Daniel T. Simon

Organic electronics for precise delivery of neurotransmitters to modulate mammalian sensory function

Significant advances have been made in the understanding of the pathophysiology, molecular targets and therapies for the treatment of a variety of nervous-system disorders. Particular therapies involve electrical sensing and stimulation of neural activity, and significant effort has therefore been devoted to the refinement of neural electrodes. However, direct electrical interfacing suffers from some inherent problems, such as the inability to discriminate amongst cell types. Thus, there is a need for novel devices to specifically interface nerve cells. Here, we demonstrate an organic electronic device capable of precisely delivering neurotransmitters in vitro and in vivo. In converting electronic addressing into delivery of neurotransmitters, the device mimics the nerve synapse. Using the peripheral auditory system, we show that out of a diverse population of cells, the device can selectively stimulate nerve cells responding to a specific neurotransmitter. This is achieved by precise electronic control of electrophoretic migration through a polymer film. This mechanism provides several sought-after features for regulation of cell signalling: exact dosage determination through electrochemical relationships, minimally disruptive delivery due to lack of fluid flow, and on-off switching. This technology has great potential as a therapeutic platform and could help accelerate the development of therapeutic strategies for nervous-system disorders.

Electrocardiographic Recording with Conformable Organic Electrochemical Transistor Fabricated on Resorbable Bioscaffold

Organic electrochemical transistors are fabricated on a poly(L-lactide-co-glycolide) substrate. Fast and sensitive performance of the transistors allows recording of the electrocardiogram. The resu ...

Detection of Glutamate and Acetylcholine with Organic Electrochemical Transistors Based on Conducting Polymer/Platinum Nanoparticle Composites

The aim of the study is to open a new scope for organic electrochemical transistors based on PEDOT:PSS, a material blend known for its stability and reliability. These devices can leverage molecular electrocatalysis by incorporating small amounts of nano-catalyst during the transistor manufacturing (spin coating). This methodology is very simple to implement using the know-how of nanochemistry and results in efficient enzymatic activity transduction, in this case utilizing choline oxidase and glutamate oxidase.

Controlling Epileptiform Activity with Organic Electronic Ion Pumps

In treating epilepsy, the ideal solution is to act at a seizures onset, but only in the affected regions of the brain. Here, an organic electronic ion pump is demonstrated, which directly delivers on-demand pure molecules to specific brain regions. State-of-the-art organic devices and classical pharmacology are combined to control pathological activity in vitro, and the results are verified with electrophysiological recordings.

Therapy using implanted organic bioelectronics

Implanted organic bioelectronics provide possible alternative to existing pain treatments. Many drugs provide their therapeutic action only at specific sites in the body, but are administered in ways that cause the drug’s spread throughout the organism. This can lead to serious side effects. Local delivery from an implanted device may avoid these issues, especially if the delivery rate can be tuned according to the need of the patient. We turned to electronically and ionically conducting polymers to design a device that could be implanted and used for local electrically controlled delivery of therapeutics. The conducting polymers in our device allow electronic pulses to be transduced into biological signals, in the form of ionic and molecular fluxes, which provide a way of interfacing biology with electronics. Devices based on conducting polymers and polyelectrolytes have been demonstrated in controlled substance delivery to neural tissue, biosensing, and neural recording and stimulation. While providing proof of principle of bioelectronic integration, such demonstrations have been performed in vitro or in anesthetized animals. Here, we demonstrate the efficacy of an implantable organic electronic delivery device for the treatment of neuropathic pain in an animal model. Devices were implanted onto the spinal cord of rats, and 2 days after implantation, local delivery of the inhibitory neurotransmitter γ-aminobutyric acid (GABA) was initiated. Highly localized delivery resulted in a significant decrease in pain response with low dosage and no observable side effects. This demonstration of organic bioelectronics-based therapy in awake animals illustrates a viable alternative to existing pain treatments, paving the way for future implantable bioelectronic therapeutics.

