Guosong Hong, Stanford University
Sahika Inal, King Abdullah University of Science and Technology
Jonathan Rivnay, Northwestern University
Tzahi Cohen-Karni, Carnegie Mellon University
Available on demand
Available on demand - EL07.09.01
Graphene Oxide Modulating the Bioelectronic Properties of Penicillinase Immobilized in Lipid Langmuir-Blodgett Films
Luciano Caseli1,Fabio Scholl1,José Siqueira Junior2
Universidade Federal de São Paulo1,Universidade Federal do Triângulo Mineiro2Show Abstract
Conjugating bioinspired systems with graphene oxide can provide systems with an active layer that combines materials with different functionalities. Bioinspired systems are particularly an interesting alternative for incorporating bioactive species, enabling a molecular environment favorable to some biomolecule properties, such as enzyme activity. In the same sense, graphene oxide (GO), in addition to presenting biocompatibility, has optical and electrical properties that encourage its application in systems of biological interest. In this work, the interaction of the enzyme penicillinase with the phospholipid di-myristoyl phosphatidic acid (DMPA), conjugated with graphene oxide (GO), was studied as Langmuir and Langmuir-Blodgett (LB) films. The incorporation of the enzyme and GO in the phospholipid floating monolayer was evaluated through measurements of surface pressure-area isotherms, surface elasticity, Brewster angle microscopy (BAM), and Polarization-Modulation Infrared Reflection-Absorption Spectroscopy (PM-IRRAS). The Langmuir films were stabilized with the presence of GO, as identified by the results obtained with the employed techniques. They showed that the enzyme was incorporated in the DMPA monolayers, with its secondary structure being preserved, as identified by PM-IRRAS. Also, the interaction of the mixed lipid-enzyme films with GO located in the aqueous subphase of the monolayers in the form of colloidal dispersion could be identified, forming homogeneous films as observed by BAM. The monolayer stabilization supported the transfer of these hybrid films onto solid substrates using the LB technique, characterized by fluorescence spectroscopy and transfer ratio. The enzymatic activities of the solid devices were then measured by using UV-visible spectroscopy. The approach was effective in co-immobilizing penicillinase and GO, which were co-transferred to solid supports as an ultrathin film with the phospholipid. The presence of GO allowed to improve the identification of the signals for penicillinase detection by electronic excitation and luminescent emission. Also, films with GO increased the catalytic efficiency of the devices towards the hydrolysis of the beta-lactam ring. The presence of GO in the enzyme/lipid LB film not only tuned the catalytic activity of penicillinase, but also conserved its enzyme activity after weeks. The feasibility of the supramolecular device nanostructured as ultrathin films to detect penicillin was essayed in a capacitive electrolyte−insulator−semiconductor (EIS) sensor device. Viability as a penicillin sensor was demonstrated with capacitance/voltage and constant capacitance measurements, exhibiting regular and distinctive output signals for all concentrations used in this work. Therefore, these results may be related to the nanostructured system as an ultrathin film and the synergism between the compounds on the active layer, leading to a surface morphology that allowed a fast analyte diffusion owing to an adequate molecular accommodation, which preserved the penicillinase activity. Therefore, this work demonstrates that the incorporation of graphene oxide in LB films composed of penicillinase and DMPA boosts the biosensing properties of the hybrid ultrathin film as EIS devices for biosensing applications.
Available on demand - EL07.09.02
Adaptive Self-Recoverable Electronic Epineurium
Sungkyunkwan University1Show Abstract
Soft neuroprosthetics capable of bi-directionally monitoring sensory signals and delivering feedback motor information have pursued the perfect replacement for damaged nerves. Although such valuable efforts have been made to the long-term stability of the peripheral neural interfaces, nerve compression and tissue-induced device fatigue issues still remain challenging due to the lack of optimal materials that simultaneously meet tissue-device modulus matching, biocompatibility, and electrical/mechanical self-recovery. Here, we report a tissue-adaptive self-recoverable electronic epineurium that can prevent its electrical degradation induced by repetitive, non-uniform, and severe structural deformation occurred at a rat’s sciatic nerve as well as undesired nerve compression. Such performances originate from its unique mechanical properties: i) spontaneous rearrangement of a ligand-decorated Au nanoshell-coated Ag flakes dispersed in a tough self-healing polymer matrix and ii) dynamic stress relaxation of the electronic epineurium enabling its mechanical adaptation to nerve modulus. Through these properties, we successfully demonstrate stable bidirectional neural recording and stimulation in vivo even under the harsh mechanical deformation.
Available on demand - EL07.09.03
A Protein-Based Free-Standing and Proton Conducting Transparent Polymer as a Sustainable Material for Large Scale Sensing Applications
Technion–Israel Institute of Technology1Show Abstract
In a world of depleted resources, and with our current acceptance that the materials we make can have a severe impact on the world, we now understand that we need to reconsider our strategy of making new materials. Accordingly, two materials-related approaches have been formulated. The first approach focusing on the environmental impact of the materials, also known as environmental chemistry, while the second approach is making/synthesizing new materials using green chemistry principals, also known as sustainable chemistry. The use of carbon-based polymers is a good example for the endeavor of making environmentally friendly materials, though not all polymers are environmentally friendly and many of them are not being synthesized in a green chemistry approach. In here, we are focusing on polymers exhibiting efficient ion transport capabilities, and specifically, proton conduction. Inspired by the natural role of mediating protons, we use proteins as the sole starting material for the formation of the polymer. Unlike synthetic polymers, protein-based polymers have inherent biocompatibility and biodegradability properties that promote their use in biomedical applications, either on the skin or in vivo. However, to date, protein-based proton conducting polymers cannot be translated to real applications due to two main reasons. The first being the low reported conductivity values compared to common synthetic proton conducting polymers, whereas the measured conductivity (at ambient conditions) across protein-based polymers are usually <1 mS●cm-1, while the one of common polymers is >5 mS●cm-1. The second most important challenge to overcome is the material formation protocol, whereas most of the conductive protein-based polymers have used genetically expressed proteins, which is not a viable solution as it is costly and time-consuming, even upon upscaling, and accordingly, cannot result in having highly affordable proteins in bulk quantities needed for the formation of materials in large scale. Here, we introduce a new sustainable approach of making proton conducting polymers using affordable and naturally available bovine serum albumin (BSA) proteins, which is in part due to being a ‘waste product’ of the extensive bovine industry. Hence, our choice of protein is both sustainable in terms that we are recycling waste products, in oppose of synthesizing or expressing something new, as well as highly economical with a commercial price tag of less than 2 USD●gr-1 of the protein starting material. An added novelty of our new approach here is in its simplicity, which is a one-pot process involving merely dissolving the protein at the right solvent mixture, polymerization and casting it. We show that by using our new methodology, we can form free-standing (self-supporting), insoluble transparent films with high measured proton conductivity at ambient conditions of ~5 mS●cm-1, and highly attractive mechanical properties of the polymer, capable of stretching ~5 times its length. We show that an added value of using proteins as the building blocks is the breadth of functional groups, which are the amino acids residues, allowing performing a variety of post synthetic modifications, and in here we use them to increase the proton conductivity across the polymer. Taking into consideration the polymer stretchability, water containing, biocompatibility and biodegradability nature, we foresee its direct translation in various biomedical applications. Here, we show an immediate application route for our new polymer by its use as a solid-state ion conducting polymer in electrical sensing of physiological signals, replacing the current cumbersome use of a conductive gel.
Available on demand - EL07.09.04
Flexible Graphene-Based Wireless mHealth System for Non-Invasive Stress Monitoring
Jiaobing Tu1,Rebeca Torrente-Rodriguez1,Yiran Yang1,Jihong Min1,Wei Gao1
California Institute of Technology1Show Abstract
Prompt and accurate detection of stress is essential to human performance analysis, stress-related disorder diagnosis, and mental health monitoring. Current approaches such as questionnaires are very subjective. To avoid stress-inducing blood sampling and to realize continuous, non-invasive, and real-time stress analysis at the molecular levels, we investigate the dynamics of a stress hormone, cortisol, in human sweat using an integrated wireless sensing device based on laser-enabled flexible graphene sensors that are mass producible at low cost. Highly sensitive, selective, and efficient cortisol sensing is enabled by a flexible sensor array that exploits the exceptional performance of laser-induced graphene for electrochemical sensing. We report a strong correlation between sweat and circulating cortisol and demonstrate the prompt determination of sweat cortisol variation in response to acute stress stimuli. Moreover, we demonstrate, for the first time, the diurnal cycle and stress-response profile of sweat cortisol, revealing the potential of dynamic stress monitoring enabled by this mHealth sensing system.
Available on demand - EL07.09.05
Sub-Micrometer/Second Biofluidic Flow-Velocity Quantification Using a Graphene Single Electrode
Xiaoyu Zhang1,Eric Chia1,Xiao Fan1,Jinglei Ping1
University of Massachusetts Amherst1Show Abstract
Miniaturized meter-on-chip electrical tools for interrogating biofluidic flow velocity offer the promise of long-term flow monitoring in healthcare, disease-progression surveillance, and tissue engineering. Low-dimensional materials are ideal for converting flow velocities into electrical signals at high spatiotemporal resolution but typical flow micro/nanosensors are either of transistor device structure that suffers from the thermodynamic limitation of sensitivity or in the form of bundled electrodes that are prone to signal-degradation, biofouling, and clogging. We report the quantification of biofluidic flow velocity with ultra-high sensitivity (sub-micrometer/second) and more than six-months stability by measuring the flow-generated triboelectric current at a one-atom-thick graphene single electrode. The graphene electrode responds to rapid, micrometer/second changes in the whole blood flow in a microfluidic channel that simulates that in human capillary. The research paves the way to next-generation meter-on-a-chip devices for in vivo body fluid monitoring and may lead to uncovering new biological and physiological phenomena.
Available on demand - EL07.09.06
A Novel Room Temperature Human Exhalation CO2 Sensor Based on PEI-PEG/ZnO/NUNCD/Si Heterojunction System
Ching Chang1,Chi-Young Lee1,Nyan-Hwa Tai1
National Tsing Hua University1Show Abstract
Gas sensors based on semiconductor have outstanding sensitivity as compared with the oxide-based devices. However, the high operation temperature has greatly hindered progress for practical application. Chronic obstructive pulmonary disease (COPD) is the leading cause of death worldwide, and the patients with severe COPD with or without exacerbation tend to have airflow obstruction leading to increased levels of CO2 and subsequent hypercapnic respiratory failure. At present, the difficulty of detection lies on the professional operation, and the patients suffer great discomfort during the arterial blood sampling and collection processes. All these facts reduce patient’s willingness to test and inspect their physical health. Thus, a non-invasive monitoring of CO2 levels is crucial for these patients.
Nitrogen-incorporated ultrananocrystalline diamond (NUNCD) film exhibits the excellent properties in biosensing, and Polyetherimide-Polyethylene glycol (PEI-PEG) polymer layer reveals great capability of CO2 capturing. This work focuses on ameliorating the sensitivity and the selectivity of present semiconductor CO2 sensor. From the theoretical regression analyses of the experimental results, we find that the response of the PEI-PEG/ZnO/NUNCD/Si electrode is contributed from two main reaction layers, the adsorption layer (PEI-PEG) and the electric transfer layer (ZnO/NUNCD). The selectively is dominated by PEI-PEG adsorption layer and the sensitivity is directly related to the changes in the work function of the ZnO/NUNCD interface according to the obtained results.
In this study, we adopted Si substrate for the growth of NUNCD. After the surface of NUNCD is completely deposited with flower-like ZnO, the surface becomes extremely rough showing high surface area. In addition, the high aspect ratio (>10) of flower-like ZnO structure, formed by ZnO nanoparticles, can provide more adsorption area. As a result, the sensitivity can be improved due to its higher surface area.
The CO2 concentration in healthy human exhalation ranges from 4.6 to 5.9%, while that of COPD patients ranges from 6.5 to 7.9%. Thus, our aim is to measure CO2 concentrations ranging from 4 to 15%. The electrode was tested periodically using CO2 concentrations of 15, 10, 8, 6, 4, and 2%. The results show that the electrode is sensitive to CO2 concentration because of the electrode shows distinct responses under different CO2 concentrations. The sensing performance of CO2 shows goods linear regression with R2 = 0.994. The results of PEI-PEG/ZnO/NUNCD/Si heterojunction CO2 sensor demonstrate the performance of the electrode with excellent sensitivity and selectivity at room temperature. Therefore, the development of a simple CO2 sensor suitable for medical and commercial is urgent for patients to obtain earlier diagnosis and treatment.
Available on demand - EL07.09.07
Control of the Debye Length at the Electrolyte-Oxide Interface of bioFETs with Tunable Surface Electric Fields
Ie Mei Bhattacharyya1,Gil Shalev1,2
Ben Gurion University of the Negev1,The Ilse-Katz Institute for Nanoscale Science & Technology, Ben Gurion University of the Negev2Show Abstract
Biosensors based on field-effect devices (bioFETs) have gained immense research over the past few decades because of their numerous advantages over existing technologies. Yet, their commercialization remains very limited. The biggest challenge for bioFET realization is the extremely short Debye screening length at high ionic strengths. This problem becomes significantly more severe at the solution-oxide interface due to high ion concentration induced by the charged oxide surface groups which cripples any attempt to use field-effect mechanism to detect the presence of the target analytes. In this work, we propose an electrostatic approach to remove the excess concentration of counterions at the double layer (DL), thereby forcing the DL ion concentration to match the bulk concentration . This consequently forces bulk screening length at the DL, thus ‘exposing’ target biomolecules to the underlying FET. In order to achieve this, local tunable surface electric fields are introduced to the DL using surface passivated-metal electrodes. The effect of these electric fields on the DL ion distribution are examined numerically and analytically. Also, the feasibility of the proposed approach is demonstrated numerically for a fully-depleted silicon-on-insulator based bioFET. We show how a significant twofold increase in the threshold voltage shift is achieved due to the presence of target molecules upon the removal of the surface excess ion population.
 I. M. Bhattacharyya, G. Shalev, Electrostatically-governed Debye screening length at the solution-solid interface for biosensing applications, ACS Sensors, 2020, 5, 1, 154-161. https://doi.org/10.1021/acssensors.9b01939
Available on demand - EL07.09.08
Detecting Cancer Biomarkers Electrically Using Single-Molecule Techniques—Understanding Electrical Fingerprints at the Nucleic Acid Bioelectronic Interface
Keshani Pattiya Arachchillage1,Subrata Chandra1,Juan Artes Vivancos1
University of Massachusetts Lowell1Show Abstract
Cancer kills more than 8 million people per year and it is one of the most frequent causes of death globally.1 Cancer biomarkers are promising for detecting cancers early.2 There are various methods to analyze biomarkers and liquid biopsy is one of them.3 Blood samples, or other body fluids, can contain circulating free tumor nucleic acids (ctNA) that can be used as cancer biomarkers.3 Detecting ctNA in the blood is challenging, because of the low ctNA concentration and the low frequency of mutations compared to wild-type sequences.3 Nanotechnology bioelectronics methods can help to address this challenge. In particular, the Scanning Tunneling Microscopic (STM)-assisted break junctions method (STM-BJ)4 has recently allowed the first demonstration of detection and identification of RNA from E.Coli via single-molecule conductance.5 This is an ideal method for liquid biopsy bioelectronics since it could detect cancer biomarkers such as ctNAs in liquid biopsy samples non invasively and quantify them with high sensitivity and specificity.3
In this work, we characterize ctNAs using the STMBJ to measure and compare the bioelectronics fingerprints of these ctNAs. The main hypothesis of the study is that the sequences of ctNAs can be used to detect cancers, by finding their unique electronic fingerprints. We focus the study on KRAS, BRAF, and Nras as effective cancer biomarkers, based on the recent literature.6,7 We have obtained some preliminary data for RNA sequences for a few candidate biomarkers and we expect to understand the bioelectronics interface between genetic material(ctNA) and nanostructured electrodes. Our results pave the way for the early detection of bioelectronics fingerprints from biomarkers, such as ctDNA and ctRNA,3 through liquid biopsy using nanotechnology. These methods may allow beginning treatments early, potentially saving many lives from cancer patients in the future.
1. Campbell PJ, Getz G, Korbel JO, et al. Pan-cancer analysis of whole genomes. Nature. 2020;578(7793):82-93. doi:10.1038/s41586-020-1969-6
2. Henry NL, Hayes DF. Cancer biomarkers. Mol Oncol. 2012;6(2):140-146. doi:10.1016/j.molonc.2012.01.010
3. Das J, Kelley SO. High-Performance Nucleic Acid Sensors for Liquid Biopsy Applications. Angew Chemie - Int Ed. 2019. doi:10.1002/anie.201905005
4. Xu B, Tao NJ. Measurement of single-molecule resistance by repeated formation of molecular junctions. Science (80- ). 2003;301(5637):1221-1223. doi:10.1126/science.1087481
5. Li Y, Artés JM, Demir B, et al. Detection and identification of genetic material via single-molecule conductance. Nat Nanotechnol. 2018;13(12):1167-1173. doi:10.1038/s41565-018-0285-x
6. Rheinbay E, Nielsen MM, Abascal F, et al. Analyses of non-coding somatic drivers in 2,658 cancer whole genomes. Nature. 2020;578(7793):102-111. doi:10.1038/s41586-020-1965-x
7. Detection of BRAF mutation in thyroid papillary carcinomas by mutant allele-specific PCR amplification (MASA) in: European Journal of Endocrinology Volume 154 Issue 2 (2006). https://eje.bioscientifica.com/view/journals/eje/154/2/1540341.xml. Accessed June 8, 2020.
Available on demand - EL07.09.09
Polydopamine as a Soft Material for Integration of Metabolically Active Photosynthetic Bacteria in Bioelectronics
Massimo Trotta2,Danilo Vona1,Gabriella Buscemi1,2,Roberta Ragni1,Francesco Milano2,Gianluca Farinola1
Università degli Studi di Bari Aldo Moro1,Consiglio Nazionale delle Ricerche2Show Abstract
Photosynthetic microorganisms and their subparts represent a very promising tool for the integration of biological photo transducers in bioelectronics and bioelectronic devices. [1,2] Light absorbed by these organisms can be converted into several energy forms exploitable for many external processes. Collect, extract, and transfer electrons from the photosynthetic microorganisms to electrodes represent one of the main issues in Extracellular Electron Transfer (EET). Unfortunately, EET often reduce microorganism’s viability or leave bacteria in quiescent states inhibiting their reproduction. We present here a procedure for improving the communication between the bacterial cells and the electrode that does not jeopardize the activity and the viability of the bacteria. Cells from the purple non-sulphur bacterium Rhodobacter sphaeroides grown under photosynthetic conditions were used as model to test the ability of polydopamine to function as coating material that does not produce detrimental effect nor to the morphology of the cell, nor its basic metabolism, similarly to what previously reported in polygallic acid .
