that an increase in growth temperature to 300C results in improved crystallinity and decreased surface roughness. These measurements also indicated that the films have ~1015 cm-3 carriers, and we anticipate that new films will have ~1017 cm-3 carriers as a result of doping with aluminum. Upon exposing the completed sensor to a test gas, we expect the source-drain current to decrease in the n-type ZnO-FET and increase in the p-type SWNT-FET. The aptamers will be selective for cadaverine, and we expect no sensor response to structurally related molecules.
This work was supported by the National Science Foundation (Cooperative Agreement 1003907) and by the WVU Center for Neuroscience COBRE PPG grant to G. Spirou.
1. Hagen, J. A. et al., (2010). DNA aptamer functionalized zinc oxide field effect transistors for liquid state selective sensing of small molecules.pdf. Proceedings of the SPIE, 7759(775912), 8. doi:10.1117/12.860574
2. Klug, S. J., & Famulok, M. (1994). All you wanted to know about SELEX. Molecular biology reports, 20(2), 97-107.
9:00 AM - SS3.03
Peptide-based Templates for Controlling Electronic Properties of Organic Chromophores
Nandita S Bhagwat 1 Kristi L Kiick 1
1University of Delaware Newark USAShow Abstract
Alignment, orientation and distance between organic chromophores mediate structure-property relationships, and are therefore being studied to enhance the performance of organic and polymeric semiconductor materials. Biological molecules such as peptides and polypeptides have been extensively used to study intermolecular interactions by manipulating the intermolecular distances at the nano-scale level. We have therefore employed a similar approach to effectively display an array of organic chromophores (oxadiazole-containing phenylenevinylene oligomers) in a co-facial or anti-facial manner using a PEGylated helical peptide scaffold. The chromophores are strategically positioned in the range of 6-17 Å from each other, as dictated by the chemical and structural properties of the peptide. Circular dichroic (CD) spectroscopy showed the helical nature and the exciton coupled-CD suggested side chain interaction depending on the distance and dihedral angle between chromophores. An increased separation of 17Å resulted in the chromophores behaving as isolated species even though they are positioned on the same face of the helix. For the rest of the scaffolds, chromophores positioned on the same side of the helix interacted with each other whereas the chromophores placed on the opposite face did not have apparent influence on the electronic properties. Finally, the differences in the emission spectra and excited species formed as a function of chromophore presentation were indicated by photoluminescence and absorbance
9:00 AM - SS3.04
Charge Transfer, Electron Transfer and Electronic Transport through Biomaterials
David Cahen 1 David Lederman 2 Israel Pecht 1 Mordechai Sheves 1
1Weizmann Inst. of Science Rehovot Israel2West Virginia University Morgantown USAShow Abstract
Electrical charges in biological SYSTEMS are mostly transported as ions and thus charge transfer often refers to ionic transport. Electron TRANSFER (ET) is, however, a thoroughly studied and important process in biology, associated with specialized proteins such as cytochromes. Several of these proteins are involved in what is called an ELECTRON TRANSPORT CHAIN where occurs via REDOX REACTION between the individual components and may also be associated with ion transport, as in proton-coupled electron transfer and H+ pumping across membranes.
A redox reaction is composed of two half-reactions, an oxidation and a reduction one. We stress that a redox reaction has 2 important steps: -1- an integral number of electron charges passes from one species to another; -2- the change of charge state results in a nuclear reorganization and relaxation. The 2nd step is important because normally a redox reaction in a molecule is associated with a change in coordination, often aided by interactions with solution species.
REDOX CHEMISTRY is intimately connected to biological ET. Such ET processes can be studied in several ways, such as photon-induced electron transfer, which include at least in part excited state processes, or by electrochemical cell studies, which mostly probe the ground state. Remarkably, the two processes can be and are often compared with each other and together yield much of present under-standing of biological ET.
Recently the study of electron TRANSPORT (ETp) across ‘dry&’ single protein or protein monolayer has attracted much interest and developed into a new area of interdisciplinary research. ‘Dry&’ means that all but the tightly bound water molecules are removed. Experiments have been done, using scanning probe microscopy techniques as well as macroscopic, ‘solid&’ state-like configurations, developed originally for molecular electronics. Even if the sample is immersed in a liquid, such experiments differ from ET measurements by the use of ion-blocking, electronically conducting electrodes, where ion transport is not part of the measured process. We postulate that this implies that in ETp no actual redox process, as defined above, takes place in the conducting protein. Therefore, the ETp and ET processes differ from one another at a fundamental level.
Given the fundamental difference between ETp and ET processes, the question is whether the two are related such that information about ET can be garnered from ETp experiments. ETp studies of Azurin (cf. Li et al., this symp.) indicate that the ETp and ET properties of this protein are correlated with each other. Therefore, even though ETp does not involve the biologically occurring full redox process, it apparently still provides insights into ET mechanisms. Understanding how this can be may improve our knowledge of ET and, conversely, may allow use of existing ET knowledge to search for new ETp - efficient bioelectronic materials.
9:00 AM - SS3.05
A Real Time Single-cell Protein Assay from Living Cells Based on a Nanostraws Platform
Yuhong Cao 1 Xi Xie 1 Alex Xu 1 Nick Melosh 1
1Stanford Stanford USAShow Abstract
Single Cell Analysis (SCA) has draw a huge attention in recent years, for it unveils cell activities that population-average assays unable to do. Most of the existing methods for SCA, Including microfluidic flow cytometry, or mass cytometry, require special cell treatments, such as cell lysis or intracellular protein labeling before assays. Hence, real-time single cell intracellular protein assay/analysis on the same cell samples are impossible with such techniques. In recent year, vertical nanowire array has been reported to physically penetrate cell membrane, and has been used in the field of intracellular delivery and intracellular electrical recording. Recently, our lab reports nanostraws platform that provides intracellular access by penetrating plasma membrane and forming stable nanostraw-cytosol fluidic interface. Building on the nanostraw fabrication technique, here we develop a system for real time single-cell protein assay from living cells based on nanostraws platform. Cells are cultured on nanostraws membrane and get penetrated. As reported in the previous work, nanostraws are permanently stay across cell membrane and connected with cytoplasm. Intracellular proteins are diffusing through nanostraw channels, which are further collected and detected by well-developed protein assay like ELISA and ELISPOT. Simulations based on diffusion model and kinetic model are developed to facilitate the understanding of this detection system. Our system is expect to have impact on the fields of single cell detection, and provides tool for the field of cellular reprogramming and cellular systems biology.
9:00 AM - SS3.06
Stretchable Electronics for Biochemical Sensing
Hyun-joong Chung 1 2 Matthew Sulkin 3 Igor R. Efimov 3 John A. Rogers 2
1University of Alberta Edmonton Canada2University of Illinois Urbana USA3Washington University St. Louis USAShow Abstract
In-vivo chemical sensing in biological systems can enable new, important functionality it preventive medicine, as well as in fundamental physiological studies. For example, regions of the heart or brain that undergo ischemia exhibit sudden changes in local chemistry, including sharp reductions in pH near the affected cells. Recently developed classes of stretchable electronics allow conformal wrapping on the surface of the brain, the epidermis or the heart, for various forms of sensing and intervention. In this presentation, we described materials approaches to enhanced performance in these systems, and schemes to expand their capablities. Firstly, we describe silicon metal oxide field effect transistors that exploit thermal oxides, and take forms that provide pathways for their integration onto nearly any surface. Here, ultrathin devices are fabricated and then released from single crystalline silicon substrates. These devices can be deterministically assembled onto any substrate (plastic, rubber, glass or others) and then used as building blocks for biochemical sensors, including pH and protein sensors. Secondly, we present an array of potentiometric pH sensors integrated conformally onto the epicardial surfaces of explanted hearts. Here, the evolution of local pH values during ischemia and recovery are mapped as a function of time. In this presentation, material selection, fabrication techniques, and biomedical applications of the aforementioned devices are discussed.
9:00 AM - SS3.08
On Chip Sensing and Manipulation of Human Mesenchymal Stem Cells by Electrical Cell-substrate Impedance Sensing Devices Using Bioconjugated Organic Electrodes
Yu-Sheng Hsiao 1 Chiung Wen Kuo 1 Peilin Chen 1
1Academia Sinica Taipei TaiwanShow Abstract
An optically transparent poly(3,4-ethylenedioxythiophene) (PEDOT) organic electrode based electrical cell-substrate impedance sensing (ECIS) device has been developed to investigate the behavior of human mesenchymal stem cell (hMSC) on various bioconjugated peptide-PEDOT surfaces. The advantages of our ECIS devices include real-time detection, label-free and capability of integration with microfluidic system. In addition, unlike the metallic electrode based ECIS system, the transparency of our devices made it possible to observe cellular behavior on an inverted microscope without perturbing the experiment. The working electrodes consist of poly(3,4-ethylenedioxythiophene): poly(styrenesulfonate) (PEDOT:PSS) electrodes with several circular areas (250 um in diameter) exposed to the cell culture medium. The rest of the PEDOT electrodes was covered by photoresist for insulating purpose. We first conducted a control experiment on ECIS device by culturing the hMSC on the chip. According to our result, the impedance increased reflected the hMSC proliferation, attachment and motility during the first 16 hours of cell culture. It has been shown in a previous report that different differentiation types of mesenchymal stem cells (for example, osteoblast and adipocyte lineages) have distinct dielectric properties, therefore featuring different impedance profiles. In addition, we applied the electrical wound-healing assay to study the self-renewal properties of hMSC on the PEDOT:PSS surfaces. It can be clearly seen that when a voltage of 2.5V at 40k Hz was applied to the device for 120 seconds, the number of hMSC on the detection area decreased. The system recovered after two hours. To understand the fate of the wounded cells, we stained the hMSC immediately after wound healing assay with a live/dead assay (Molecular Probes Invitrogen) where the dead cells was found to be restricted to the circular organic electrode. Since the impedance profiles for different lineages are different, we can use our devices to study how the cell-surface interaction influences the differentiation of hMSC. It is known that cells attach to surfaces through binding to the extracellular matrix (ECM) elements. Therefore, the differentiation of hMSC cells may be regulated by the ECM protein. In our system, we are capable of investigating how ECM molecules influence the differentiation of hMSC by conjugating the organic electrodes with various peptides derived from ECM proteins such as, RGD peptide, vitronectin (VN), laminin (LM) and long fibronectin sequence (LFN).
9:00 AM - SS3.09
Highly Sensitive Ammonia Detection Based on Organic Field Effect Transistors with Tris(Pentafluorophenyl)Borane as Receptor
Weiguo Huang 1 Kalpana Besar 1 Rachel LeCover 1 Howard E Katz 1 Ana Maria Rule 2 Patrick N Breysse 2
1Johns Hopkins University Baltimore USA2Johns Hopkins University Baltimore USAShow Abstract
We have increased organic field-effect transistor (OFET) ammonia response using tris-(pentafluorophenyl)borane (TPFB) as receptor. OFETs with this additive detect concentrations of 450 ppb v/v, with a limit of detection of 350 ppb, the highest sensitivity yet from semiconductor films; in comparison, when triphenylmethane (TPM) and triphenylborane (TFB) were used as an additive, no obvious improvement of sensitivity was observed. These OFETs also show considerable selectivity with respect to common organic vapors, and stability to storage. Furthermore, excellent memory of exposure was achieved by keeping the exposed devices in a sealed container stored at -30 °C, the first such capability demonstrated with OFETs.
