Enzyme-Mediated Organic Neurohybrid Synapses

Abstract

The development of organic artificial synapses that exhibit biomimicry features also may enable a more seamless integration of neuroelectronic devices in the nervous system, allowing artificial neuromodulation to be perceived as natural behavior by neuronal cells. Nevertheless, the capability to interact with both electroactive and non-electroactive neurotransmitters remains a challenge since state-of-the-art devices mainly rely on the oxidation of electroactive species. Here, the study proposes an organic artificial synapse engineered to enable interaction with non-electroactive species present in the central nervous system. By integrating a conductive polymeric film functionalized with platinum nanoparticles, the device can catalyze the oxidation of electroactive molecules (i.e., H₂O₂) resulting from neurotransmitter-specific enzymatic reactions following an enzymatic functionalization, therefore exhibiting neuromorphic functions driven by non-electroactive neurotransmitters. The creation of devices that can interact with or monitor these neurotransmitters can be seen as a significant step toward innovative technologies to expand the understanding of the mechanisms underlying neurological disorders and the development of novel, more effective treatments for them.

Keywords: electrochemical neuromorphic organic devices; glutamate sensing; neuroelectronics.

Figure 1

Enzyme‐functionalized ENODe's structure and functioning. a) Schematic of the ENODe function emulating the signal processing of a biological synapse with a presynaptic stimulation occurring at the gate electrode functionalized with Pt NPs and the neurotransmitter‐specific enzyme and a postsynaptic response that occurs at the semiconductive channel. The channel current modulation, which is driven by the protons obtained from the enzymatic reaction at the gate electrode, is highlighted. b) Optical spectrometric measurements of the PEDOT:PSS film before and after the electrodeposition of Pt NPs showing the partial preservation of PEDOT:PSS transparency after the functionalization with 15 cycles. SEM image showing the composite film morphology. c) Cyclic Voltammetry of pristine PEDOT:PSS film before (continuous line) and after functionalization (dashed line) when H₂O₂ is added to the electrolyte and in the same voltage window. It shows the presence of current peaks related to the H₂O₂ redox reactions. d) Output curve of the Pt NPs‐functionalized ENODe in DPBS (continuous line) and 1 mm H₂O₂ (dashed line), showing the higher channel current depletion in H₂O₂ solution as the V_GS value increases from −0.2 to 0.8 V. e) Transconductance values obtained from the transfer curves measured in DPBS (continuous line) and at three different H₂O₂ concentrations.

Figure 2

ENODe's opto‐electronic neuromorphic operation. In all measurements, the first value of the channel current, denoted with I₀, was subtracted from the I_DS to compare devices with different baseline currents. a) Channel current response to a single voltage pulse, highlighting short‐term modulation during the on‐phase of the voltage pulse. b) Channel current response to sequential voltage pulses, showing long‐term modulation in terms of non‐reversible current baseline modulation. c) The response of the same ENODe to sequential voltage pulses before and after Pt NPs functionalization. Device response was monitored in the case of bare electrolyte (continuous curves) and in 1 mm H₂O₂ solution (dashed curves) before and after the functionalization, showing a clear long‐term modulation of the baseline current only in the case of the functionalized device operating in presence of the synaptic modulator. d) Schematic of ENODe's opto‐electronic operation under optical illumination while the optical fiber records the light transmitted through the electrochromic post‐synaptic terminal. From left to right: the post‐synaptic response when H₂O₂ is not present at the gate/electrolyte interface; the electrochemical reaction occurring at the gate electrode when H₂O₂ is present in solution and the H⁺ resulting from the Pt‐catalyzed H₂O₂ oxidation reaction; the enhanced post‐synaptic response due to the H⁺‐related polymer de‐doping at ENODe's channel (the darken region highlights a further de‐doping). e) Opto‐electronic measurements when sequential voltage pulses are applied. From top to bottom: presynaptic stimulation (V_GS pulses); channel current time‐response and related absorbance changes extracted from monitoring the light transmitted through the post‐synaptic terminal during ENODe electrical operation in DPBS and at different H₂O₂ concentrations. f) Absorbance and conductance variations at different H₂O₂ concentrations, quantifying post‐synaptic long‐term modulation.

Figure 3

Glutamate‐driven neuromorphic functions of the enzyme‐functionalized ENODe. a) Schematic of the enzyme‐functionalized ENODe post‐synaptic response when a pre‐synaptic stimulus occurs. From left to right: the post‐synaptic response when glutamate is not present at the gate/electrolyte interface; the mechanism of the enzymatic reaction occurring at the gate electrode when glutamate is present in solution and the H⁺ resulting from the Pt‐catalyzed H₂O₂ oxidation reaction; enhanced post‐synaptic response due to the H⁺‐related polymer de‐doping at ENODe's channel (the darkened region highlights a further de‐doping). b) Transconductance values of the enzyme‐functionalized ENODe obtained from the transfer curves measured in DPBS (continuous line) and in three different glutamate concentrations. c,d) Long‐lasting pulse response when glutamate is added in the electrolyte solution at 220 s, showing further depletion of the channel current at different glutamate concentrations and related current depletion quantification, respectively (capacitive peaks at the onset and the offset of the pulse were not filtered). e) Channel current response to a single voltage pulse, highlighting short‐term modulation during the on‐phase of the voltage pulse. f) Channel current response to sequential voltage pulses, showing long‐term modulation in terms of non‐reversible current baseline modulation when glutamate is present in the electrolyte solution. g) Error bar plot of conductance variations at different glutamate concentrations, quantifying post‐synaptic long‐term modulation.

Figure 4

ENODe mimicking biological learning‐forgetting process. The channel current was monitored during ENODe operation in 1 mm glutamate solution by considering, for each point, the current values taken at the end of each pulse (pink curve). The blue line represents the learning threshold that is reached by the ENODe at the end of the learning phase. Fresh glutamate solution was added in the microfluidic channel at the end of each forgetting phase.