Acknowledgements: Funded by the FET-Open project HyPhOE (Grant agreement ID: 800926)
1. Reggente M, Politi S, Antonucci A, Tamburri E, Boghossian AA (2020) Design of Optimized PEDOT-Based Electrodes for Enhancing Performance of Living Photovoltaics Based on Phototropic Bacteria. Advanced Materials Technologies 5 (3):Artn 1900931. doi:10.1002/Admt.201900931
2. Milano F, Punzi A, Ragni R, Trotta M, Farinola GM (2019) Photonics and Optoelectronics with Bacteria: Making Materials from Photosynthetic Microorganisms. Adv Funct Mater 29 (21):1805521. doi:10.1002/adfm.201805521
3. Vona D, Buscemi G, Ragni R, Cantore M, Cicco SR, Farinola GM, Trotta M (2020) Synthesis of (poly)gallic acid in a bacterial growth medium. Mrs Advances 5 (18-19):957-963. doi:10.1557/adv.2019.466
Available on demand - EL07.09.10
Integration of Bacterial Photoenzymes onto Electrodes—Towards Photosynthesis-Driven Optoelectronics
Gianluca Farinola1,Gabriella Buscemi1,Marco Lo Presti1,Roberta Ragni1,Rossella Labarile1,Francesco Milano2,Danilo Vona1,Massimo Trotta3
Università degli Studi di Bari Aldo Moro1,CNR-ISPA2,CNR-IPCF3Show Abstract
Photosynthetic microorganisms and their molecular components represent attractive tools for harvesting and conversion of solar light in integrated bioelectronic transducers .
We have recently investigated several approaches for adressing the Reaction Center (RC) photoenzyme, extracted from the purple non sulfur photosynthetic bacterium Rhodobacter sphaeroides, in optoelectronic devices for conversion of solar energy into photocurrent . The RC has been covalently anchored on molecular organic semiconductors with reactive linkers, and the resulting active layer has been used in photodetector configuration . A supramolecular approach based on specific interaction with another protein (Cytochrome C) has been used to create an oriented layer of RC on the gate electrode of an organic transistor device, resulting in the first example of light-driven Electrolite Gated Organic Field Effect Transistor (LEGOFET) based on a photoenzyme . More recently, we have used polydopamine (PDA) for attaching RC directly onto ITO electrodes, by simple polymerization of dopamine in aqueous media . However, this convenient approach suffers from the low transparency of PDA, which limits the light absorption of the embedded RC. To overcome this issue, PDA has been tailored into a more transparent copolymer by using a degradative functionalization with ethylendiamine. After the encapsulation of RC into polydopamine, the diamine additive modifies the polymer structure, conferring modulable fluorescence properties to the RC-PDA nanoparticles, reducing their size and increasing the general transparency of the polymer. This leads to an enhancement of the light response of RC, with augmented production of charge separated states.
 F. Milano, A. Punzi, R. Ragni, M. Trotta, G. M. Farinola, Adv. Funct. Mater., 29, 1805521, (2019).
 A. Operamolla, R. Ragni, F. Milano, R. R. Tangorra, A. Antonucci, A. Agostiano, M. Trotta, G. M. Farinola, J. Mater. Chem. C., 3, 6471, (2015).
 E. D. Glowacki, R. R. Tangorra, H. Coskun, D. Farka, A. Operamolla, Y. Kanbur, F. Milano, L. Giotta, G. M. Farinola, N. S. Sariciftci, J. Mater. Chem. C., 3, 6554-6564, (2015).
 M. Di Lauro, S. la Gatta, C. A. Bortolotti, V. Beni, V. Parkula, S. Drakopoulou, M. Giordani, M. Berto, F. Milano, T. Cramer, M. Murgia, A. Agostiano, G. M. Farinola, M. Trotta, F. Biscarini, Adv. Electron. Mater., 6, 1900888, (2020).
 M. Lo Presti, M. M. Giangregorio, R. Ragni, L. Giotta, M. R. Guascito, R. Comparelli, E. Fanizza, R. R. Tangorra, A. Agostiano, M. Losurdo, G. M. Farinola, F. Milano, M. Trotta Adv. Electron. Mater., 6, 2000140, (2020).
Available on demand - EL07.09.12
Self-Healable, Recyclable and Reconfigurable Wearable Electronics
University of Colorado Boulder1Show Abstract
Stretchable/flexible electronics has attracted tremendous attention in the past 2-3 decades due to the combination of its superior mechanical attributes and electrical performance. It can be applied in places that are not accessible by traditional rigid printed circuit boards (PCBs), such as seamless integration with soft tissues and organs of human body for healthcare, bio-inspired curvilinear imagers and artificial skins that mimic the mechanical and electrical properties of natural skin. Among all the exciting applications, wearable electronics represents one of the most important, as it is the most accessible to people, and can be integrated onto the surface of human body to provide many useful functions, including physical activity tracking, health monitoring, drug delivery, human-computer interface, and virtual/augmented reality. More recently, various chemistry and mechanisms have been explored to enable self-healability and degradability in wearable electronics.
All these developments could lead to an exciting bright future of applying technological advancements to improve the wellbeing of people and the society. However, on the other hand, mass production and application of electronics generate a large amount of electronic waste. By 2021, the total electric waste is estimated to reach 52.2 million tons, and the majority of the waste cannot be appropriately recycled. The consequence is that a large amount of heavy metals and other hazardous substances have been entering the eco-system, causing serious environmental problems and human health issues. To resolve this issue, we here report a fully recyclable multifunctional wearable electronic system, which can simultaneously provide excellent mechanical stretchability, self-healability and reconfigurability. Such wearable electronics is achieved by heterogeneous integration of rigid (chip components), soft (dynamic covalent thermoset polyimine) and liquid (eutectic liquid metal) materials through advanced mechanical design and low-cost fabrication method. In such wearable electronic system, off-the-shelf chip components provide high-performance sensing and monitoring of the human body, including physical motion tracking, temperature monitoring, and sensing of acoustic and electrocardiogram (ECG) signals. They are interconnected by intrinsically stretchable and robust liquid metal circuitry, and encapsulated by dynamic covalent thermoset polyimine matrix. Bond exchange reactions in the polyimine network, together with the flowability of liquid metal, enable the wearable electronics to self-heal from damage and to be reconfigured into distinct configurations for different application scenarios. Furthermore, through transimination reactions, the polyimine matrix can be depolymerized into oligomers/monomers that are soluble in methanol and are separated from the chip components and liquid metal. All recycled materials and components can be reused to fabricate new materials and devices.
Available on demand - EL07.09.13
Wireless Power Transfer System for Smart Contact Lenses
Takeo Miyake1,Taiki Takamatsu1,Hu Lunjie1,Xiao Te1,Qi Zhang1
Waseda University1Show Abstract
Electronic contact lenses have been attracted much attention as health monitoring biosensors, wearable displays, and electrically-stimulated eye accommodation devices. Recent examples of their use are glucose sensing, lactate sensing, intraocular pressure measuring, light-emitting diode (LED) displays, and corneal electroretinogram recordings. As electrical lenses make continuous contact with the eyeball surface, their power source and all components must be flexible and safe. Constructing power sources on contact lenses is especially challenging, because the power device must be mounted on the restricted area of the lens without obstructing the vision. Here, we have developed wireless power transfer (WPT) system for smart contact lenses. The WPT system is based on two types of inductance(L)-capacitance(C) resonant circuits at the resonant frequency of 13.56 MHz . Recently, we have developed a hybrid power generation device comprising a wireless power transfer system and a bioabsorbable metal–air primary battery, which provides a multifunctional direct current (DC) and/or alternating current (AC) output .
 Advanced Materials Technologies, 4, 1800671, 2019.
 Advanced Functional Materials, 30, 1906225, 2020.
Available on demand - EL07.09.14
Late News: Design of Novel Conjugated Polymers for Organic Electrochemical Transistor Biosensors
Maximilian Moser1,Sahika Inal2,Iain McCulloch1,2
University of Oxford1,King Abdullah University of Science and Technology2Show Abstract
Organic electrochemical transistors (OECTs) are bioelectronic devices that have gained significant attention recently, as they have shown excellent performances as biomolecule sensors, implantable brain signal recorders, neuromorphic computing elements and many other biomedical applications.1 Currently, the aqueous dispersion, poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS), has established itself as the OECT benchmark material, predominantly due to its commercial availability. PEDOT:PSS-based OECTs however display several disadvantages; namely i) their moderate OECT performances (quantified by the material-only dependent figure of merit μC*), ii) their depletion-mode of operation, iii) their inability to conduct electrons and iv) PEDOT:PSS’ highly complex structure preventing the formulation of structure-property relationships for future material design.2 Based on these limitations, this work focuses on synthesizing novel, cheap and solution processable glycol-ether (GE) functionalized conjugated polymers to advance OECT and hence biosensor performance, while concomitantly also establishing design-rules for the development of future OECT materials.
Several molecular design strategies are investigated. These range from tailoring the GE side chain length, to varying the nature of the aromatic building blocks and modifying the chemical composition of the solubilizing chains.3–5 Ultimately, we show how judicious optimization of the molecular structures, involving polymer energy level, polymer morphology and polymer electroactive swelling modulation, allows us to achieve unprecedented performance and stability benchmarks with μC* values of 522 F V-1 cm-1 s-1 (c.f. typically ~40 F V-1 cm-1 s-1 for the PEDOT:PSS benchmark)6 and devices retaining 98% of their initial current over 2 h of continuous electrochemical cycling.4 We then proceed to show how the combined performance and stability advances of our newly developed materials can be exploited in the fabrication of higher performing biosensors, including better sensitivity and lower power consumptions.
1. J. Rivnay, S. Inal, A. Salleo, R. M. Owens, M. Berggren and G. G. Malliaras, Nat. Rev. Mater., 2018, 3, 17086.
2. M. Moser, J. F. Ponder, A. Wadsworth, A. Giovannitti and I. McCulloch, Adv. Funct. Mater., 2019, 29, 1807033.
3. M. Moser, L. R. Savagian, A. Savva, M. Matta, J. F. Ponder, T. C. Hidalgo, D. Ohayon, R. Hallani, M. Reisjalali, A. Troisi, A. Wadsworth, J. R. Reynolds, S. Inal and I. McCulloch, Chem. Mater., 2020, 32, 6618.
4. M. Moser, T. C. Hidalgo, J. Surgailis, J. Gladisch, S. Ghosh, R. Sheelamanthula, Q. Thiburce, A. Giovannitti, A. Salleo, N. Gasparini, A. Wadsworth, I. Zozoulenko, M. Berggren, E. Stavrinidou, S. Inal and I. McCulloch, Adv. Mater., 2020, 32, 2002748.
5. M. Moser, A. Savva, K. Thorley, B. D. Paulsen, T. C. Hidalgo, D. Ohayon, H. Chen, A. Giovannitti, A. Marks, N. Gasparini, A. Wadsworth, J. Rivnay, S. Inal and I. McCulloch, Angew. Chem. Int. Ed., 2020, DOI: 10.1002/anie.202014078.
6. S. Inal, G. G. Malliaras and J. Rivnay, Nat. Commun., 2017, 8, 1767.
Available on demand - EL07.09.15
Late News: Flexible Complementary Logic Circuit Featuring Two Identical Organic Electrochemical Transistors
Lorenzo Travaglini1,Adam Micolich1,Claudio Cazorla1,Erica Zeglio2,Antonio Lauto3,Damia Mawad1
University of New South Wales1,KTH Royal Institute of Technology2,Western Sydney University3Show Abstract
Conjugated polymers are commonly used as the electroactive channel in organic electrochemical transistors (OECTs).1 Combination of p-type and n-type materials allow the realization of complementary logic circuits that would drastically impact on the sophistication of organic electronic devices. Improved functionalities can be achieved by building complementary circuits featuring two or more OECTs. To date, this aim is strictly related to the development of organic materials with respectively reliable hole and electron transport.2 Coupling these two types of materials in circuits is challenging because of the requirement to have matching charge transport properties. While p-type OECTs are widely available, n-type OECTs are less common mainly due to poor performances and stability of the active material in aqueous electrolyte.3
In this study, we build a complementary logic circuit using a pair of OECTs featuring only polyaniline (PANI) as the channel material in both transistors.4 PANI is chosen due to its unique behavior exhibiting a peak in current versus gate voltage when used as an active channel in an OECT. The voltage-transfer characteristic demonstrates the ability to switch from 0 to the supply voltage (VDD = ± 0.2 V) within a potential window suitable for physiological media, obtaining excellent performances with gain up to 7. We investigate concurrently the electrochemical and optical properties as the OECT was in operation to better understand the transfer characteristics of PANI. We further demonstrate the engineering of the complementary circuit into a flexible bioelectronic that operates in aqueous electrolyte.4 Our approach of using one material simplifies the synthesis and processing design and eliminates the need of sourcing a material with matching performance.
1. Rivnay, J., Inal, S., Salleo, A., Owens, R. M., et al. Nat. Rev. 3, 17086 (2018).
2. Sun, H., Vagin M., Wang, S., Crispin, X., et al. Adv. Mater. 30, 1–7 (2018).
3. Giovannitti, A., Nielsen, C., Sbircea, DT. et al. Nat. Commun 7, 13066 (2016)
4. Travaglini, L., Micolich, A., Cazorla, C., Zeglio, E., et. al. Adv.Funct. Mater. 2007205 (2020)
Available on demand - EL07.09.16
Late News: Solid-State Organic Electrochemical Transistors (OECTs) with Biomaterials for Electronic and Neuromorphic Applications
Tung Nguyen-Dang1,Kelsey Harrison1,Alana Dixon1,Alexander Lill1,Erin Lewis1,Shantonu Biswas1,Yon Visell1,Thuc-Quyen Nguyen1
University of California, Santa Barbara1Show Abstract
Organic Electrochemical Transistors (OECTs) have emerged as a promising technology for the development of future bioelectronic and wearable devices. Indeed, a wide range of applications of low-operating voltage and low-power consumption OECTs in electronics are demonstrated, including flexible integrated circuits, wearable biosensors and in implantable brain recording devices. High-performance OECTs require high ionic conductivity and consequently, the majority of current work focus on the device physics and the applications of devices with liquid electrolytes. Nevertheless, liquid components in the transistors could severely impede their long-term stability and complicate their miniaturization. Tremendous attention has therefore been drawn to the development of solid-state materials for solid-state OECTs, among which biomaterial electrolytes are attractive candidates, thanks in part to their biocompatibility and environmental friendliness.Thus far, however, biomaterial-based OECTs have not been systematically studied. There still remains uncertainty surrounding the nature of the doping/dedoping process in the working principle of biomaterial-based OECTs, and as a result, there is a lack of strategies to enhance the performance of these transistors for applications. Here, we present a systematic study of biomaterial-based solid-state OECTs in which biogels consisting of gelatin and glycerol, two food-grade materials, are chosen as the model solid electrolyte. Such gels are fundamentally attractive for bioelectronics and wearable applications due to their superior and tunable electrical and mechanical properties. Their highly processability allows for the fabrication of all-solid-state organic transistors in conventional top-gate-bottom contact configuration and in novel printing-oriented floating-gate coplanar-contact configuration. By analysing the temperature dependence of the biogel OECTs and that of the gel electrolytes, we reveal the role of protonic doping/dedoping in the operation of these transistors. We then establish a relation between morphology and protonic-conductivity of the gels, allowing for the fabrication of gel-based OECTs with high performance. To illustrate this unique flexibility in tuning biogel OECT performance, we demonstrate solid-state organic transistors with high ON/OFF ratio and transconductance, possible ms-switching speed, and six-month stability in ambient air. Understanding ion-conduction in biogel OECTs also leads to better control of their state-retention property, enabling their employment as artificial synapses with various synaptic functions, such as frequency-based short-term and long-term plasticity. With advances in stretchable wearable electronic devices and in solid-state neuromorphic devices, we believe that naturally occurring gels, and gelatin-glycerol gels in particular, will play an essential role in the next generation of sustainable, bio-compatible electronics. As such, our study herein paves the way for the development of biomaterial-based electronics by providing guiding principles for future works that employ biomaterials in OECTs.
Available on demand - EL07.09.17
Late News: Tuning Strain Sensor Performance via Programmed Thin-Film Crack Evolution
Juan Zhu1,Xiaodong Wu1,Jasmine Jan1,Ana Arias1
University of California, Berkeley1Show Abstract
Stretchable mechanosensors with specific mechanosensitivity and stretchability are ideal for a wide range of applications, from large deformation monitoring to subtle vibration detection. Currently, it is still a great challenge to fabricate stretchable mechanosensors with highly tunable stretchability and sensitivity with facile fabrication techniques. In this work, multifunctional sensors made from a metal film supported on an elastomer in conjunction with a novel programable cracking technology are reported. The cracking mechanism of the metal film can be effectively regulated by the surface chemistry of the elastomer, which results in finely controlled crack morphologies, allowing for strain sensors with well-defined sensitivity and stretchability. Benefitting from this strategy, our sensors demonstrate distinctive characteristics including unprecedented tunability, high sensitivity (Gauge Factor (GF) > 10000), broad stretchability (up to 100%), fast frequency response (5.2 Hz), and good cyclic stability (over 1000 cycles). Based on their superior performance, the sensors can be used for monitoring both subtle and drastic deformations in real-time. The fabrication process presented here, with one material system and a single approach, demonstrates a facile and efficient method for fabrication and regulation of strain sensors, making it an attractive approach for potential applications in wearable sensors, electronic skin and health monitoring platforms.
Available on demand - EL07.09.18
Late News: Stable and Conductive PEDOT:PSS:MXene Composites for Bioelectronics
Shofarul Wustoni1,Sahika Inal1
King Abdullah University of Science and Technology1Show Abstract
Poly(3,4-ethylenedioxythiophene) (PEDOT) doped with poly(styrene sulfonate) (PSS) is the most commonly used conducting polymer in organic bioelectronics. However, electrochemical capacitances exceeding the current state-of-the-art are required for enhanced transduction and stimulation of biological signals. The long-term stability of conducting polymer films during device operation and storage in aqueous environments remains a challenge for routine applications. In this work, we electrochemically synthesize a PEDOT composite comprising the water dispersible two-dimensional conducting material Ti3C2 MXene. We find that incorporating MXene as a co-dopant along with PSS leads to PEDOT:PSS:MXene films with remarkably high volumetric capacitance and stability, outperforming single dopant-comprising PEDOT films, i.e., PEDOT:PSS and PEDOT:MXene electropolymerized under the same conditions on identical surfaces. Furthermore, we demonstrate the use of a PEDOT:PSS:MXene electrode as an electrochemical sensor for sensitive detection of dopamine (DA). The sensor exhibited an enhanced electrocatalytic activity toward DA in a linear range from 1 µM to 100 μM validated in mixtures containing common interferents such as ascorbic acid and uric acid.1 PEDOT:PSS:MXene composite is easily formed on conductive substrates with various geometries and can serve as a high performance conducting interface for chronic biochemical sensing or stimulation applications.
1 S. Wustoni, A. Saleh, J.K. El-Demellawi, A. Koklu, A. Hama, V. Druet, N. Wehbe, Y. Zhang, S. Inal, MXene improves the stability and electrochemical performance of electropolymerized PEDOT films, APL Materials 8(12) (2020) 121105.
