Electrochemical and Electrical Biosensors for Wearable and Implantable Electronics Based on Conducting Polymers and Carbon-Based Materials.

Bioelectronic devices are designed to translate biological information into electrical signals and vice versa, thereby bridging the gap between the living biological world and electronic systems. Among different types of bioelectronics devices, wearable and implantable biosensors are particularly important as they offer access to the physiological and biochemical activities of tissues and organs, which is significant in diagnosing and researching various medical conditions. Organic conducting and semiconducting materials, including conducting polymers (CPs) and graphene and carbon nanotubes (CNTs), are some of the most promising candidates for wearable and implantable biosensors. Their unique electrical, electrochemical, and mechanical properties bring new possibilities to bioelectronics that could not be realized by utilizing metals- or silicon-based analogues. The use of organic- and carbon-based conductors in the development of wearable and implantable biosensors has emerged as a rapidly growing research field, with remarkable progress being made in recent years. The use of such materials addresses the issue of mismatched properties between biological tissues and electronic devices, as well as the improvement in the accuracy and fidelity of the transferred information. In this review, we highlight the most recent advances in this field and provide insights into organic and carbon-based (semi)conducting materials' properties and relate these to their applications in wearable/implantable biosensors. We also provide a perspective on the promising potential and exciting future developments of wearable/implantable biosensors.

Flexible 3D printed microwires and 3D microelectrodes for heart-on-a-chip engineering.

We developed a heart-on-a-chip platform that integrates highly flexible, vertical, 3D micropillar electrodes for electrophysiological recording and elastic microwires for the tissue's contractile force assessment. The high aspect ratio microelectrodes were 3D-printed into the device using a conductive polymer, poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS). A pair of flexible, quantum dots/thermoplastic elastomer nanocomposite microwires were 3D printed to anchor the tissue and enable continuous contractile force assessment. The 3D microelectrodes and flexible microwires enabled unobstructed human iPSC-based cardiac tissue formation and contraction, suspended above the device surface, under both spontaneous beating and upon pacing with a separate set of integrated carbon electrodes. Recording of extracellular field potentials using the PEDOT:PSS micropillars was demonstrated with and without epinephrine as a model drug, non-invasively, along within situmonitoring of tissue contractile properties and calcium transients. Uniquely, the platform provides integrated profiling of electrical and contractile tissue properties, which is critical for proper evaluation of complex, mechanically and electrically active tissues, such as the heart muscle under both physiological and pathological conditions.

Wet-printing of PEDOT:PSS Microelectrodes for Gastric Slow Wave Recording.

Bioelectrical slow waves are fundamental to maintaining the normal motility of the gastrointestinal tract. Slow wave abnormalities are associated with several major digestive disorders. High-resolution electrical mapping arrays have been used to investigate pathological slow wave abnormalities. However, conventional electrode substrate materials are opaque with high mechanical modulus, which leads to non-compliance and sub-par contact with the organ, without additional manipulations. Here we developed highly conformal and transparent conducting polymer electrode arrays using the extrusion wet-printing technique. The performance of electrodes for the electrophysiological recording of the gastric slow wave was validated using in a pig model, against a previously validated reference array over 100 s recording window. The conducting polymer electrodes registered comparable frequency to the reference array ( 3.31±0.20 cpm vs. 3.27±0.07 cpm, p = 0.067), with lower amplitude ( 372±237 vs. ), and signal to noise ratio ( 10.92±7.83 vs. [Formula: see text]). Further adjustments to the deposition parameters and contact material will improve the performance of the conducting polymer array for future experimental applications. Clinical Relevance- These conducting polymer electrodes provide better compliance and minimized mechanical mismatch to the gut tissue thus allowing long-term monitoring and stimulation of the gut. This could be potentially extended to other organs as well.

Comparison of gold and PEDOT:PSS contacts for high-resolution gastric electrical mapping using flexible printed circuit arrays.

