Researchers develop an artificial neuron closely mimicking the characteristics of a biological neuron

Clinical Trials & Research

In a recent article published in Nature Materials, researchers reported a conductance-based organic electrochemical neuron (c-OECN) that mimicked biological signaling in neurons, especially activation/inactivation of their sodium and potassium channels.

Study: Ion-tunable antiambipolarity in mixed ion–electron conducting polymers enables biorealistic organic electrochemical neurons. Image Credit: MattLphotography/Shutterstock

Background

Neurons crosstalk and process information primarily via the sodium and potassium ion channels (in the cell membrane) through spike generation in membrane potentials (also called action potential). Silicon and organic semiconductors-based neurons mimic only limited neural features. Moreover, they operate at time and spike voltages radically varied from those witnessed in biology.

Consequently, they require the coupling of supplementary sensing elements to act as neuromorphic sensors. A circuit more closely mimicking biological neurons should be able to activate and inactivate faster like a sodium channel and activate post a delay like a potassium channel.

In this context, organic electrochemical transistors (OECTs) are an attractive option. They have multiple desirable features, such as exceptional sensing capabilities for biological and physical plus chemical signals. Moreover, they are biocompatible, switch speeds readily, operate at low voltages, and exhibit coupled ionic–electronic transport properties, which are controllable via external dopants.

For example, poly(benzimidazobenzophenanthroline) (BBL) is a useful OECT. It exhibits reduced electrical conductivity on high electrochemical doping by forming multiply charged species having reduced mobility.

About the study

In the present study, researchers utilized the ion-tunable antiambipolarity of BBL to mimic the activation and inactivation of sodium channels in neurons, giving rise to a c-OECN. First, they synthesized BBL by polycondensation of naphthalene tetracarboxylic dianhydride (NDA) and 1,2,4,5 tetraaminobenzene tetrahydrochloride (TABH) in poly(phosphoric acid) (PPA).

For casting a thin film of BBL, they dissolved it in methanesulfonic acid (MSA) at 100 °C for 12 hours, then cooled it to room temperature to obtain the BBL–MSA solution. The team used an established protocol for OECT fabrication. Next, they tested the OECT, followed by a simulation of the spiking features of c-OECNs using two models, K-OECT and Na-OECT. Finally, they interfaced the fabricated c-OECN with the mouse’s vagus nerve.

Organic electrochemical polymers mimicked neurons

Unique Gaussian behaviors unleash the possibility of chemical-specific responses. Thus, it seems feasible to alter the antiambipolar response using amino acids such as γ-butyric acid (GABA) and glutamine with different amine group configurations. Adding 3.3 mM of GABA or glutamine causes changes in the VP of the OECT electrolyte solution and the channel’s conductance. Perhaps, due to the effect of hydrogen-bonding interactions of these molecules with BBL.

Thus, as a channel material, BBL exhibits a stable, exclusive, and reversible antiambipolar behavior in a three-terminal arrangement. In a circuit, it could be analogous to the states of the voltage-gated sodium channel in a neuron model. Notably, at 4.15 eV (electron affinity), BBL could sustain high doping levels. However, it did not exhibit any conformational disorder, thus, enabling reversibility.

The c-OECN circuit used two OECTs—Na+-OECT and K+-OECT, with the latter having a thicker BBL film (50 nm vs. 20 nm used in Na+-OECT ) to allow higher currents through the potassium channel. Using these, the researchers demonstrated that the c-OECN action potential typically exhibited all the features of a biological action potential, viz., de-, re-, and hyperpolarization.

Conclusion

To conclude, the study demonstrated that, unlike previously used OECTs,  c-OECNs remarkably mimicked most critical biological neural features. The c-OECN mimicked biological neurons remarkably well, spiking at 100 Hz frequencies, replicating most critical neuron features, and exhibiting stochastic response in the presence of noise. It also enabled amino acid-based spiking modulation, which, in turn, helped stimulate nerves in vivo.

Furthermore, it operated as an event-based sensor transducing such biochemical signals to stimulate the mouse vagus nerve, demonstrating closed-loop regulation of physiology. Most importantly, it used a mixed ion–electron conducting ladder-type polymer with ion-tunable antiambipolar properties.

Journal reference:

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