Symposium BM07 : Bioelectronics—Fundamentals, Materials and Devices

Recently, extraordinary performances of natural creatures living in various conditions have been explored to understand their reversible dry/wet adhesion, including gecko feet, insect secretion, mosquito needles or endoparasitic worm’s proboscis, octopus suction cups, and slug’s footpad with viscous mucus. Extensive studies on the adhesive properties of such animal skins have revealed various multiscale architectures inducing various physical interactions. The attachment phenomena of various hierarchical architectures found in nature have extensively drawn attention for developing highly biocompatible adhesive on skin or wet inner organs without any chemical glue. Structural adhesive systems have become important to address the issues of human-machine interactions by smart outer/inner organ-attachable devices for diagnosis and therapy.
Breakthroughs in flexible and conductive materials have accentuated the development of wearable or organ-attachable bioelectronics for stable biosignal monitoring and drug delivery. For such medical applications, the devices need to manifest conformal contact on human skin even under dynamic movements, as well as repeatable, long-term attachment without skin irritations or chemical contaminations. Here, we investigated an artificial reversible wet/dry adhesion systems biologically inspired by the suction cups of octopi and amphibian’s pad. Our biologically inspired architectures exhibit strong, reversible, highly repeatable adhesion to silicon wafers, glass, and rough skin surfaces under various conditions. Applying these bioinspired architectures to interfacial adhesive layers can attribute to developing skin-attachable or implantable bioelectronics for health diagnosis, controlled drug therapeutics, and achieving multifunctional integrated devices for ubiquitous-healthcare systems.

Flexible and ultrathin substrates supporting microelectronic components have the potential to spur the development of pervasive healthcare and the internet of things by providing sensors and bioelectronics that can provide seamless and imperceptible integration. We will describe our ongoing work to develop sensing electronics on microns-thin bacterial nanocellulose for human monitoring applications. The porosity and hydrophobicity of nanocellulose sheets offer advantages that typical plastics cannot provide, such wicking of analytes and absorption of inks. We have developed a printing method to form nanocellulose printed circuit boards (PCBs), and created a simple low temperature soldering process to form circuit structures using standard surface-mount components on our nanocellulose PCBs. This has been used to create nanocellulose decals that measure human body temperature and perform pulse oximetry. We have also developed self-powered electronics for sensing of bioanalytes, such as glucose. For all applications, the fabrication processes are solution-based and requires only ambient processing, and therefore simple, potentially low-cost, and can be aimed for a wide range of applications.

The vast amount of biological mysteries and biomedical challenges faced by human provide a prominent drive for seamlessly merging electronics with biological living systems (e.g. human bodies) to achieve long-term stable functions. Towards this trend, the main bottlenecks are the huge mechanical mismatch between the current form of rigid electronics and the soft biological tissues.

In this talk, I will first describe a new form of electronics with skin-like softness and stretchability, which is built upon a new class of intrinsically stretchable polymer materials and a new set of fabrication technology. As the core material basis, intrinsically stretchable polymer semiconductors have been developed through the physical engineering of polymer chain dynamics and crystallization based on the nanoconfinement effect. This fundamentally-new and universally-applicable methodology enables conjugated polymers to possess both high electrical-performance and extraordinary stretchability.[1] Then, proceeding towards building electronics with this new class of polymer materials, the first polymer-applicable fabrication platform has been designed for large-scale intrinsically stretchable transistor arrays.[2] As a whole, these renovations in the material basis and technology foundation have led to the realization of circuit-level functionalities for the processing of biological signals, with unprecedented mechanical deformability and skin conformability. Equipping electronics with human-compatible form-factors has opened a new paradigm for wearable and implantable bio-electronic tools for biological studies, personal healthcare, medical diagnosis and therapeutics.[3]

[1] J. Xu^#, S. Wang^# …… Z. Bao Science 355, 59-64 (2017).
[2] S. Wang^#, J. Xu^# …… Z. Bao Nature 555, 83-88 (2018).
[3] S. Wang^#, J. Y. Oh^#, J. Xu^#, H. Tran, Z. Bao Accounts of Chemical Research 51, 1033–1045 (2018).

Human sensory organs such as the skin have evolved to have excellent sensing performance and ultra-robustness. Electronic versions of skin have witnessed tremendous interest and development over the last decade¹. Functional soft, flexible and stretchable materials are crucial to the continued evolution of skin-like sensor applications in emerging robotic systems², new human-machine interfaces and life-like prosthetics³.

Here, I will discuss our recent work in next generation technologies for bio-electronic skins using an integrated hybrid materials approach that synergizes the best qualities of organic and inorganic materials. For example, recent developments in self-healing polymeric systems have propelled the exciting notion that electronic systems can repair themselves when damaged⁴. Bio-inspired digitization of analog signals have also enabled us to develop artificial mechano-receptors that optically interfaces with neurons⁵. These sensor and materials technologies would be extremely applicable in an increasingly advanced cybernetic and Artificial Intelligence (AI) robotics future.

1. Hammock, M. L., Chortos, A., Tee, B. C. K., Tok, J. B. H. & Bao, Z. 25th anniversary article: The evolution of electronic skin (E-Skin): A brief history, design considerations, and recent progress. Adv. Mater. 25, 5997–6038 (2013).
2. Larson, C. et al. Highly stretchable electroluminescent skin for optical signaling and tactile sensing. Science 351, 1071–4 (2016).
3. Lipomi, D. J. et al. Skin-like pressure and strain sensors based on transparent elastic films of carbon nanotubes. Adv. Mater. 23, 1771–1775 (2012).
4. Tan, Y. J., Wu, J., Li, H. & Tee, B. C. K. Self-Healing Electronic Materials for a Smart and Sustainable Future. ACS Appl. Mater. Interfaces 10, 15331–15345 (2018).
5. Tee, B. C. K. et al. A skin-inspired organic digital mechanoreceptor. Science (80-. ). 350, 313–316 (2015).

Driven by the ever-growing needs for developing portable, easy-to-use, noninvasive diagnostic tools, biomedical sensors that can be integrated on textiles or even directly on human skin have come to fruition. Wearable sensor technologies that seamlessly interface electronics with human skin can be especially promising for detecting a wealth of biologically relevant signals ranging from neuro-muscular activity, to electrophysiology, even to metabolite profiles.

In this work, we present a simple and low cost platform fabricated on a tattoo paper used for on-skin electromyography (EMG) measurements. The electrodes comprising the conducting polymer poly(3,4-ethylenedioxythiophene) doped with polystyrene sulfonate (PEDOT:PSS) are directly inkjet-printed on the tattoo paper. Addressing the integration challenge common for stretchable electronic devices, we connect the tattoo electrodes to the acquisition system through a textile in the form of a wristband comprising of printed PEDOT:PSS contacts. While the textile wristband conforms around the “tattooed” skin, it enables a reliable contact with the electrodes beneath due to its conformability around the limb. We show that this tattoo/textile electronics system, which does not rely on gels or expensive metallic materials, is able to detect the biceps activity of the arm during muscle contraction for a period of seven hours, with comparable performance to conventional wet biopotential electrodes. Combining the tattoo electronics with the electronic textile allows for facile integration of skin-like electrodes with external electronics.