9:00 AM - SS3.10
Humidity, Temperature, and Contact Dependence in H+-FET Devices
Erik Josberger 1 Yingxin Deng 2 Jungho Jin 2 Marco Rolandi 2
1University of Washington Seattle USA2University of Washington Seattle USAShow Abstract
Proton transport is important in many natural phenomena. Preeminent examples include ATP oxidative phosphorylation in mithochondria, the HCVN1 voltage gated proton channel, light activated proton pumping in bacteriorhodopsin, and the proton conducting single water file in the antibiotic gramicidin. In gramicidin, protons hop along hydrogen bonded water molecules following the Grotthuss mechanism. Based on this proton transport, we have demonstrated a polysaccharide H+-field-effect transistor. In this device, proton conduction between PdHx source and drain occurs along a hydrated polysaccharide film. This maleic chitosan film has a carboxyl group which acts as a proton donor in a manner analogous to an electron donor in silicon. The proton transport in this device is highly sensitive to the environment. The temperature of the device controls the intrinsic charge carrier concentration, while the humidity of the atmosphere affects the hydration level of the maleic chitosan film and therefore controls the formation of a hydrogen bond network. The hydrogen gas concentration around the device determines the density of carriers in the palladium, which controls the contact-film potential barrier. In this work, we expand our characterization of this system by measuring the effect of each of these parameters on device performance, and compare the system&’s behavior with that of traditional silicon electronics. Understanding the similarities between these systems will allow the application of existing semiconductor device techniques to the creation of novel bio-devices, with broad applications.
9:00 AM - SS3.11
Controlling Manipulation, Stimulation, and Rupture of Giant Unilamellar Vesicles on Si Substrate for Lipid Bilayer Array
Yoshiaki Kashimura 1 Ruaridh Forbes 1 Yukihiro Tamba 2 Koji Sumitomo 1 Keiichi Torimitsu 1
1NTT Basic Research Laboratories Atsugi Japan2Suzuka National College of Technology Suzuka JapanShow Abstract
Microarrays of lipid bilayers fabricated on a substrate have attracted a lot of attention because they are a promising platform for bioanalyses and biodevices. We have already fabricated an array of microwells sealed with lipid bilayers on a Si substrate . If biomolecules such as peptides, receptors, and membrane proteins can be positioned in the suspended membranes, the system mimics the nature cell membrane authentically. To achieve this, it is essential to develop a technique for fabricating multicomponent microwell arrays where the contents of the microwells and the lipid compositions differ. Methods have been reported for fabricating lipid bilayer arrays, and these include the vesicle fusion method  and the self-spreading method . However, these techniques however cannot be applied to our device structure because neither can seal microwells. In this presentation, we describe a new approach for fabricating multicomponent microwell arrays sealed with lipid bilayers based on the manipulation of single giant unilamellar vesicles (GUVs). This is a versatile technique for fabricating lipid bilayer microarrays and it also overcomes the above-mentioned issue.
GUVs were prepared from a mixture of 1,2-diphytanoyl-sn-glycero-3-phosphocholine (DPhPC), and cholesterol by using the electroformation method. The GUVs were then filtered with a 12 mu;m pore membrane to exclude small lipid vesicles. We used GUVs with diameters in the 30-100 mu;m range for our experiments. Handling a single GUV was performed using a glass micropipette (ca. 15 mu;m diameter). Custom-made apparatus was used to control the aspiration force and the position of the micropipette. Using this system, we developed fundamental techniques that are useful for fabricating lipid bilayer arrays. First, single GUVs can be picked up and then released at the preferred position. Second, only targeted GUVs can be stimulated chemically without affecting other GUVs by using another micropipette as an injector. Third, the injection of Ca2+ ions makes it possible to control GUV rupture precisely. Applying the above techniques to microwell devices, we have successfully demonstrated the fabrication of a microwell array sealed with lipid bilayers thus confirming different contents inside the wells, which is impossible to achieve using conventional methods.
 K. Sumitomo et al., Biosens. Bioelec., 31 (2012) 445.
 P. S. Cremer et al., J. Am. Chem. Soc., 121 (1999) 8130.
 K. Furukawa et al., Langmuir, 27 (2011) 7341.
9:00 AM - SS3.12
Application of Solution-processed Oxide Thin-film Transistors in DNA Biosensors
Si Joon Kim 1 Joohye Jung 1 Doo Hyun Yoon 1 Keun Koo Lee 1 2 Sreekantha Reddy Dugasani 2 Sung Ha Park 2 Hyun Jae Kim 1
1Yonsei University Seoul Republic of Korea2Sungkyunkwan University Gyeonggi-do Republic of KoreaShow Abstract
Recently, “label-free” methods for detecting DNA have been developed as a substitute for fluorescence technique. Among these methods, thin-film transistor (TFT) devices are suitable candidates due to high sensitivity, direct transduction, and low-cost fabrication. Previously, our research group has reported a method for detecting artificial DNA nanostructure using oxide TFT for the first time . Since there are negatively charged phosphate groups on the DNA backbone, significant decreases in field-effect mobility and on-current (Ion) were observed. For an in-depth analysis of DNA detection mechanism, we investigated the electrical characteristics, structural and phase properties with and without DNA immobilization in this study. First, when gate voltage (VG) swept from -5 V to +30 V repeatedly, we observed a progressive shift of threshold voltage in the positive direction. This phenomenon indicates that during the periods of sweeping VG, electrons are trapped at the DNA nanostructure. Because the concentration of DNA nanostructure was fixed, no more degradation of Ion was observed. Second, the structure of oxide TFT device was confirmed using cross-sectional high-resolution transmission electron microscopy. The porous oxide thin-film was observed and it was expected extremely useful in DNA biosensors due to its large surface area. Finally, the X-ray diffraction patterns were measured to observe phase variations of oxide thin-films with and without DNA immobilization. These results indicate that DNA nanostructure was just immobilized on the oxide surface by electrostatic interactions with no other effect and the direct effect on the electrical response implies oxide TFT could be applicable to DNA biosensors.
 S. J. Kim, B. Kim, J. Jung, D. H. Yoon, J. Lee, S. H. Park, and H. J. Kim, Appl. Phys. Lett. 100, 103702 (2012).
9:00 AM - SS3.15
Development of Biocompatible Conductive Nanotube Films to Investigate Cell Contractile Forces
Debora Winnie Lin 1 Zhenan Bao 1
1Stanford University Stanford USAShow Abstract
Single-walled carbon nanotubes (SWNTs) have shown promise for use in organic electronic applications including thin film transistors, conducting electrodes, and biosensors. There is a current need to rapidly process SWNTs from solution phase to substrates in order to produce device structures. In terms of SWNT film deposition, previous studies were able to adsorb SWNTs by drop casting, airbrush spray coating, spin coating, vacuum filtration, electrophoretic deposition, and Langmuir-Blodgett deposition. Furthermore, researchers have found that surfaces covalently functionalized with primary amines have been shown to selectively adsorb semiconducting SWNT. However, this and similar techniques are dependent upon environmentally sensitive surface modification techniques. Hence, we explored the potential of substrates modified with physisorbed polymers, poly(L-lysine) (PLL), as a possible alternative methodology. In this work, we detail a number of methods for depositing SWNTs onto various substrate materials using amine-rich PLL and other methods of covalently functionalizing the surface with primary amines. Furthermore, devices were constructed using these methods to observe if cell movement on the surface would elicit changes in the device performance. SWNT adsorption and alignment were characterized by atomic force microscopy (AFM). SWNT surface density was strongly dependent upon the adsorbed concentration of PLL on the surface, spin coating speed, and SWNT solution concentration. Another benefit for using PLL as an adhesion layer was for its biocompatibility with cells. Results from examining mitochondrial hydrogenase activity and Live/Dead fluorescence assay suggest that the PLL SWNTs spin-coat devices exhibited higher biocompatibility with NIH-3T3 fibroblast cells than the drop cast SWNTs devices possibly due to differences of substrate surface roughness. To further elucidate the effect of SWNT roughness on biocompatibility, cell morphology was observed on substrate surfaces of varying SWNT network density using a spray coating method. Additional cells lines with relevant characteristics were also tested for their biocompatibility which included C2C12 myotubes and cardiomyocytes. Furthermore, to observe if cell contractile forces on the device surfaces would elicit a change in electrical performance, 2-terminal resistance measurements were taken at different stages of cell adhesion onto the surface. We envision these conducting biocompatible SWNT networks could potentially be used as biosensors to investigate cell adhesion mechanics or provide a method for cancer diagnostics.
9:00 AM - SS3.16
Developing Lab on a Chip Based Microfluidic Platform for Heavy Metal Detections
Hanyuan Zhang 1 Honglei Gou 2 Nianqiang Wu 2 Yuxin Liu 1
1West Virginia University Morgantown USA2West Virginia University Morgantown USAShow Abstract
Environmental and occupational exposure to heavy metals is an emerging health concern. Microfluidic based biosensor technologies are expecting to provide inexpensive, field-deployable tools for rapid, on-site detection of heavy metals. For example, an accurate, fast, and affordable analysis of blood components is the prime interest for biosensor applications in medicine research. Plasma separation is important for specific downstream detection of heavy metals from patient bloods, such as preventing contamination of the plasma with blood cells&’ DNA and haemoglobin. Flow cytometry, centrifugation and filtration methods are conventional methods for blood cell separations. However, the sophistication of these techniques requires increasingly higher levels of skills, larger volume of samples, longer processing time, and may significantly alter the results of subsequent analysis, which make them not applicable for on-site analysis techniques. We have developed a microfluidic device for separating the plasma from the whole human blood. The blood separator can separate minimum volumes of blood samples with less cell damages, and is expected to integrate with electrochemical electrodes to realize a faster, cheaper, automatic, and more comprehensive approach for on-site analysis techniques. The microfluidic blood plasma separator exploits combinations of hydrodynamic effects: the Zweifach-Fung bifurcation law and the blood flow focusing effect together with centrifugation effects after a constriction. In addition, we developed an on-chip mixer and micro-valves. On-chip micro-valves are essential for fluidic controlling and integrated LOC multiplex heavy metal detections. The proper sealing of valves is important to controlling different solutions and avoiding contamination during operation. The micro-valves can quickly respond to the pressure applied and released, and can close and open the microchannels within short period of time.