Available on demand - EL07.09.19
Late News: Amplification with Microfluidics Integrated N-Type Organic Electrochemical Transistor Sensor
Anil Koklu1,David Ohayon1,Shofarul Wustoni1,Adel Hama1,Xingxing Chen1,Iain McCulloch1,Sahika Inal1
King Abdullah University Science and Technology1Show Abstract
The organic electrochemical transistor (OECT) can translate biochemical binding events into an electrical signal with particularly high amplification. We herein present a compact and self-sufficient glucose sensor based on an n-type OECT.1 The n-type polymer cast at the channel and on the gate electrode has specific interactions with the enzyme glucose oxidase, allowing for direct detection of glucose rather than hydrogen peroxide. The OECT was integrated with a microfluidic system, enabling higher channel current and transconductance, which, in turn, resulted in higher detection sensitivity, lower detection limit and an enhanced signal to noise ratio (SNR) compared to its microfluidic-free counterpart. Owing to the low noise endowed by the microfluidics, the low magnitude gate current changes (~pA) upon enzymatic reaction could be resolved, revealing that while the relative changes in gate and drain currents are similar, the drain current output has a higher SNR. Our microfluidic-integrated design provides new insights into the mechanisms allowing for high sensor sensitivities, while the combination of redox enzymes and n-type polymers presents a new avenue for the development of portable and autonomous lab-on-a-chip technologies.
1. Koklu, A., Ohayon, D., Wustoni, S., Hama, A., Chen, X., McCulloch, I., & Inal, S. (2020). Microfluidics integrated n-type organic electrochemical transistor for metabolite sensing. Sensors and Actuators B: Chemical, 329, 129251.
Guosong Hong, Stanford University
Sahika Inal, King Abdullah University of Science and Technology
Jonathan Rivnay, Northwestern University
Tzahi Cohen-Karni, Carnegie Mellon University
EL07.01: Neurotechnology I
Wednesday AM, April 21, 2021
8:00 AM - *EL07.03.03
A Look at Nonlinear Optic Polymers in Bioelectronics and Beyond
University of Central Florida1Show Abstract
Bioelectronics, the integration of biology with electronics, encompasses sub-topics such as bioimaging, and transduction or actuation of biochemical or physiochemical signals using wearable or implantable devices. One component that these sub-topics have in common is the generation of large amounts of data, which feeds into Big Data. With Big Data comes emerging areas of AI-ML, data mining, deep learning, and neural networks. While bioelectronic topics and complementary disciplines are receiving significant attention, there is at least one other topic to consider: How to handle the transmission and storage of such large volumes of data? Copper wire is the traditional material to transmit information, but the theoretical speed and volume limits, at which electrons can travel through copper wire, are near capacity and cannot accommodate the projected global data demands. Compelling solutions using fiber optic cables are on the horizon as, compared to copper, they can handle 6000x the bandwidth, are of lower cost, lighter weight, and maintain lower temperatures. A bottleneck, however, for replacing copper with fiber optics cables, on the scale necessary to sustain our data transmission and storage needs, is the limited availability of nonlinear optic (NLO) materials that are necessary for optical modulation – which operate similar to the “on-off” modulation in electronics for coding information using 0s and 1s. Beyond optical modulators, NLOs also find broad application in areas such as: imaging, (bio)sensors, and terahertz spectroscopy. NLO materials are either inorganic such as lithium niobate, or organic such as electro optic polymers, wherein an asymmetric chromophore is combined with a glassy, amorphous polymer. This talk will cover the development and characterization of a new family of easy to synthesize, stable, asymmetric chromophores, and their subsequent use in electro optic polymers for in demand, NLO modulator and sensing applications.
8:25 AM - EL07.01.02
Multi-Dimensional Fuzzy Graphene Bioelectronic Actuators
Raghav Garg1,Daniel San Roman1,Yingqiao Wang1,Tzahi Cohen-Karni1
Carnegie Mellon University1Show Abstract
The ability to manipulate the electrophysiology of electrically active cells and tissues has enabled a deeper understanding of healthy and diseased states. This has primarily been achieved via bioelectronic actuators that interface engineered materials with biological entities. Graphene has gained recent interest as a building-block for bioelectronic actuators due to its advantageous electrochemical properties and biocompatibility. However, functional graphene bioelectronics exhibit a two-dimensional (2D) topology. This leads to inherent performance limitations due to the limited exposed surface-area and poor interactions with interfaced cells and tissues. Ideal geometry of graphene-based actuators needs to leverage the material’s high surface-area-to-volume ratio to facilitate maximum interaction with the electrode.
Here we report a breakthrough three-dimensional (3D) topology of graphene: 3D fuzzy graphene (3DFG), for actuation of electrically active cells and tissues. Using a bottom-up approach, we synthesize an interconnected network of free-standing graphene flakes. The 3D topology leads to enhanced surface-area compared to planar surfaces allowing 3DFG microelectrodes to exhibit lower electrode impedance than planar microelectrodes. 3DFG also exhibits greater cathodic charge storage capacity (CSCC) and charge injection capacity (CIC). We further combine one-dimensional (1D) Si nanowires (NWs) with 3DFG to fabricate a truly 3D topology of graphene: NW-template 3D fuzzy graphene (NT-3DFG). The increased surface-area of NT-3DFG enhances the exhibited CSCC and CIC. This enables miniaturization of graphene-based microelectrodes to ultra-microelectrodes for functional bioelectronics. Our results demonstrate the importance of extending the topology of nanomaterials to 3D to push the physical and functional limits of conventional bioelectronics.
8:40 AM - *EL07.01.03
University of Cambridge1Show Abstract
One of the most important scientific and technological frontiers of our time is the interfacing of electronics with the human brain. This endeavour promises to help understand how the brain works and deliver new tools for diagnosis and treatment of pathologies including epilepsy, Parkinson’s disease, and brain cancer. Current solutions, however, are limited by the materials that are brought in contact with the tissue and transduce signals across the biotic/abiotic interface. Using novel organic materials coupled with thin substrates we make implants that are biocompatible and show exceptional performance in multimodal recordings and stimulation of the brain. I will outline examples of devices that simultaneously monitor the electrical and metabolic activity of the brain, and devices that locally deliver drugs with excellent spatiotemporal control. I will further discuss how the interface with soft robotics can enable devices that change shape and thereby decrease the invasiveness of neurosurgery.
9:05 AM - EL07.01.04
Biological Modulation from Micro-Supercapacitor-Like Mesoporous Carbon Membranes
Aleksander Prominski1,2,Bozhi Tian1,2
The University of Chicago1,University of Chicago2Show Abstract
Electrical stimulation devices find numerous therapeutic applications, such as in the treatment of heart defects, epilepsy, and Parkinson's diseases. It is critical to search for new materials and methods to make these treatments safe and affordable to everyone in need. Design of bioelectronic devices requires materials with mechanical and electrochemical compliance to the cells and tissues to minimize their invasiveness. Recently, carbon nanostructures have been studied as bioelectronics components due to their excellent electrical and mechanical properties and the past success in energy research. Nevertheless, there is still a strong need to advance synthetic methods for the fabrication of cost-effective and safe carbon-based bioelectronics.
In this presentation, I will first discuss the synthesis of hierarchical meso- and macroporous carbon membranes using micelle-assisted self-assembly, as well as the fabrication of binder-free carbon-based microelectrode arrays using SU-8 as flexible support. The material design allows us to optimize its mechanical compliance and to leverage its biocompatible electrochemical properties for efficient biological stimulations. Inspired by micro-supercapacitors used in energy research, we explored the application of a comb-like interdigitated electrode design for in vitro stimulation and training of cells. For example, we applied the confined electric field to cardiomyocyte monolayer and achieved efficient overdrive pacing and subthreshold levels of training in vitro. We also explored the stimulation of retina and heart ex vivo and stimulation of a sciatic nerve in vivo, demonstrating efficient coupling between the carbon nanostructures and excitable tissues. Our results illustrate a promise of applying porous carbon materials for biological modulation and how traditional energy research tools can be adapted to design bioelectronic systems.
9:20 AM - *EL07.01.05
Multiscale Bioelectronics from Liquid-Phase Processing of Nanoscale Carbides
University of Pennsylvania1Show Abstract
Bioelectronic technologies are enabling paradigm-shifting approaches to diagnosing and treating a number of disorders of the central and peripheral nervous systems. While tremendous progress has been made in the last decade, current bioelectronic interfaces are still dramatically inadequate to address the mechanical, chemical, and electrical properties of nervous structures. Nanostructured carbon materials are uniquely positioned to address these challenges, as they combine remarkable electronic and electrochemical properties, with intrinsically high mass-specific surface area and mechanical flexibility. Furthermore, they can be easily integrated within scalable solution-based processing, thus allowing easy modulation of their electronic, mechanical, and optical properties.
In this talk, I will discuss how nanoscale soft conductors can be engineered into high-resolution, minimally invasive bioelectronic interfaces designed to seamlessly map and control the activity of excitable circuits at multiple scales. Specifically, I will introduce novel bioelectronic interfaces based on 2D transition metal carbides (a.k.a. MXenes) for recording and stimulation. I will discuss the fundamental electronic and electrochemical behavior of MXenes as well as present scalableliquid-phase processes to translate the remarkable molecular properties into high-resolution interfaces with customizable scale and coverage. Finally, I will present examples of applications in multiscale mapping and microstimulation of bioelectrical circuits in vivo in different models.
EL07.02: Poster Session I
Wednesday PM, April 21, 2021
11:45 AM - EL07.02.01
Late News: Graphene Based Nanopore Sequencing—An Assessment on the Current State of Next Gen Sequencing
Kiara Gonzalez-Gonzalez1,Samuel Escobar1,Marcel Grau1,Solimar Collazo Hernandez1,Ernesto Espada1,Brad Weiner1,Gerardo Morell1
University of Puerto Rico at Río Piedras1Show Abstract
Using solid-state nanopores to sequence DNA is a promising third generation sequencing method. Graphene is used because it can provide a suitable membrane for sequencing applications. Sequencing DNA with graphene nanopores is a topic of interest for many researches, but how does it work? As the DNA molecule passes through the nanopore, the nanopore will eventually be blocked by the negatively charged DNA molecule. Each nucleotide has presented a distinct current blockage signal as it interacts with the nanopore via the formation of temporary Van der Waals interactions. Therefore, the differentiation of each base is possible since we can observe different sources reporting distinct ionic currents for each nucleotide. It is by this principle that the DNA is sequenced. Here, we present how Graphene Nanopores could be ideal for DNA Sequencing by taking into consideration many factors that may help overcome the challenges that have been found within this method. These factors include: the functionalization - whether it is hydrogen functionalization, hydroxyl functionalization, or nitrogen functionalization - of the graphene, the number of graphene layers needed, the type of nanopore used, type of DNA, among others. All these variables have to be taken into consideration in order to obtain single-base resolution with all the advantages that graphene-nanopore sequencing has to offer.
11:50 AM - EL07.02.02
Bioresorbable Primary Battery Built on Core-Double-Shell Zinc Microparticle Networks
Yutao Dong1,Jun Li1,Xudong Wang1
University of Wisconsin–Madison1Show Abstract
Bioresorbable electronics, which decomposed in the physiological environment after a designed period of stable function and corresponding byproducts are resorbed and vanish, have gained increasing interests in state-of-the-art biomedical implants for pre-diagnosis, monitoring and treatment of diseases, drug delivery which only requires the function for a certain period of time. [1,2] Compared to other transient power supplies, such as piezoelectric nanogenerators, supercapacitors, bioresorbable batteries are promising power source with higher energy density and continuous output which typically are composed of bioresorbable material that degrade into non-toxic contents in physiological environment during and/or after discharge. State-of-the-art bioresorbable batteries are built upon Mg or Zn metal-based galvanic cells due to their good biosafety and electrochemical activity. Due to extreme high chemical activity of Mg, current Mg-based bioresorbable batteries all exhibited fluctuating voltage output and rapid output drops without a controllable lifetime, which cannot meet the requirements of an implantable power supply. Additionally, the fast degradation rate could induce localized releasing of concentrated hydroxyl ions, leading to inflammation or other harmful effects.  Compared to Mg, Zn metal has moderate degradation rate which can circumvent undesirable local pH increase and minimize gaseous hydrogen evolution.  Furthermore, in all bioresorbable metal-based galvanic cell systems, although both anode and cathode are needed, it is the metal anode that dictates overarching electrochemical reaction and most battery characteristics. Nevertheless, almost all current models were built on bulky foils or plates, where their degradation occurred naturally on the metal surface. Therefore, there was no control over the degradation rate, direction and sequence, and thus all showed a poor controllability on the battery output and lifetime, which further limits their practical applications.
In this work, we report a bioresorbable zinc primary battery anode filament built on Zn micro-particles (MPs) coated with chitosan and Al2O3 nano-films. This battery filament exhibited a well-controlled dissolution direction and rate due to the mesoscale MP assembly, and the protective coatings. When discharged in 0.9% NaCl saline, single Zn MP filament with a 0.17 x 2 mm2 cross-section exhibited a stable voltage output of 0.55 V at a current of 0.01 mA, where the current and voltage output could be simply designed by integration of the battery filaments in parallel or in series, respectively. The operational time could be directly adjusted by the length of filament. A stable 200-hour discharging time was achieved by a 15 mm Zn MP filament. By increasing the filament cross-sectional area, higher current output can be achieved at the same discharging voltage, raising the output power. The final discharging byproducts, mostly ZnO/Zn(OH)2, could slowly dissolve in biofluids, making this composite filament completely degradable. This complete bioresorbable primary battery showed a full level of control of output and lifetime, providing a promising solution to in vivo powering transient bioelectronics.
11:55 AM - EL07.02.03
Single-molecule Electrical Detection and Characterization of Biomolecules for New Bioelectronics Applications in Biophysics and Biomedicine
Juan Artes Vivancos1,Keshani Pattiya Arachchillage1,Subrata Chandra1
University of Massachusetts Lowell1Show Abstract
The fundamental understanding of diverse processes in biology requires bridging the gaps between studies at different levels; organisms, tissues, cells, biomolecular complexes, and, ultimately, individual biomolecules. Biophysical characterization studies require new integrated experimental and computational approaches leading to a complete quantitative picture. Single-molecule biophysics has experienced a boom in the last decades. Not only the developments in optical microscopy1 have allowed researchers to study biological details of fundamental processes with a high resolution, but nanoscience tools such as Scanning Probe Microscopies,2 have led to biophysical studies at the single-molecule level. Notably, Scanning Tunneling Microscopy(STM)2 has enabled researchers to perform single-molecule bioelectronic studies, including nucleic acids3-6.
Herein, we introduce examples of the new biomaterials science projects in our lab, where we are integrating these methods for the study of different biological systems. In particular, we recently demonstrated the first single-molecule electrical detection of a biologically-relevant nucleic acid6,7. We are now applying these methods to:
# The study of the biomolecular interactions in the RNA Induced Silencing Complex at the individual complex level and,
# The single-molecule electrical detection of circulating tumor nucleic acids for the study of cancer biomarkers and the early diagnostics through liquid biopsy.
These methods and results could be applied to numerous biological problems, paving the way to a new body of knowledge in biophysics and materials science. On the applied research front, enabling single-molecule electrical detection in biomedical research and diagnostics constitutes a step forward in biosensors; this novel method is potentially simpler, faster, and cheaper than the established methods such as optical detection or PCR-based methods. These measurements are the first single-molecule electrical investigation of sequences from human origin.
1.WE Moerner and M Orrit.Science, 283(5408):1670–1676, 1999.
2.G Binnig, H Rohrer, C Gerber, and E Weibel. Physical review letters, 49(1):57, 1982.
3. JM Artes, Y Li, J Qi, MP Anantram, and J Hihath. Nature communications, 6:8870, 2015.
4.JM Artes, J Hihath, and I Diez-Perez. Biomolecular electronics. In Molecular Electronics: An Experimental and Theoretical Approach,281–323. Pan Stanford, 2015.
5. Y Li, JM Artes, and J Hihath. Small, 12(4):432–437, 2016.
6. Y Li, JM Artes, B Demir, S Gokce, HM Mohammad, M Alangari, MP Anantram, E Oren, and J Hihath. Nature Nanotechnology, 13(12):1167, 2018.
7. J Veselinovic, M Alangari, Y Li, Z Matharu, J M Artés, E Seker, and J Hihath. Electrochimica Acta, 2019.
12:00 PM - EL07.02.04
Understanding Different Biomolecular Interactions by Single-Molecule Electrical Methods
Subrata Chandra1,Keshani Pattiya Arachchillage1,Juan Artes Vivancos1
University of Massachusetts Lowell1Show Abstract
Biomolecular interactions are fundamental for any cellular function in organisms. Understanding the interface between electronic materials and biological interactions with single molecule resolution can create a bridge between the knowledge gaps at different levels in organisms, tissues, cells, and, ultimately in individual molecules. This knowledge could also have a broader impact in elucidating the molecular basis of many diseases.  There is an urgent need for new concepts that appropriately describe the behaviour of biological interactions at the single-molecule level using bioelectronics. Determining the biophysical aspects of these interactions is also essential to understand the fundamental biology at interfaces which can tune the functionality and biocompatibility of next-generation bioelectronic devices.
Biomolecular electronics methods based on scanning probe microscopies can act as a promising alternative tool for measuring these interactions electrically. We use single-molecule electrical methods to study electrical signals at these bioelectronic interfaces using the Scanning tunneling microscope-assisted break junction method (STM-BJ). This technique has enabled the measurement of charge transport properties of biomolecules by reproducible conductance histograms related to the biomolecular structure and conformations. STM-BJ measurements have recently shown the detection of RNA:DNA hybrids from E-coli by measuring their electrical conductance properties at the single-molecule level.  We aim at having a complete understanding of the interactions between different components of the RNA Induced Silencing Complex (RISC) applying these methods. RISC is a multiprotein complex that uses the siRNA or miRNA as a template to recognize complementary mRNA and plays a pivotal role in regulatory mechanisms.  This electrical approach also gives us a good opportunity to understand the signal transduction in RNA induced gene regulatory process.
The first step in our investigation is demonstrating the single molecule electrical detection of dsRNA. Next, we will measure the conductance of a protein (Argonaute) – dsRNA complex. This can give us a better understanding of the formation of the multiprotein complex and allowing the study of the thermodynamics and kinetics of regulation of gene expression at the individual complex level. The future work for this research will be exploring the specificity of these interactions, kinetics of those adducts and measure the thermodynamic quantities of those physical interactions. Lastly, we could use these fundamental results for designing next-generation smart biomaterials and biosensors that may address improved biological performances and advanced health monitoring in the future.
1. Discher, Dennis, et al. "Biomechanics: cell research and applications for the next decade." Annals of biomedical engineering 37.5 (2009): 847.
2. Ryan, Daniel P., and Jacqueline M. Matthews. "Protein–protein interactions in human disease." Current opinion in structural biology 15.4 (2005): 441-446.
3. Artés, Juan Manuel, et al., (2016). Biomolecular Electronics in Molecular Electronics: An Experimental and Theoretical Approach. Bâldea, I. (Ed.). CRC Press.