We have developed fabric biomedical electrode array where silver paste, conductive polymer and ionic liquid gel are printed and insulation layers are formed with hot melt film on the fabric substrate.
Recently, wearable electronic devices such as Microsoft Hololens, google glass, sportsband, or other tools have been developed and commercialized for human healthcare monitoring and information tools. Among wearable electronic devices, wearable ECG or EMG electrodes are promising for human motion sensing tools. Especially for monitoring human hand or foot motion sensing, the biomedical electrode array which is made of fabric is necessary.
To make biomedical electrodes array, new fabrication process of fabric multilayer electrodes which consists of biomedical electrode parts to contact human skin and the wiring parts from biomedical electrodes parts to the amplifiers are required. Previous study (S. Takamatsu,et.al., "Direct patterning of organic conductors on knitted textiles for long-term electrocardiography," Scientific Reports, vol. 5, 15003(7pp), Oct 2015.) reports single layer fabric electrodes, but the multilayer electrodes has not been fabricated on the fabric and the biomedical electrode array has not been achieved. The most difficult fabrication process to make multilayer electrodes is to construct insulation layer between multiple electrode because most of the insulation inks are dissolved by the solvent of second layer electrode ink(i.e., toluene), or dissolve the first layer electrode with the solvent of the insulation ink. Our new fabrication process of fabric multilayers consists of the electronic ink printing and hot-melt film sticking on the fabric. Laser cut hot melt film is placed on the electrode printed film and heated to stick to the film as insulation layer. Hot melt film has the advantages in which the hot melt film is not dissolved in the solvent of inks and can combine several layers of functional fabric and films.
The developed fabrication process of fabric biomedical electrode array with printable electronic ink and hot-melt film for Electromyography is following steps. 1. Silver paste wiring electrode is printed on the stretchable polyurethane film. 2. Laser cut hot melt film is placed on the electrode and heated. 3. The patterned urethane film is attached on the knit fabric with hot melt film. 4. Conductive polymer of PEDOT PSS and ionic liquid gel is patterned on another knit fabric for making biomedical electrode part. 5. Wiring part fabric and biomedical electrode fabric are attached by hot melt film and glue. By using our process, the 2x5 array biomedical electrode which has 1cm² biomedical electrodes parts and 0.5 mm wide wiring can be successfully fabricated. The impedance between electrodes and human skin is less than 1 MOhm, which is useful for EMG monitoring. Thus, our process will useful for wearable multi array of EMG measurement.

Accurate, imperceptible and long-term monitoring of vital biopotential signals promises to revolutionize healthcare industry by shifting from costly and uncomfortable hospital visits to in-home usage. Currently available wearable electronics are typically rigid with non-conformal skin contact resulting in poor data quality, necessitating the integration of such bioelectronics [1] directly onto the skin [2]. Increasing the conformity of the artificial electronic skin to the soft, irregular and stretchable human skin typically results in improved signal quality and user comfort [3].

We report on the fabrication of self-adhesive and conformable to highly irregular three-dimensional soft surfaces, sub-300 nm thin dry electrodes that produce biopotential (sEMG and sECG) recordings of excellent quality (SNR). The electrodes are based on thermally evaporated thin film (100 nm) of Au, sandwiched between two layers (100 nm each) of CVD-deposited biocompatible parylene (parylene/Au/parylene). They are fabricated on glass substrates, with fluorinated polymer (85 nm) and poly(vinyl alcohol) (PVA, 5 µm) sacrificial layers used for delamination and ease of handling. Parylene is etched away at the skin-interface side, allowing for direct Au contact with the skin. Following delamination, electrodes are placed on pre-stretched human skin and sprayed with H₂O to remove PVA, forming a skin/Au/parylene structure. The skin is then dried and relaxed, with the ultra-thin film conforming to the skin groves via wan der Waals forces [4], without any additional adhesives.

These simple-to-fabricate and use, ultra-thin sensors show single-day electrical and mechanical stability of up to ten hours. Their bending stiffness was calculated to be comparable to stratum corneum, the uppermost layer of human skin, at ~0.33 pNm², which is over two orders of magnitude lower than the bending stiffness of a 3.0 µm thin sensor. Compared with the thicker sensor, its impedance also decreased by almost two orders of magnitude. Laminated on a pre-stretched elastomer, the sensor forms wrinkles with a period of 17 µm and amplitude of 4 µm, agreeing with theoretical calculations.

In contrast to wet adhesive Ag/AgCl electrode, with skin vibrations of up to ~15 µm, the sensor demonstrates motion artifact-less sEMG monitoring. Additional impedance and sEMG measurements reveal that the decrease of impedance, as well as the motion artifact-less operation, is likely due to improved skin adhesion of the sub-300 nm thin sensor.

With compatible fabrication to our previously demonstrated sub-300 nm thin electronics [5], this demonstrates a path for integration of skin-laminated systems consisting of sensors and electronics.

[1] M. Irimia-Vladu, et al., Adv. Fun. Mat. 20, 4069-4076 (2010)
[2] T. Yokota, et al., Science Adv. 2, e1501856 (2016)
[3] D.H Kim, et al., Nature Mat. 9, 511-517 (2010)
[4] M. Fernandez, et al., Biomed Inst. Tech. 34, 125 (2000)
[5] R. Nawrocki, et al., Adv. Ele. Mat. 2, 4 (2016)

In order to improve the signal accuracy and long-term monitoring of electronics on biological skin, it is essential to achieve a conformal and robustly adhered electronics/biological skin interface. Here, we suggest a biocompatible calcium (Ca)-modified silk adhesive for robust epidermal electronics on biological skin. At optimized weight ratio of silk:Ca²⁺ of 70:30, the silk adhesive shows strong adhesion force (> 600 N/m) through enhanced mechanical interlocking at interface. The physical mechanism facilitates a high adhesion on various substrates and a reusability of silk adhesive. Moreover, a water-degradability of silk adhesive shows the easy detachment without any high external force. With the multifunctional characteristics such as reusability, biocompatibility, and water-degradability, we fabricate the practical epidermal electronics: strain sensor, touch sensor, and long-term drug delivery system to demonstrate the potential of the proposed silk adhesive.