Bioelectronic neural pixel: Chemical stimulation and electrical sensing at the same site

Significance Electronically and ionically conducting polymers provide a unique means to translate electronic addressing signals into chemically specific and spatiotemporally resolved delivery, without fluid flow. These materials have also been shown to provide high-fidelity electrophysiological recordings. Here, we demonstrate the combination of these qualities of organic electronics in multiple 20 × 20 µm delivery/sensing electrodes. The system is used to measure epileptic activity in a brain slice model, and to deliver inhibitory neurotransmitters to the same sites as the recordings. These results show that a single-cell-scale electrode has the ability to both record and chemically stimulate, demonstrating the local effects of therapeutic treatment, and opening a range of opportunities in basic neuroscience as well as medical technology development. Local control of neuronal activity is central to many therapeutic strategies aiming to treat neurological disorders. Arguably, the best solution would make use of endogenous highly localized and specialized regulatory mechanisms of neuronal activity, and an ideal therapeutic technology should sense activity and deliver endogenous molecules at the same site for the most efficient feedback regulation. Here, we address this challenge with an organic electronic multifunctional device that is capable of chemical stimulation and electrical sensing at the same site, at the single-cell scale. Conducting polymer electrodes recorded epileptiform discharges induced in mouse hippocampal preparation. The inhibitory neurotransmitter, γ-aminobutyric acid (GABA), was then actively delivered through the recording electrodes via organic electronic ion pump technology. GABA delivery stopped epileptiform activity, recorded simultaneously and colocally. This multifunctional “neural pixel” creates a range of opportunities, including implantable therapeutic devices with automated feedback, where locally recorded signals regulate local release of specific therapeutic agents.

Admittance spectroscopy of polymer-nanoparticle nonvolatile memory devices

Nonvolatile resistive memory consisting of gold nanoparticles embedded in the conducting polymer poly(4-n-hexylphenyldiphenylamine) examined using admittance spectroscopy. The frequency dependence ...

Chemical delivery array with millisecond neurotransmitter release

Addressable organic electronic neurotransmitter delivery array with switching ~50 ms, approaching synaptic signaling speed. Technologies that restore or augment dysfunctional neural signaling represent a promising route to deeper understanding and new therapies for neurological disorders. Because of the chemical specificity and subsecond signaling of the nervous system, these technologies should be able to release specific neurotransmitters at specific locations with millisecond resolution. We have previously demonstrated an organic electronic lateral electrophoresis technology capable of precise delivery of charged compounds, such as neurotransmitters. However, this technology, the organic electronic ion pump, has been limited to a single delivery point, or several simultaneously addressed outlets, with switch-on speeds of seconds. We report on a vertical neurotransmitter delivery device, configured as an array with individually controlled delivery points and a temporal resolution of 50 ms. This is achieved by supplementing lateral electrophoresis with a control electrode and an ion diode at each delivery point to allow addressing and limit leakage. By delivering local pulses of neurotransmitters with spatiotemporal dynamics approaching synaptic function, the high-speed delivery array promises unprecedented access to neural signaling and a path toward biochemically regulated neural prostheses.

A Four‐Diode Full‐Wave Ionic Current Rectifier Based on Bipolar Membranes: Overcoming the Limit of Electrode Capacity

Full-wave rectification of ionic currents is obtained by constructing the typical four-diode bridge out of ion conducting bipolar membranes. Together with conjugated polymer electrodes addressed with alternating current, the bridge allows for generation of a controlled ionic direct current for extended periods of time without the production of toxic species or gas typically arising from electrode side-reactions.

Fixed p-i-n junction polymer light-emitting electrochemical cells based on charged self-assembled monolayers

The authors report on enhanced efficiency of polymer light-emitting electrochemical cells (LECs) by means of forming a n-doping self-assembled monolayer (SAM) at the cathode-polymer interface. The addition of the SAM, a silane-based salt with structural similarity to the commonly used LEC n-dopant tetra-n-butylammonium, caused a twofold increase in quantum efficiency. Photovoltaic analysis indicates that the SAM increases both the open-circuit voltage and short-circuit current. Current versus voltage data are presented which indicate that the SAM does not simply introduce an interfacial dipole layer, but rather provides a fixed doping region, and thus a more stable p-i-n structure.