4. Xu, Bingqian, and Nongjian J. Tao. "Measurement of single-molecule resistance by repeated formation of molecular junctions." science 301.5637 (2003): 1221-1223.
5. Artés, Juan Manuel, et al. "Conformational gating of DNA conductance." Nature communications 6.1 (2015): 1-8.
6. Li, Yuanhui, et al. "Detection and identification of genetic material via single-molecule conductance." Nature nanotechnology 13.12 (2018): 1167-1173.
7. Zhang, Yokota, Werner. Dubitzky, et al., RNA-induced Silencing Complex (RISC), in Encyclopedia of Systems Biology, Editors. 2013, Springer New York: New York, NY. p. 1876-1876.
12:05 PM - EL07.02.05
Inkjet-Printed Stretchable PEDOT:PSS-Based Electrodes and Interconnects for Wearable Health Monitoring Devices
Li-Wei Lo1,Haochuan Wan1,Junyi Zhao1,Chuan Wang1
Washington University in St. Louis1Show Abstract
Stretchable conductor is one of the key components in soft electronics that allows seamless integration of electronic devices and sensors on elastic substrates. Its unique advantages of mechanical flexibility and stretchability has enabled a variety of wearable or bioelectronic devices that can comfortably adapt to curved skin surface for long-term health monitoring applications. Here, we report a PEDOT:PSS-based stretchable material that can be patterned using a simple inkjet printing process while exhibiting low sheet resistance and accommodating mechanical deformations. We have systematically studied the effect various types of polar solvent additives on the electrical performance of the ink. The polar solvent induces the phase separation of the PEDOT and PSS grains and changes the conformation of PEDOT chain which leads to a more conductive film due to the charge hopping along the percolated PEDOT network. The optimal ink formulation is achieved by adding 5wt% of ethylene glycol into pristine PEDOT:PSS aqueous solution which results in a sheet resistance of as low as 58 Ω/sq. Elasticity can also be achieved by blending the above solution with soft polymer poly(ethylene oxide) (PEO). Thin-films of PEDOT:PSS-PEO polymer blends patterned by inkjet printing exhibits low sheet resistance of 84 Ω /sq and can resist up to 50% of tensile strain with minimal changes in electrical performance. With its low sheet resistance and high mechanical stability under deformations, we have further demonstrated the use of the polymer blend as stretchable interconnects on thin PDMS substrate for photoplethysmography (PPG) sensor for heart rate and cardiac output monitoring and stretchable dry electrodes for electrocardiography (ECG) recording applications.
12:10 PM - EL07.02.06
Late News: Characterization by Electric Impedance Sensing of Normal Cell and Cancer Cell Attachment and the Effects of Ginseng
Maddy Behravan3,Alejandra Martinez1,Steffi Kong2
University of Glasgow1,St George's University2,Converse College3Show Abstract
This research introduces an application of an electric impedance sensing technique to investigate cell attachment of normal epithelial cells (HaCAT) and cancerous cells (A431) before and after addition of Ginseng. In this study, an impedance sensing system is used to measure and characterize real-time changes in electric impedance (resistance and capacitance) with respect to an alternating current (AC) applied to HaCAT and A431 cell colonies. The impedance data is related to the properties of cell spreading, attachment, and delamination. The effect of Ginseng at various dosages on these cellular properties was inferred from impedance data. The initial impedance data show that resistance is greater for A431 cells than HaCAT cells and that capacitance for A431 cells is less than the capacitance for HaCAT cells. Further, the data shows the resistance for HaCAT cells and for A431 cells increases with time, and the capacitance for both decreases with time. The impedance data analysis shows that Ginseng does not alter the impedance of HaCAT cellular matrix significantly over a long period. Ginseng results in partial detachment and reattachment of A431 cell-to-cell bonds, thus reordering the cellular matrix. This effect is not seen in HaCAT cell colonies.
12:15 PM - EL07.02.07
Late News: Flexible Intra-Cardiovascular Monitoring Sensor and Electrode Device
Ulises Vidaurri Romero1
University of Texas Rio Grande Valley1Show Abstract
In recent years, triboelectric nanogenerators (TENGs) have been the center of attention for research due to its wide range of applications as microsystem components, energy harvesting devices, and heath monitoring sensors. The flexibility and ability to produce energy of the TENGs are perfect attributes for a health monitoring sensor as well as an alternative to the conventional medical devices. This research focuses on an Intra-Cardiovascular Monitoring Sensor and Electrode Device (ICMSED) that is biocompatible, cost-effecive, and has high response to size ratio than other devices in its category. The framework can be implemented to achieve sensory applications as well as an electrical impulse supplier to the heart like a defibrillator in case of any cardiovascular failure. The fabrication of the device shows the combination of flexible Nitinol, with Poly-Dimethyl Siloaxane (PDMS) and Poly-Vinylidene Flouride (PVDF) polymers. Flexible nitinol wires are dip coated with these functional polymers and intertwined to achieve the framework. Nitinol wires are bi-laterally connected with the polymer coated nitinol sheets, which upon constant contact and separation within the cardiovascular system is capable to yield electrical output. Thus, as synthesized device can provide real-time data of vascular vibrations, vascular pressure, heartbeats per minute, Cardiac arrest, and defibrillation of the heart and vascular system. With its high output-to-size ratio, this Nitinol triboelectric nanogenerator is a promising step to a new chapter in medical advancements and devices.
Cardio vascular system, Pacemaker, Nanogenerator, Triboelectric, Defibrillator, Health monitoring, Nitinol, Electrode, PDMS, PVDF
12:20 PM - EL07.02.08
A Microfluidic Ion Sensor Array
Harika Dechiraju1,Chunxiao Wu1,John Selberg1,Brian Nguyen1,Pattawong Pansodtee1,Manping Jia1,Mircea Teodorescu1,Marco Rolandi1
University of California, Santa Cruz1Show Abstract
A balanced concentration of ions is essential for biological processes to occur. For example, [H+] gradients power adenosine triphosphate synthesis, dynamic changes in [K+] and [Na+] create action potentials in neuronal communication, and [Cl−] contributes to maintaining appropriate cell membrane voltage. Sensing ionic concentration is thus important for monitoring and regulating many biological processes. This work demonstrates an ion-selective micro-electrode array that simultaneously and independently senses [K+], [Na+], and[Cl−] in electrolyte solutions. To obtain ion specif icity, the required ion-selective membranes are patterned using microf luidics. As a proof of concept, the change in ionic concentration is monitored during cell proliferation in a cell culture medium. This microelectrode array can easily be integrated in lab-on-a chip approaches to physiology and biological research and applications.
12:25 PM - EL07.02.09
Late News: Biodegradable Piezoelectric Ultrasonic Transducer for Brain Drug Delivery
Thinh Le1,Thanh Nguyen1
University of Connecticut1Show Abstract
The blood-brain barrier (BBB), comprised of monolayers of endothelial cells, which prevents most therapeutics from accessing the brain tissue, is the major hurdle for treating brain diseases. The ultrasound has been shown to be the most effective tool to disrupt the BBB. However, an external focused ultrasound system is complicated and tedious since it required MRI monitoring and a bulky transducer system, while the current implanted ultrasound transducers rely on non-degradable, toxic materials. Poly-L-lactic acid (PLLA), a biocompatible and biodegradable polymer, has been reported to exhibit piezoelectricity when appropriately processed. This research presents an air-backed unfocused biodegradable piezoelectric ultrasonic transducer made from piezoelectric electrospun nanofibers PLLA that can be implanted on the skulls to temporarily and locally disrupt the BBB for delivering drugs into the brain. The device will safely self-degrade, causing no harm to the body and avoiding invasive brain surgery for removal. We have also shown that the dextran model (3 kDa) can be delivered to the parenchyma of the mice brain by utilizing the ultrasound generated by this device. The improvements of this device can impact various medical fields such as sonodynamic therapy, sonothrombolysis, or ultrasound imaging.
12:30 PM - EL07.02.11
WITHDRAWN 4/16/2021 EL07.02.11 Machine Learning-Driven Bioelectronics for Closed Loop Control of Cells
John Selberg1,Mohammad Jafari1,Manping Jia1,Juanita Mathews2,Pattawong Pansodtee1,Harika Dechiraju1,Chunxiao Wu1,Sergio Cordero1,Sophia Jannetty2,Miranda Diberardinis2,Mircea Teodorescu1,Michael Levin2,Marcella Gomez1,Marco Rolandi1
University of California, Santa Cruz1,Tufts University2Show Abstract
Bioelectronic devices that control the delivery and removal of ions from solution offer a unique pathway for interfacing electronics with biology. Protonic devices that specifically act upon protons are of interest because pH is a critical factor in essentially all biological processes. Bioelectronic devices that interact with regulatory signals such as cell membrane electrical potential are important because this property regulates numerous aspects of cell function and movement of chemicals and charges into and out of cells. Despite its importance for bioengineering and synthetic morphology applications, spatial control of membrane potential in vitro has been difficult to achieve. Here, we demonstrate using a proton pump array device controlled with an adaptive machine learning controller that we can dynamically control membrane potential in human induced pluripotent stem cells contained within a microfluidic channel. Given the importance of membrane potential in cell function, differentiation, and proliferation, this proof-of-concept opens up many possibilities in bioelectronic closed-loop control of cell systems.
12:35 PM - EL07.02.12
Programmable Soft Liquid-Metal Electronics by Micromechanical Valving
Xiangchao Zhu1,Daniel Freitas2,Yixiang Li1,Sierra Catelani1,Ismail Araci2,Ahmet Yanik1
University of California1,Santa Clara University2Show Abstract
The Internet of Things (IoT) is envisioned as a global infrastructure interlinking the physical and cyber worlds through “smart” objects continuously interacting with each other. It is predicted that IoT will connect more than 50 billions of “things” to each other by 2020, and have an economic impact surpassing 36 trillion of dollars by the year 2025. This will require tremendously large numbers of next-generation radio-frequency (RF) devices that can adapt to specific tasks, collect a wide variety of physical information, and exchange data wirelessly through communication networks. Reconfigurability in RF electronics is conventionally achieved by implementation of dynamically controllable components including semiconductor diodes and micro-electromechanical systems. However, these systems have certain limitations: nonlinearities and losses in p-i-n diodes and varactors cause degradation of the RF spectrum and yield low quality-factor responses, while MEMS switches demanding high strength fields suffer from self-actuation. Use of liquid-metals, offering high Q-factor response of a conductor in a versatile reconfigurable form, is an attractive alternative to these conventional approaches that use solid metals. Liquid-metal based reconfigurable methods, however, require large length scale (mm – cm) repositioning of liquid-metals in order to reshape them into a new electrical configuration, rendering long switching times.
Here, we introduce a scalable and electrically reconfigurable electro-microfluidic platform merging injection-based liquid-metal electrodes and micromechanical pneumatic microvalves. Without loss of generality, we demonstrate a PRogrammable INterdigitated Transducer (PRINT), an electro-acoustic RF transducer consisting of a sophisticated arrangement of two interlocking flexible comb-like electrodes conjugated with large arrays of individually addressable micromechanical valves. PRINT possesses precise and dynamically reconfigurable resonance tuning capability and high Q-factor (~ 334) resonance characteristics, both of which are challenging to achieve simultaneously. By directly compressing and modulating the electrical contacts between different liquid-metal microfluidic channel regions via microvalve actuation, we create electrically isolated regions with ultrasmall volumes (75 – 300 picolitres) and realize fast tuning of on-demand electrode configurations in a dynamic, reversible, and reliable way. Our electro-fluidic approach is distinctively different from the conventional methods that rely on emptying and refilling by pressure-driven flow or reshaping of the bulk material through electrowetting, electrocapillarity or electrochemical reactions. Our device architecture and reconfiguration scheme, employing microfluidic large-scale integration (mLSI) techniques, is generic and scalable to thousands of microvalves and hundreds of addressable chambers that are integrated in a single microfluidic chip. Complex reconfigurable device architectures for a number of different applications in the fields of RF electronics and electromagnetics could be created using on-chip multiplexers.
12:40 PM - EL07.02.13
Late News: A Novel Green Bilayer Dielectric for High Performance Organic Thin-Film Transistors
Mathieu Tousignant1,Nicole Rice1,Jukka Niskanen1,Chloé Richard1,Benoit Lessard1
University of Ottawa1Show Abstract
Smart packaging is an emerging multi billion-dollar industry that relies on integrated flexible and inexpensive sensors to provide critical information such as temperature, pH, and time to aid with quality assurance. However, for these sensors to be incorporated into a wide variety of packaging they need to be flexible, biodegradable, and low cost.1
These issues can be addressed using organic electronics, where carbon-based materials are used as the active layer within electronic devices. For example, organic thin film transistors (OTFTs) are commonly used in sensing applications. One of the active layers within an OTFT is the dielectric. The dielectric facilitates charge accumulation at the interface between the dielectric and the organic semiconductor when a source-gate voltage is applied. Ideally, we want a dielectric material with a high dielectric constant (high-k) and low leakage current. Unfortunately, most polymer dielectrics that meet these requirements are not environmentally friendly.
However, poly(vinyl alcohol) (PVA) meets these requirements. It is a biodegradable, water soluble, high-k dielectric polymer. While, it does have some drawbacks such as poor film forming, sensitivity to moisture and large leakage currents; we found that the addition of low weight percentages of cellulose nanocrystals improved the film forming capabilities by increasing the viscosity of the solutions.2 Building upon these findings, a thin layer of polycaprolactone (PCL) was deposited on top of our PVA dielectric to reduce the moisture sensitivity and leakage currents of PVA. PCL is a hydrophobic, low-K, biodegradable polymer with good insulating properties. The PCL layer was functionalized with toluene diisocyanate (TDI), which can be thermally cross-linked to the hydroxyl groups of PVA at the TDI-PCL/PVA interface. Bilayer crosslinking increased the thin film stability and facilitated orthogonal processing of the semiconducting layer. The fabricated PVA/PCL metal-insulator-metal capacitors were found to be highly stable, even after being exposed to 95% relative humidity, unlike pure PVA based devices. Finally, the TDI-PCL dielectric was used in the fabrication of single walled carbon nanotube top gate bottom contact OTFTs. When compared against native PVA, the TDI-PCL/PVA dielectric showed similar mobilities of ~1 cm2/Vs, a reduced average hysteresis of 0.2 V compared to 2.85 V for PVA, a negative threshold voltage shift and greater on/off ratios with a lower device variation. When compared against silicon dioxide the TDI-PCL/PVA dielectric had a six-fold decrease in operating voltage for both the output and transfer curves. These results demonstrate a novel method for using green dielectrics in high performing OTFTs while mitigating challenges associated with thin film processing and moisture sensitivity.
1 Chen, S. et al. J. Food Sci. 85, 517–525 (2020)
2 Tousignant, M. N. et al. Langmuir 36, (2020)
12:45 PM - EL07.02.14
Late News: On Processing Sputtered Iridum Oxide Films (SIROF) for Neural Interfaces
Tiffany Huang1,Jens Duru2,Zhijie Chen1,Ludwig Galambos1,Theodore Kamins1,Daniel Palanker1
Stanford University1,ETH Zürich2Show Abstract
Porous sputtered iridium oxide films (SIROF) are relied upon for a variety of applications, including pH sensors and neural stimulation and recording electrodes. For neural applications, their ability to store and inject a high amount of charge is particularly important. This capability depends on the state of the material itself and access to its porous microstructure, which can be affected by a number of processes during fabrication. Of notable interest is the effect of heat treatment. Several processing steps require the use of heat, such as high temperature lithography (i.e., the SU-8 prebake typically performed at 150-250°C) or annealing of etch-related defects (i.e., a forming-gas anneal performed at 425°C). The currently available studies in this area are limited and relegated to effects of short anneals done by differential thermal analysis or temperature during deposition of SIROF. Additionally, the usage of aluminum as a sacrificial layer for electrical contacts would necessitate aluminum etchants used on SIROF, and the effect of such etchants has not been evaluated in the literature. Finally, ensuring that photoresist deposition on top of SIROF has no adverse effect and can be easily removed would give full confidence to depositing resist on SIROF for its protection during the device fabrication and release.
Here, we report on SIROF charge storage capacity (CSC) as a function of temperature and demonstrate only minimal effect of heating up to 300°C. We also show that two common etchants for aluminum, MF-26A (2.3% tetramethylammonium hydroxide (TMAH)) and Aluminum Etch 80:3:15 NP (60-80% phosphoric acid, 5-15% acetic acid, and 1-5% nitric acid), significantly decreased SIROF capacitance and should thus be avoided in its processing. Additionally, we show that resist (20 μm spray-coated of a mixture of 7.5% SPR 220-7, 68% MEK, and 24.5% PGMEA) significantly decreases the SIROF capacitance, likely due to contamination of its pores, and thus affects performance in neural stimulation applications. We demonstrate that its capacitance can be restored by cleaning with N-methyl-pyrrolidine based solution Remover 1165 (5 min soak at 80°C followed by a 2 hr soak in NaClO). These results provide information about proper processing of SIROF for preservation of its charge injection capabilities for neural interfacing devices.
12:50 PM - EL07.02.15
Bioelectronic Control of Chloride Ions and Concentration with Ag/AgCl Contacts
Manping Jia1,Harika Dechiraju1,John Selberg1,Marco Rolandi1
University of California, Santa Cruz1Show Abstract
Translation between ionic currents and measurable electronic signals is essential for the integration of natural systems and artificial bioelectronic devices. Chloride ions (Cl−) play a pivotal role in bioelectricity, and they are involved in several brain pathologies, including epilepsy and disorders of the autistic spectra, as well as cancer and birth defects. As such, controlling [Cl−] in solution can actively influence biochemical processes and can be used in bioelectronic therapies. Here, we demonstrate a bioelectronic device that uses Ag/AgCl contacts to control [Cl−] in solution by electronic means. We do so by exploiting the potential dependence of the reversible reaction, Ag + Cl− ↔ AgCl + e−, at the contact/solution interface, which is at the basis of the well-known Ag/AgCl reference electrode. In short, a negative potential on the Ag/AgCl contact transfers Cl− from the contact to the solution with increasing [Cl−] and vice versa. With this strategy, we demonstrate precise spatiotemporal control of [Cl−] in solution that can be used to affect physiological processes that are dependent on [Cl−]. As proof-of-concept, we use [Cl−] control to influence the membrane voltage on human pluripotent stem cells.
EL07.03: Neurotechnology II
Wednesday PM, April 21, 2021
2:15 PM - *EL07.03.01
Ultraflexible Electrodes for Brain Disorders
Rice University1Show Abstract
Brain functions and dysfunctions involve complex interactions between neural, vascular and other cellular activities in a dynamic and spatially resolved manner. This vast complexity demands the ability to simultaneously detect multifaceted brain activities at sufficient spatiotemporal resolutions and to longitudinally track their evolution over a long period of time. In this talk, I will discuss our efforts to meet these needs. These efforts include: 1) the development of ultra-flexible intracortical electrodes (the NanoElectronic Threads -- NETs) to prolong the recording longevity of spiking activities; 2) massively scaling up the recording channel number, density and coverage over brain regions; 3) integrating functional optical imaging techniques with long-lasting electrical recordings to resolve and track hemodynamic and neural activities longitudinally in ischemic brains, and 4) further extension of the spatiotemporal coverage by the co-implantation of NETs into deeper brain structures and a near-cortex-wide cranial window. These neurotechnology advances enables new opportunities for detecting, understanding, and potentially treating a broad spectrum of neurological and neurodegenerative disorders.