The goal of this project is to create a class of electronic materials that can measure signals and interface with the nervous system for two-way communication with biological systems. The project is exploring two classes of materials. (1) Metallic nanoislands on single-layer graphene for cellular electrophysiology and wearable sensors. We have used these materials to measure the forces produced by the contractions of cardiomyocytes using a piezoresistive mechanism. Separately, we have developed orthogonal methods of stimulating myoblast cells electrically while measuring the contractions optically (a modality we nicknamed as “piezoplasmonic”). We have also used these sensors to measure the swallowing activity of head-and-neck cancer patients who have received radiation therapy and are at risk of dysphagia arising from fibrosis of the swallowing muscles. The combination of strain sensing, surface electromyography, and machine learning can be used to measure the degree of dysphagia. (2) We have developed ionically conductive organogels for haptic feedback. Medical haptic technology has myriad potential applications, from robotic surgery and surgical training, to tactile therapy for premature infants and patients with neurological impairment.

We present an implantable sheet-type flexible electronic sensor system for long-term simultaneous monitoring of an electrocorticogram (ECoG) from the brain surface and local field potential (LFP) from the deep brain. Ultrasoft gel electrodes provide a minimally invasive interface consisting of highly conductive nano-conductive materials including Ag-based nanowires, thermoplastic polymers, and bio-compatible gels. The gel composite shows conductivity greater than 10,000 S/cm and can be stretched more than 100% without any reduction to its electrical and mechanical performance. Hence, it can be stretched across arbitrarily curved surfaces, including the ultrasoft brain surface.

By integrating ultrafsoft gel electrodes, an ultraflexible amplifier, and a wireless Si-LSI platform with a thin-film battery, we intend to demonstrate the applications of long-term implantable wireless sheet sensors, including 64-channel sheet-type electric potential monitoring systems. This wireless system with soft gel electrodes can measure biological signals of less than 1 μV. Taking full advantage of this system, simultaneous signals from the cerebral cortex in the ECoG and LFP have been wirelessly measured in animal experiments including non-human primates for over a month. Long-term biocompatibility, electrical performance, and mechanical stretchability and durability are discussed for the integration of nanomaterials and processes and wireless low-noise sheet-type systems.


This research is partially supported by the Brain Mapping by Integrated Neurotechnologies for Disease Studies (Brain/MINDS) from Japan Agency for Medical Research and development, AMED.

In the last few decades the quality of life has significantly improved due to the achievements of biomedical technology. Innovative healthcare solutions contributed to these advances by decreasing costs and making health assessment easier and more accessible. Versatile biochemical sensors targeted to health biomarkers and bioanalytes (metal ions, proteins, amino acids, glucose, lactate, etc.) can non-invasively monitor the health status of the user by analyzing external body fluids (sweat, saliva, tear fluid) alternative to blood.[1,2] On-demand biosensing is envisaged due to the versatility of sensing platforms that can adapt to specific needs in terms of target biomarkers and health issues to monitor. To this regard, several recognition systems, including antibodies, enzymes, and inorganic nanomaterials can be used to modify the sensors to achieve high selectivity towards target analytes. In this scenario, recent advances in microfabrication, sensor technologies and data transmission led to the developments of point-of-care (PoC) diagnostics.
Here we present few examples of biosensors for painless and on-demand self-assessment of health conditions. In particular, we describe a non-invasive electrochemical sensor for the non-enzymatic analysis of tear glucose.[3] Electrochemical sensing is chosen among other types of transduction because it is well suited for simple, rapid, and cost-effective personalized medicine devices. Electrodes are fabricated on soft and flexible materials using inkjet printing and then modified with CuO microparticles (CuO-µPs) to carry out non-enzymatic detection of glucose. This detection mechanism is based on the CuO-catalyzed electro-oxidation of glucose in alkaline environment, due to the electrochemical conversion of CuO into strong oxidizing Cu(III) species such as CuOOH or Cu(OH)⁴⁻. Glucose detection is achieved by CA, with an excellent linearity observed in the 3–700 µM range, matching typical glucose levels in tears. A sensitivity of 850 µA mM⁻¹cm⁻² and a limit of detection (LOD) of 2.99 µM are calculated. This sensor shows good selectivity, reproducibility, and life-time, resulting in a reliable tool for painless and non-invasive self-assessment of diabetes, as confirmed by tests on tear samples.
Personalized and non-invasive sensing technologies allow to easily and frequently monitor the health status of an individual as often as needed. This helps make early-stage detection simpler and more convenient, thus enhancing the efficacy of therapeutic treatments. Rapid and cheap PoC diagnostics also allows improving the life style of patients, by interfering in low or negligible extent to their daily activities.

References
[1] A. Romeo, et al. Lab Chip 16, 1957 (2016)
[2] D. Vilela, et al. Lab Chip 16, 402 (2016)
[3] A. Romeo, et al., Appl. Mat. Today 10, 133 (2018)

With increasing demand for the detection of delicate bio-signals for medical electronics, the Internet of Things (IoT), E-skin and flexible integrated circuit (IC) devices, an enhancement in sensitivity has become a major issue in flexible mechanosensors, however, overcoming the limited sensitivity remains problematic. Here, we introduce mechanosensors inspired by spiders having an ulltrasensitivity, durability. For ultrasensitivity and durability, we considered the geometrical effects in cracks and self-healable polymers. By controlling crack depth by simple propagating process, the sensitivity of our sensor shows ~15,000 in 2% strain, which is the world best sensitivity value. Due to the high sensitivity, the signal-to-noise-ratio is 6 times higher than before, up to ~35 so that it can be used in sensing human voice clearly. Also, self-healable polymer helps to recover the crack gaps after 25,000 cycles. We introduce the possilibility of semi-permanent uses over 1,000,000 cycles in our sensors. The spider inspired sensory system with high sensitivity and durability would provide versatile novel applications such as E-skins, devices for medical applications, and IoT applications etc.

Ionic and electronic conduction mechanisms are underpinned by fundamentally different physics [1]. For example, ions diffuse through a conducting matrix via centre of mass transport that can be described by classical processes. Electrons and holes are quantum mechanical entities characterised by delocalisation, tunnelling or hopping. These fundamental differences impose radically different length-and-time-scales on ionic and electronic conduction – and generally speaking the solid-state physics of ions and electrons have remained two very different fields requiring different skill sets [2]. However, bioelectronics, where a central challenge is the transduction between ion and electron currents, is a scientific collision point between the two worlds.
In my talk I will summarise the major differences between ionic and electronic solid state electrical conduction. I will also describe methods that can probe the relevant time-and-length scales in order to identify and disentangle the native signatures of each carrier type [3, 4]. A number of model systems and devices will be exemplified that allow the study of ion and electron conduction processes, and indeed provide a means to test prototypical concepts in transduction and bioelectronic logic interfaces [5, 6].