9:00 AM - SS3.17
Red and Near-infrared Solution-processed Light Emitting Diodes for Wearable Medical Devices
Claire Meyer Lochner 1 Ana Claudia Arias 1
1UC Berkeley Berkeley USAShow Abstract
Solution-processed electronic materials have the potential to yield devices that are flexible and conformal to the human body. We are developing the components needed for the fabrication of wearable flexible pulse oximeters. Pulse oximeters are medical devices that monitor a person&’s blood oxygen concentration while under general anesthesia or suffering from a respiratory condition. Here, we present the characterization of polymer-based light emitting diodes (PLEDs) designed specifically for pulse oximetry, which requires red and near-infrared light sources to calculate the ratio of oxygenated to de-oxygenated hemoglobin. Red PLEDs with peak emission at 644nm have been fabricated from a 20:60:20 blend of poly(9,9-dioctyl-fluorene-co-N-(4-butylphenyl)-diphenylamine) (TFB), Poly[(9,9-di-n-octylfluorenyl-2,7-diyl)-alt-(benzo[2,1,3]thiadiazol-4,8-diyl)] (F8BT), and Poly((9,9-dioctylfluorenyl-2,7-diyl)-alt-(4,7-bis(3-hexylthiophen-5-yl)-2,1,3-benzothiadiazole)-2',2''-diyl) (TBT) with an ITO/PEDOT:PSS(40nm)/TFB(15nm)/TFB:F8BT:TBT(100nm)/LiF(1nm)/Al(100nm) structure. The tri-blend emissive layer is spun from o-xylene. The TFB component serves as a hole transporting material and the F8BT component is an electron transporting material. These two components transfer injected holes from the anode and electrons from the cathode (respectively) to the TBT component, where radiative exciton recombination occurs resulting in an electroluminesnce peak at 644nm. This red PLED has an irradiance of 3.5µW/cm2 and .27% external quantum efficiency at 4.5V operating voltage. IR LEDs have been achieved by optically pumping core-shell CdS/PbS quantum dots with a peak emission at 850nm upon excitation at 644nm from the red PLED.
9:00 AM - SS3.18
SiC-based 1D Nanostructures for Bio-nano-technologies
Maelig Ollivier 1 2 Laurence Latu-Romain 1 Mickael Martin 1 Arnaud Mantoux 3 Edwige Bano 2 Thierry Baron 1
1LTM-CNRS Grenoble France2IMEP-LAHC Grenoble France3SIMaP Grenoble FranceShow Abstract
Recently, elaboration of one-dimensional (1D) nano-objects has been intensely studied because of the great potential applications of these structures in many fields such as nanoelectronics. In the particular case of SiC-based 1D nanostructures, although power electronics has driven researches these last years, one can observe the rapidly increasing interest of bio-nano-technologies for these structures. Indeed, in addition to the remarkable electrical and physical properties of silicon carbide (SiC) material -such as high breakdown field, high band gap and high thermal conductivity-, the biocompatibility of SiC is becoming very attractive, compared to Si.
Thanks to an original process based on the carburization of silicon nanowires (Si NWs), we are able to produce different SiC-based nanostructures: Si-SiC core-shell nanowires (Si-SiC NWs), SiC nanotubes (SiC NTs) and SiC nanowires (SiC NWs). This original process, which relies on controlling the outdiffusion of Si atoms through SiC, can be monitored by the temperature, the pressure and the time of carburization.
Firstly, Si NWs are obtained by a plasma etching of a (100) Si substrate. These Si NWs are controllable in size and diameter, depending on the etching conditions. Then these Si NWs are introduced into a hot-wall CVD furnace where the carburization occurs.
The main flow is composed by a mixture of hydrogen diluted into argon. During the rising of temperature, pressure is kept constant at a level preventing the Si sublimation and methane, used as carbon precursor, is sent at 800°C until the plateau of carburization. At this instant, a ~2 nm thick, single crystalline, SiC layer, entirely covers the surface of Si NWs. Note that if the process is stopped here, Si-SiC NWs have been elaborated.
Depending on what kind of nanostructures will be elaborated the carburization parameters will change: a higher temperature (varying from 1000°C to 1200°C) and a higher carburization time (varying from 1 to 60 min) will enhance the outdiffusion of Si atoms, leading to SiC NTs, while a high pressure (varying from 0.01 to 750 Torr) will limit the outdiffusion and will favour Si-SiC NWs.
These SiC-based nanostructures are characterized morphologically and chemically by SEM, FIB-SEM and TEM microscopies, and also with micro-Raman spectroscopy.
Finally, with the combination of the controllable dimensions of Si NWs and the monitoring of Si outdiffusion during the carburization process, it is possible to obtain the desired nanostructures -Si-SiC NW, SiC NW or SiC NT-, and to control their dimensions and the 3C-SiC layer thickness in each case. These SiC-based nanostructures, thanks to the good crystalline quality of the 3C-SiC layer and its physical properties may become a very promising nano-object for biotechnology. For example Si-SiC NWs can be used to make a nano-sensor for DNA detection, using functionalized SiC shell in contact with biological environment and Si core as transistor channel.
9:00 AM - SS3.19
Process Integration Study of Packaging Materials for Implant Applications
Karl Malachowski 1 John Oamp;#8217;Callaghan 1 Lisbet Lagae 1 Dries Braeken 1 Hilde Jans 1 Tomakazu Miyazaki 2 Deniz Tezcan 1
1IMEC Belgium Leuven Belgium2JSR micro N.V. Leuven BelgiumShow Abstract
A polymer material selection based on biocompatible materials from JSR Corporation was carried out to develop a universal packaging platform for applications in the field of implantable electronics. The focus of this development study is on materials biocompatibility and its integration into a semiconductor process scheme. 50µm thin silicon chips with 1cm x 1cm dimensions are used to mimic a CMOS device. The device assembly starts with an implementation of a first layer, called HS, by spin-on technique on top of a 200mm silicon wafer. This layer is not a part of the active packaging stack but is needed for later release of the packaged device from the substrate. On top the base photopatternable packaging layer, called WPR, is spun-on and patterned. A subsequent adhesive layer, called PA, is patterned on top of the WPR layer to enable a good adhesion of the CMOS device chip. A pick and place tool is used for precise assembly of the chip. The stack is embedded with another WPR layer. Its patterning enables the accessibility of the CMOS chip functions as well as the definition of the outer package dimensions. Due to the usage of the HS release layer all individual packages can be gently released from the substrate. To ensure biocompatibility of the package, materials are tested and only materials with promising in-vitro biocompatibility results are further processed. Finally to proof the packaging concept and material qualification, some of the packages were implanted in-vivo for two months, which resulted in a very low foreign body response reaction.
9:00 AM - SS3.20
Gravure Printed Films of Peptoids for Application in Electronic Devices
Kevin D Pease 1 Felippe J Pavinatto 1 Brian Lunt 1 Gloria Olivier 2 Ronald N Zuckermann 2 Ana Claudia Arias 1
1University of California, Berkeley Berkeley USA2Lawrence Berkeley National Laboratory Berkeley USAShow Abstract
Peptoids are a class of bio-mimetic, sequence-specific synthetic oligomers that have a chemical composition similar to proteins. The ease and efficiency of synthesis combined with the high diversity of available monomers make peptoids an appealing material for a wide variety of applications. In addition, peptoids are specifically appealing for their potential biological activity, allowing for applications such as bio-molecule sensing. In order to fulfill their potential for biosensing, these materials need to be reliably deposited in thin film form and integrated with other materials to form a device structure. Printing allows for inexpensive fabrication of devices and reduced manufacturing costs. Printed methods have been successfully applied to conjugated polymers processed from solution to fabricate electronic devices. In this work, we have demonstrated the deposition of printable peptoid thin films with a gravure printer.
The peptoid studied is PC, which consists of 18 repetitions of the dimer Npe-Nce, where Npe is N-(2-phenylethyl) glycine and Nce is N-(2-carboxyethyl) glycine. This peptoid was used at a concentration of 20µM in a solvent of water and ethylene glycol (EG). The most important ink properties were characterized and optimized for successful and consistent printing such as viscosity, surface tension and particle size. The ratio of water to EG was optimized at 1:5 (water:EG), resulting in a viscosity of 11cP which is suitable for gravure printing. The resulting ink surface tension, approximately 52.9 mN/m, is also compatible with the technique, and the absence of large aggregates was confirmed by dynamic light-scattering.
Peptoids were printed on plastic PET (polyethylene terephthalate) substrates. Surface treatment with a long (over 20 min) exposure to UV light or 30 seconds in 75 W plasma showed to be crucial for uniform spreading of the solution over the surface. We found that solution concentration and drying conditions have an impact on the resulting film morphology. While films dried at RT present some round-shaped aggregates on the surface, films dried on the hot plate are more clean as attested by optical microscopy. The gravure films are being printed on silver electrodes for electrical characterization and possible application as the gate dielectric in thin film transistors. The inks are also being modified for inkjet-printing, which is complementary to gravure printing.
9:00 AM - SS3.22
Characterization of Bioluminescent Bacterial Biofilm
Satoshi Sasaki 1
1Tokyo University of Technology Hachioji JapanShow Abstract
Bacterial bioluminescence is realized by choosing suitable carbon source such as glycerol and several electrolytes as liquid broth materials. Bacterial bioluminescence can be, therefore, regarded as an example of a system that converts common chemical substances into light. Besides the studies for the stabilization of bacterial bioluminescence, investigation has been performed for the initial reason of its oscillation. Recent studies indicate that by the irradiation of a near-UV light bacterial bioluminescence from colonies can be controled (reversibly inhibited). Fabrication of a bacterial drawing pad (or a rewritable 2D memory) with 1 mu;m resolution would be, therefore, possible, if the bacterial cells can be attached homogenously on a flat surface. As a measurement of luminescence from one single bacterial cell is possible using a EM-CCD camera, luminescent bacterial cells can be, if they are implanted in a biofilm, a novel non-contact probe that can monitor [O2] or toxisity inside a biofilm. Objective of this study is to characterize the bioluminescence from bacterial biofilm of Photobacterium kishitanii, and to discuss the possible relationship between the biofilm formation stage and the oscillatory behavior of luminescence.
9:00 AM - SS3.24
A New Approach to Bioelectronics: Lipid Membrane Intercalating Conjugated Oligoelectrolytes Facilitate Electron Transfer between Microbes and Electrodes
Alexander Thomas 1 Logan Garner 1 Guillermo Bazan 1
1UCSB Santa Barbara USAShow Abstract
The emerging field of bioelectronics relies on the ability of microorganisms to interact with electrodes. For example, microbial fuel cells (MFCs) harness the energy of electrons released from the metabolic oxidation of sugars and other organic matter. Furthermore, bioelectrosynthesis is a fascinating reversal of this process in which electrons are injected into a microbe via an electrode in order to drive its metabolism. Both systems rely on the critical interface between microbe and electrode and thus a limitation of these technologies is that not all microorganisms contain the inherent capacity to interact with electrodes. This constraint is overcome in some cases through the use of diffusion based electron shuttles: small redox active molecules that are able to reversibly transport electrons between the microbe and electrode, but are not without drawbacks. We are taking a different approach by investigating specifically designed membrane intercalating compounds based on organic semiconductors that do not act as traditional electron shuttles.
Phenylene vinylene materials possess great charge transporting properties and have been used in many studies concerning molecular transconductance. A certain class of oligo(phenylene vinylene)s with ionic functionalities, more generally referred to here as conjugated oligoelectrolytes (COEs), were synthesized in order to impart aqueous solubility and expand the application of these molecules. Incidentally, amphiphilic COEs have been shown to spontaneously intercalate into the lipid membranes of cells. Their insertion and ordered orientation within a lipid bilayer bridges the otherwise insulating membrane with a conductive ‘molecular wire.&’ Recently, these molecules (at low micromolar concentrations) have afforded performance enhancements in MFCs run with yeast, E. coli and wastewater, presumably by creating a more intimate and efficient microbe/electrode interface.