2:40 PM - EL07.03.02
Late News: New Frontiers for Wireless, Battery-Free and Fully Implantable Neuromodulation Tools— Transcranial Optogenetic Stimulation and Multimodal Operation in Freely Flying Animals
University of Arizona1Show Abstract
Wireless, battery-free and fully implantable tools for the interrogation of the central and peripheral nervous system have quantitatively expanded the capabilities to study mechanistic and circuit level behavior in freely moving subjects. The light weight and small footprint of such devices enables full subdermal implantation that results in the capability to perform studies with minimal impact on subject behavior and yields broad application in a range of experimental paradigms.
Yet, current limitations in wireless power delivery require invasive modes of stimulus delivery that penetrate the skull and disrupt the blood brain barrier, causing tissue displacement, neuronal damage, and scarring. Power delivery constraints also sharply curtail arena volume, limiting operation to mostly rodent subjects in well controlled arena sizes. Here, we implement digitally managed, highly miniaturized, capacitive power storage to wireless and subdermal implants. This approach enables power delivery to optoelectronic components to enable two classes of new applications: transcranial optogenetic activation up to 5 mm deep into the brain without the need to penetrate the blood brain barrier and substantially increased arena volumes for rodents with a quadrupling of experimental arenas for wireless optogenetics to over 1 m2 in size. By combining this technique with deep neural net enabled behavior guided primary antenna design we report multimodal optogenetic stimulation and physiological recording in freely flying songbirds for the first time and demonstrate optogenetic manipulation of song renditions, highlighting the capability to expand neuromodulation to a variety of animal model species.
2:55 PM - *EL07.01.01
Wireless, Closed-Loop Photostimulation of the Nervous System Enabled by Miniaturized and Compliant Optoelectronic Implants
Stephanie Lacour1,Frederic Michoud1,Claudia Kathe1,Corey Seehus2,Philipp Schoenle3,Qiuting Huang3,Clifford Woolf2,Gregoire Courtine1
EPFL1,Harvard Medical School2,ETHZ3Show Abstract
In the past decade, multiple approaches for optical stimulation of neurons have been proposed, mainly focused on the brain. Optogenetic activation of axons in the spinal cord or the peripheral nerves has specific challenges related to their anatomy, softness, opacity and demanding mechanics. We propose a wireless and implantable neurotechnology that offers safe and long-term photostimulation of any targeted neurons and pathways in untethered and unrestricted mice. The implantable system consists of (1) a conformable array of high efficiency micro-scale light emitting diodes, (2) elastic thin-film interconnects that dampen effects of local motion and join the LEDs via (3) a subcutaneous cable and (4) an ultraminiaturized, battery powered, head-mounted, wireless recording and stimulation platform. The platform is operated via a handheld tablet that displays a real-time preview of the acquired physiological signals, the timing of the photostimulation, and a feedback on the accurate delivery of the configured current.
The talk will review the design and manufacturing of the implantable system, highlighting critical steps to engineer compliant optoelectronic interfaces, safe and spatially-selective photostimulation in freely behaving animals. The versatility and robustness of the system will be demonstrated in the context of pain fibers modulation in the peripheral nerves and closed-loop control of spinal cord wherein the onset of a burst of muscle activity instantly triggers photostimulation.
3:20 PM - *EL07.03.03
Magnetic Materials for Miniature Wireless Bioelectronics
Rice University1Show Abstract
Electrical stimulation of neural circuits is a key tool for studying brain function and developing new therapies for neurological disorders. Traditionally, these electrical stimulators include an implanted pattern generator (IPG) that includes a battery and a tether connecting the device to the stimulating leads. These components are one of the most common failure points of the system and comprise the vast majority of the implant volume. To create miniature neural implants without lead wires or large IPGs recent work as turned to wireless data and power delivery to miniaturize neural stimulators. The challenge for these devices, however, is the fact that the body absorbs electromagnetic radiation often used to power miniature devices making it difficult to deliver sufficient power within operational safety limits. Here, we describe how magnetoelectric (ME) materials offer an efficient method to power millimeter-sized neural implants, achieving power levels of several mW well within the safety limits for human operation.
3:45 PM - *EL07.03.04
Modulating Neurophysiology with Multifunctional Fibers
Massachusetts Institute of Technology1Show Abstract
Integration of multiple disparate materials within flexible fibers has permitted simultaneous probing and modulation of multiple neurophysiological processes in behaving subjects. In this talk, I will highlight the recent materials and fabrication advances that extend applications of multimaterial fibers to long-term studies of brain dynamics, delivery and probing of neurochemicals, and modulation of neural circuits connecting the brain and the peripheral nervous system. For instance, I will show applications of hydrogels as a means of tuning the modulus of the fibers as well as a tool for drug delivery. Convergence drawing will be introduced as a means to expand the array of materials compatible with fiber fabrication. Finally, I will discuss the introduction of solid-state devices into fibers, and demonstrate their applications for wireless control of behavior and physiology.
EL07.04: Materials for Bioelectronics
Wednesday PM, April 21, 2021
5:15 PM - *EL07.04.01
Bioelectronic Modulation with Soft-Hard Composites
Bozhi Tian1,Aleksander Prominski1
The University of Chicago1Show Abstract
Biointerface devices can probe fundamental biological dynamics and improve the lives of human beings. However, the direct application of traditional rigid electronics onto soft tissues or cells can cause signal transduction and biocompatibility issues, due to mechanical mismatch at the biointerfaces. One common mitigation strategy is the use of nanostructures or soft-hard composites to form more biocompatible interfaces with target cells or tissues. My group integrates nanoscience and soft matter physics with biophysics to study several semiconductor- or conductor-based biointerfaces. In this talk, I will first pinpoint domains where semiconductor properties can be leveraged for biointerface studies. Next, I will present a few recent studies from our lab and highlight key bioelectrical mechanisms underlying the non-genetic optical or electrochemical modulation interfaces. The non-genetic and soft-hard composite-based methods have the potential to overcome the limitations of current metal electrode-based devices such as bulk and cell membrane disruption, and are not dependent on genetic modifications. Finally, I will discuss new tissue-like materials and other biological targets that could catalyze future advances.
5:40 PM - EL07.04.02
Exceptionally Tough and Self-Healing Polymer Blend for Electronic Skin
Sung Hwa Hong1
University of Toronto1Show Abstract
Electronic skin is an emerging platform with multifunctionalities such as pressure, strain, temperature and humidity sensors while being soft, self-healable, flexible and stretchable. Such multifunctional materials are suitable for soft robotics, wearable devices and prosthetics. However, low toughness and manufacturability hinders the translation of the technology into practical applications.
Toughness is influenced by chemical structure of polymers and crosslinker. For instance, thermoplastic polyurethane (TPU) is a commercially available polymer that has suitable mechanical properties for smart skin applications. However, most of TPUs have high elastic modulus and does not exhibit self-healability. There have been some attempts to endow self-healability, but the rate of healing typically took more than weeks for recovery. Recently, a TPU was labelled with covalently crosslinkable disulfide group and tuned with varying hard segments. This TPU with loosely packed hard segment facilitated the healing by thiol-disulfide exchange reaction. However, its Young’s modulus above 5 MPa limits the application for smart skin.
Herein, we report TPU blended with a synthesized self-healing polymer for highly tough and self-healable material. The self-healing polymer with a low Young’s modulus is synthesized by using industrially friendly free radical polymerization involving methacrylic acid that enables crosslinking through metal-ligand interaction. This type of bond can be broken and re-formed easily, thus promotes self-healing. Subsequently, this polymer was blended with PU and electrospinning process was used to induce the film formation. Dynamic mechanical analyzer results revelated that the resulting film exhibits a toughness of 70 MJ/m3 and heals from macro-damages within 5 hrs. The film was further coated with polypyrrole endowing electrical conductivity. The material has been examined as a piezoresistive sensor and supercapacitor as to show its versatility for electronic skin application.
5:55 PM - *EL07.04.03
Green Bioelectronic Interfaces Made from Protein Nanowires
University of Massachusetts Amherst1Show Abstract
Biosystems are made from biomaterials (e.g., protein), whereas conventional electronic systems or interfaces are made from non-biological materials. This leads to some inherent gap in terms of material compatibility in interfacing electronics with biosystems. We explore the possibility of making active electronic devices from protein nanowires harvested from microbe Geobacter sulfurreducens for 'green' bioelectronic systems/interfaces. We show how we can utilize the unique properties in the protein nanowires to realize energy devices, sensors, and computing devices, the three key basic elements for integrated electronic interfaces/systems. Specifically, we show 1) energy devices made from the protein nanowires can continuously harvest electric energy from ambient humidity to provide sustainable energy solution to microsystems; 2) neuromorphic devices (e.g., memristors) made from protein nanowires can achieve biological-amplitude functions for ultralow-power computation; and 3) protein nanowires can serve as the active sensing element in constructing electronic biosensors. The perspective of integrated systems/interfaces based on these elements will also be discussed.
6:20 PM - EL07.04.04
Late News: Energetic Control of Redox-Active Polymers Towards Safe Organic Bioelectronic Materials
Stanford University1Show Abstract
In my presentation, I will explain the common electrochemical side reactions between redox-active conjugated polymers and aqueous electrolytes in ambient conditions. We find that electron-rich polymers such as PEDOT:PSS or pg2T-TT can undergo electron transfer reactions with molecular oxygen (oxygen reduction reaction), forming hydrogen peroxide (H2O2) as a side product. H2O2 itself is an oxidant that can cause harm to biological environments and devices and can also impact the device performance such as increasing the OFF currents of organic electrochemical transistors (OECTs). The origin for the side reaction is an electron transfer from the electron-rich conjugated polymers to molecular oxygen dissolved in the electrolyte where the ionization potential (IP) of the redox-active polymer determines if the reaction occurs spontaneously. By designing and synthesizing redox-active polymers with large ionization potentials (IP > 4.9 eV), we show that the side reaction can be avoided during the operation of electrochemical devices in ambient conditions. When tested in the OECT, the materials achieve low OFF currents (nAs), high ON/OFF ratios of >105, and excellent redox-stability during continuous operation. This study elucidates the interaction of redox-active conjugated polymers and molecular oxygen which has previously been overlooked with potentially critical issues for operating electrochemical devices in oxygen-containing aqueous electrolytes (biological environments).
 A. Giovannitti, D.-T. Sbircea, S. Inal, C. B. Nielsen, E. Bandiello, D. A. Hanifi, M. Sessolo, G. G. Malliaras, I. McCulloch, J. Rivnay, Proc. Natl. Acad. Sci. 2016, 113, 12017.
 A. Giovannitti, R. B. Rashid, Q. Thiburce, B. D. Paulsen, C. Cendra, K. Thorley, D. Moia, J. T. Mefford, D. Hanifi, D. Weiyuan, M. Moser, A. Salleo, J. Nelson, I. McCulloch, J. Rivnay, Adv. Mater. 2020, 32, 1908047.
6:35 PM - *EL07.04.05
Controlling the Properties of Organic Mixed Ionic-Electronic Conductors Using Living Radical Polymerization
University of Delaware1Show Abstract
Organic mixed ionic-electronic conductors (OMIECs) are materials capable of bridging the gap between biological entities (‘soft’ and ionically conductive) and electronic devices (‘hard’ and electronically conductive). They have therefore been used extensively in biosensors, organic electrochemical devices (OECTs), and wearable and implantable electronics. Among these OMIECs, the polyelectrolyte complex poly(3,4-ethylene dioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) is the most commonly used for bioelectronic interfaces owing to its high conductivity, water and air stability, biocompatibility, and commercial availability. While the latter makes it easy to adopt and incorporate in devices, it limits our ability to modify the structure of PEDOT:PSS to achieve specific properties and performance. A possible solution to tune the properties of PEDOT:PSS is to use additives (plasticizers, polymers, crosslinkers, surfactant…). While effective at achieving the desired performance, additives often lead to other, sometimes undesirable, effects; making it difficult to predict and/or rationalize structure-property relationships. To address this issue, the Kayser laboratory specializes in modifying the PSS component to understand and intrinsically tailor the mixed ionic-electronic conduction, degradability, mechanical properties, and dynamic behavior of PEDOT:PSS derivatives. We use living radical polymerization techniques (e.g., reversible addition-fragmentation chain transfer polymerization, RAFT) to synthesize PSS with a control over the molecular weight and dispersity. For example, we found that we can precisely increase the conductivity of PEDOT:PSS, compared to its commercial form, without using external additives by synthesizing PSS with low molecular weight and dispersity (Mn = 48 kDa, PDI = 1.2). We are currently studying how these changes in the structure of PSS affect the transconductance of PEDOT:PSS in OECT devices. Another important factor for the integration of PEDOT:PSS in bioelectronics, besides conductivity, is its mechanical properties and compliance. In its commercial form, PEDOT:PSS is relatively ‘hard’ (Young’s modulus ~ MPa) and poorly stretchable (< 5%) which limits its use in wearable and implantable devices.1 We have developed a method to obtain intrinsically stretchable samples by preparing block copolymers of PSS with poly(ethylene glycol methyl ether acrylate) (PEGMEA).2 We are now exploring a similar copolymer strategy to obtain conductive materials with dynamic mechanical properties (i.e., stimuli-responsive PEDOT:PSS). A combination of published data and preliminary results will be presented that highlight our ability to control the intrinsic properties of PEDOT:PSS for applications in bioelectronics and human-machine interfaces.
1 Kayser and Lipomi Adv. Mater. 2019, 31, 1806133.
2 Kayser et al. Chem. Mater. 2018, 30, 4459.
Guosong Hong, Stanford University
Sahika Inal, King Abdullah University of Science and Technology
Jonathan Rivnay, Northwestern University
Tzahi Cohen-Karni, Carnegie Mellon University
EL07.05: Poster Session II
Thursday AM, April 22, 2021
8:05 AM - EL07.05.02
EMIm-OTf Ionogel Coated Fibres—Characterisation and Development, Aiming at Ionic Smart Textiles
Claude Huniade1,Shayan Mehraeen2,Edwin Jager2,Tariq Bashir1,Nils-Krister Persson1
The Swedish School of Textiles - University of Borås1,Linköping University2Show Abstract
Ions are prevalent within bioelectronics, as they are the main charge carriers in living systems. In contrast to electronic systems, ionic ones are closer to what can be found in our body; in muscles, neurons and nerves.
Textiles are a much used biomedical material, both in vivo and in vitro due to its membrane character, high efficient area, softness, biocompatibility and biodegradability. Modifying the physicochemical properties of the core or the surface of textile has been reported a countless amount of times, but still, its use in a bioelectrical context is limited.
Fibres are the building blocks of textiles and what make textiles an architected class of material. Then ionically conductive fibres are of great interest.
Here, we show the preparation of iono-conductive textile fibres through the (semi-)continuous dip-coating of ionogel on the cellulose-based viscose.
Ionogels are composed of salts in liquid state and a 3-dimensional solid network, in our case an ionic liquid (IL), 1-Ethyl-3-methylimidazolium trifluoromethanesulfonate, commonly named EMIm OTf or EMIm Triflate, and a thiol acrylate network, allowing the mobility of the ions within or in/out of the gel. This specific combination is a first effort towards the development of ionic textile fibres and ionic smart textiles, as a variety of ILs with different cations and anions exists, potentially allowing a large amount of different combinations.
We investigate how the coating of this ionogel affects the mechanical properties as well as the conductivity in AC or DC arrangement and their relation to temperature and humidity. Also, the thermal stability and sensitivity of degradation of the fibre system is studied.
Moreover, we introduce different textile structures, and potential applications directed to bioelectronics.
8:10 AM - EL07.05.03
Proton-Activated Synaptic Plasticity of Synaptic Transistors Based on Peptide
Min-Kyu Song1,Seok Daniel Namgung2,Daehwan Choi1,Hyeohn Kim2,Hongmin Seo2,Misong Ju2,Yoon Ho Lee2,Taehoon Sung1,Yoon-Sik Lee2,Ki Tae Nam2,Jang-Yeon Kwon1
Yonsei University1,Seoul National University2Show Abstract
With the recent advances on artificial intelligence, the need for advanced computing processors has been enormously growing to eliminate von Neumann bottleneck in conventional computing processors. To overcome this barrier, novel devices inspired by human brain have been newly proposed. Human brain processes neural signals with 1011 neurons and 1014 synapses which are connected in parallel while it consumes only 20 W which is extremely low compared to the super computers including IBM’s Pohoiki Springs which consumes up to 500 W to emulate elementary brain tasks. To mimic the energy efficiency of biology, researchers in the area of nanoelectronics have proposed various neuromorphic devices. Among them, synaptic transistors have been regarded as the essential component for spiking neural network that emulates synaptic plasticity that pre-synaptic spikes induce timing-dependent post-synaptic responses.
In this work, we demonstrate the novel synaptic transistors that can be turned on and off by controlling humidity. Tyrosine-rich peptide was utilized for proton control layer (PCL) that proton conducting property is exponentially regulated by controlling humidity. IGZO and Au were used as a semiconducting layer and electrode, respectively. Electrical characteristics were measured as a function of relative humidity (RH). Long range gating effect was observed only in highly humid condition while no gating effect was observed in ambient condition. Capacitance-voltage (C-V) characteristics and impedance analysis indicate that the threshold effect of the electrostatic coupling is due to electric double layer (EDL) of protons in the peptide film. On the basis of this phenomenon, we demonstrate the synaptic functions of the device at high humidity including paired pulse facilitation (PPF), spike-number dependent plasticity (SNDP) and transition from short-term plasticity (STP) to long-term plasticity (LTP). This result demonstrates not only the expansion of the controllability of synaptic function that proton is another control, but also the emulation of proton activation in acid sensing ion channel in biological synapse.
8:15 AM - EL07.05.04
Late News: Current-Driven Organic Electrochemical Transistor for the Assessment of Biological Barriers
Katharina Lieberth1,Maximilian Brückner1,Fabrizio Torricelli2,Volker Mailänder1,3,Paschalis Gkoupidenis1,Paul Blom1
Max-Planck-Institute1,University of Brescia2,University Hospital JGU Mainz3Show Abstract
To use the organic electrochemical transistor (OECT) as a biosensor is of great importance, as it is a state-of-the-art technique in the field of drug delivery. Allowing ion-to-electron conversion and having a high amplification of gating due to volumetric capacitance, enables the OECT to operate with aqueous electrolytes at low voltages. When using the OECT as an inverter in a current-driven configuration, a constant current is applied at the channel by an external power supply. It was found that the OECT offers an enhanced sensitivity compared to standard transfer characteristics of an OECT. The impact of measurement scan rate on the inverter characteristics was also studied. Even small changes in the ionic current can be detected, which is required to study tight junction modulation. Tight junction barriers of epithelial cell layers impede the transcellular pathway of nutrients and drugs from organs into the blood.[5,6] Hence, monitoring the effect of external stimuli such as poly-L-lysine (PLL) on tight junction modulations is crucial for drug delivery. As a well-established model for oral drug delivery, the epithelial colon carcinoma (Caco-2) cell line, found in the small intestine, was used to evaluate reversible modulation of tight junctions over time, under the effect PLL. Investigating PLL-concentration and TJ-modulation time dependence resumed that the exposure to a medium concentration of PLL initiates reversible modulation, whereas a too high concentration induces an irreversible barrier disruption. To support electrical measurements occluding-staining has been performed using immunofluorescence imaging. The results demonstrate the suitability of OECTs to in-situ monitor temporal barrier modulation and recovery, which can offer valuable information for drug delivery applications.