[1] N. Amdursky, E. Glowacki & P. Meredith, Advanced Materials, 2018, (in press)
[2] P. Meredith, C. J. Bettinger, M. Irimia-Vladu, A. B. Mostert and P. E. Schwenn, Reports on Progress in Physics, 2013, 76, 034501
[3] A. B. Mostert, B. J. Powell, F. L. Pratt, G. R. Hanson, T. Sarna, I. R. Gentle and P. Meredith, Proceedings of the National Academy USA, 2012, 109, 8943-8947
[4] A.B. Mostert, S.B. Rienecker, C. Noble, G.R. Hanson & P. Meredith, Science Advances, 2018, 4(3), eaaq1293
[5] M. Sheliakina, A.B. Mostert & P. Meredith, Materials Horizons, 2018, 5, 256-263
[6] D.J. Carrad, A.B. Mostert, A.R. Ullah, A.M. Burke, H.J. Joyce, H.H. Tan, C. Jagadish, P. Krogstrup, J. Nygard, P. Meredith & A.P. Micolich, Nanoletters, 2017, 17(2), 827-833

We have recently developed the organic electrolytic photocapacitor (OEPC), a nanoscale optoelectronic device for eliciting action potentials in neurons. Herein, we cover in detail the physical mechanisms behind the charge generation and dynamics of charging and capacitive coupling in these devices using optoelectronic/electrochemical measurements combined with simulation and modeling. Electrochemical impedance measurements allow corroboration of these models, and reveal the nature of photocapacitive and photofaradaic effects in the devices. Using scanning probe microscopy techniques, we have evaluated the mechanical properties of the nanocrystalline films, finding relatively low Young’s moduli in the range of 500 MPa. In order to take a reductive approach compared with previous measurements of neurons and electrogenic tissues, we have validated the performance of OEPCs using nonexcitable cells, xenopus laevis oocytes. We find rapid membrane potential changes in the range of tens to hundreds of millivolts are induced by OEPC devices, showing extremely effective capacitve coupling and explaining previous findings of action potential generation. The overall result of our work is a fuller physical and mechanistic understanding of this novel device platform, and a roadmap for guiding future development.

Organic electrochemical transistors (OECTs) are receiving a great deal of attention due to the ability to efficiently transduce biological signals. The working principle of OECTs relies on the modulation of the conductivity of an organic semiconductor, which can be modified by applying a potential at the gate electrode and driving electrochemical redox reactions in aqueous solution (doping/de-doping of the organic semiconductor). OECTs can either be operated in accumulation^1–3 or depletion mode⁴ where the operation in accumulation mode has the advantage of lowering the operational voltage and therefore improve the power consumption of the device (device is in an off state rather than an on state when no gate voltage is applied). Recently, high performing OECT materials have been reported based on electron rich alkoxybithiophene copolymers which show low oxidation potentials in aqueous electrolytes and enable OECT operation at low voltages. ²
However, one drawback of these easily oxidizable polymers is that the copolymers can become oxidized by reactions with oxygen from ambient air. This result in the formation of p-doped polymers and superoxide anions (O₂^-) where the latter is a reactive radical and might cause harm to biological systems or degrade the organic semiconductor. As a result of this oxidation reaction, a constant gate voltage would need to be applied to keep the material in its neutral state (and the device off).
We will present the development of an air-stable conjugated polymers based on donor-acceptor type copolymer. The copolymer shows reversible redox reaction at potentials below 0.3 V vs Ag/AgCl. When exposed to aqueous ambient conditions, the polymer does not become oxidized. Long-term stability tests were carried out where devices were exposed to ambient conditions for more than 6 months with no sign of degradation. The polymer shows a good stability when charged with up to one hole per repeat unit (polaron) with transconductances in the range of 80 S/cm (at -0.7 V). This work demonstrate the importance of chemical design strategies for the development of accumulation mode OECT materials to mitigate reactions with oxygen in aqueous electrolytes and ambient conditions.

1. Inal, S. et al. Adv. Mater. 26, 7450–7455 (2014).
2. Giovannitti, A. et al. Proc. Natl. Acad. Sci. 113, 12017–12022 (2016).
3. Nielsen, C. B. et al. . J. Am. Chem. Soc. 138, 10252–10259 (2016).
4. Khodagholy, D. et al. Nat. Commun. 4, 2133 (2013).

Mixed organic ionic and electronic conductors are being explored for a wide range of applications, from bioelectronics to neuromorphic computing, artificial muscles and energy storage applications. These materials exploit the simultaneous transport properties of ionic and electronic carriers to enable novel device functions. Recently, polymer semiconductors have received significant amounts of attention because of their flexibility, biological compatibility and ease of fabrication. These materials, particularly thiophene-based polymers such as poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate)(PEDOT:PSS) and related derivatives, have demonstrated significant enhancements in performance in a relatively short amount of time, with transconductance values of PEDOT:PSS transistors surpassing those achieved even with graphene.

Through our NSF Designing Materials to Revolutionize and Engineer our Future (DMREF) award with researchers at Cornell University and the University of Chicago, we have been investigating the synthesis of ethylene-glycol functionalized polythiophenes, their thin film morphology, and their ionic and electronic conductivities, and comparing against theoretical predictions. In this talk, the effect on the density of the ethylene-glycol side chains and their pattern of placement on ionic conductivity will be discussed.

This talk will give an overview about our recent activities on electronic and ionic conductivity in conjugated and redox polymer thin films with different molecular architectures. Preparation of films is done either by electropolymerization or solution deposition followed by morphology tuning, e.g. by solvent vapor annealing.[1]
We are particularly interested in three-dimensional architectures based on branched monomers such as terthiophenes (3T) or triphenylamines (TPA). TPA redox moieties are useful to allow for electrochemical or chemical crosslinking of as-deposited films. Both, with TPA redox polymers[2] and with polymers which bear TPA as pending redox moieties of linear polythiophenes[3] we could perform successful crosslinking and simultaneous doping of polymer films. The films provide very high stabilities with high electronic conductivities as evidenced by cyclic voltammetry coupled with in-situ conductance measurements and four-point-probe measurements. In the case of 3T we have reported on homopolymer and copolymer films of 3T and ethylenedioxythiophene which allow polymer-analogous reactions to induce ionic functionalities, thereby creating branched conjugated polyelectrolyte films.[4], [5]
To get a better understanding on mixed conductivity in polymer films, we have recently performed a study on electronic and ionic conductivity of linear conjugated polyelectrolytes by impedance spectroscopy and dc-measurements.[6] The clear dependence of the conductivities as function of humidity and degree of doping will be discussed in the talk in more detail.