Motility of the stomach is governed by an electrophysiological event termed gastric slow waves. High-resolution (HR) bioelectrical mapping involves placing array of electrodes over the surface of the stomach to record gastric slow waves. Conductive polymer materials have recently been applied to great effect in cardiology and neurophysiology due to its compliant and biocompatible properties. The aim of this study was to quantify the performance of poly(3,4-ethylenedioxythiophene) doped with poly(styrenesulfonate) (PEDOT:PSS) deposited on a flexible print circuit electrode array for gastric slow wave HR mapping. The Au electrodes were coated with PEDOT:PSS at 1 V and different levels of charges (0.3-1.2 mC). HR mapping alongside standard Au electrodes was performed in three anesthetized pigs. Overall, the PEDOT:PSS electrodes detected both antegrade and retrograde slow wave propagations, with comparable frequency, velocity and signal-to-noise ratio to the Au electrodes. Differences between the two electrodes were noted in terms of amplitude and downstroke gradient. The findings of this study will inform designs of future stretchable and implantable HR mapping electrode arrays for gastrointestinal recording and stimulation therapies.

Human Neural Tissues from Neural Stem Cells Using Conductive Biogel and Printed Polymer Microelectrode Arrays for 3D Electrical Stimulation.

Electricity is important in the physiology and development of human tissues such as embryonic and fetal development, and tissue regeneration for wound healing. Accordingly, electrical stimulation (ES) is increasingly being applied to influence cell behavior and function for a biomimetic approach to in vitro cell culture and tissue engineering. Here, the application of conductive polymer (CP) poly(3,4-ethylenedioxythiophene)-polystyrenesulfonate (PEDOT:PSS) pillars is described, direct-write printed in an array format, for 3D ES of maturing neural tissues that are derived from human neural stem cells (NSCs). NSCs are initially encapsulated within a conductive polysaccharide-based biogel interfaced with the CP pillar microelectrode arrays (MEAs), followed by differentiation in situ to neurons and supporting neuroglia during stimulation. Electrochemical properties of the pillar electrodes and the biogel support their electrical performance. Remarkably, stimulated constructs are characterized by widespread tracts of high-density mature neurons and enhanced maturation of functional neural networks. Formation of tissues using the 3D MEAs substantiates the platform for advanced clinically relevant neural tissue induction, with the system likely amendable to diverse cell types to create other neural and non-neural tissues. The platform may be useful for both research and translation, including modeling tissue development, function and dysfunction, electroceuticals, drug screening, and regenerative medicine.

Direct Writing and Characterization of Three-Dimensional Conducting Polymer PEDOT Arrays.

Direct writing is an effective and versatile technique for three-dimensional (3D) fabrication of conducting polymer (CP) structures. It is precisely localized and highly controllable, thus providing great opportunities for incorporating CPs into microelectronic array devices. Herein we demonstrate 3D writing and characterization of poly(3,4-ethylenedioxythiophene)-polystyrenesulfonate (PEDOT:PSS) pillars in an array format, by using an in-house-constructed variant of scanning ion conductance microscopy (SICM). CP pillars with different aspect ratios were successfully fabricated by optimizing the writing parameters: pulling speed, pulling time, concentration of the polymer solution, and the micropipette tip diameter. Especially, super high aspect ratio pillars of around 7 µm in diameter and 5000 µm in height were fabricated, indicating a good capability of this direct writing technique. Additions of an organic solvent and a cross-linking agent contribute to a significantly enhanced water stability of the pillars, critical if the arrays were to be used in biologically relevant applications. Surface morphologies and structural analysis of CP pillars were characterized by scanning electron microscopy and Raman spectroscopy, respectively. Electrochemical properties of the individual pillars of different heights were examined by cyclic voltammetry using a double-barrel micropipette as an electrochemical cell. Exceptional mechanical properties of the pillars, such as high flexibility and robustness, were observed when bent by applying a force. The 3D pillar arrays are expected to provide versatile substrates for functionalized and integrated biological sensing and electrically addressable array devices.