Neural pathology is characterized by electrical and chemical dysregulation in distinct brain circuits. Chemical dysregulation can be monitored by measuring the local biochemical composition of interstitial fluid (ISF). ISF composition is dynamic, requiring that any neural sampling technique enable rapid parallel sampling of multiple biomarkers. The current state-of-the-art in neural sampling, microdialysis, enables the collection of small, highly concentrated neurochemicals from ISF via diffusion across a semipermeable membrane. It cannot measure larger neuropeptides or the contents of extracellular vesicles with high temporal resolution and in parallel. We have developed a micro-invasive tool that addresses this challenge. Our device, a nanofluidic pump coupled to a micro-invasive probe (80 μm outer diameter), enables direct sampling of ISF from distinct neural nodes (65 nL/min). Sampled fluid is analyzed via liquid chromatography-tandem mass spectrometry to detect neuropeptides at <i>in vivo </i>concentrations. This represents a fundamental shift from microdialysis, which tracks small neuropeptides abundantly present in the brain, to a device that can sample the complete <i>in vivo </i>biochemical milieu with pinpoint spatiotemporal resolution. We anticipate this platform will enable a deeper understanding of the onset, mechanism, and progression of diverse neural pathologies.

Micro-invasive biochemical sampling of brain interstitial fluid for investigating neural pathology

2019 Fall National Meeting

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