[1] G.L. Schulz, S. Ludwigs, Adv. Funct. Mater. 27, 2017, 1603083.
[2] O. Yurchenko, J. Heinze, S. Ludwigs, Chem. Phys. Chem. 11, 2010, 1637.
[3] P. Reinold, K. Bruchlos, S. Ludwigs, Polymer Chemistry 8, 2017, 7351.
[4] M. Goll, A. Ruff, E. Muks, F. Goerigk, B. Omiecienski, I. Ruff, R.C. González-Cano, J.T. Lopez Navarrete, M.C. Ruiz Delgado, S. Ludwigs, Beilstein J. Org. Chem. 11, 2015, 335.
[5] T.V. Richter, C. Bühler, S. Ludwigs, J. Am. Chem. Soc. 134, 2012, 43.
[6] R. Merkle, P. Gutbrod, P. Reinold, M. Katzmaier, R. Tkachov, J. Maier, S. Ludwigs, Polymer 132, 2017, 216.

TBA

Neuromorphic computing could address the inherent limitations of conventional silicon technology in dedicated machine learning applications. Recent work on silicon-based asynchronous spiking neural networks and large crossbar-arrays of two-terminal memristive devices has led to the development of promising neuromorphic systems. However, delivering a parallel computation technology, capable of implementing compact and efficient artificial neural networks in hardware, remains a significant challenge. Organic electronic materials offer an attractive alternative to such systems and could provide neuromorphic devices with low-energy switching and excellent tunability, while being biocompatible and relatively inexpensive.

This talk describes state-of-the-art organic neuromorphic devices and provides an overview of the current challenges in the field and attempts to address them¹. We demonstrate a novel concept based on an organic electrochemical transistor² and show how some challenges in the field such as stability, linearity and state retention can be overcome³.

Furthermore, we investigate chemical doping mechanisms in the active material for improved material functionality and demonstrate that this device can be entirely fabricated on flexible substrates, introducing neuromorphic computing to large-area flexible electronics and opening up possibilities in brain-machine interfacing and adaptive learning of artificial organs.

¹ van de Burgt et al. Nature Electronics, 2018
² van de Burgt et al. Nature Materials, 2017
³ Keene et al. J Phys D, 2018

Anisotropic conductive films, which consist of electrically conductive particles dispersed in nonconductive media, are increasingly being applied to establish high-density electrical bonds between electronic boards and chips. However, current anisotropic composites utilize metallic particles, often nickel and epoxy-based media, that require high thermocompression energy for bonding. Therefore, they have limited applicability in thin-film, conformable, and plastic-based devices that are used in bioelectronic applications. Furthermore, these materials are not biocompatible, significantly limiting their use in biological systems. We hypothesized that replacing the metallic particles with conducting polymer particles combined with a biocompatible nonconducting matrix would address this limitation. We developed a novel anisotropic conducting polymer (ACP) consisting of poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) (PEDOT:PSS) conducting polymer particles dispersed in a matrix of crosslinked chitosan (CS). To determine the permeability of PEDOT:PSS to CS, we characterized the resistances of thin CS-based films sandwiched with PEDOT:PSS and gold pads. We investigated the particle size, structure, density and distribution of pure PEDOT:PSS particles and PEDOT:PSS-coated CS particles. The anisotropy was defined by the ratio of horizontal and vertical impedance between interconnects. We benchmarked the anisotropy of the developed ACPs by geometrically varying an array of gold electrodes. The final ACP, which was created at 70°C with minimal pressure, yielded anisotropy of 10⁵-10⁶. The ACP was then used to maintain precise connections between a high density conformable implantable neural probe and back-end electronics. It enabled complete chronic in vivoimplantation of these electronics with minimal encapsulation layers, highlighting applicability for use in bioelectronic and clinical devices

Over the past 10 years, regenerative medicine has witnessed a significant technological and scientific advancement. For instance, numerous revolutionary progress in stem cell science as well as additive manufacturing, namely 3D printing, have opened up new horizons in research and brought them closer to reality than ever before. However, for more sophisticated indications, fabrication of biological structures such as human tissues and organs may require an optimized procedure to obtain the impeccable final product. Therefore, the need for biocompatible electronic devices is a focus of attention in academia and industry. Moreover, biodegradable electronic devices for healthcare applications can also produce a revolution in the electronics industry and reduce electronic waste products. Currently, thousands of tons of silicon that is used to manufacture computers, cell phones, and other devices are discarded into the environment annually. It is critical that such waste be curtailed. Here, we report a systematic investigation on finding biocompatible/degradable functional electronic materials. To address this aim two different approaches were employed: 1-study the electronic properties of biomaterials, 2- study the biocompatibility of functional electronic materials. Materials with energy band gap between 1 to 3 eV are categorized as semiconductors and bigger than 3 eV as insulators. Various biomaterials were sought in terms of energy band diagram. Most biomaterials showed energy band gap bigger than 3 eV confirming them as insulators, for example, fibrinogen, glycerol, and gelatin showed 3.54, 3.02, 3.0 eV. Meanwhile, a few biomaterials were found as semiconductors such as phenol red in the cell culture medium with 1.96 eV energy band gap. On the other hand, the biocompatibility of organic semiconductors, such as P3HT and PCBM for different cell types such as satellite cells were examined. The cells were exposed to the thin layer of films prepared with the organic materials, and essential biomarkers (Desmin and MF20) were used to determine the consequence effect on the cells, their functionality, proliferation, and differentiation. The outcomes of this research can be used to fabricate biocompatible/degradable electronic devices for medical applications.

Deciphering complex neural circuits relies on the developments of neural interface devices with good biocompatibility, mechanical compliance, high spatial resolution, and high quality recording. There has been significant development in neural interface devices in the past decades, mostly based on silicon and metal electrodes or contact printed film electrodes. More recently, thermally drawn polymer fibers have been utilized as neural recording probes which exhibit good flexibility and biocompatibility. However, due to the low conductivity of conventional polymer electrodes, the size of a polymer fiber probe is typically much larger compared to the size of a single neuron in order to have the overall impedance fall in the recordable range, resulting in a poor spatial resolution of these probes. Therefore, it is of great importance to reduce the impedance of the polymer electrode while maintaining the miniaturized footprint in order to increase the spatial resolution and minimize the brain damage. In this study, we deposited metallic nanostructures on the tip of the polymer fiber probe to enhance the electrical properties as well as the electrophysiological recording performance. Soft nanolithography patterning technique was utilized to create dense vertical 3D nanopillar nanoelectrodes on the small area of the flexible polymer fiber tips via gold nanohole array masks. Because of the large surface area of the nanopillar nanoelectrode structure, the resulting impedance of the modified electrode has been reduced to be able to capture neural signals. The power density of local field potential (LFP) from both the modified and unmodified electrode showed the better recording performance of the modified one. Finally, we evaluated these nanoelectrode integrated polymer fiber probes in terms of chronic recording and long term tissue response. These results show that nanoelectrode-based surface modification can significantly reduce the impedance of polymer electrodes, thus increase the spatial resolution and improve the electrophysiology recording performance of polymer fiber probes.