On the bioelectrosynthesis front, COEs have found utility in facilitating electron injection into Shewanella oneidensis MR-1 to drive the biological reduction of fumarate to succinate. The mechanism of action of COEs in this system is currently under investigation in hopes of yielding insight for future applications and molecular design.
9:00 AM - SS3.27
Nanostraw-Electroporation System for Highly Efficient Intracellular Delivery and Transfection
Xi Xie 1 Alex Xu 1 Sergio Leal 2 Yuhong Cao 1 Craig Garner 2 Nicholas Melosh 1
1Stanford University Stanford USA2Stanford University Stanford USAShow Abstract
Introduction of gene materials into mammalian cells with high transfection efficiency is challenging in biological and medical research. Building on the previous fabrication technique of nanostraw on polymer substrate, here we develop a novel localized electroporation system for highly effective intracellular delivery and transfection while cell viability is maintained. Due to the close interface between cell membrane and nanostraw, electric field can be highly focused and locally induce transient permeability on a very small area of plasma membrane. Small voltage (5 - 20 V) and short duration time (20 mu;s- 200 mu;s) of electrical pulse serves as a valve in controlling the penetration of nanostraw on cell membrane and driving biomolecule into cytoplasm. The advantage of our nanostraw-electroporation over other porous membrane based electroporation device in that electric field is better confined to a very small area of cell membrane above the tip of nanostraw, hence the poration is highly effective while perturbation to cell is minimal. Significant improvement in dye delivery and plasmid transfection was shown on Chinese hamster ovary (CHO) cells, as well as Human Embryonic Kidney 293T cells (HEK) and Hela cells. In addition to spatial and temporal control, the system is demonstrated to offer good dose control and be able to provide high-yield co-transfection (simultaneous transfection of two or more DNA plasmid or RNA) and sequential transfection (transfection of one type or more types of DNA plasmid/RNA at different days) to the same cells. The versatility, stability and efficiency of the nanostraw-electroporation system serve as a powerful and reliable platform for high-throughput intracellular delivery and transfection. We anticipate this platform will serve as a universal delivery tool for the field of cellular reprogramming, cellular systems biology and high-throughput drug screening.
9:00 AM - SS3.28
Aptamer-based Surface Plasmon Resonance Biosensor for Prostate Specific Antigen
Jing Zhou 1 Bob E Feller 1 Andre Knoesen 2 Robert D Miller 1
1IBM Almaden Research Center San Jose USA2University of California - Davis Davis USAShow Abstract
Aptamers are nucleic acid oligomers that can act as receptors for proteins and small molecules. Using a process called SELEX (systematic evolution of ligands by exponential enrichment), aptamers can be produced to specifically target a biomolecule. Compared to monoclonal antibodies, aptamers have the similar levels of binding specificity and affinity. However, as a recognition element for biosensors, aptamers have many advantages over monoclonal antibody, including fast and cost-effective production via solid state chemical synthesis, ease of modification and functionalization and stability in extreme conditions and long-term storage. In addition aptamers are much smaller (down to 2-3 nm) than antibodies (15 nm). This allows the aptamer to bring analytes closer to the sensing surface, which results in higher signals.
In this work, we developed a surface plasmon resonance (SPR) biosensor for detection of prostate specific antigen (PSA), a biomarker for prostate caner. DNA aptamer against PSA was immobilized on gold surface and organosilicate coated on gold. The sensing surface was also passivated with polyethylene glycol to eliminate non-specific binding. PSA and aptamer interactions in solution were studied by electromobility gel shift assay. The process of detection of PSA under physiological conditions was studies by SPR, ellipsometry and XPS.
9:00 AM - SS3.29
Patterning of Multiple Biomolecules Using Orthogonal Processing
Carol Newby 1 Jin Kyun Lee 2 Priscilla Taylor 1 Kari Midthun 1 Barbara Baird 1 Christopher Ober 1
1Cornell University Ithaca USA2Inha University Incheon Republic of KoreaShow Abstract
Biomolecules cannot be patterned with conventional organic photolithographic materials because the solvents used in deposition, development and stripping damage most biomolecules. We have developed a fluorinated resist system that is compatible with bio-systems and non-damaging to biomolecules. Fluorinated solvents, such as hydrofluoroethers (HFEs) are immiscible with organic and aqueous solutions. Our group has previously used the chemical orthogonality they possess to develop photoresists for patterning organic electronic materials . We showed that both HFEs and the fluorinated resist could be applied repeatedly to biomolecules and DNA without degrading them. We go on to demonstrate the use of the fluorinated resist, in combination with nanoimprint lithography, to pattern protein features from 100 µm down to 2 µm. Unlike many other techniques used to pattern proteins this process can easily be repeated ad infinitum in order to pattern more than one type of protein on the same substrate . This technique could, in the future, be used for the fabrication of biosensors, studying cell-cell interactions and even aid in the development of tissue engineering.
 P. G. Taylor, J.-K. Lee, A. A. Zakhidov, M. Chatzichristidi, H. H. Fong, J. a. DeFranco, G. G. Malliaras, and C. K. Ober, “Orthogonal Patterning of PEDOT:PSS for Organic Electronics using Hydrofluoroether Solvents,” Advanced Materials, vol. 21, no. 22, pp. 2314-2317, (2009)
 K. A. Midthun, P. G. Taylor, C. Newby, M. Chatzichristidi, P. S. Petrou, J.-K. Lee, S. E. Kakabakos, B. B. Baird, C. K. Ober, "Orthogonal Patterning of Multiple Biomolecules using an Organic Fluorinated Resist and Imprint Lithography," in press (2012)
9:00 AM - SS3.31
Charge Transport in DNA Molecules
Roy Vellaisamy 1
1City University of Hong Kong Hong Kong Hong KongShow Abstract
In this work, we demonstrate ambipolar charge transport in double stranded DNA molecules with pronounced current characteristics using a field effect transistor (FET) structure. In view of the increasing interest in developing electronic devices based on DNA molecules, we analysed the charge transport and electronic properties of DNA based devices. There are three aspects that we would discuss on this presentation:
(1) charge hopping between DNA molecules is possible, showing that they can be used as bulk semi conductors, similarly to other macro-molecules, in the construction of electronic devices.
(2) importance of packing between the DNA molecules and their pronounced ambipolar charge transport characteristics in DNA based FET devices,
(2) ordered stretching (combing) of DNA molecules over long distances and high electron and hole mobility in DNA based devices using simple and inexpensive molecular combing techniques.
9:00 AM - SS3.32
Bio-organic Field Effect Transistors Based on Crosslinked Deoxyribonucleic Acid
Cigdem Yumusak 1 2 Birendra Singh 3 James G. Grote 4 Niyazi Serdar Sariciftci 1
1Johannes Kepler University Linz Austria2Yildiz Technical University Istanbul Turkey3CSIRO Molecular and Health Technologies Clayton Australia4Air Force Research Laboratory 45433-7707 USAShow Abstract
The use of biopolymers derived from Deoxyribonucleic Acid (DNA) in organic electronics is rapidly becoming an area of interest in the scientific community because of their many attractive features. These biological materials demonstrate excellent electrical and optical properties when modified with surfactant cations. Low voltage bio-organic field effect transistors (BiOFETs) have been fabricated using DNA-based biopolymers as gate insulators. The observed large hystereses in BiOFETs using DNA-hexadecyltrimethylammmonium (CTMA) complexes have been discussed as a performance limiting issue. In this report, we analyzed the origin of these hysteresis and we present the idea of crosslinking the whole composite polymer for improving the BiOFET performance.
9:00 AM - SS3.33
In Situ Measurement of Organic Electrochemical Transistors as Biosensors for Barrier Tissue Integrity
Marc Ramuz 1 Leslie Jimison 1 Roisin Owens 1 George Malliaras 1
1Ecole Nationale Supamp;#233;rieure des Mines, CMP-EMSE, MOC Gardanne FranceShow Abstract
We present the integration of an organic electrochemical transistor (OECT) with an epithelial cell monolayer to create a cell based sensor for barrier tissue integrity. Epithelial cell monolayers serve as functional barriers in the body, tightly controlling the flux of ions. Ion transport between cells is regulated by protein structures known as tight junctions. The ability to measure the function of tight junctions provides information about barrier tissue and is indicative of certain disease states. Poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) has the ability to conduct both electronic and ionic carriers, offering a unique platform for communication between biological systems and electronics. In an OECT, the electronic drain current within the PEDOT:PSS channel is modulated by ionic current between an electrolyte and the polymer. In the present device architecture, cell monolayers act as a barrier to the ionic current. Channel current is used to detect ion transport through the cell layer.
Barrier tissue models have a short lifetime outside of physiologically relevant storage conditions; we therefore develop a setup where long term in situ measurements with OECTs can be performed. Intestinal Caco-2 cells or kidney MDCK cells are grown inside a cell culture incubator while continuously measuring the OECT performance. Multiple OECTs can be connected to the data acquisition (DAQ) board which allows multiplex measurement in a simple and cheap manner. This provides important real time information regarding barrier tissue integrity. The introduction of pathogenic agents, such as Salmonella Typhimurium, to a healthy cell monolayer results in degradation of tight junction proteins and can be monitored throughout the time-course of infection. The resulting increase in ionic current due to degradation of barrier tissue integrity can be observed via the OECT. The biosensor presented here provides a vehicle for fundamental research in the life sciences, facilitating the study of barrier tissue and factors affecting its integrity and allows for the development of realistic in vitro cell models.
SS1: Electron Transfer in Biological Systems
Christopher F. Blanford
Tuesday AM, April 02, 2013
Westin, 2nd Floor, Metropolitan Ballroom I
9:30 AM - *SS1.01
Electron Tunneling and Electron Transport between Biomolecules and Electrodes
David H Waldeck 1
1University of Pittsburgh Pittsburgh USAShow Abstract
We report on the nature and mechanism of charge transfer between biomolecules (proteins and nucleic acids) and electrodes. A particular focus of the talk will be our most recent work on Peptide Nucleic Acid (PNA), a synthetic analog of DNA. The aminoethylglicyne backbone bestows PNA duplexes with an enhanced stability, compared to their DNA analogs, and resistance to enzymatic cleavage, making them desirable candidates for biosensor technologies, molecular electronics, and biomedical applications. We will compare the conductivity of single PNA oligonucleotides trapped within molecular junctions, formed using Scanning Probe Spectroscopy techniques, and the charge transfer properties of self-assembled monolayers of ferrocene-terminated PNA duplexes. We will discuss how these different measurements investigate different aspects of the electron transfer. Although simple models predict a linear correlation between the molecular conductance and the charge-transfer rates, the experimental data show a power-law relationship within a specific class of structures, and a lack of correlation when a more diverse group of molecules are compared. We describe a recent theoretical model that can account for these differences by including variations in the energy barrier heights for charge transport and the bath-induced electronic decoherence experienced by the molecules in the two different measurements, STM-BJ and electrochemical rates.
