Dion Khodagholy

In vivo recordings of brain activity using organic transistors

In vivo electrophysiological recordings of neuronal circuits are necessary for diagnostic purposes and for brain-machine interfaces. Organic electronic devices constitute a promising candidate because of their mechanical flexibility and biocompatibility. Here we demonstrate the engineering of an organic electrochemical transistor embedded in an ultrathin organic film designed to record electrophysiological signals on the surface of the brain. The device, tested in vivo on epileptiform discharges, displayed superior signal-to-noise ratio due to local amplification compared with surface electrodes. The organic transistor was able to record on the surface low-amplitude brain activities, which were poorly resolved with surface electrodes. This study introduces a new class of biocompatible, highly flexible devices for recording brain activity with superior signal-to-noise ratio that hold great promise for medical applications.

NeuroGrid: recording action potentials from the surface of the brain

Recording from neural networks at the resolution of action potentials is critical for understanding how information is processed in the brain. Here, we address this challenge by developing an organic material–based, ultraconformable, biocompatible and scalable neural interface array (the ‘NeuroGrid’) that can record both local field potentials(LFPs) and action potentials from superficial cortical neurons without penetrating the brain surface. Spikes with features of interneurons and pyramidal cells were simultaneously acquired by multiple neighboring electrodes of the NeuroGrid, allowing for the isolation of putative single neurons in rats. Spiking activity demonstrated consistent phase modulation by ongoing brain oscillations and was stable in recordings exceeding 1 weeks duration. We also recorded LFP-modulated spiking activity intraoperatively in patients undergoing epilepsy surgery. The NeuroGrid constitutes an effective method for large-scale, stable recording of neuronal spikes in concert with local population synaptic activity, enhancing comprehension of neural processes across spatiotemporal scales and potentially facilitating diagnosis and therapy for brain disorders.

Highly Conformable Conducting Polymer Electrodes for In Vivo Recordings

Electronic devices that interface with living tissue have become a necessity in clinics to improve diagnosis and treatments. Devices such as cardiac pacemakers and cochlear implants stimulate and monitor electrically active cells, restoring lost function and improving quality of life. On a more fundamental level, most breakthroughs in our understanding of the basic mechanisms of information processing in the brain have been obtained by means of recordings from implantable electrodes. [ 1–3 ] Materials science is playing a pivotal role in this fi eld. For example, state-of-the-art implantable electrodes are microfabricated devices that contain high-density arrays of metal sites on a silicon shank (silicon probes). [ 4 ] Still, as neuroscience continues to advance and more options for electrical intervention become a reality for patients (ocular implants, deep-brain stimulation for epilepsy and Parkinson’s disease), [ 5 ] there is a tremendous need for developing advanced materials solutions for the biotic/abiotic interface. One such example is the necessity to develop electrodes that can conform to the curvilinear shapes of organs (e.g., the surface of the brain or its sulci) and form high-quality electrical contacts. Such surface electrodes are needed for electrocorticography (ECoG), which is increasingly used for functional mapping of cognitive processes before certain types of brain surgery (e.g., tumors) or for diagnosis purposes (e.g., epilepsy). [ 6 ] Placed on the somatosensory cortex, surface electrode arrays are also being used in brain-machine interfaces, an assistive technology for people with severe motor disabilities. [ 7 ] In contrary to silicon probes that penetrate the brain and cause tissue damage, these arrays are placed on the surface of the brain and are hence less invasive.

High-performance transistors for bioelectronics through tuning of channel thickness

Transistors with tunable transconductance allow high-quality recordings of human brain rhythms. Despite recent interest in organic electrochemical transistors (OECTs), sparked by their straightforward fabrication and high performance, the fundamental mechanism behind their operation remains largely unexplored. OECTs use an electrolyte in direct contact with a polymer channel as part of their device structure. Hence, they offer facile integration with biological milieux and are currently used as amplifying transducers for bioelectronics. Ion exchange between electrolyte and channel is believed to take place in OECTs, although the extent of this process and its impact on device characteristics are still unknown. We show that the uptake of ions from an electrolyte into a film of poly(3,4-ethylenedioxythiophene) doped with polystyrene sulfonate (PEDOT:PSS) leads to a purely volumetric capacitance of 39 F/cm3. This results in a dependence of the transconductance on channel thickness, a new degree of freedom that we exploit to demonstrate high-quality recordings of human brain rhythms. Our results bring to the forefront a transistor class in which performance can be tuned independently of device footprint and provide guidelines for the design of materials that will lead to state-of-the-art transistor performance.

Direct measurement of ion mobility in a conducting polymer.

Using planar junctions between the conducting polymer PEDOT:PSS and various electrolytes, it is possible to inject common ions and directly observe their transit through the film. The 1D geometry of the experiment allows a straightforward estimate of the ion drift mobilities.

Tools for probing local circuits: high-density silicon probes combined with optogenetics.

To understand how function arises from the interactions between neurons, it is necessary to use methods that allow the monitoring of brain activity at the single-neuron, single-spike level and the targeted manipulation of the diverse neuron types selectively in a closed-loop manner. Large-scale recordings of neuronal spiking combined with optogenetic perturbation of identified individual neurons has emerged as a suitable method for such tasks in behaving animals. To fully exploit the potential power of these methods, multiple steps of technical innovation are needed. We highlight the current state-of-the-art in electrophysiological recording methods, combined with optogenetics, and discuss directions for progress. In addition, we point to areas where rapid development is in progress and discuss topics where near-term improvements are possible and needed.

Organic electrochemical transistor incorporating an ionogel as a solid state electrolyte for lactate sensing

Room temperature Ionic liquids (RTILs) have evolved as a new type of solvent for biocatalysis, mainly due to their unique and tunable physical properties.[1] In addition, within the family of organic semiconductor-based sensors, organic electrochemical transistors (OECTs) have attracted particular interest.[2] Here, we present a simple and robust biosensor, based on a OECT, capable of measuring lactic acid using a gel-like polymeric materials that endow RTIL (ionogel)[3] as solid-state electrolyte both to immobilise the enzyme and to serve as a supporting electrolyte.[4] This represents the first step towards the achievement of a fast, flexible, miniaturised and cheap way of measuring lactate concentration in sweat.

Easy‐to‐Fabricate Conducting Polymer Microelectrode Arrays

A simple and versatile fabrication process is used to define conducting polymer microelectrode arrays (MEAs), patterning at the same time the recording electrodes as well as the insulating layer. Thanks to the low impedance of poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) (PEDOT:PSS) electrodes, these MEAs allow in vitro recording of action potentials from rat hippocampus slices.

Measurement of Barrier Tissue Integrity with an Organic Electrochemical Transistor

The integration of an organic electrochemical transistor with human barrier tissue cells provides a novel method for assessing toxicology of compounds in vitro. Minute variations in paracellular ionic flux induced by toxic compounds are measured in real time, with unprecedented temporal resolution and extreme sensitivity.

Organic Electrochemical Transistors with Maximum Transconductance at Zero Gate Bias

By varying device geometry we have engineered organic electrochemical transistors that exhibit their maximum transconductance at zero gate bias. This enables the design of a simplified amplifying transducer, allowing for improved integration with biomedical systems where prolonged gate bias can be detrimental.