As our understanding of the brain’s physiology and pathology progresses, increasingly sophisticated materials and technologies are required to advance discoveries in systems neuroscience and develop more effective diagnostics and treatments for neuropsychiatric disease. Localizing brain signals may assist with tissue resection and intervention strategies in patients with such diseases. Precise localization requires large and continuous coverage of cortical areas with high-density recording from populations of neurons while minimizing invasiveness and adverse events. We describe a large-scale, high-density, organic electronic–based, conformable neural interface device (NeuroGrid) with embedded integrated circuitry capable of simultaneously recording local field potentials (LFPs) and action potentials from the cortical surface. We demonstrate the feasibility and safety recording with such devices in anesthetized and awake subjects. Highly localized and traveling physiological and pathological LFP patterns were recorded, and correlated neural firing provided evidence about their local generation. Application of NeuroGrid technology to disorders such as epilepsy may improve diagnostic precision and therapeutic outcomes while reducing complications associated with invasive electrodes conventionally used to acquire high-resolution and spiking data.

Adhesion quality and biocompatibility are the main obstacles to a successful use of conducting polymers coatings on metal microelectrodes for recording and stimulation. Such microelectrodes have very small dimensions, resulting in a high impedance. One way to address this problem is to deposit a conducting polymer, PEDOT, on their electroactive area to lower the impedance and reduce the foreign body reaction [1]. However, the small size of such microelectrodes and the poor adhesion of conducting polymers on most inorganic substrates remain practical difficulties for large scale production. In our recent experiments using electrochemical polymerization, we explored the influence of different solvents (acetonitrile, propylene carbonate) [2] and electropolymerisation methods (potentiodynamic, galvanostatic, pulsed deposition) on the adhesion of an electropolymerized thin layer of PEDOT:BF4 on platinum electrodes. We also investigated the use of a diazonium salt as an anchoring layer for PEDOT on platinum [3]. We evaluated the stability of our PEDOT-coated electrodes ex vivo by passive aging in physiological solutions and under repeated electrical stimulations, similar to those used for deep drain stimulation. Finally, we investigated in vivo aging to hopefully gain more insights on the stability of our PEDOT coating in contact with living tissues.

[1] Ludwig, K. A., Uram, J. D., Yang, J., Martin, D. C., & Kipke, D. R. (2006). Chronic neural recordings using silicon microelectrode arrays electrochemically deposited with a poly (3, 4-ethylenedioxythiophene)(PEDOT) film. Journal of neural engineering, 3(1), 59.
[2] Poverenov, E., Li, M., Bitler, A., & Bendikov, M. (2010). Major effect of electropolymerization solvent on morphology and electrochromic properties of PEDOT films. Chemistry of Materials, 22(13), 4019-4025.
[3] Chhin D., Polcari D., Bodart-Le Guen C., Tomasello G., Cicoira F., Schougaard S. Diazonium-based anchoring of PEDOT on Pt/Ir electrodes via Diazonium Chemistry. Journal of The Electrochemical Society. (publication pending)

Transparent microelectrode arrays have emerged as promising tools for measuring neural signals with high spatiotemporal resolution by combining simultaneous electrophysiology and optical modalities. However, scaling down transparent microelectrodes to the size of single neuron is challenging since traditional transparent conductors are limited by their capacitive electrode/electrolyte interface. By reliably stacking individual layers of metal and low-impedance coatings in a same nanomeshed pattern, we demonstrated an innovative bilayer nanomesh approach to address this limitation with system-level, high electrode performance. Specifically, we successfully achieved Au/PEDOT:PSS bilayer nanomesh microelectrodes with site area down to ~ 314 μm², comparable to the size of a single neuron, while possessing impedance of 130 kΩ at 1 kHz. Furthermore, fabricated 32-channel bilayer-nanomesh microelectrode arrays(MEA) have demonstrated over 90% yield on average, with down to 10% impedance variation among all electrode channels. Meanwhile, the bilayer nanomesh MEAs showed excellent compatibility with state of the art Ultra-Wide Band links for wireless recording and real-time stimulation artifact cancellation with a 100,000× signal/error ratio. Finally, in vivo electrophysiology recording with simultaneous 2-photon imaging on the mice visual cortex further validated the functionality and significance of our transparent MEA. The highly-transparent 32-channel bilayer nanomesh MEA allowed both wide-field epifluorescence and 2-photon Ca⁺⁺ imaging of visual cortex and surrounding areas with successful detection of visual evoked potentials from multi-unit activity, while with no significant inflammation of the cortex due to the MEA implantation after 20 days. The results here established the bilayer nanomesh microelectrode approach as a practical pathway towards large-scale, high-density transparent arrays, with broad utility in neuroscience and medical practices.

The complexity of neural activities has challenged both neuroscience research and clinical practice for decades. Understanding neuronal dynamics and information processing performed by neural populations requires advanced technologies with high-resolution sensing and stimulation capability. Clinical neuromodulation therapies widely used for neurological disorders also depend on the ability to manipulate the dynamics of neural circuits. Conventional neural interfaces offering electrical, optical, or chemical signals have greatly advanced our understanding of neural functions, however, most of these technologies are based on a single functionality. Combining multiple functionalities in a single system has recently been pursued as an integrative approach in new neurotechnology development. Graphene has recently emerged as a neural interface material offering several outstanding properties, such as optical transparency, flexibility, high conductivity, functionalization and biocompatibility. The unique combination of these properties in a single material system makes graphene an attractive choice for multi-modal probing of neural activity. In this talk, I will present our recent work on graphene-based neural interfaces, highlight key applications, and finally discuss future directions and potential advances for graphene-based neurotechnologies in both basic neuroscience research and medical applications.

A soft, fully biocompatible, stretchable strain sensor device based on ultra-thin stretchable electronics is reported. The sensor is able to monitor stretch of the bladder wall, via a resistive strain sensing approach. The stretchable sensor is used to determine bladder stretch, and hence volume, without the need for complex and invasive surgical procedures used currently, enabling the development of new safer and cheaper treatment options for various urological conditions. Such instances where a means to monitor bladder stretch could be invaluable are for sufferers of overactive bladder syndrome (OAB), urinary urge incontinence or after spinal cord injury.

Thermally evaporated Cr/Au thin films (~ 150 nm) on compliant, stretchable polyurethane (PU) film (≤ 50 µm), were deposited to produce resistive sensors. The sensors were patterned into a ‘dogbone’ design by laser patterning, with sensor W and L dimensions on the mm scale. The sensors display a linear response as a function of strain from 0 to 50 %, and as sensor length increases, sensor sensitivity as a function of strain increases. We show that the sensitivity is highest for L = 6 mm, at 3.18 Ω/%-strain, which is around 15 times higher than the sensitivity for L = 2 mm, at 0.21 Ω/%-strain. Furthermore, cycling tests performed on sensors of various length reveal that the devices display good stability, with virtually no hysteresis.