10:00 AM - SS1.02
Solid State Electron Transport via Proteins: The Role of the Prosthetic Group
Nadav Amdursky 1 Lior Sepunaru 1 Israel Pecht 1 Mordechai Sheves 1 David Cahen 1
1Weizmann Institute of Science Rehovot IsraelShow Abstract
Intramolecular electron transfer (ET) in proteins has been extensively studied with an aim of resolving its mechanisms. Most of the studies are done in solution, to imitate the natural surroundings of the proteins. In recent years, solid state experiments have done to explore electron transport (ETp) via proteins, mainly by the use of scanning probe microscopy, which is defined by and limited to a nanoscopic contact area. Here we report on results of macroscopic solid state ETp measurements of proteins, to study the mechanism(s) as a function of temperature, in the range of 20-400K. This approach relies on forming a monolayer of the examined protein between two electrically conducting, ionically blocking, electrodes. The results of such measurements provide a wealth of data, including ETp activation parameters.
We focused on two of the widely studied ET proteins, cytochrome C (CytC) and azurin (Az), and on the well-studied proton pump protein, bacteriorhodopsin (bR). The main common property of these three proteins is the presence of a prosthetic group: heme, Cu ion and retinal for CytC, Az and bR, respectively. We find that the prosthetic group is a major factor for ETp via the protein, in terms of current amplitutudes and mechanism. These prosthetic groups not only impart ‘ETp properties onto their host proteins, but they can significantly alter the ETp characteristics of other proteins as well. This is illustrated by non-covalently binding to human serum albumin (HSA) a variety of small molecules such as hemin (the prosthetic group of CytC) or retinoate (a derivative of retinal, the prosthetic group of bR). After characterizing this binding (‘doping&’) we show that HSA becomes the most conducting protein among all those that we studied. The implications of our studies are that suitably doped proteins may find use in bio-sensors and as biocompatible electronic charge-carrying elements in future bioelectronic device structures.
10:15 AM - SS1.03
Single Molecule Direct Measurement of Electron Transfer in Cytochrome P450rsquo;s and the Effect of Bound Substrates
Chris Bostick 1 Peter M Gannett 1 John E Jett 1 David Lederman 2
1West Virginia University Morgantown USA2West Virginia University Morgantown USAShow Abstract
Cytochrome P450&’s (P450&’s) are a large family (>11,000) of heme based proteins that play a crucial role in metabolism of exogenous substrates and oxygen transport. At the center of their mechanism of action is the ability for an electron to be transferred from an electron donor, Cytochrome P450 Reductase, to the center heme group. Although there have been extensive studies on electron transfer (ET) in heme based proteins, the process still remains unclear. Electrochemical studies have had some success in systems where the P450 is in solution or is an integral part of the electrode. However, these studies have been hampered by the ability of P450&’s to aggregate and a lack of control of the interactions with substrates. Our lab has developed a platform that isolates single P450&’s on gold nano-pillars. Using this platform we have probed isolated P450&’s using conducting probe atomic force microscopy (CP-AFM) and have obtained ET profiles of Cytochrome P450 CYP2C9 alone and in the presence of different substrates. Using CP-AFM we are able to probe the electronic properties of a single or small group of P450 enzyme molecules alone or with substrate bound. The data show a correlation between the conductivity of the ET profile and the rate at which the given substrate is metabolized by the P450. The I-V curves show that the barrier height was lowered by a quickly metabolized activator effector pair flurbiprofen and dapsone. In addition, there was an increase in barrier height in the presence of aniline, a CYP2C9 inhibitor, meaning decreased ease of ET. These experiments will allow us to gain a better understanding of ET, and can open up a new realm of studies. .
We acknowledge support from the National Science Foundation (Cooperative Agreement 1003907) and NIH (GM081348).
10:30 AM - SS1.04
Towards Systematic Bioelectronics: Conduction and Electron Transfer through Amino Acids
Lior Sepunaru 1 2 David Cahen 1 Mordechai Sheves 2 Israel Pecht 3 Robert Lovrincic 1
1Weizmann Institute of Science Rehovot Israel2Weizmann Institute of Science Rehovot Israel3Weizmann Institute of Science Rehovot IsraelShow Abstract
Amino acids are the protein&’s building blocks. The mechanism of electron transfer (ET) and electron transport (ETp), i.e., solid-state conduction via amino acids rather than via highly structured native proteins has been frequently addressed in peptides. The contribution of H-bonds, secondary structure and specific side chains of amino acids to ET and ETp has been examined in several recent works. In the present study we have investigated the role of homo-oligopeptides of different lengths in a linear sequence. We aim at understanding the roles that features of different amino acids play in electron transfer and electronic transport (solution electrochemistry vs. solid-state conduction) by examining only the backbone and side chain perspectives (no secondary structure). This is performed by a dual approach of cyclic voltammetry of the homo-oligopeptide with a Ferrocene terminal group in a solution and solid state electronic current-voltage measurements as function of temperature. The latter is done with mesoscopic contacts. Such systematic examination of current via amino acids with a linear sequence sets initial conditions for their behavior in more complex structures such as hetero-oligopeptides and proteins. The self-assembled homo-oligopeptide monolayers are characterized by Polarization Modulation Infrared Reflection Adsorption Spectroscopy, ellipsometry and Inelastic Tunneling spectroscopy. We will report our initial results on oligo-lysine, oligo-tryptophan and oligo-Alanine (Three distinct representatives of amino acids sub groups), and compare between them, in terms of transport mechanisms and current transport efficiency.
11:15 AM - *SS1.05
The Chirality Induced Spin Selectivity (CISS) Effect - From Spintronics to Electron Transfer in Biology
Ron Naaman 1
1Weizmann Institute Rehovot IsraelShow Abstract
Spin based properties, applications, and devices are commonly related to magnetic effects and to magnetic materials. Hence, most of the development in spintronics is currently based on inorganic materials. Despite the fact that the magnetoresistance effect has been observed in organic materials, until now spin selectivity of organic based spintronics devices originated from an inorganic ferromagnetic electrode and was not determined by the organic molecules themselves. In several studies, however, it was found that chiral organic molecules can act as spin filter for photoelectrons transmission, in electron transfer, and in electron transport.
Results will be presented from several recent experiments and some implications and applications will be discussed.
11:45 AM - SS1.06
Ab Initio Modeling of Electronic Properties of DNA-metal Contact Systems: Comparison to Experiments
Jianqing Qi 1 Suranga Edirisinghe 2 Anant M. P. Anantram 1
1University of Washington Seattle USA2Georgia State University Atlanta USAShow Abstract
The electronic properties of DNA can be used in new techniques for disease detection, sensing and devices. As a nanoscale material, the large distance between two nearby stacking bases, flexibility of the strand and variability in the surrounding environments make the charge transport in DNA a significantly richer phenomenon than crystalline nanoengineered materials such as nanotubes and nanowires, which have comparable dimensions. In this work, we model the zero-bias conductance for four different DNA strands that were used in Ref. . Our approach consists of three elements: (i) experimental data , (ii) ab initio calculations of DNA and (iii) the use of two parameters to determine the decoherence rates. We first study the role of the backbone by comparing the coherent transmission for strands with backbones and strands whose backbones have been deleted. We find that the backbone can alter the coherent transmission significantly at some energy points by interacting with the bases, though the overall shape of the transmission stays similar for the two cases. More importantly, we find that the coherent electrical conductance is tremendously smaller than what the experiments measure . We consider DNA strands under a variety of different experimental conditions and show that even in the most ideal cases (coupling to the metal contacts, the assumption of the ideal B-form strand), the calculated coherent conductance is much smaller than the experimental conductance. To understand the reasons for this, we carefully look at the effect of decoherence. Decoherence of electrons in DNA arises because of the interaction with the noisy environmental fluctuations and the lattice vibrations. By including the effect of decoherence, we show that our model can rationalize the experimentally measured electrical conductance of the four different strands, both qualitatively and quantitatively. We find that the effect of decoherence on G:C base pairs is crucial in obtaining conductance values that are close to the experiments. However, the decoherence on G:C base pairs alone does not explain the experimentally determined dependence of conductance in strands containing a number of A:T base pairs. The electrical conductance in experiments is found to decrease by six times for every two additional A:T base pairs. To explain this experimentally observed dependence and the magnitude of the conductance, we find that including decoherence on A:T base pairs (which are barriers for hole transport) is essential. By fitting the experimental trends and magnitudes in the conductance of the four different DNA molecules , we estimate for the first time that the deocherence rate is 6 meV for G:C and 1.5 meV for A:T base pairs.  Ajit K Mahapatro, Kyung J Jeong, Gil U Lee and David B Janes, Nanotechnology, 18, 195202 (2007)  Jianqing Qi et. al, http://www.ee.washington.edu/faculty/anant/publications/JianqingQiPaper.pdf
12:00 PM - SS1.07
Bioprocessing Device Composed of Azurin/DNA Biohybrid Material to Modulate Electron Transfer
Si-Youl Yoo 1 Taek Lee 1 Junhong Min 2 Jeong-Woo Choi 1
1Sogang University Seoul Republic of Korea2Chung-Ang Univeristy Seoul Republic of KoreaShow Abstract
Various bioelectronic devices combined with biomaterial and conventional electronic device have been developed. The unique functions, which biomolecules possess inherently, such as self-assembled conformation and specific recognition, have been introduced to molecular electronic devices to overcome physical and functional limitation of conventional electronic device. In biological system, information is transferred in one-way traffic, stored analogically, and processed flexibly. These characteristics of biosystem could inspire some new concepts of bioelectronics device, such as multi-functional biomemory device, and logic gate based on biomolecules.
In our previous works, we developed biomemory devices for information storage, which have various types and functions, based on the electron transfer mechanism of metalloproteins [1-2]. In this study, we firstly developed bioprocessing system that can modulate the signals of the proposed biomemory device by outer input materials. To produce hybrid material for bioprocessing system, a single strand DNA modified with thiol group was attached with sulfo-SMCC. This DNA/sulfo-SMCC complex was conjugated with recombinant azurin by chemical ligation method. The immobilization of azurin/DNA hybrid materials on the gold surface was confirmed by atomic force microscopy and Raman spectroscopy. The thiol group in the end of DNA strand played a role of signal receptor module. To demonstrate modulation functions, various materials as input parameters were added to prepared azurin/DNA hybrid materials on a chip. The signal of azurin/DNA hybrid materials on a chip was regulated and enhanced by metal ion, and metal nanoparticle, respectively, and transistor effect was achieved in case of using quantum dot as an input material.
The proposed concept of bioprocessing device is a new approach which controls electron trnasfer between biomolecules artificially, and these results should be directly applied to realization of biocomputing system consisting of biomolecules, which has whole functions of signal transfer, information storage, and signal processing, in near future.
This research was supported by The Nano/Bio Science & Technology Program (M10536090001-05N3609-00110) of the Ministry of Education, Science and Technology (MEST), by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MEST) (2011-0000384) and by the Ministry of Knowledge Economy (MKE) and Korea Institute for Advancement in Technology (KIAT) through the Workforce Development Program in Strategic Technology.
