Fiber-Based Electrochemical Biosensors for Monitoring pH and Transient Neurometabolic Lactate.

Marsilea A Booth,Seongjun Park,Melinda Hersey,Martyn G Boutelle,Sally A N Gowers,Molly M Stevens,Parastoo Hashemi,Isabelle C Samper,Polina Anikeeva

doi:10.1021/acs.analchem.0c05108

Abstract

Developing tools that are able to monitor transient neurochemical dynamics is important to decipher brain chemistry and function. Multifunctional polymer-based fibers have been recently applied to monitor and modulate neural activity. Here, we explore the potential of polymer fibers comprising six graphite-doped electrodes and two microfluidic channels within a flexible polycarbonate body as a platform for sensing pH and neurometabolic lactate. Electrodes were made into potentiometric sensors (responsive to pH) or amperometric sensors (lactate biosensors). The growth of an iridium oxide layer made the fiber electrodes responsive to pH in a physiologically relevant range. Lactate biosensors were fabricated via platinum black growth on the fiber electrode, followed by an enzyme layer, making them responsive to lactate concentration. Lactate fiber biosensors detected transient neurometabolic lactate changes in an in vivo mouse model. Lactate concentration changes were associated with spreading depolarizations, known to be detrimental to the injured brain. Induced waves were identified by a signature lactate concentration change profile and measured as having a speed of ∼2.7 mm/min (n = 4 waves). Our work highlights the potential applications of fiber-based biosensors for direct monitoring of brain metabolites in the context of injury.

Highlights

Chemical monitoring of human tissue for health is becoming an increasingly critical target.[1,2] Focusing on the brain, being able to monitor dynamic changes in neurochemicals is an important pursuit.[3]
When the solution flow was changed from the Phosphate-buffered saline (PBS) fluidic channel to the ferrocenecontaining channel, an increase in current was observed as expected at two fiber electrodes, demonstrating the use of the microfluidics to characterize the electrochemical response
The preliminary data demonstrate a potential use by coupling the fluidic component with electrochemical measurements at the electrodes; with development one could perfuse and measure a compound of interest at the fiber surface

Summary

Introduction

Chemical monitoring of human tissue for health is becoming an increasingly critical target.[1,2] Focusing on the brain, being able to monitor dynamic changes in neurochemicals is an important pursuit.[3] Microdialysis is an FDAapproved sampling technique to monitor human tissue in the clinic.[4] It is able to measure multiple analytes at a single probe since the sensors are located outside the body. This external location means that sensor calibration is more straightforward than calibration of implanted sensors. The relatively large diameter of clinical microdialysis probes can damage tissue, invoking a foreign body response after implantation,[7] an effect that can be mitigated by retrodialysis of antiinflammatory agents such as dexamethasone,[8] or using custom microfabricated probes with reduced dimensions.[9,10]

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Conclusion