The highest sensitivity sensors were subsequently tested in vitro on an isolated pig bladder. The sensors were attached onto the external wall of the bladder using a biocompatible hydrogel adhesive. The bladder was repeatedly filled and emptied using a syringe system designed to mimic natural bladder behaviour. As bladder volume changes, the sensor changes resistance as a function of stretch, and displays very good repeatability over several bladder filling/emptying cycles. We found a maximum sensitivity of 0.1 Ω/ml for the most sensitive device. Our sensors pave the way towards completely implantable health monitoring systems of the future.

Neurotechnology provides a potential platform for novel material-based strategies that can refashion the existing neural interface technologies. The current widely-used neural interfaces are dry, brittle and inorganic in nature, warranting a new soft material candidate for the development of tissue-compliant and mechanically-robust electrode interfaces that show great affinity to the wet surfaces of the biological tissues. Here, we report, soft and excellently conformal electrode interfaces designed on hydrated silk films that can conform to the wet slimy surfaces of the rat cortex. To the best of our knowledge, this is the first such demonstration of functional silk electrical interfaces for the wet in vivo environs of the cortex. This work represents a significant step towards soft implantable bioelectronics.
Metallized silk substrate (~15 μm thick) carrying the gold electrode patterns (~ 100 nm thick) is integrated with a patterned silk superstrate (~15 μm thick) to yield a silk electrode array. A flexible interconnect is connected to the array to facilitate electrical readouts from the electrode sites. The silk arrays are then water-annealed (~12 h) to render them nontransient.
We deployed the silk arrays on the rat cortex (S1FL region) to demonstrate the in vivo applicability of the nontransient silk interfaces. We noted that the cortical array laminated conformably on the nonplanar surface of the cortex. A rat transient ischemia (TIA) model was employed to demonstrate ECoG recording capability of the silk array. ECoG recordings prior to (serving as baseline) and following induction of stroke provided functional validation of the silk cortical array. A cranial window was created to deploy the silk array. The cerebral blood vessel in which a blood clot is to be induced, was located. The ECoG array was then deployed upon the S1FL region of the cranial window. The selected cerebral blood vessel (diameter 80 μm) was observed clearly via the transparent silk window of the silk array. Injection of Rose Bengal and shining of laser light (CW laser, 532 nm) through the transparent silk substrate induced a blood clot in the cerebral blood vessel. The evoked potentials captured by the individual electrode sites of the silk array prior to the induction of stroke represent the baseline ECoG recordings. These recorded responses were evoked through forepaw stimulation. Induction of blood clot led to a suppression of the evoked ECoG activity, captured cleanly by the silk array.
In this work, we reported the feasibility of realizing nontransient soft conformal silk electrode arrays for interfacing with the cortical surface in rat model. We observed that the silk arrays are soft and could couple intimately to the wet surfaces of the rat cortex. To the best of our knowledge, this is the first such demonstration of silk neurotechnology for the cortex and can impact basic neuroscience research and clinical trial industry.

Conductive polymers have been widely explored as a coating of inorganic substrates for biological signal recording and stimulation, but their poor adhesion to inorganic substrates represents the main limit for their in vivo application and current solutions make use of long and complicated processing steps [1-3]. In this work, stainless steel wire electrodes composed of twisted wires have been coated with conductive polymers through electropolymerization for muscle signal recording in small animals. Two solutions consisting in Dopamine:Polypyrrole/PEDOT bilayer and PEDOT processed in propylene carbonate are proposed to increase the polymer adhesion to the metal. The electrodes have been electrochemically characterized, and the adhesion and electrochemical stability have been evaluated through ultrasonication and phosphate buffer solution soaking test. Our work gives new insights on the adhesion enhancement of conductive polymers to inorganic substrates allowing for simple and fast solutions that will improve the durability and efficiency of conductive polymer coated electrodes.
[1] S. Carli et al. "Conductive PEDOT Covalently Bound to Transparent FTO Electrodes," J. Phys. Chem. C, vol. 118, no. 30, pp. 16782-16790, 2014.
[2] L. Ouyang et al. "Enhanced PEDOT adhesion on solid substrates with electrografted P(EDOT-NH₂)," Sci. Adv., vol. 3, no. 3, 2017.
[3] X. Luo et al. "Highly stable carbon nanotube doped poly(3,4-ethylenedioxythiophene) for chronic neural stimulation," Biomaterials, vol. 32, no. 24, pp. 5551-5557, 2011.

The incidence of neurological disorders like epilepsy, Parkinson’s disease, stroke, dementia, addiction and major mental illness is growing, as the world’s population ages. Response to medications for these conditions has plateaued, paving the way for a revolution in implantable devices as the next wave of effective treatments for these “brain network disorders.” Key to developing these new devices are advances in computation, batteries, sensors and closed loop algorithms. New and more versatile materials is one of the main requirements and drivers of innovation in new medical devices and technologies. In this lecture I will outline major applications in the area of neurodevices/ brain computer interfaces, present unmet needs, and discuss the path to clinically translate innovations from the laboratory to patients. I will give examples from our own research and other labs on this path, touch on common failure modes and novel tools for collaboration, bringing engineers, clinicians and industry together to advance clinical care.

During the past decades, neural electrodes have been developed as promising interface technology for direct communication with the neural tissues for diagnosis of the nervous disorders and treatment of the injury. Considering the significant material mismatch between the external implant and native tissue, a thin coating is employed on the electrode sites as an intermediate layer to bridge the difference. However, great challenges still exist regarding the long-term performance of the electrode coating in vivo.
In this study, a tubular electrode coating made of poly(3,4-ethylenedioxythiophene) (PEDOT) and carbon nanotube (CNT) was designed, targeted to long-term neural recording. The PEDOT-CNT nanotube coating was fabricated and showed compatibility with flexible polyimide electrode. The coating exhibited a 3D network-like structure made of hollow tube with an outer diameter of ~700nm and wall thickness of ~90nm. The electroactivity of the PEDOT-CNT coating was investigated using electrochemical impedance spectroscopy and cyclic voltammetry. The coated electrode sites showed significantly decreased impedance and increase charge storage capacity compared to bared site, which would allow more charge transfer at the interface and increase the sensitivity during neural recording. To test the mechanical adhesion of the PEDOT-CNT nanotube coating, ultrasonic treatment was employed in the study. The PEDOT-CNT nanotube could sustain 20min sonication with less than 20% delamination area while the PEDOT-PSS nanotube showed more than 60% delamination area after 5min treatment. The incorporation of CNT significantly reinforced the nanotube structure and improved the mechanical durability against sonication which would address the delamination issue of PEDOT coating and support chronic recording. We have also studies the different deposition condition and their effects on the morphology, electrical property and mechanical property of the coating. In vitro culture of neurons showed positive neuron attachment and neurite extension on PEDOT-CNT nanotube immobilized with poly-lysine and laminin.