 T. Lee, S. -U. Kim, J. Min, J. -W. Choi, Adv. Mater., 22 (2010) 510
 T. Lee, J. Min, S. -U. Kim, and J. -W. Choi, Biomaterials 32 (2011) 3815
12:15 PM - SS1.08
Investigating Charge Transport in dsDNA by STM Break Junction Technique
Limin Xiang 1 2 Shaoyin Guo 1 Nongjian Tao 1
1Arizona State University Tempe USA2Arizona State University Tempe USAShow Abstract
Studying on charge transport in dsDNA (double-strands Deoxyribonucleic acid) is crucial to understanding the biological functions of DNA and developing DNA-based technologies. To date, many methods have been developed to understand the charge transport process, e.g. photochemistry, electrochemistry and direct conductance measurements.
The conductance value of a single dsDNA junction can be achieved via scanning tunneling microscope break junction (STM-BJ) technique developed by Tao group in 2003(1). It is well known that dsDNA is HOMO (Highest Occupied Molecular Orbital) transport dominated while the hole transport efficiency through the G&C base pairs is higher than that through the A&T base pairs(2-4). Previously it has been shown that the resistance (inverse of conductance) of (GC)n (n=4,5,6,7, with thiol terminated groups) sequences is proportional to the length, indicating a hopping transport mechanism(5). Herein, a new type of amino linker group directly bound to the T base is introduced to the dsDNA&’s for measurements. While still linearly scaled with length, the resistance values show that the new sequences, A(CG)nT (n=3,4,5,6), is nearly 4 times more conductive than the corresponding thiol terminated (CG)n sequences. The resistance per CG base pair, α (in R = R0 + αL) value is 0.57 M#8486;, which is one order of magnitude lower than that for the thiol linker (5.5 M#8486;/per CG). This can be attributed to the fact that the holes bypass the nonconductive sugar backbone through the amino linker. Additionally, a series of ACnGnT (n=3, 4, 5, 6) sequences were also studied. All of them are 20% to 80% more conductive than corresponding A(CG)nT sequences. This can be explained by the formation of a higher HOMO level when G bases are aligned, thus resulting in a lower energy barrier with respect to the Fermi level of the electrodes(6). Such work will shed light on charge transport studies of more complex dsDNA sequences, as well as the design of DNA based nanoelectronic devices.
(1) Xu, B.; Tao, N. J. Science 2003, 301, 1221.
(2) Giese, B. Acc. Chem. Res. 2000, 33, 631.
(3) Jortner, J.; Bixon, M.; Langenbacher, T.; Michel-Beyerle, M. E. Proc. Natl. Acad. Sci. U. S. A. 1998, 95, 12759.
(4) Berlin, Y. A.; Burin, A. L.; Ratner, M. A. Journal of the American Chemical Society 2000, 123, 260.
(5) Xu; Zhang; Li; Tao Nano. Lett. 2004, 4, 1105.
(6) Saito, I.; Takayama, M.; Sugiyama, H.; Nakatani, K.; Tsuchida, A.; Yamamoto, M. J. Am. Chem. Soc. 1995, 117, 6406.
12:30 PM - SS1.09
Programmable DNA-templated Nanowires
Mary Nora Dickson 1 Dominique A. Ingato 1 Anthony M. Burke 1 Linh Doan 1 Alon A. Gorodetsky 1
1University of California, Irvine Irvine USAShow Abstract
Organic nanowires consisting of π-conjugated building blocks are model systems for fundamental studies of charge transport. We have drawn inspiration from standard, automated phosphoramidite-based oligonucleotide synthesis and prepared organic nanowires consisting of stacked perylene bisimide building blocks arranged on a DNA-like backbone. This approach is advantageous because it furnishes one-dimensional nanowires with precisely controlled length, geometry, and sequence context. The solid support synthesis technique and DNA-like backbone also greatly simplify nanowire handling and purification. We have self-assembled monolayers of our thiol-functionalized nanowires at gold surfaces and investigated their properties with electrochemical and scanning probe techniques. Our studies hold significance both for fundamental charge transport studies and for the development of organic semiconductor materials with programmable emergent electronic properties.
12:45 PM - SS1.10
Electrical Response of DNA at the Nanoscale
Rahim Esfandyarpour 1 2 Mehdi Javanmard 2 James Harris 1 Ronald Davis 2 1
1Stanford University Stanford USA2Stanford Genome Technology Center Palo Alto USAShow Abstract
Direct electrical detection of biomolecules without the need for any labeling or tagging can play an extremely important role in fulfilling the dream of personalized medicine. Detection of proteins, nucleic acids and cells is dominantly performed using optical fluorescence based techniques, which more costly and timely than electrical detection due to the need for expensive and bulky optical equipment and the process of fluorescent tagging. In this presentation we will discuss our study of the electrical properties of DNA on the nanoscale using a nanoelectronic probe we have developed. Our nanostructure consists of four thin film layers: a conductive layer at the bottom acting as an electrode, an oxide layer on top, another conductive layer on top of that, with a protective oxide above. AC voltage is applied the tip of the structure and the impedance measured. We use this structure to study the dielectric response of DNA situated near the tip of the sensor. Presence of DNA near the tip results in an increase in current across the sensing electrodes. We propose that this stems from two basic mechanisms. One of the basic mechanisms behind the electrical response of DNA molecules in solution under an applied alternating electrical field stems from the formation and relaxation of the induced dipole moment. The mobile charge in and around the DNA allows for a dipole to be induced in the DNA when undergoing an AC field. The second mechanism is likely the tunneling of electrons through the biomolecules. As a result of both of these mechanisms we observe an increase in current with an increase in DNA concentration. In this presentation, we will discuss the fabrication of our nanostructure, the theory of electrical response of biomolecules at the nanoscale, and also our experimental results which verify our theory.
Aleksandr Noy, Lawrence Livermore National Laboratory and University of California Merced
Nurit Ashkenasy, Ben Gurion University of the Negev
Christopher F. Blanford, University of Manchester
Arash Takshi, University of South Florida
Symposium Support Aldrich Materials Science
Asylum Research, an Oxford Instruments Company
Journal of Materials Science
Journal of the Royal Society Interface
SS5: Bioelectronic Devices and Integrated Sensors
Wednesday PM, April 03, 2013
Westin, 2nd Floor, Metropolitan Ballroom I
2:30 AM - *SS5.01
Are H+ and OH- in Proton Wires the Same as Electron and Holes in Semiconductors?
Marco Rolandi 1
1University of Washington Seattle USAShow Abstract
The quest for smaller and faster computing has focused on controlling the flow of electrons and holes in nanoscale molecular structures. In living systems, protonic and ionic currents are the basis for all information processing. As such, artificial devices based on protonic and ionic currents offer an exciting opportunity for bionanoelectronics. Proton transport in nature is important for ATP oxidative phosphorylation, the HVCN1 voltage gated proton channel, light activated proton pumping in bacteriorhodopsin, and the proton conducting single water file of the antibiotic gramicidin. In these systems, protons move along hydrogen bond networks formed by water and the hydrated biomolecules (proton wires). Along these wires, protons hop according to the Grotthuss mechanism. Here, I will draw an analogy between the Grotthuss proton transport and electronic semi conductivity. Acids are described as H+ donors and bases are described as H+ acceptors. These functional groups yield H+ and OH- (proton hole) conducting devices in parallel with n-type and p-type electronic semiconductors. Results from complementary H+-FETs will be discussed in light of this description. In turn, insights from these devices may be used to see proton transport in biological systems from an alternate perspective.
3:00 AM - SS5.02
10x10 Field-effect Transistor Biosensors Array Chip for Detecting Uncharged or Feebly Charged Small Molecules
Gun Yong Sung 1 Chil Seong Ah 1 Chan Woo Park 1 Jong-Heon Yang 1 Wan-Joong Kim 1 Kwang Hyo Chung 1 Yo Han Choi 1 Jongcheol Hong 1
1ETRI Daejeon Republic of KoreaShow Abstract
Complementary metal oxide semiconductor (CMOS)-compatible field-effect transistor (FET) biosensors are useful tools for the diagnosis of various diseases, because they can electronically detect and analyze biomolecules, such as proteins,DNA, and small molecules, in real-time and with high sensitivity. In particular, CMOS-compatible FET biosensors that are produced by a top-down method utilize conventional semiconductor processes, which provide highly reproducible and uniform sensor characteristics that are suitable for mass production, however, despite the advantages of CMOS-compatible FET biosensors, most studies have been limited to the detection of biomolecules that have net electrical charges, such as proteins and DNAs. The FET approach for detecting small molecules, such as hormones, toxins, drugs, environmental pollutants, agrichemicals, and antibiotics is not applicable for a reproducible and portable sensor diagnosis because they are uncharged or feebly charged small molecules, despite their demands in many fields.
In this presentation, a new technique for the detection of uncharged or feebly charged small molecules (<400 Da) using Si field-effect transistor (FET) biosensors that are signal-enhanced by gold nanoparticle (NP) charges under dry measurement conditions will be introduced. NP charges are quickly induced by a chemical deposition (that is, Au deposition) and the indirect competitive immunogold assay, and strongly enhance the electrical signals of the FET biosensors. For the validation of signal enhancement of FET biosensors based on NP charges and detection of uncharged or feebly charged small molecules, mycotoxins (MTXs) of aflatoxin-B1 (AFB1), zearalenone (ZEN), and ochratoxin-A (OTA) were used as target molecules. According to our experimental results, the signal is 100 times more enhanced than the use of the existing solution FET biosensing techniques. Furthermore, this method enables the FET biosensor to quantitatively detect target molecules, regardless of the ionic strengths, isoelectric points (pI), or pHs of the measured sample solutions.
 Biosensors and Bioelectronics 33 (2012) 233-240.
This work was supported by the Smart IT Convergence System Research Center funded by the Ministry of Education, Science and Technology as Global Frontier Project (CISS-2011-0031866).
3:15 AM - SS5.03
Catechol-modified Chitosan System as a Bio-amplifier for Schizophrenia Treatment Analysis
Hadar Ben-Yoav 1 Thomas E Winkler 2 Eunkyoung Kim 3 Deanna L Kelly 4 Gregory F Payne 3 Reza Ghodssi 1 2
1University of Maryland College Park USA2University of Maryland College Park USA3University of Maryland College Park USA4University of Maryland School of Medicine Baltimore USAShow Abstract
We present the development of an electrochemical-active biomaterial probe for schizophrenia treatment analysis through redox activity amplification of the antipsychotic clozapine towards its integration in lab-on-a-chip (LOC) devices. The probe consists of the naturally derived polymer chitosan modified with catechol to provide a redox capacitor system. These modifications significantly increase the electrochemical signal generated by clozapine, improving signal-to-noise ratio and the overall performance of the biosensor. Electrochemical testing results indicated a 3.3-fold amplification in the signal generated by clozapine and modified electrodes, with a better functional response and a detection limit of 0.5 µM.
Schizophrenia is a lifelong chronic and devastating disorder with few advances in treatment in recent years. Clozapine is the most effective antipsychotic for schizophrenia treatment. Yet, it remains underutilized because of its frequent blood draws required for monitoring and adverse side effects. Real time monitoring of efficacy and safety through therapeutic plasma ranges will enable personalized medicine and lead to better utilization of this medication. A promising solution are LOCs, which are translational microsystems providing numerous advantages in clinical diagnostics, bringing bench top methods into the point-of-care. Here we aim towards the development of a chitosan-based probe for clozapine signal amplification and its integration with miniaturized LOC for real time analysis of clozapine blood levels.