 N. Y. Shim, D. A. Bernards, D. J. Macaya, J. A. DeFranco, M. Nikolou, R. M. Owens, G. G. Malliaras, Sensors 2009, 9896.
 J. Rivnay, P. Leleux, M. Sessolo, D. Khodagholy, T. Hervé, M. Fiocchi, G. G. Malliaras, Adv. Mater. 2013, 25, 7010.
 M. Ghittorelli, L. Lingstedt, P. Romele, N. I. Crâciun, Z.M. Kovács-Vajna, P.W.M. Blom, F. Torricelli, Nat. Commun. 2018, 1441;
 L. V. Lingstedt, M. Ghittorelli, M. Brückner, J. Reinholz, N. I. Crâciun, F. Torricelli, V. Mailänder, P. Gkoupidenis, P. W. M. Blom, Adv. Healthcare Mater. 2019, 8, e1900128.
 M. Ramuz, A. Hama, M. Huerta, J. Rivnay, P. Leleux, R. M. Owens, Adv. Mater. 2014, 7083.
 L. H. Jimison, S. A. Tria, D. Khodagholy, Gurfinkel M., E. Lanzarini, A. Hama, G. G. Malliaras, R. M. Owens, Adv. Mater. 2012, 5919.
 G.T.A. McEwan, M. A. Jepson, B. H. Hirst, N. L. Simmons, Biochem. et Biophys.Acta 1993, 1148, 51.
 M. S. Balda, K. Matter, Seminars in cell & developmental biology 2000, 11, 281.
 K. Lieberth, M. Brückner, F. Torricelli, V. Mailänder, P. Gkoupidenis, P.W.M. Blom, Adv. Mater. Tech. 2021 (accepted)
8:20 AM - EL07.05.05
Novel Metal-Organic Frameworks with Enhanced Sensitivity and Accuracy for the Electrochemical Sensing for Anti-HCV Agent
Mahmoud Saleh1,Mona A. Mohammed1,Nageh Allam1
The American University in Cairo1Show Abstract
Herein, we report the electrochemical voltammetric determination of anti-Hepatitis C Virus (HCV) agent with a novel Metal-Organic Framework (MOF) material that shows a higher and enhanced response in addition to its simple preparation in comparison to the previous studies. The MOF/ CPE platform has shown to enhance the electrochemical oxidation and detection of the anti-HCV agent in comparison to the bare Carbon Paste Electrode (CPE). The synthesized MOF has been characterized using Fourier transform infrared spectroscopy, X-ray powder diffraction, UV-visible absorption spectroscopy, scanning electron microscopy, high-resolution transmission electron microscopy, Raman spectroscopy, cyclic voltammetry, square wave voltammetry, and electrochemical impedance spectroscopy. Under the optimized conditions, the MOF/ CPE platform has showed a linear response for the anti-HCV drugs’ concentrations in Britton Robinson Buffer (BRB) solution, urine and plasma with high recoveries and lower Limit of Detection (LOD) and Limit of Quantification (LOQ) in comparison to the current literature.
8:25 AM - EL07.05.06
Semiconducting Bacterial Biofilm Based on Graphene-MoS2 Template and Component Dependent Gating Behavior
Sanhita Ray1,Arpita Das2,Anjan Dasgupta1
University of California1,University of Calcutta2Show Abstract
In this paper, we report for the first time, the synthesis of a semiconducting biofilm. Photosynthetic bacterial biofilm has been used to weave together MoS2 nanosheets into an adherent film grown on interdigitated electrodes. Liquid-phase exfoliation of bulk MoS2 powder was used to obtain MoS2 nanosheets. A synchronous-fluorescence scan revealed the presence of two emission maxima at 682nm and 715nm for the MoS2 suspension. Such maxima with bandgap energy 1.82 and 1.73 eV corresponding to the single and double layer of MoS2. The presence of such single and multi-layered structures was confirmed by Raman spectroscopy, FTIR studies, and electron microscopy. The current-voltage (I-V) studies of such a bio-nano hybrid revealed the emergence of the gated nature of the current flow. This Schottky diode like behavior, reported earlier for Graphene-biofilm junctions, is also observed in this case. Gating voltage depended on the composition of the biofilm. The semiconductor biofilms, when studied using electrochemical impedance spectroscopy, revealed characteristic Nyquist and Bode plots, suggesting special circuit-equivalence for each film. A semiconductor-living material hybrid points towards usefulness as a sensor base.
8:30 AM - EL07.05.07
Late News: Study of Bio-Modified Gold Electrode for Forefront Point-of-Care Sensors
Lucia Sarcina1,Eleonora Macchia2,Luisa Torsi1,2
Università degli Studi di Bari Aldo Moro1,Åbo Akademi University2Show Abstract
In the last decade, there has been a growing demand for rapid, cost-effective point-of-care (POC) platforms for early detection of clinically relevant biomarkers. This need gave rise to the implementation of novel bioelectronic systems, capable of interfacing biological samples with smart electronic devices. Thus, the robustness of transistor technology has been applied to the functional sensing of clinically relevant species, through the Electrolyte-gated Organic Field Effect Transistors (EGOFET) technology. Here a huge transducing surface is settled on the gate electrode by conjugating specific bio-elements, for the recognition of relevant analytes, such as protein, DNA strands or enzyme substrates. The subsequent interaction between the sensing pairs cause a variation on the electrode work-function, which is traduced in a sensor output modification, even at low analyte concentrations. This technology has been already employed for the label-free detection at the physical limit of different antigens such as the HIV-p24 protein. The sensor selectivity could be guaranteed by the proper functionalization of the sensing electrode. Thus, gold surfaces bio-modification has been deeply studied to investigate best configurations for the anchoring of specific antibodies, for the recognition of the target proteins, by means of a real-time Surface Plasmon Reference (SPR) assay. Through the well-known method of self-assembly of alkylthiols on gold, densely packed layer of 1011-1012 antibodies/cm2 are covalently bound to the electrode and subsequently exposed to HIV-1 p24. Moreover, for testing the selectivity of the functionalized surface, the SPR response to a non-binding analyte, namely human C-reactive protein, was further investigated. In this perspective, the same method has been applied to the study of more complex systems as the detection of relevant bacteria. Both the SPR platform and EGOFET apparatus have been characterized, to assess functionalization procedures and electronic sensing evidences, competitive with current POC assays.
 C. Dincer, R. Bruch, A. Kling, P. S. Dittrich, G. A. Urban, Trends Biotechnol. 2017, 35, 728.
 E. Macchia, R. A. Picca, K. Manoli, C. Di Franco, D. Blasi, L. Sarcina, N. Ditaranto, N. Cioffi, R. Österbacka, G. Scamarcio, F. Torricelli, L. Torsi, Mater. Horizons 2020, 7, 999.
 L. Sarcina, L. Torsi, R. A. Picca, K. Manoli, E. Macchia, Sensors (Switzerland) 2020, 20, 1.
 E. Macchia, L. Sarcina, R. A. Picca, K. Manoli, C. Di Franco, G. Scamarcio, L. Torsi, Anal. Bioanal. Chem. 2020, 412, 811.
8:35 AM - EL07.05.08
Late News: Floating Gate Organic Electrochemical Transistors
Erica Zeglio1,Shirin Khaliliazar1,Mahiar Hamedi1,Anna Herland1,2
KTH Royal Institute of Technology1,Karolinska Institutet2Show Abstract
Organic electrochemical transistors (OECTs) are electronic devices having conjugated polymers in conducting or semiconducting form as core components. In a typical OECT configuration, the channel is made by a drain and source metal contacts connected by a conjugated polymer film, which is then separated from a gate electrode by an electrolyte. The mixed electronic/ionic conductivity of conjugated polymers allows for low operating voltages, high amplification, and adaptability to various form factors, making OECTs appealing devices for bioelectronics, including biosensors and electrophysiological sensors.
For such sensing applications, it would be beneficial to explore configurations where the channel is physically separated from the target fluid containing the analyte or biological system of interest. Floating gates were introduced in electrolyte-gated transistors to provide such physical separation between the amplification and sensing compartments (though maintaining electronic connection). This configuration offers two main advantages: 1) the conjugated polymer and electrolyte can be chosen only based on device performance to maximize amplification, and 2) the sensing area can be built to optimize sensing in contact with biological fluids, such as electrolyte composition and electrode functionalization strategy (e.g. using simple thiol functionalization chemistry).
Here, we present an OECT with a floating gate configuration. We explore the effect of floating gate parameters (e.g. geometry and composition) on OECT operating and sensing performance. Our data suggest that the floating gate geometry is a promising strategy to maximize amplification while minimizing the volume of electrolyte required at the sensing area – something important for biological applications where the volume of the analyte is limited (e.g. DNA sensing).
 E. Zeglio, O. Inganäs, Adv. Mater. 2018, 30, 1.
 L. Bai, C. G. Elósegui, W. Li, P. Yu, J. Fei, L. Mao, Front. Chem. 2019, 7, 313.
 S. P. White, K. D. Dorfman, C. D. Frisbie, J. Phys. Chem. C 2016, 120, 108.
 S. P. White, K. D. Dorfman, C. D. Frisbie, Anal. Chem. 2015, 87, 1861.
8:40 AM - EL07.05.09
In-Operando Kinetic of PEDOT:PSS Electrochemical Doping
Gonzague Rebetez1,Olivier Bardagot1,Julien Réhault1,Natalie Banerji1
University of Bern1Show Abstract
Organic Electrochemical Transistors (OECTs) are sensitive sensors used in increasingly challenging biologic applications such as wearable textiles with integrated biosensors and in vivo recording of brain activity.1,2 They can be described as an ionic circuit embedded with an electronic circuit. The former arises from ions penetrating the organic channel upon gate bias, while the latter arises form source-drain electron flow across the organic channel.3 Even if our knowledge on OECT behavior and their performance has increased drastically during the last years, a complete picture of these two circuits and how they interact is still missing. Here, we innovatively combine two spectroscopic techniques to study the ionic and electronic transport processes in OECTs:
1) Time-resolved in-operando UV-vis-NIR absorption spectroscopy unravels the kinetics of the ionic circuit. This measurement monitors the ion penetration into the organic channel and the subsequent electrochemical doping processes with millisecond temporal resolution. Thanks to our multivariance curve resolution analysis,4 we extracted the neutral, polaron and bipolaron dynamics, providing insights to the limiting steps of the dedoping/redoping processes.
2) In-operando THz steady-state absorption spectroscopy investigates the electronic circuit. This measurement probes the nature and the nanoscale conductivity of the charges inside the organic channel.5 Connected to the doping level, the nanoscale conductivity grants further understanding about the nature of the interaction between the ionic and electronic circuit.
Results on PEDOT:PSS, the current state-of-the-art material in OECT applications, will be presented.
1. Gualandi I., Marzocchi M., Achilli A. et al. Textile Organic Electrochemical Transistors as a Platform for Wearable Biosensors. Sci Rep 6, 33637 (2016).
2. Khodagholy D., Doublet T., Quilichini P. et al. In vivo recording of brain activity using organic transistors. Nat Commun 4, 1575 (2013).
3. Rivnay J., Inal S., Salleo A. et al. Organic electrochemical transistors. Nat Rev Mater 3, 17086, (2018)
4. De Juan A., Jaumot J., Tauler R. Multivariate Curve Resolution (MCR). Solving the mixture analysis problem. Anal. Methodes 6, 4964-4976 (2014)
5. Unuma T., Yamada N., Nakamura A. et al. Direct observation of carrier delocalization in highly conducting polyaniline. Appl Phys Lett 103, 053303 (2013)
8:45 AM - EL07.05.10
Late News: Biocompatible and Biodegradable Solid-State Electrolyte for Organic Transistors
Young Jin Jo1,Tae-il Kim1
Sungkyunkwan University1Show Abstract
Organic electronics are essential components of bio-integrated due to their flexibility and stretchability. There are various issues related to mechanical properties similar to those of skin, tissues and organs, reliability of electrical characteristics under deformations, biocompatibility, biodegradability and low-voltage operation. electrolyte-gated transistors (EGTs) are candidates for decrease of operating voltage using electrolyte as dielectrics in organic transistors. Electrolytes reduce the voltage of organic transistors by high capacitance from the electrical double layers. However most of electrolytes are liquid state that requires harsh passivation layer for stable working in the biological environment. Also, synthetic ion gel based on ionic liquid and polymers has not been proved as being biocompatible and biodegradable. Here, we suggest a novel concept of solid-state electrolytes based on biocompatible levan polysaccharide for organic transistor. We also used choline based biocompatible and biodegradable ionic liquid by coupling acidic components found in nature. The electrolyte is flexible and highly transparent, also can be served as both dielectric and substrate for organic transistors. Therefore, we fabricated organic transistor on free-standing electrolyte films directly and we also utilized the electrolyte based organic transistors for measuring bio-signals on the skin or heart due to their flexibility, biocompatibility and biodegradability.
8:50 AM - EL07.05.11
Late News: Catalytic Properties of Electropolymerized Poly(3,4–ethylenedioxythiophene) Films in Biological Media
Prem Nayak1,David Ohayon1,Shofarul Wustoni1,Sahika Inal1
Various electrocatalytic and photocatalytic devices, promising for use as power supplies of bioelectronic devices, rely on oxygen reduction reaction (ORR). Poly(3,4–ethylenedioxythiophene), PEDOT, is an efficient ORR catalyst with hydrogen peroxide (H2O2) being the major product. Although H2O2 is an excellent green fuel for batteries and fuel cells, and an industrial oxidant, it is toxic for living systems when PEDOT films are used in bioelectronic devices. In this work, we investigated the ORR behavior and H2O2 production of a series of electropolymerized PEDOT films. By varying the counterion (monomeric vs. polymeric), including a hydroxyl terminated EDOT monomer in the polymer architecture, or adding a conductivity enhancer in the reaction mixture, we aimed to understand the synthetic parameters that govern the ORR properties. We found that the pristine doping level of the polymer – influenced by counterion type and the presence of the conductivity enhancer – controls the ORR pathway in PEDOT films. High levels of intrinsic doping leads to films with H2O2 as the ORR product. Using this information, we synthesized a new PEDOT derivative for which H2O is the major ORR product. This systematic work will aid designing conducting polymers and choosing operational parameters that (i) maximize film performance in catalytic applications, and (ii) minimize the production of harmful chemicals in bioelectronic devices.
8:55 AM - EL07.05.12
Late News: A Microfluidic and Nanoporous Membrane Integrated Organic Electrochemical Transistor for amyloid-β detection
Anil Koklu1,Shofarul Wustoni1,Valentina Musteata1,David Ohayon1,Maximilian Moser2,Iain McCulloch2,1,Suzana Nunes1,Sahika Inal1
King Abdullah University Science and Technology1,University of Oxford2Show Abstract
Alzheimer's disease (AD) is a neurodegenerative disorder associated with a severe loss in thinking, learning, and memory functions of the brain. A common pathological indicator found in AD-affected brains is the aggregates of a protein named amyloid-β (Aβ). In this work, we developed an organic electrochemical transistor (OECT) integrated with a microfluidic platform and a nanoporous membrane for the label-free detection of Aβ aggregates in human serum. The nanoporous membrane is functionalized with Congo red (CR) showing a strong affinity for Aβ aggregates. The detection relies on the modulation of the electric field between the gate and the channel as the aggregates are captured by the membrane. Integration of the OECT with the microfluidics enables minute amounts of fluids to be processed and reduces the sample incubation time. Novel p-type and n-type semiconductors used at the OECT channel improve the sensitivity, decrease the detection limit, and lower the power requirements, ranking these sensors’ performance beyond the state-of-the-art Aβ sensors. The high transconductance of the OECT, the precise porosity of the membrane, and the compactness endowed by the microfluidic enables protein detection as low as fM concentrations and over eight orders of magnitude wide concentration range in only 1 µL of human serum.
EL07.06: Biosensors and In Vitro Platforms
Thursday PM, April 22, 2021
10:30 AM - *EL07.06.01
In Vitro Biomimetic Electronic Platforms
Istituto Italiano di Tecnologia1Show Abstract
The interface between biological cells and non-biological materials has profound influences on cellular activities, chronic tissue responses, and ultimately the success of medical implants and bioelectronic devices. The optimal coupling between cells, i.e. neurons, and materials is mainly based on surface interaction, electrical communication and sensing.
In the last years, many efforts have been devoted to the engineering of materials to recapitulate both the environment (i.e. dimensionality, curvature, dynamicity) and the functionalities (i.e. long and short term plasticity) of the neuronal tissue to ensure a better integration of the bioelectronic platform and cells.
On the one hand, here we explore how the transition from planar to pseudo-3D nanopatterned inorganic and organic materials have introduced a new strategy of integrating bioelectronic platforms with biological cells under static and dynamic conditions. Although a spontaneous penetration does not occur, adhesion processes are such that a very intimate contact can be achieved. On the other hand, we investigate how organic semiconductors can be exploited for recapitulating electrical neuronal functions such as long term and short term potentiation. In this way, both the topology and the material functionalities can be exploited for achieving in vitro biohybrid platforms for neuronal network interfacing.
10:55 AM - EL07.06.02
About the Amplification Factors in Organic Bioelectronic Sensors
Eleonora Macchia1,Luisa Torsi1
Università degli Studi di Bari Aldo Moro1Show Abstract
Several three-terminal organic bioelectronic structures have been proposed so far to address the needs for a variety of biosensing applications. The most popular ones utilized organic field-effect transistors operated in an electrolyte, to detect both proteins and genomic analytes. They are endowed with selectivity by immobilizing a layer of bio-recognition elements. These features along with the foreseen low-cost for their production, make them very appealing for point-of-care biomedical applications. However, organic bioelectronic transistors do not always exhibit a performance level beyond state-of-the-art electrochemical sensors, which have been dominating the field for decades. This review offers a perspective view based on a systematic comparison between the potentiometric and amperometric electrochemical sensors and their organic bioelectronic transistor counterparts. The key-relevant aspects of the sensing mechanisms are reviewed for both, and when the mathematical analytical expression is actually available, the amplification factors are reported as the ratio between the response of a rationally designed transistor (or amplifying circuit) and that of a homologous electrochemical sensor. The functional dependence of the bioelectronic sensor responses on the concentration of the species to be detected enabling their correct analytical quantification, is also addressed.
