Multiplexed neurochemical sensing with sub-nM sensitivity across 2.25 mm2 area

Nofar Mintz Hemed; Fuu-Jiun Hwang; Eric T Zhao; Jun B Ding; Nicholas A Melosh

doi:10.1016/j.bios.2024.116474

Multiplexed neurochemical sensing with sub-nM sensitivity across 2.25 mm² area

Biosens Bioelectron. 2024 Oct 1:261:116474. doi: 10.1016/j.bios.2024.116474. Epub 2024 Jun 6.

Authors

Nofar Mintz Hemed¹, Fuu-Jiun Hwang², Eric T Zhao³, Jun B Ding⁴, Nicholas A Melosh⁵

Affiliations

¹ Department of Materials Science and Engineering, Stanford University, Stanford, CA, USA.
² Department of Neurosurgery, Stanford University, Stanford, CA, 94305, USA.
³ Department of Chemical Engineering, Stanford University, Stanford, CA, 94305, USA.
⁴ Department of Neurosurgery, Stanford University, Stanford, CA, 94305, USA; Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA, 94305, USA.
⁵ Department of Materials Science and Engineering, Stanford University, Stanford, CA, USA. Electronic address: nmelosh@stanford.edu.

PMID: 38870827
DOI: 10.1016/j.bios.2024.116474

Abstract

Multichannel arrays capable of real-time sensing of neuromodulators in the brain are crucial for gaining insights into new aspects of neural communication. However, measuring neurochemicals, such as dopamine, at low concentrations over large areas has proven challenging. In this research, we demonstrate a novel approach that leverages the scalability and processing power offered by microelectrode array devices integrated with a functionalized, high-density microwire bundle, enabling electrochemical sensing at an unprecedented scale and spatial resolution. The sensors demonstrate outstanding selective molecular recognition by incorporating a selective polymeric membrane. By combining cutting-edge commercial multiplexing, digitization, and data acquisition hardware with a bio-compatible and highly sensitive neurochemical interface array, we establish a powerful platform for neurochemical analysis. This multichannel array has been successfully utilized in vitro and ex vivo systems. Notably, our results show a sensing area of 2.25 mm² with an impressive detection limit of 820 pM for dopamine. This new approach paves the way for investigating complex neurochemical processes and holds promise for advancing our understanding of brain function and neurological disorders.

Keywords: Dopamine; Electrochemical impedance spectroscopy; Microelectrode array; Microwire array; Molecular imprinting polymer.

MeSH terms

Animals
Biosensing Techniques* / instrumentation
Biosensing Techniques* / methods
Brain / metabolism
Dopamine* / analysis
Electrochemical Techniques* / methods
Equipment Design
Humans
Limit of Detection*
Microelectrodes*
Neurotransmitter Agents / analysis

Substances

Dopamine
Neurotransmitter Agents