Chitosan has been found to be a very versatile biomaterial that can be easily integrated into LOC as a thin film. Following electro-active catechol grafting, a redox capacitor is formed. In this study we demonstrate the ability to use clozapine as an oxidizing mediator that can diffuse through the chitosan film and be electrochemically oxidized at the electrode. The generated oxidizing current can be amplified by a continuous cycle of clozapine reduction in the presence of catechol followed by clozapine re-oxidation. This continuous redox reaction increases the total charge generated by clozapine, amplifies the resulted current and improves its detection performance. We present the biofabrication, integration, and characterization of the electrochemically-active chitosan-catechol system in both macro- and micro-systems. The modified system demonstrated 3.3-fold signal improvement, better sensitivity, and high dynamic range compared to unmodified electrodes, with the ability to detect 0.5-50 µM clozapine concentrations. The translation of this system into a miniaturized LOC is presented with a 2.8-fold improved signal and superior functionality compared to unmodified system. These results demonstrate the merits of this technology in creating translational hybrid micro-devices that will allow treatment teams to do blood analysis on-site, guiding the development of interventions to prevent or reduce detrimental side effects.
3:30 AM - SS5.04
Digital Microfluidic Impedance Network for High-throughput Investigation of Cellular Response to Electrical Field
Siwei Zhao 1 Jinzhen Fan 1 Min Zhao 2 Tingrui Pan 1
1University of California, Davis Davis USA2University of California, Davis Sacramento USAShow Abstract
Recent advances in bioelectricity research has shown that exogenous electrical field (E field) can effectively regulate the activities of tissues and cells, including neuron regeneration1, wound healing1 and myocardium alignment and coupling2. Despite the promising evidence, current experimental methods for study of cellular response to E field suffer from low throughput, cumbersome setup and unpredictable electric stimulation. In order to fully understand the mechanism and optimize the stimulation, a high-throughput electrical stimulation device with multi-field strength generation, highly controlled E field distribution and miniaturized system configuration is highly desired. In this paper, we present a novel digital microfluidic impedance network to achieve the aforementioned goals.
The design of our digital microfluidic impedance network is inspired by the R-2R resistor ladder network for digital signal processing, which consists of a series of horizontal and vertical microfluidic resistors (microscale flow chamber) arranged in ladder-like configuration. Each branching point in the ladder structure operates as a current divider, splitting the current into the downstream branches at fixed ratio determined by the impedance match of the two branches. Therefore, a current gradient with constant ratio and the corresponding E field gradient can be generated in the horizontal or vertical microfluidic resistors. Overall, our digital microfluidic impedance network allows virtually infinite expansion of the E field gradient (fixed input resistance of R-2R ladder structure), highly predictable E field generation (well-defined microfluidic resistor dimension) and higher system integration with reduced sample usage (miniaturized device design).
The digital microfluidic impedance network device is designed with a splitting ratio of 1:1 and 9-level ladder structure, which generates a 9-level E field gradient with common ratio of 2 and magnitude spanning 2 orders of magnitude. The device is fabricated on PDMS using replica molding, followed by reversible bonding to a Mylar substrate coated with micropatterned Al electrodes. The cells are suspended in cell culture medium with pH buffer and then injected into the device. After cell attachment, the E field is applied through the Al electrodes to stimulate cellular activities. We have measured the E field gradient generated in the digital microfluidic impedance network using Ag/AgCl electrodes. It spans from 40mV/cm to 6V/cm with common ratio of 2.01±0.36, which is well consistent with our theoretical prediction. The E field gradient generated on digital microfluidic impedance network can be highly valuable for the study of mammalian cell migration, division and alignment in response to electric stimulation.
1. C. D. McCaig, A. M. Rajnicek, B. Song et al., Physiol Rev 85 (3), 943 (2005).
2. M. Radisic, H. Park, H. Shing et al., Proc Natl Acad Sci U S A 101 (52), 18129 (2004).
3:45 AM - SS5.05
Probing the Nanoscale Structure and Dynamics of Biosensors on Electrode Surfaces with Single-molecule Resolution
Eric A. Josephs 1 Tao Ye 2
1University of California, Merced Merced USA2University of California, Merced Merced USAShow Abstract
The surfaces of biosensors and bioelectronic devices—often biomolecules adsorbed onto an electrode—are generally characterized by ensemble techniques which record the average properties of many molecules over relatively large areas. As a result, several important questions remain regarding the surface and its molecular-scale structure, which ultimately determines the reliability, robustness, and reproducibility of these systems: how are the molecules distributed on the surface at the nanoscale? What are the conformations of individual molecules and how are they affected by the local chemical environment or by applied electric fields, which are used in a variety of sensing schemes? Because functionalized surfaces can be highly heterogeneous, how is the structure and behavior of the biomolecules perturbed by interactions with defects on the surface?
Using in situ electrochemical atomic force microscopy and carefully tailoring the surface interactions, we are able to directly resolve the nanoscale, electric field-dependent conformations of individual DNA molecules on a model biosensor surface—thiolated DNA tethered to a gold electrode which has been passivated by hydroxyl-terminated alkanethiol self-assembled monolayers (SAM). High-resolution imaging reveals a dramatic sensitivity to assembly conditions, choice of alkanethiol molecules, and the nature of the defects within the monolayer on the spatial distribution and orientation of the DNA on the surface. Defects in the SAM significantly perturb the conformations and adsorption/desorption kinetics of the tethered DNA in response to applied electric fields. On the other hand, the SAM may be actively disrupted and molded by the DNA at different potentials. We find that by observing the dynamic conformational responses of the DNA to cycling electrode potentials, we can extract not only the kinetic rates of adsorption/desorption in response to the electric fields but also the extent to which rates may vary among molecules within the context of each DNA's local chemical environment. Such details would otherwise be difficult to discern through existing ensemble characterizations of nucleic acid sensors. These results underscore the importance of characterizing the systems at the relevant length scale in the development of electrically switchable biofunctional surfaces and bioelectronic devices.
4:30 AM - *SS5.06
Proteins in Bio-electronics: Materials and Devices
Shachar Richter 1
1Tel Aviv Univ Tel Aviv IsraelShow Abstract
In their natural environment proteins are essential components in living bodies. However, one can exploit the properties of some of these macromolecules to construct novel types of composite materials that fit for bioelectronics applications. Among many examples are the Mucin proteins which are water-soluble compounds that can easily host hydrophobic moieties and thus can form water soluble bio-composites. Using these materials we have demonstrated several bio-electronic devices. Some examples are:
(i) Light-emitting bio-composites which are used to construct light emitting coating and electrically driven light emitting devices (including white-“LED”).
(ii) Control over the electrical properties of nano-sized junctions via “natural” and site-controlled doping.
(iii) Green synthesis of nano-particles in Mucins. Several examples will be shown including chiral nano-particles and core-shell structures.
1. Hendler N, et.al. (2011) Effecient separation of dyes by mucin:towards bio-inspired white-luminescent devices. Adv. Mater. 23,4261
2. Hendler N, et.al (2011) Bio-Inspired Synthesis of Chiral Silver nanoparticles in Mucin Glycoprotein. Chem. Commun. 47 , 7419 .
3. Mentovich et.al (2009) Large-Scale Fabrication of 4-nm-Channel Vertical Protein-Based Ambipolar Transistors. Nano Lett. 9:1296.
4. Mentovich et.al. Doped Biomolecules in Miniaturized Electric Junctions (2012) ,J. Am. Chem Soc., 134, 8468.
5:00 AM - SS5.07
Inactivation Processes in Immobilised Multicopper Oxidases Studied by an Electrochemical Quartz Crystal Microbalance (EQCM)
Christopher Francis Blanford 1 Kulveer Singh 1 2
1University of Manchester Manchester United Kingdom2University of Oxford Oxford United KingdomShow Abstract
Multicopper oxidases such as laccase and bilirubin oxidase are efficient electrocatalysts for the technologically important four-electron reduction of dioxygen to water. Immobilizing these enzymes on conductive electrode surfaces allows us not only to analyze their catalytic behaviour but also to harness their efficient catalysis in the cathodes of fuel cells. Adsorption to solid surfaces such as gold, however, is known to cause rearrangements to the enzyme structure, and may also place the enzyme in an orientation where electron transfer to the molecule is slow relative to the enzyme&’s intrinsic rate of catalysis. Deciphering the mechanisms through which these and other redox-active enzymes undergo changes in shape, orientation and function is key to their effective use in technological applications.
We used an electrochemical quartz crystal microbalance (EQCM) to monitor the adsorption of bilirubin oxidase from the fungus Myrothecium verrucaria on both bare and thiol-modified gold-coated sensors. Electrochemical measurements of the immobilized protein film give sensitive feedback on activity and orientation, while subtle changes in crystal frequency and the resonator&’s energy dissipation rate reveals coverage of the enzymes and the rigidity of their mechanical coupling to the electrode. For example, chronoamperometric measurements revealed catalytic activity of the enzyme diminished over time while the mass of enzyme deposited remained relatively constant, suggesting that an inactivation process or conformational change is responsible for loss of activity. In contrast, during potential cycling measurements adsorbed enzyme appeared to desorb, before settling consistently at approximately half the mass that was first adsorbed while catalytic activity is reduced dramatically. When the enzyme has been covalently attached to the surface and the potential is cycled, the mass remains roughly constant, but the activity diminishes rapidly to zero.
These findings should guide the use of this bilirubin oxidase in enzymatic bio-fuel cells.
5:15 AM - SS5.08
High-density Feedthrough Technology for Hermetic Biomedical Micropackaging
Emma Claire Gill 1 John Antalek 1 Fred M Kimock 3 Patrick J Nasiatka 2 Armand R Tanguay 2 James D Weiland 2
1Morgan Technical Ceramics New Bedford USA2University of Southern California Los Angeles USA3Four Circle, Inc. Macungie USAShow Abstract
Implantable electronic biomedical devices are used clinically to diagnose and treat an increasing number of medical conditions. Such devices typically employ hermetic packages that often incorporate electrical feedthroughs made with conventional ceramic-to-metal bonding technologies. This sealing technology is well established, and provides robust hermetic seals, but is both limited in the number and spacing of electrical leads. Emerging devices for interfacing with the human nervous system, however, will require a large number of external electrical leads implemented in a miniaturized packaging configuration. Commercially-available feedthrough technologies are currently incapable of providing external electrical contacts with spacings as small as 200 microns, and thus are neither compatible with integrated circuit I/O (input/output) pad spacings nor with miniature implantable packages. We report the development of a hermetic high-density feedthrough (HDF) technology that allows for conductive path densities as high as 1,000 per cm2 that is capable of supporting neural interface devices. The fabrication process utilizes multilayer high temperature co-fired ceramic (HTCC) technology in conjunction with platinum leads. Before co-firing, green alumina substrates are interleaved with linear, parallel Pt trace arrays in either wire or thin foils to form the electrical feedthroughs. Layered stacks of spatially isolated traces are first compacted into a composite, and then fired to achieve densification. After firing, the densified multilayered composite compacts are sliced perpendicular to the Pt traces and lapped to produce multiple feedthrough arrays with a high density of leads (conductors). Both hermeticity and biocompatibility of such implantable feedthroughs are important, as both moisture and positive mobile ion contamination from the saline environment of the human body can lead to compromised performance or catastrophic failure. HDFs made using this process with 100 conductors and lead-to-lead spacings as low as 400 microns have been helium leak tested repeatedly and found to exceed industry-accepted standards with helium leak rates in the range of 10(e-11) mbar-l/s. The spacing of the current prototype matches industry standard neural interface technology and can be scaled to higher densities with lead-to-lead spacings as small as 200 microns. The reported HDF process has several distinct advantages over prior approaches, including the provision of a large number of conductive feedthrough leads suitable for flip-chip bonding with sub-mm lead-to-lead spacings (pitch) and the use of materials (alumina and platinum) already used in medical implants. The implementation of such an HDF technology allows for significant package miniaturization, allowing greater flexibility in surgical placement as well as less invasive procedures for implantable electronic biomedical devices.
