Electropolymerization processing of side-chain engineered EDOT for high performance microelectrode arrays.

Microelectrode Arrays (MEAs) are popular tools for in vitro extracellular recording. They are often optimized by surface engineering to improve affinity with neurons and guarantee higher recording quality and stability. Recently, PEDOT:PSS has been used to coat microelectrodes due to its good biocompatibility and low impedance, which enhances neural coupling. Herein, we investigate on electro-co-polymerization of EDOT with its triglymated derivative to control valence between monomer units and hydrophilic functions on a conducting polymer. Molecular packing, cation complexation, dopant stoichiometry are governed by the glycolation degree of the electro-active coating of the microelectrodes. Optimal monomer ratio allows fine-tuning the material hydrophilicity and biocompatibility without compromising the electrochemical impedance of microelectrodes nor their stability while interfaced with a neural cell culture. After incubation, sensing readout on the modified electrodes shows higher performances with respect to unmodified electropolymerized PEDOT, with higher signal-to-noise ratio (SNR) and higher spike counts on the same neural culture. Reported SNR values are superior to that of state-of-the-art PEDOT microelectrodes and close to that of state-of-the-art 3D microelectrodes, with a reduced fabrication complexity. Thanks to this versatile technique and its impact on the surface chemistry of the microelectrode, we show that electro-co-polymerization trades with many-compound properties to easily gather them into single macromolecular structures. Applied on sensor arrays, it holds great potential for the customization of neurosensors to adapt to environmental boundaries and to optimize extracted sensing features.

Analog programing of conducting-polymer dendritic interconnections and control of their morphology.

Although materials and processes are different from biological cells', brain mimicries led to tremendous achievements in parallel information processing via neuromorphic engineering. Inexistent in electronics, we emulate dendritic morphogenesis by electropolymerization in water, aiming in operando material modification for hardware learning. Systematic study of applied voltage-pulse parameters details on tuning independently morphological aspects of micrometric dendrites': fractal number, branching degree, asymmetry, density or length. Growths time-lapse image processing shows spatial features to be dynamically dependent, and expand distinctively before and after conductive bridging with two electro-generated dendrites. Circuit-element analysis and impedance spectroscopy confirms their morphological control in temporal windows where growth kinetics is finely perturbed by the input frequency and duty cycle. By the emulation of one's most preponderant mechanisms for brain's long-term memory, its implementation in vicinity of sensing arrays, neural probes or biochips shall greatly optimize computational costs and recognition required to classify high-dimensional patterns from complex environments.

PEDOT:PSS organic electrochemical transistors for electrical cell-substrate impedance sensing down to single cells.

The adhesion of cells on organic electrochemical transistors (OECT) is investigated down to a single cell resolution using an impedimetric readout method of the transistors. For this purpose a fabrication protocol for micro-sized OECTs based on Poly(3,4-ethylenedioxythiophene):poly(styrene sulfonic acid) (PEDOT:PSS) was developed. OECTs with gate dimensions of 20 µm × 20 µm with cut-off frequencies up to 10 kHz at -3 dB were fabricated. Impedance spectra of the OECTs changed drastically when HEK 293 cells were adhered to the OECT gates. To confirm the single-cell sensitivity, individual cells were removed from the device surface with patch-clamp pipettes while impedance measurements were performed. In addition, the calcium chelator EGTA was used to demonstrate the reproducible activation and deactivation of tight gap junctions in Madin Darby Canine Kidney cells adhered on the OECT gates. We applied an analytical mathematical model combined with an electrically equivalent circuit model to describe the measured impedance spectra and to calculate the cell-related parameters of the adherent cells. The novel technique of impedimetric readout of OECTs for the detection of single cell adhesion offers various future applications.

PEDOT:PSS organic electrochemical transistor arrays for extracellular electrophysiological sensing of cardiac cells.

Electrophysiological biosensors embedded in planar devices represent a state of the art approach to measure and evaluate the electrical activity of biological systems. This measurement method allows for the testing of drugs and their influences on cells or tissues, cytotoxicity, as well as the direct implementation into biological systems in vivo for signal transduction. Multi-electrode arrays (MEAs) with metal or metal-like electrodes on glass substrates are one of the most common, well-established platforms for this purpose. In recent years organic electrochemical transistors (OECTs) made of poly(2,3-dihydrothieno-1,4-dioxin)-poly(styrenesulfonate) (PEDOT:PSS) have as well shown their value in transducing and amplifying the ionic signals in biological systems. We developed OECT devices in a wafer-scale process and used them as electrophysiological biosensors measuring electrophysiological activity of the cardiac cell line HL-1. Our optimized devices show very promising properties such as good signal-to-noise ratio as well as the ability to record fast components of extracellular signals. Combined with an easy, cost effective fabrication and the transparency of the polymer, this platform offers a valuable alternative to traditional MEA systems for future cell sensing applications.

Human T cells monitored by impedance spectrometry using field-effect transistor arrays: a novel tool for single-cell adhesion and migration studies.

Cytotoxic T lymphocytes (CTLs) play an important role in the immune system by recognizing and eliminating pathogen-infected and tumorigenic cells. In order to achieve their function, T cells have to migrate throughout the whole body and identify the respective targets. In conventional immunology studies, interactions between CTLs and targets are usually investigated using tedious and time-consuming immunofluorescence imaging. However, there is currently no straightforward measurement tool available to examine the interaction strengths. In the present study, adhesion strengths and migration of single human CD8(+) T cells on pre-coated field-effect transistor (FET) devices (i.e. fibronectin, anti-CD3 antibody, and anti-LFA-1 antibody) were measured using impedance spectroscopy. Adhesion strengths to different protein and antibody coatings were compared. By fitting the data to an electronically equivalent circuit model, cell-related parameters (cell membrane capacitance referring to cell morphology and seal resistance referring to adhesion strength) were obtained. This electronically-assessed adhesion strength provides a novel, fast, and important index describing the interaction efficiency. Furthermore, the size of our detection transistor gates as well as their sensitivity reaches down to single cell resolution. Real-time motions of individually migrating T cells can be traced using our FET devices. The in-house fabricated FETs used in the present study are providing a novel and very efficient insight to individual cell interactions.