(188h) Electrochemical Biosensors for In Vivo Neurochemical Analysis

The key to understanding the underlying mechanism of complex behaviors and disorders at the molecular-level relies on the ability to monitor neurotransmitter release and metabolite levels in the brains of freely moving animals. Therefore, the capability to simultaneously monitor multiple analytes in vivo would greatly facilitate our understanding of the connection between neurochemistry and behaviors. Previously reported analytical methods, such as microdialysis and fast-scan cyclic voltammetry, either did not have adequate temporal/spatial resolution or require specialized instrumentation.

To this end, we designed and fabricated a permselective membrane-based amperometric biosensing platform, targeting a group of non-electroactive analytes (e.g., glucose, glutamate, and choline), which showed high sensitivity, selectivity and fast response time (e.g., less than a few seconds).[1-4] The developed sensing platforms were successfully transferred to silicon-based microelectrode array microprobes. The underlying sensing mechanism was based on the electrochemical quantification of hydrogen peroxide, which is the end-product of oxidase-based enzymatic reactions. We achieved sensor selectivity against interferents by modifying the electrode surfaces with suitable permselective polymers (e.g., polyphenylenediamine and Nafion). The deposited polymers acted as size and charge exclusion membranes, which allow hydrogen peroxide molecules to pass through to the electrode surface while excluding common interferents (e.g., ascorbic acid and dopamine) present in the brain extracellular fluid. Additionally, we created an electrochemically deposited and nano-based on-probe iridium oxide (IrOx) reference electrode, eliminating the external bulky and inflammatory Ag/AgCl reference electrode.[1-3]

Leveraging the developed biosensors, on-probe IrOx reference electrode, novel PDMS-based thin-film transfer and enzyme microstamping technologies, we provided a unique approach to fabricate complete multifunctional neural probes.[1] The microprobes were able to simultaneously detect multiple analytes in vivo and deliver agents in situ and in a controlled manner. The integration of essential functions on a single platform removes the need for implanting multiple probes, with the dual benefits of reducing brain damage and surgical complexity. Furthermore, to minimize the mechanical mismatch between soft neural tissues and implants, we presented a liquid metal-enabled flexible and stretchable neural probe with ultra-large tunable stiffness for deep-brain electrochemical sensing and agent delivery.[2] Our flexible microprobes displayed mitigated inflammatory responses in vivo, as compared to silicon-based devices.

Reference

[1] B. Wang*, X. Wen*, et al. “A Multifunctional Neural Microprobe for Simultaneous Multi-Analyte Sensing and Chemical Delivery,” Lab on a Chip, 2020, 20, 1390-1397.

[2] X. Wen*, B. Wang*, et al. “Flexible, Multifunctional Neural Probe with Liquid Metal Enabled, Ultra-Large Tunable Stiffness for Deep-Brain Chemical Sensing and Agent Delivery,” Biosensors and Bioelectronics, 2019, 131, 37-45.

[3] B. Wang*, L. Feng* et al. “A Complete Electroenzymatic Choline Microprobe Based on Nanostructured Platinum Microelectrodes and an IrOx On-probe Reference Electrode,” Electroanalysis, 2019, 31, 1249-1253.

[4] B. Wang*, B. Koo* et al. “Microbiosensor Fabrication by Polydimethylsiloxane Stamping for Combined Sensing of Glucose and Choline,” Analyst, 2018, 143, 5008-5013.

*These authors contribute equally.