5:30 AM - SS5.09
Organic Active Matrix Amplifier System of 1-mu;m Thickness for Multi-channel Surface Electromyogram Measurement
Tsuyoshi Sekitani 1 2 Tomoyuki Yokota 1 2 Naoji Matsuhisa 1 2 Martin Kaltenbrunner 1 2 Yusuke Inoue 1 2 Masaki Sekino 1 2 Hiroshi Fuketa 1 2 Makoto Takamiya 1 2 Takayasu Sakurai 1 2 Takao Someya 1 2
1Univ. of Tokyo Tokyo Japan2JST/ERATO Tokyo JapanShow Abstract
We developed an ultrathin, mechanically flexible organic active matrix amplifier on a 1.2-mu;m-thick polyethylene naphthalate (PEN) film to amplify weak myoelectric potential (amplification factor: ~200). To validate the ultraflexible organic amplifier system, we developed a 64-channel surface electromyogram (EMG) measurement sheet (SEMS) with 2-V organic transistors on an ultraflexible PEN film for prosthetic hand control. Distributed and shared amplifier architecture enables in situ amplification of a myoelectric signal with a 4-fold increase in EMG electrode density.
A 2D array of organic amplifiers (active matrix amplifier system) was fabricated directly on a 1.2-mu;m-thick ultraflexible PEN substrate. The amplifier was fabricated using an inverter with a pseudo-CMOS layout comprising four p-channel organic transistors. The flexible, p-type channel was formed using dinaphtho[2,3-b:2prime;,3prime;-f]thieno[3,2-b]thiophene (DNTT), and gate dielectrics were formed with 4-nm-thick aluminum-oxide and a 2-nm-thick self-assembled monolayer. A waterproof hybrid encapsulation stack comprising a 200-nm-thick Au layer sandwiched between 100-nm- and 1.2-µm-thick parylene layers was deposited on the transistors to serve as a passivation layer against oxygen diffusion, humidity, and mechanical attrition in vivo, and as an overcoat layer for enhancing mechanical flexibility and durability, because the organic semiconducting layer is located at the neutral stain position. DNTT transistors showed mobility exceeding 2 cm2/Vs at 2 V; the pseudo-CMOS operated within 2 V, and the signal gain was above 400.
A surface EMG measures a voltage waveform produced by skeletal muscles on skin. It is an important tool for applications detecting the human will of motion, such as that of prosthetic hands and prosthetic legs, because EMG measurement is noninvasive. In the application of a prosthetic hand, a multipoint EMG measurement is required to precisely control the hand. However, conventional multipoint measurements with a passive electrode array have two problems: 1) a long measurement time, which is unpleasant because the EMG electrodes attached to the skin are not fully flexible; and 2) the degraded signal integrity of EMG, because the number of wires between the electrodes and the front-end circuits increases with increasing measurement points. To overcome these problems, an SEMS that integrates an EMG electrode array and a front-end amplifier array with 2-V organic transistors on a 1-mu;m-thick ultraflexible film and that can control prosthetic hands was developed. The developed SEMS enables long-time measurement without any discomfort or signal integrity degradation.
Although circuit design and system configuration of proposed device will be presented in 2013 IEEE International Solid-State Circuits conference by our group, we will present materials, device processes and structures of 1-mu;m-thick organic circuits for detecting myoelectric potential at MRS, for the first time.
5:45 AM - SS5.10
Scanning Transmission X-Ray Microscopy of Macromolecular Bio-functional Coatings on Silicon Nanowires
Tony van Buuren 1 A. Noy 1 Jonathan Lee 1 T. Willey 1 Michael Bagge-Hansen 1
1Lawrence Livermore National Laboratory Livermore USAShow Abstract
Nature has evolved a set of sophisticated biological machines for accomplishing molecular-level tasks including membrane receptors, channels, and pumps. Development in nanoscale engineering has enabled bioelectronics that can mimic and/or interact with these biological systems. Bio-functionalized Si nanowires are thought to be a promising candidate for the construction of electrochemical devices. We have developed and demonstrated assembly of 1-D phospholipid bilayers on a variety of nanomaterials, including silicon nanowires. These biomimetic lipid bilayers serve as a general host matrix for bio-functional components such as membrane proteins. Though meaningful technological advancement of these materials has been made, critical questions about the structural and chemical composition remain.
We present results from the first Scanning Transmission X-ray Microscopy (STXM) investigation of 1D lipid bilayers on silicon nanowires. STXM provides the high spatial resolution, chemical selectivity and the ability to probe a liquid system needed to investigate the structure of these bio-nanomaterials. In STXM a focused x-ray beam produced by a zone plate illuminates a sample and we then collect the subsequent transmitted x-rays. The transmitted intensity can be measured as a function of energy to give high spatial resolution element specific x-ray absorption spectra, or as a function of beam position to produce x-ray images. Si NWs in a liquid suspension can be clearly imaged at an x-ray energy near the Si K-absorption edge. We were also able to measure the C and P XAS associated with a phospholipid bilayer on the surface of a single Si nanowire. Polarization effects observed in the C XAS have been used to probe the order and orientation of the lipid bilayer. STXM experiments were conducted at beamline 188.8.131.52 of the Advanced Light Source Lawrence Berkeley Laboratory.
SS4: Cell and Tissue Bioelectronic Interfaces
P. Leslie Dutton
Wednesday AM, April 03, 2013
Westin, 2nd Floor, Metropolitan Ballroom I
9:45 AM - *SS4.01
Nanoelectronics Meets Biology
Charles M. Lieber 1
1Harvard University Cambridge USAShow Abstract
Nanoscale materials enable unique opportunities at the interface between the physical and life sciences, and the interface between nanoelectronic devices and biological systems makes possible communication between these two diverse systems at the length scale relevant to biological function. In this presentation, the development of nanowire nanoelectronic devices and their application as powerful tools for the life sciences will be discussed. First, a brief introduction to nanowire nanoelectronic devices as well as comparisons to other tools will be presented to illuminate the unique strengths and opportunities enabled at the nanoscale. Second, illustration of detection capabilities including signal-to-noise and applications for real-time label-free detection of biochemical markers down to the level of single molecules will be described. Third, the use of nanowire nanoelectronics for building interfaces to cells and tissue will be reviewed. Multiplexed measurements made from nanowire devices fabricated on flexible and transparent substrates recording signal propagation across cultured cells, acute tissue slices and intact organs will be illustrated, including quantitative analysis of the high simultaneous spatial and temporal resolution achieved with these nanodevices. Fourth, emerging opportunities for the creation of powerful new probes based on controlled synthesis and/or bottom-up assembly of nanomaterials will be described with an emphasis on the creation of nanowire probes capable of intracellular recording at scales heretofore not possible with existing electrophysiology techniques. Last, we will take a look ‘out-of-the-box&’ and consider what the future might hold in terms of merging nanoelectronics with cell networks in three dimensions to ‘synthesize&’ ‘cyborg&’ tissues. The applications for such hybrid systems for drug screening in three-dimensional tissue models as well as powerful prosthetic interfaces will be discussed. The prospects for blurring the distinction between nanoelectronic and living systems in the future will be highlighted.
10:15 AM - SS4.02
Nanoscale Diamond Solution-gated Field-effect Transistors for Extracellular Recording of Action Potentials
Moritz V. Hauf 1 Lucas H. Hess 1 Tobias Schneider 1 Jose A. Garrido 1
1Technische Universitaet Muenchen Garching GermanyShow Abstract
In the past few years interfacing nerve tissue with electronic devices has led to remarkable advances in the field of bioelectronics. Whereas most devices are based on either metal electrodes or silicon transistors, we investigate diamond as it allows to fabricate solution-gated field-effect transistors (SGFETs) based on a two-dimensional hole gas. These devices have already proven to combine a high sensitivity with low noise . In comparison to silicon-based FETs no gate oxide is required, since the large electrochemical potential window of diamond allows the direct contact between semiconductor and electrolyte. Further, the electric double layer of the diamond/electrolyte interface provides a capacitance of 2 µC/cm2 over a large potential window . Additionally, the lack of trap states at an oxide interface minimizes the electronic noise in diamond-based devices. Furthermore, diamond shows an extremely high stability and good biocompatibility with biological systems.
In the past , we have managed to extracellularly record cell signals with relatively large diamond SGFETs where single cells mostly cover only part of a transistor&’s gate area. Here, we extend the concept of a surface conductive channel to the nanometerscale. As a result, the channel is always fully covered by a cell, providing maximum signal transduction. Furthermore, it enables to spatially resolve electrical processes at the interface between diamond and cells. We fabricate arrays of 64 transistors on a single-crystalline hydrogen-terminated surface with channel dimensions below 100nm. These devices are capable of monitoring the spreading of spontaneous action potentials through a layer of HL-1 cardiomyocytes. Furthermore, we use them for a detailed study of the cell transistor coupling when measuring the opening and closing of voltage-gated potassium channels in human embryonic kidney cells. The low noise level allows to observe not only the potential change in the cleft, which is driven by the ionic membrane current, but also we are able to detect related changes in the ion concentration in the cleft. Our work demonstrates the great potential of nanoscaled diamond-based solution-gated field-effect transistors for the extracellular recording of electrogenic signals from cells.
 Dankerl, M. et al. Hydrophobic Interaction and Charge Accumulation at the Diamond-Electrolyte Interface. Phys. Rev. Lett. 106, 196103 (2011)
 Hauf, M.V. et al. Low-frequency noise in diamond solution-gated field effect transistors. Appl. Phys. Lett. 97, 093504 (2010)
 Dankerl, M. et al. Diamond transistor array for extracellular recording from electrogenic cells. Adv. Funct. Mater. 19, 2915-2923 (2009)
10:30 AM - SS4.03
An Ultra-low Voltage Organic Transistor-based System for Electrophysiological Applications
Andrea Spanu 1 2 Stefano Lai 2 Piero Cosseddu 2 3 Massimo Barbaro 2 Sergio Martinoia 1 Annalisa Bonfiglio 2 3
1University of Genoa Genoa Italy2University of Cagliari