11:10 AM - EL07.06.03
Unraveling Enzyme/Conjugated Polymer Interactions for High Performance Metabolite Sensors
David Ohayon1,Sahika Inal1
King Abdullah University of Science and Technology1Show Abstract
The tight regulation of metabolite metabolism in the body is crucial for balanced physiological function and any irregularities in metabolite uptake or consumption underlie various diseases. In our previous work, we demonstrated the development of a third-generation metabolite sensor, i.e., a microscale electrochemical device comprising an n-type conjugated polymer at the channel and as the gate electrode coating, which detects lactate or glucose without the need of an electron mediator.1-2 Here, we adopt a more fundamental approach to understand how the molecular structure of the n-type polymer enables the adsorption of the enzyme glucose oxidase on its surface. We investigate the interactions of the enzyme with six different n-type polymers which have the same backbone but different side chains. We find that depending on the polymer surface properties, governed by the nature of the side-chains, the enzyme changes its conformation and footprint, which in turn determines the sensor sensitivity. Our work provides new guidelines for the structure-performance relationships of electronic materials with enzymes, crucial for the development of enzymatic metabolite biosensors and biofuel cells.
1. Ohayon, D.; Nikiforidis, G.; Savva, A.; Giugni, A.; Wustoni, S.; Palanisamy, T.; Chen, X.; Maria, I. P.; Di Fabrizio, E.; Costa, P. M. F. J.; McCulloch, I.; Inal, S., Biofuel powered glucose detection in bodily fluids with an n-type conjugated polymer. Nature Materials 2019.
2. Pappa, A. M.; Ohayon, D.; Giovannitti, A.; Maria, I. P.; Savva, A.; Uguz, I.; Rivnay, J.; McCulloch, I.; Owens, R. M.; Inal, S., Direct metabolite detection with an n-type accumulation mode organic electrochemical transistor. Sci. Adv. 2018, 4 (6).
11:25 AM - EL07.06.04
Conjugated Molecularly Imprinted Polymers for Biological Sensing
Christina Kousseff1,Shofarul Wustoni2,Fani Taifakou1,Sahika Inal2,Christian Nielsen1
Queen Mary University of London1,King Abdullah University of Science and Technology2Show Abstract
The structure-based tuneability of the electronic and optical properties of conjugated polymers have enabled their application across a range of fields, including energy harvesting, photovoltaics, and medical imaging. However, in the context of biological sensing, the use of conjugated polymers has thus far incorporated little specificity in terms of covalent modification.
Developing robust, highly selective, biologically compatible sensing platforms is of critical importance because the measurement of analyte concentrations in biological samples is crucial for the management or detection of many diseases. For example, fluctuations above or below the optimal range of sodium ion concentration in many bodily fluids can impact blood pressure, nerve and muscle function, while glucose concentration in the blood must be monitored constantly in diabetes. Currently, commercial glucose sensors and many proposed alternatives rely on enzymes, which are expensive and subject to temperature and pH sensitivity, instability, and leaching over time. Meanwhile, other devices are based on complex composite designs featuring separate components to impart conductivity, analyte binding, or selective response. Synthetic strategy with conjugated polymers, especially using the technique of molecular imprinting, enables the efficient combination of analyte specificity, biological interfacing and electroactive or optical functionality into a single multipurpose material. In addition, these entirely organic systems offer affordability, stability, biocompatibility, and simple design and fabrication.
However, due to the well-known difficulties associated with the covalent modification of one of the most effective polymers for this application, poly(3,4-ethylenedioxythiophene) (PEDOT), one of the main challenges in this area thus far has been the attainment of specificity at a molecular level. I will present my work on the concept, design and synthesis of novel molecularly imprinted, electroactive polymers for biological sensing. This includes the creation of a sodium-chelating electrochromic polymer, and a cross-linked glucose-binding electroactive material, both based on covalently modified PEDOT. I will discuss the selectivity and sensing behaviour of these materials in response to the respective analytes, their properties when incorporated into transistor devices, and how this highly adaptable approach can be applied to create a range of materials for many applications across the field of biological sensing.
11:40 AM - EL07.06.05
Ultra High Density Optical Nanoelectrode Arrays: Multi Million-Plex Electrophysiological Measurements with Subcellular Resolution
Ahsan Habib1,Xiangchao Zhu1,Uryan Can2,Maverick McLanahan1,Pinar Zorlutuna2,Ahmet Yanik1
University of California1,University of Notre Dame2Show Abstract
Since the first measurement of the nerve impulse by Hermann von Helmholtz in 1849, understanding how a network of neurons works has been one of the biggest scientific, engineering, and medical challenges . The challenge remains unsolved in the realm of electrical technology, which has limited spatial resolution mainly due to the need for on-chip signal conditioning elements and tighter upper limits for the low noise transfer of spiking cell information by a multiplexed wire . Here, we turn optics since light offers unprecedented spatiotemporal resolution and information-carrying capabilities . Achieving electrophysiological recordings through optical means, on the other hand, largely depends on our ability to recruit reliable electro-optic translators converting electrophysiological signals into photons. After decades of research, state-of-the-art translators cannot provide the high signal-to-noise ratio requirements because of the low photon counts (e.g., voltage sensitive dyes) or low electric-field sensitivities (e.g., quantum dots). We recently invented a novel electro-optic probe by merging nanoionics, plasmonics, and electrochromism that we term "electro-plasmonic field probe" for the transduction of electrophysiological signals into high photon count optical signals . Using the electro-plasmonic nanoprobe, we demonstrated a large scattering intensity change of ~7 % for low field values of 8 × 10-2 mV/nm consistent with the extracellular electric field. Our field probe compares favorably with the quantum dots that provide a ~11% change in photoluminescence signals for an applied field of 10 mV/nm. This field sensitivity is nearly two orders of magnitude lower than that of the electro-plasmonic nanoprobe. Moreover, our electrochromically loaded plasmonic nanoelectrodes have 10-100 million times larger cross sections than those of the widely-adopted genetically incorporated fluorescence molecules and therefore provide an extremely large signal-to-shot-noise ratio (~60-200) with a single loaded nanoelectrode compared to a low signal-to-shot-noise ratio (< 10) that millions of genetically incorporated fluorescence molecules could achieve. In our experiments, we realize extracellular label-free optical detection of electrophysiological activity with high signal-to-noise ratios at three orders of magnitude low light intensity conditions compared to genetically incorporated fluorescence molecules and demonstrate sub-millisecond temporal response time measurements (< 0.2 ms). Our novel approach presents a quantum technological leap for label-free optical imaging of electric-field dynamics with high spatiotemporal resolution.
 Alivisatos AP, et al. The Brain Activity Map. Science 339, 1284 (2013).
 Tsai D, Sawyer D, Bradd A, Yuste R, Shepard KL. A very large-scale microelectrode array for cellular-resolution electrophysiology. Nature Communications 8, 1802 (2017).
 Scanziani M, Hausser M. Electrophysiology in the age of light. Nature 461, 930 (2009).
 Habib A, Zhu X, Can UI, McLanahan ML, Zorlutuna P, Yanik AA. Electro-plasmonic nanoantenna: A nonfluorescent optical probe for ultrasensitive label-free detection of electrophysiological signals. Science Advances 5, eaav9786 (2019).
11:55 AM - *EL07.06.06
Micro-Invasive Interfaces for Interstitial Fluid Sampling in the Brain and Beyond
Massachusetts Institute of Technology1Show Abstract
Introduction: Biochemical dysregulation underlies many pathologies. Diagnosis and treatment of biochemical dysregulation involves monitoring biomarkers in bodily fluids. While methods for sampling bodily fluids such as blood are well-established, there is a need for robust micro-invasive methods for sampling the interstitial fluid (ISF) between cells, especially in delicate tissues such as the brain. The current state-of-the-art in neural ISF sampling, microdialysis, enables the collection of small, highly concentrated neurochemicals from ISF via diffusion across a semipermeable membrane. Large probe sizes (> 150 μm) limit spatial resolution, which leads to tissue scarring and limits chronic recording. Membranes also limit measuring neuropeptides and proteins, which are prone to nonspecific absorption and are present at very low concentrations in ISF, and preclude measuring dense core extracellular vesicles (EVs), which play critical roles in cell-cell signaling. There is thus a critical need for a micro-invasive interface that is membrane-free and enables sampling small ISF volumes from the brain. Such a platform can be readily adapted to other tissues in vivo, and also enables precise spatial and longitudinal tracking of biomarkers in tissue engineered constructs. We anticipate this tool will enable a deeper understanding of the onset, mechanism, and progression of diverse pathologies.
Methods: We have designed and built a micro-invasive membrane-free platform that enables direct sampling of ISF from tissues in vivo and engineered tissues in vitro. The platform is composed of flexible hollow borosilicate probes (80 μm outer diameter, 50 μm inner diameter) coupled to a custom-made nanofluidic peristaltic pump (nanopump). Peristaltic flow within the nanopump is driven by the sequential contraction of nickel titanium alloy wires around flexible tubing (1 mm outer diameter, 100 μm inner diameter). The contraction of the wires is controlled via electrical currents that heat the material and trigger a phase transition. This simple two-component design enables bidirectional flow within a single lumen with nanoliter precision (3 nL stroke volume) and negligent dead volume (< 30 nL), capabilities not demonstrated by other low-flow pumps. Sampled fluid is analyzed via liquid chromatography-tandem mass spectrometry (LC-MS/MS) with processing protocols optimized for proteomics.
Results & Discussion: We have shown that our micro-invasive probes can be inserted into tissues in vivo and engineered tissues in vitro with minimal scarring. In fact, when the probes are chronically implanted in rodent brains, they demonstrate negligible gliosis and retain fluidic functionality for a year post-implantation. Performing nanopump-driven in vivo ISF sampling from the substantia nigra in three rats revealed this method was robust and repeatable. Of the 136 peptides identified, 77 overlapped with another biological replicate, while 28 were detected in all replicates. These included several biomarkers of interest such as brain acid soluble protein-1, myelin basic protein, gamma enolase, transthyretin, and kinesin-like protein 15. Ongoing studies will enable chronic tracking of covariant neuropeptides and EVs in physiological and pathological states. We have also shown that deploying this ISF sampling platform in vitro in engineered tissues of the central and peripheral nervous system enables spatially focused tracking of biomarkers in a high-throughput manner.
Conclusions: We have developed a novel tool for investigating the biochemical basis of diverse pathologies, with proof-of-concept demonstrations in one of the most challenging in vivo environments, the brain, as well as in diverse engineered tissues in vitro. Our ISF sampling platform has the potential to generate new fundamental knowledge and enable more accurate diagnosis and treatment of disorders caused by biochemical dysregulation.
EL07.07: Flexible Bioelectronics
Thursday PM, April 22, 2021
1:00 PM - EL07.07.01
Evaluation of Partially Cracked Organic/Inorganic Multilayer Barrier Coatings for Compliant Bioelectronic Interfaces
Kyungjin Kim1,Matthias Van Gompel2,Kangling Wu1,Florian Bourgeois2,Yves Leterrier1,Stephanie Lacour1
École Polytechnique Fédérale de Lausanne1,Comelec SA2Show Abstract
A critical challenge to overcome to deploy miniaturized and compliant implantable bioelectronic interfaces in vivo is the design, synthesis, and validation of barrier coatings that combine hermeticity, biocompatibility, and microfabrication in agreement with physiological and therapeutic timescales.
Thin-film barriers prepared with vacuum deposition methods, e.g. atomic layer and chemical vapor deposition (ALD and CVD), are a promising strategy for conformal and hermetic coatings. Although ALD offers ultrathin metal oxides at low deposition temperature and low WVTR (< 10-4 g.m-2.d-1), the presence of pinholes and defects hinder further improvement. Thus, to be suitable for in vivo conditions, organic-inorganic multilayers are investigated to offer a low water vapor transmission rate (WVTR < 10-6 g.m-2.d-1) by separating such defects in the inorganic layers with the organic layer. Parylene C is an excellent candidate among engineered polymer films because of its low permeability and useful combination of dielectric properties and conformability. Besides, a wide range of medical implants already uses Parylene coatings. We, therefore, focused on a process enabling growth of the alternating stack of Parylene C and ALD Al2O3 / TiO2 multilayers within a single deposition chamber. Then, we assessed the chemical transport properties of these barrier films in parallel with their mechanical reliability and structural durability during flexural deformation.
The multilayer stack was deposited in a novel hybrid deposition equipment from Comelec SA, allowing for alternating deposition of Parylene then Al2O3 / TiO2 films within a single batch process chamber and at low process temperature. Pristine samples were first characterized by a thin-film corrosion test, leakage current monitoring across interdigitated electrodes, and lifetime tests of coated optoelectronic devices under accelerated aging conditions. Then, we studied and observed channel cracks formed within the organic/inorganic multilayer structure using an in-situ optical microscopy tensile test and scanning electron microscopy with combined modeling. We calculated the fracture energies of the multilayers and applied these parameters to predict their failure mode. A cross-sectional area of a multilayer film strained to crack onset strain was ion-polished, and imaging confirmed the proposed channel crack configuration. Finally, we assessed the lifetime of structures coated with cracked multilayers, which surprisingly displayed an extended lifetime equivalent to 3 years.
In summary, we have developed a multimodal characterization protocol to assess thin-film hermetic coating. Organic-inorganic multilayers are proposed as a potential solution for thin-film hermetic coating for in-vivo applications.
1:15 PM - *EL07.07.02
Interfacing Skin-Inspired Electronics with Biological Systems
Stanford University1Show Abstract
Skin is the body’s largest organ, and is responsible for the transduction of a vast amount of information. This conformable, stretchable, self-healable and biodegradable material simultaneously collects signals from external stimuli that translate into information such as pressure, pain, and temperature. The development of electronic materials, inspired by the complexity of this organ is a tremendous, unrealized materials challenge. However, the advent of organic-based electronic materials may offer a potential solution to this longstanding problem. Over the past decade, we have developed materials design concepts to add skin-like functions to organic electronic materials without compromising their electronic properties. These new materials and new devices enabled arrange of new applications in medical devices, robotics and wearable electronics. In this talk, I will discuss several projects related to engineering conductive materials and developing fabrication methods to allow electronics with effective electrical interfaces with biological systems, through tuning their electrical as well as mechanical properties. The end result is a soft electrical interface that has both low interfacial impedance as well as match mechanical properties with biological tissue. Several new concepts, such as “morphing electronics” and “genetically targeted chemical assembly - GTCA” will be presented.
1:40 PM - EL07.07.03
Multifunctional Artificial Artery from Direct 3D Printing with Built-in Ferroelectricity and Tissue-Matching Modulus for Real-Time Sensing and Occlusion Monitoring
Jun Li1,Xudong Wang1
University of Wisconsin-Madison1Show Abstract
Treating vascular grafts failure often requires complex surgery procedures and associates with a high mortality rate. Real-time monitoring vascular system could enable quick and reliable identification of complications and initiate safer treatments in the early stage. In this work, electric field-assisted 3D printing technology was developed to fabricate in situ-poled ferroelectric artificial arteries that offered battery-free real-time blood pressure sensing and occlusion monitoring capability. The complex functional artery architecture was made possible by the development of a printable ferroelectric bio-composite which could be quickly polarized during printing and reshaped into devised objects. Synergistic effect from the ferroelectric potassium sodium niobate (KNN) particles and the ferroelectric polyvinylidene fluoride (PVDF) polymer matrix yielded a superb piezoelectric performance (bulk-scale d33 > 12 pC N-1, confirmed by piezometer) on a par with that of commercial ferroelectric polymers. The sinusoidal architecture brought the mechanical modulus down to the same level of human blood vessels. The desired piezoelectric and mechanical properties of the 3D-printed artificial artery provided an excellent sensitivity to pressure change (0.306 mV/mmHg, R2> 0.99) within the range of human blood pressure (11.25 to 225.00 mmHg). The high pressure sensitivity and the ability to detect subtle vessel motion pattern change enabled early detection of partial occlusion (e.g., thrombosis), allowing for preventing grafts failure. This work demonstrated a promising strategy of incorporating multi-functionality to artificial biological systems for smart healthcare systems.
1:55 PM - EL07.07.04
Flexible Lab-on-Skin for Sensitive and Non-Invasive Monitoring of Circulating Metabolites and Nutrients
Yiran Yang1,Wei Gao1
California Institute of Technology1Show Abstract
Circulating nutrients and metabolites offer rich information of human health, and their levels in biofluids have been used for diagnosis, prognosis and monitoring of therapeutic outcomes. Abnormal concentrations of circulating metabolites and nutrients, in particular, are associated with health conditions such as metabolic syndrome and cardiovascular disease. Wearable sensors have attracted research attention for various biomedical applications, and sweat analysis could enable continuous and non-invasive molecular monitoring of circulating metabolites and nutrients. However, existing wearable sweat sensing platforms are primarily focused on limited electrolytes and metabolites monitored via ion selective or enzymatic electrodes. In addition, they either lack multimodal sensing functionality or require expensive micro/nanofabrication process. Here we report a mass-producible, all-laser-engraved flexible lab-on-skin platform that enables highly sensitive sweat analysis and multiplexed vital sign monitoring. Using a commercially available CO2 laser engraver, we create a mass-producible lab-on-skin platform consisting of a multimodal laser-engraved graphene (LEG) sensor and laser-engraved microfluidics. The mass-producible sensing layer consists of chemical graphene sensors and physical graphene sensors all engraved by laser with optimized parameters on a single sheet of polyimide. With the use of differential pulse voltammetry (DPV), concentrations of trace-level electroactive molecules (i.e. uric acid (UA) and tyrosine (Tyr)) could be measured according to the redox peak amplitude. The LEG-based physical sensors are designed with optimized geometric patterns and laser parameters for temperature sensing and piezoresistive strain sensing (i.e. respiration rate and heart rate). The laser-engraved microfluidics consist of layers of medical adhesives engraved with channels, reservoir and inlets. Validation of the chemical sensor accuracy was performed using high performance liquid chromatography (HPLC) and validation of the vital sign sensors was performed with commercial vital sign sensors. The patch was further assembled and tested on human subjects including trained athletes, gout patients, and healthy individuals. Meanwhile, participants’ serum was collected. With a purine-rich intake study, sweat and serum UA levels were compared before and after the purine intake. Results The LEG chemical sensors yielded superior electrochemical sensing performance compared to commercial sensors. Unlike commonly used commercial sensors, LEG electrodes could directly detect UA and Tyr in human sweat and saliva via DPV. The LEG vital sign sensors could accurately detect human temperature, respiration rate and heart rate, with great long-term stability. The laser-engraved microfluidics enabled efficient sweat sampling and enhanced temporal resolution for chemical sensing. The lab-on-skin patch provided accurate, stable and sensitive continuous reading while tested on body, as validated with HPLC and commercial vital sign sensors. In the trial with both trained and untrained individuals, Tyr levels were lower in trained athletes than in untrained subjects. In our pilot study involving gouty and healthy individuals, the sweat and serum UA levels were elevated in gouty individuals, and the intake of purinerich food increased both sweat and serum UA levels. Our all laser-engraved flexible lab-on-skin patch provides a mass-producible means for wearable multimodal sensing of sweat metabolites and vital signs. The promising results from the pilot study show the great potential of using sweat UA as a non-invasive gout management biomarker and using the lab-on-skin patch for continuous metabolic monitoring.