Organic electronic devices, apart from consumer applications, are presently paving the path for key applications at the interface between electronics and biology. In such applications, organic polymers are very attractive candidates, due to their distinct properties of mechanical flexibility, self-healing and mixed conduction.
My group investigated the processing conditions leading to high electrical conductivity, long-term stability in aqueous media as well as robust mechanical properties of the conducting polymer poly(3,4-ethylenedioxythiophene) doped with polystyrenesulfonate (PEDOT:PSS) [1-3].We have demonstrated that stretchable PEDOT:PSS films can be achieved by adding a fluorosurfactant to the film processing mixture and by pre-stretching the substrate during film deposition. We have achieved patterning of organic materials on a wide range of substrates, using orthogonal lithography and pattern transfer [4-5]. Recently we have discovered that PEDOT:PSS films can be rapidly healed with water drops after being damaged with a sharp blade [6] or show autonomous self-healing if processed in presence of certain additives.
My talk will deal with processing, characterization and patterning of conducting polymer films and devices for flexible, stretchable and healable electronics. I will particularly focus on the strategies to achieve films with optimized electrical conductivity and mechanical properties, on unconventional micro patterning on flexible and stretchable substrates, on the different routes to achieve films stretchability and self-healing.

F. Cicoira et al. APL Mat.3, 014911, 2015.
F. Cicoira et al.Appl. Phys. Lett. 107,053303, 2015.
3. F. Cicoira, et al. Appl. Phys. Lett. 111, 093701, 2017
F. Cicoira et al. Chem. Mater. 29, 3126-3132, 2017.
F. Cicoira et al. J. Mater. Chem.C 4, 1382–85, 2016.
F. Cicoira et al. Adv. Mater.29, 1703098, 2017.

Soft bioelectronics incorporates all the functional attributes of conventional rigid electronics in formats that enable reversible mechanical loading and, in the case of implantables, performance under physiological conditions. Understanding the underlying mechanisms of stretchable materials and establishing the performance boundaries of such devices under the multiple operation conditions are fundamental to research efforts in the field. The biomedical context also imposes a challenging experimental environment that is difficult to replicate or predict. There is an unmet need for experimental set-ups that combine multiple modes of loading e.g. mechanical, thermal, electrical, biological, and provide real-time, concurrent probing of the devices.

This talk will describe our recent efforts in constructing multimodal experimental set-ups and establishing standardized tests and experiments that can clearly define the reliability and lifetime for soft bioelectronics. Using stretchable metallization integrated in wearable sensors and spinal implants as test vehicles for the new characterization platforms, we will report on failure modes, repeatability, robustness, and reliability. These metrics are often underestimated in academic research yet critical to advance the translation of soft bioelectronics.

Living organisms mainly use nervous and endocrine systems to control the body and maintain homeostasis independently. Endocrinal signal based on the flow of special chemicals called hormone affects the body chronically and massively. When stress is applied to human body, hypothalamus releases corticotropin-releasing hormone (CRH) to the pituitary gland that generates adrenocorticotropic hormone (ACTH) which flows into the adrenal cortex, especially adrenal zona fasciculata (AZF) cell in adrenal gland. The adrenal cortex then produces cortisol, a stress hormone that rebalances body functions and performances of neural and muscular system. However, repeated and chronic stress can cause malfunctions in cortisol releasing endocrine system. Chronic stress involves accumulation of excessive and unnecessary cortisol that eventually cause several diseases such as amnesia, depression, fatigue, anxiety. It is necessary to continuously monitor the cortisol concentration to prevent such diseases which caused by chronic stress. Recently, it was revealed that the electrophysiological (EP) signal induced by ion flux through cellular membrane was responsible for hormone releasing process in corresponded endocrine organs. We assumed that accurate recording of electric signal representing physiological activities of endocrine cells could be applied to characterize cortisol change. Here, we introduce a long lasting, implantable Anchor - like flexible probe that can be used to quantify relationship between cortisol releasing level and electrophysiological (EP) signals from adrenal gland based on flexible EP sensors. This anchor – like probe penetrated through Adrenal Gland, which ensured minimal invasion to organs and stability, low impedance increment over 13 weeks. Through our research, we identified EP signal Frequency was increased in AZF cells, only induced by acute stress or ACTH injection. Thus, our team successfully determined activities of hormonal cells and relative change of cortisol hormone level under stress environment in in vivo animal model. Next, we hypothesized that electrical stimulation of surface of adrenal gland could improve or suppress activity of adrenal gland. We designed elastomer based, conformally attaching stretchable serpentine electrodes. It is known that cortisol secretion is also increased by not only stress but blood loss, therefore we extracted small doses of blood from inferior vena cava (IVC) of rat with every 5 minutes to induce artificial hemmorrhage. By comparing Cortisol concentration of Non - electrical stimulated rat with electrically stimulated showed us that high frequency electrical stimulation tend to suppress activity of AZF cell. However, low frequency electrical stimulation improved AZF cell activity, which showed higher cortisol concentration then standard cortisol concentration. This research of Adrenal gland could provide fundamental knowledge to medical applications such as stress regulator.

Conductive gel enabling precise measurement of weak electrical signals are desired for the detection of biomedical signals such as an electroencephalogram (EEG) or a fetal electrocardiogram (ECG). Since these signals are intrinsically weak less than 100 uV, the noise level has to be lowered to acquire signals with the high S/N. In general, one strategy for obtaining the high S/N ratio signal is to increase the electrode area to lower the contact resistance between skin and electrode or to shorten the length of the wiring to prevent invasion an external noise, however, we propose another option to detect signals with high quality by modifying gels on electrode. Here, we designed the biocompatible conductive gel to obtain weak EEG signals with the high S/N ratio by reducing the contact resistance and mains hum intensity.
The developed gels are based on Amylopectin contained in rice and NaCl. By just printing and heating the precursor solution on a noble metal, conductive gel can be fabricated. The impedance spectrum of gels shows almost frequency-independent characteristics through a range of 0.1 Hz to 100 kHz lower than 1kΩ. Hydrogen-boded network of Amylopectin gives sufficiently strong adhesive force to the skin with its strength comparable to adhesive plasters. Other components enable to suppress mains hum that is one of the origin of lowing the S/N ratio of EEG signals. By combining the developed gels and the wireless measurement system, we successfully obtained EEG signals from forehead. As with Ten20 conductive paste that is commonly used to measure EEG signals in hospitals, the developed gels can also detect representative brain wave like alpha waves that