2:10 PM - *EL07.07.05
Laser-Engraved Graphene-Based Wearable and mHealth Biosensors
California Institute of Technology1Show Abstract
Wearable sensors have the potential to provide rapid, non-invasive, and in-home health monitoring by real-time analyzing biomarkers in human sweat and saliva. However, most current biosensors suffer from low sensing accuracy for low-level analyte detection in biofluids and are difficult to fabricate on a large scale. In this talk, I will review our latest advances in developing fully-integrated laser-engraved graphene-based biosensors which can selectively and accurately measure a wide spectrum of sweat and saliva biomarkers including metabolites, nutrients, hormones, and proteins. The clinical value of these telemedicine platforms is evaluated through multiple human studies involving both healthy and patient populations toward metabolic monitoring and stress assessment. I will also introduce our recent work on a multiplexed wireless platform for the rapid COVID-19 test which could provide information on infection status, severity, and immunity. We envision that these telemedicine devices could open the door to a wide range of personalized healthcare applications.
2:35 PM - *EL07.07.06
High-Sensitivity and Wide-Range Capacitive Pressure Sensors Enabled by the Hybrid Responses of a Porous Nanocomposite
The University of Texas at Austin1Show Abstract
Soft pressure sensors with high sensitivity over a wide pressure range are required for various applications such as electronic skins for human-mimetic robotics and electronic tattoos for pulse pressure measurement. In the last decade, most research aiming at increasing the sensitivity of capacitive pressure sensors focused on developing dielectric materials with added air gaps and/or higher dielectric constants. After extensive research, sensitivity has been significantly improved at low pressure range, e.g. 1 kPa, but drops drastically as the pressure increases. To overcome this challenge, we present a novel soft capacitive pressure sensor employing an electrically conductive porous nanocomposite with both piezoresistive and piezocapacitive responses. The porous nanocomposite is made out of functionalized carbon nanotubes and Ecoflex and can be inexpensively fabricated without MEMS technology. The nanocomposite is 600-µm thick, 85% porous, and open cell with tubular ligaments. An ultrathin dielectric layer was added between the conductive foam and the electrode to ensure the whole device is still capacitive. The sensor has a modulus of 2 kPa and an initial impedance of 47 MΩ with a phase angle of -86°. This capacitive sensor exhibits a sensitivity of 1.95 kPa-1 within 0-1 kPa, 1.06 kPa-1 within 1-5 kPa, 0.88 kPa-1 within 5-10 kPa, 0.52 kPa-1 within 10-30 kPa, and 0.35 kPa-1 within 30-50 kPa of pressure ranges. The hybrid response is fully understood through a simplified circuit model, which has been validated by the experimental measurements. We have successfully applied this sensor to measure very subtle mechanophysiology on human body, including the pulse pressure of the jugular vein and the temporal artery.
EL07.08: Biosensors and In Vitro Platforms
Thursday PM, April 22, 2021
4:00 PM - EL07.08.01
Late News: Intrinsically Stretchable, Self-Adhesive, Conductive and Biocompatible PDA-PAM Hydrogel Electrode Enabled in Long-Term Continuous Electrophysiological Monitoring with Minimizing Motion Artifacts and Skin Irritation
Fengjie He1,Sijia Li1,Yingtao Jiang1,Shengjie Zhai1
University of Nevada, Las Vegas1Show Abstract
Since cardiovascular diseases (CVDs) are the number one cause of death in the US, long-term continuous electrocardiogram (ECG/EKG) monitoring has evolved to the forefront as a golden standard of ambulatory cardiac monitoring for precise CVDs diagnosis. However, the current commercial gel-type silver/silver chloride (Ag/AgCl) electrodes used in continuous ECG monitoring systems inevitably induce motion artifacts (noise signal) and occasionally cause signal loss. It is ascribed to the irregular impedance changes in the conductive layer between electrodes and skin resulting from the weak stretchability and decreased adhesiveness of the electrodes under intense human motion. On the other hand, some clinical cases reported that the commercial electrodes could cause severe skin irritations and allergies after long-term direct skin contact. Therefore, a self-adhesive, stretchable, and biocompatible hydrogel is highly desirable.
Polydopamine-polyacrylamide (PDA-PAM) hydrogel as a highly self-adhesive and stretchable biomaterial has been attracting tremendous attention. In particular, our previous experiments exhibited that PDA-PAM hydrogel has intrinsic electroconductive capacity due to a large amount of water (more than 70%) and abundant molecules and ions in the hydrogel. Thus, the PDA-PAM hydrogel is a perfect candidate to be integrated into ECG electrodes for continuous health monitoring. In this study, we successfully fabricated the PDA-PAM hydrogel-based ECG electrodes that can be readily connected to conventional ECG devices. As a proof of concept, three male and two female human subjects (age between 25-30 years) were employed to evaluate the proposed ECG electrodes’ long-term continuous monitoring performance in this study. The ECG experimental acquisition successfully indicated that the proposed PDA-PAM-based ECG electrodes could simultaneously record continuous ambulatory ECG signals and minimize the motion artifacts under intense exercises, including running, stair climbing, butterfly sleeve, chest expansion. Besides, a 3-hour continuous wearing of the PDA hydrogel-based ECG electrodes test also showed that the ECG signal’s quality did not degrade over time, and skin irritation such as itching or redness was not observed among all five human subjects. Notably, the signal-to-noise ratio (SNR) results of PDA-PAM-based ECG electrodes for different exercises demonstrated significant improvement compared to the commercial electrodes results (up to 59% improvement obtained from the running exercise). This significant improvement was attributed to the remarkable tissue adhesiveness and stretchability of the PDA-PAM hydrogel, which enabled the contact areas between electrode and skin to maintain consistent upon skin deformation during exercise and in turn minimized the motion artifacts in the collected signals. In summary, the developed PDA-PAM-based ECG electrodes were successfully employed in the continuous ECG monitoring with high SNR, low motion artifacts, and minimal skin irritation. Undoubtedly, the proposed PDA-PAM hydrogel will serve as a promising hypoallergenic conductive biomaterial for bioelectronics to record long-term continuous high-quality electrophysiological signals.
4:15 PM - EL07.08.02
Sapphire-Supported Nanopores for Low-Noise DNA Sensing
Pengkun Xia1,Jiawei Zuo1,Shinhyuk Choi1,Xiahui Chen1,Jing Bai1,Chao Wang1
Arizona State University1Show Abstract
Low-noise biomolecule sensing has proven to be a crucial method in biology, diagnostics, prognosis, etc. Solid-state nanopores have attracted considerable interest as a potentially high-speed, portable and low-cost solution for detecting a variety of biomolecules, such as proteins, RNA and DNA, as well as studying molecular interactions.
The high capacitive noise from conventionally used conductive silicon (Si) substrates, however, has seriously limited both their sensing accuracy and recording speed. To minimize the stray capacitance of the Si chip, conventional techniques introduce a thick insulating material at the nanopore vicinity. However, these fabrication schemes require complex, and manual processing techniques, such as selective membrane thinning, silicone/photoresist printing, glass bonding, etc, and thus are expensive, slow, and difficult to reproduce. Another approach is to replace conductive silicon with an insulating material, such as glass. The amorphous nature of glass substrates, however, prevents the formation of uniform membranes, and involves complex fabrication schemes, such as multiple lithography steps, as well as deposition and etching processes on individual chips. Accordingly, the broad availability of such glass-supported nanopore chips are very limited, primarily due to their low fabrication yield, poor reproducibility, and low throughput.
A new approach is proposed here for forming thin nanopore membranes on crystalline and insulating sapphire wafers as a means to eliminate stray capacitance from substrate conductance for low-noise biosensing. The method involves creating sapphire-supported (SaS) nanopore membranes by wet and anisotropic etching of 2-inch sapphire wafers in concentrated sulfuric and phosphoric acids, a process similar to bulk alkaline etching of Si, that has been widely used in MEMS and biosensing applications. Uniquely, we design a triangular membrane by leveraging the three-fold symmetry of the hexagonal c-plane sapphire lattice and developed a controllable process to produce nanopore membranes over a 2-inch wafer with average size as small as 10.6 μm with 6.8 μm deviation, which corresponds to picofarad level chip capacitance even considering nanometer-thin membranes in high-signal-to-noise-ratio (SNR) DNA detection. For validation, a SaS nanopore chip with a 100 times larger membrane area than conventional a silicon-supported (SiS) nanopore was tested, which showed 130 times smaller chip capacitance (10 pF) and 2.6 times smaller root-mean-square (RMS) noise current (18-21 pA over 100 kHz bandwidth, with 50 to 150 mV bias) when compared to a SiS nanopore (1.3 nF, and 46-51 pA RMS noise). Tested with 1k bp double-stranded DNA, the SaS nanopore enabled sensing at microsecond speed with a signal-to-noise ratio of 21, compared to 11 from a SiS nanopore.
By analyzing the device capacitance, noise current, and power density spectra of the SaS nanopore and comparing to the best reported SiS and glass-supported nanopores, we found our nanopore chips comparable to the best available low-noise sensors. In this work, the nanopore SNR in DNA sensing is mainly limited by the relatively large nanopore size (~7 nm) and relatively thick membranes (~30 nm). Further optimization in creating smaller nanopores (3-4 nm) and reducing membrane thickness, for example by integration with ultrathin 2D materials, is expected to greatly increase the sensitivity and boost the SNR. The SaS nanopore platform will find use in interrogating a variety of other biomolecules, and their molecular interactions at improved speed and accuracy. Beyond nanopores, our batch-processing compatible and potentially cost-effective manufacturing of the SaS membrane architecture, together with the high optical transparency of sapphire, may serve to establish a new fabrication and design strategy in bulk micromachining of sapphire wafers to broaden the applications in MEMS designs and optoelectronic devices.
4:30 PM - EL07.08.03
Late News: Biomembrane Based Organic Electronic Devices for Probing Constituent Specific Changes in Supported Lipid Bilayers
Samavi Farnush Bint E Naser1,Han-Yuan Liu1,Hui Su1,Susan Daniel1
Cornell University1Show Abstract
Supported lipid bilayers (SLBs) are extensively used to mimic and study membrane properties. However, they are generally formed on rigid, non-conducting supports which prevent label free sensing. Combing the insulating properties of biomembranes with bio-compatible conducting polymers (CPs) can enable the electrical detection of membrane disruptions and pathogen interaction. This type of sensing application broadens the use of organic electronic devices into biomedical engineering, biosensing applications, and fundamental membrane biophysics studies. To this end, we demonstrate the formation of lipid bilayers supported on a transparent, conducting polymer surface to investigate changes in membrane properties through constituent specific biomolecular interaction using both optical and electrochemical techniques. Specifically, we have studied methyl-β-cyclodextrin (MβCD) induced cholesterol transfer to and from SLBs and the binding of cholera toxin B subunit (CTB) to lipid bilayers containing GM1 receptor. For our investigation, we used PEDOT:PSS as the CP support because of its high conductivity, optical transparency, easy processing, and excellent biocompatibility. SLBs were formed on this conducting polymer via solvent assisted method since this method bypasses vesicle preparation, does not require vesicle affinity to CP surface, and is applicable to a wide range of lipid mixtures and compositions for which vesicle fusion is difficult. We confirmed the presence of the specific constituents, i.e., cholesterol and GM1 receptors in the lipid bilayers visually using fluorescence microscopy. Next, we explored the sensing capabilities of the developed platform through EIS measurements performed on PEDOT:PSS/ITO electrodes on glass substrates. We report on the successful detection and quantification of the changes in membrane properties, such as, diffusivity and resistance, resulting from cholesterol addition/deletion and receptor specific toxin binding activity using the CP supported SLBs. Our results demonstrate the tremendous potential of these platforms in biosensing application, such as, studying the therapeutic effects of βCD derivatives, drug-screening and examining drug delivery efficiency to prevent receptor specific toxin interaction with the cell membrane.
4:45 PM - *EL07.08.04
Shepherding Tissue Growth and Healing Using Bioelectric Interfaces
Princeton University1Show Abstract
Living cells have a remarkable capacity known as ‘electrotaxis’ where they can sense DC electric fields and orient their migration or growth along field lines. Such fields are surprisingly common in vivo and can be critical during embryonic development, wound healing, infection response, and tissue assembly. Essentially, ion gradients give rise to electrochemical DC fields (~1V/cm) where the field direction orients cellular motion and the strength determines migration speed. The importance of such fields in vivo raises the question of whether we can develop bioelectric interfaces to mimic or manipulate these fields in order to literally program and ‘herd’ cellular growth and motion to heal injuries faster, grow bespoke tissues, or manipulate diseased tissue. This is an exciting opportunity, but many key challenges remain to be elucidated, especially at the material level. Firstly, new materials are required for the stimulation interface to reduce electrochemical damage and improve the resolution and subtlety of electrical control. I will discuss and highlight some of these challenges using the SCHEEPDOG platform—a multi-axis, microfluidic electrobioreactor developed in my laboratory—to emphasize both the extraordinary control electrotaxis affords and critical material limitations holding back more advanced interfaces. A second key challenge area is to relate bioelectric inputs to living material outputs as a tissue reconfigures itself in response to bioelectric stimuli. Here, I will introduce new work underlining the difficulties and limitations of using bioelectric cues to impose an external behavior on a living tissue material when the target behavior clashes with the natural behavior of the tissue. Overall, this talk will provide an attempt to provide a comprehensive introduction to electrotaxis spanning the basic biointerface biology of how DC fields are transduced by living cells, the design and constraints on DC bioelectric interfaces, and key challenges and opportunities in the field for the broader materials community.
5:10 PM - EL07.08.05
Late News: Reliable, Low-Cost, Fully Integrated Hydration Sensors for Monitoring and Diagnosis of Inflammatory Skin Diseases in Any Environment
Surabhi Madhvapathy1,Heling Wang1,Jessy Kong1,Michael Zhang1,2,Jongyoon Lee1,Junbin Park1,Hokyung Jang1,Zhaoqian Xie1,3,Jingyue Cao1,Raudel Avila1,Chen Wei1,Vincent D'Angelo1,Jason Zhu1,Ha Uk Chung1,Sarah Coughlin1,Manish Patel1,4,Joshua Winograd1,Jaeman Lim1,Anthony Banks1,Shuai Xu1,Yonggang Huang1,John Rogers1
Northwestern University1,Vanderbilt University2,Dalian University of Technology3,University of Illinois at Chicago4Show Abstract
Present-day dermatological diagnostic tools are expensive, time-consuming, require substantial operational expertise, and typically probe only the superficial layers of skin (~15 μm). We introduce a soft, battery-free, noninvasive, reusable skin hydration sensor (SHS) adherable to most of the body surface. The platform measures volumetric water content (up to ~1 mm in depth) and wirelessly transmits data to any near-field communication-compatible smartphone. The SHS is readily manufacturable, comprises unique powering and encapsulation strategies, and achieves high measurement precision (±5% volumetric water content) and resolution (±0.015°C skin surface temperature). Validation on n = 16 healthy/normal human participants reveals an average skin water content of ~63% across multiple body locations. Pilot studies on patients with atopic dermatitis (AD), psoriasis, urticaria, xerosis cutis, and rosacea highlight the diagnostic capability of the SHS (PAD = 0.0034) and its ability to study impact of topical treatments on skin diseases.
5:25 PM - EL07.08.06
Late News: An Aerosol-Jet-Printed Graphene Biosensing Platform for Rapid Electrochemical Detection of Proteins and Small Molecules
Sonal Rangnekar1,Kshama Parate2,Cicero Cardoso-Pola2,Deyny Mendivelso-Perez2,3,Dapeng Jing2,Shaowei Ding2,Ethan Secor1,Emily Smith2,Jesse Hostetter2,Carmen Gomes2,Jonathan Claussen2,Mark Hersam1
Northwestern University1,Iowa State University2,U.S. Department of Energy3Show Abstract
Inexpensive and rapid diagnostic biosensing is needed more than ever and may be achieved through the development of disposable electrochemical sensors. Graphene films are an ideal material for electrochemical biosensing due to their high electrical conductivity, large surface area, and biocompatibility. However, graphene films fabricated through chemical vapor deposition are too expensive for single-use applications, and low-cost manufacturing alternatives, such as screen and inkjet printing of graphene inks, do not provide sufficient control over electrode geometry to achieve favorable electrochemical sensor performance. In this work, aerosol jet printing (AJP) is leveraged to pattern solution-processed graphene inks into high resolution interdigitated electrodes (IDE) on a flexible polyimide substrate. After thermally curing in air, the IDEs are heated in CO2 to create additional oxygen moieties on the graphene surface that are then reacted with EDC-NHS chemistry. The resultant graphene biosensing platform can be functionalized with arbitrary antibodies and blocking agents to create a highly sensitive and specific biosensor. This platform has been demonstrated for electrochemical detection of cytokines interleukin-10 (IL-10) and interferon-gamma (IFN-γ) to monitor immune system function (i.e., diagnosis of paratuberculosis in cattle) and for detection of histamine in food safety applications (i.e., determining fish spoilage). The limits of detection for each analyte (IL-10: 46 pg/mL; IFN-γ: 25 pg/mL; histamine: 31 µg/mL) and sensing ranges (IL-10: 0.1-2 ng/mL; IFN-γ: 0.1-5 ng/mL; histamine: 6-200 µg/mL) are appropriate for the respective applications. Furthermore, the biosensors are mechanically robust enough to withstand hundreds of bending cycles at high curvatures (R = 3-11 mm) with minimal change in electrical and electrochemical signals. Overall, the low cost of manufacturing and short testing time (~30 min to soak and sense) motivate the expansion of this printed graphene biosensor platform into other sensing applications, including wearable health monitoring and human health diagnostics.
5:40 PM - EL07.08.07
Late News: Electrostatic Modulation of Signaling at the Cell Membrane—Waveform- and Time-Dependent Electric Control of ERK Dynamics
Arizona State University1Show Abstract
The dynamics of extracellular-signal-regulated kinase (ERK) signaling regulates a wide variety of stimulated cellular processes and plays an important role in cell survival, motility, differentiation and proliferation. Here we show that a new range of alternative current electric field (AC EF) in the tens of KHz could non-invasively activate EGFR-Ras-ERK signaling pathway with precise timing and single-cell resolution, where electroporation or Faradaic processes have been deliberately avoided by using high-k dielectric passivated microelectrodes. We have shown that the ERK activities can be synchronized with the response time independent of the distance from the electrodes, suggesting that the inter-cellular communication and diffusion-limited processes are not involved. Series of blocker tests pinpointed that the ERK activation were triggered by EF induced EGF-independent phosphorylation of EGFR without changes in pH, Ca2+ concentration or reactive oxygen species. Interestingly, we also discovered that the cell response was sensitive to the waveform and timing of the EF, and that inhibition of ERK could also be controlled with different dynamic characteristics, strongly suggesting the electrostatic nature of the coupling between AC EF and the membrane protein. Our work suggests a new exciting possibility that the dynamic signaling initiated by membrane proteins can be non-invasively and locally modulated by specifically tuned EF.