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

> **NIH NIH R01** · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · 2021 · $614,927

## Abstract

Project Summary
The purpose of this study is for a team of materials scientists, biomedical engineers, analytical chemists, and
neuroscientists at MIT to develop a micro-invasive implantable device for monitoring the biochemical composition
of distinct brain regions. This analytical tool for sampling neurochemicals in brain interstitial fluid (ISF) promises
to provide valuable insight into the dynamics of neural circuits in physiological and pathological states. We will
apply this tool to study the role of neuropeptides in substance use disorder (SUD). The dynorphin family of
neuropeptides has long been implicated in addiction, but no current analysis tool has been able to investigate
the long-term spatiotemporal dynamics of these neurochemicals in vivo. Our goal is to demonstrate the efficacy
of our sampling platform in measuring neuropeptide expression dynamically in a rodent model of SUD. This will
lend greater insight into the biochemical basis of addiction and withdrawal, but perhaps more importantly
establish our technology as an effective technique for understanding the onset and progression of neural
diseases. Our specific goals are summarized as follows: 1) Design a minimally invasive and implantable device
for sampling ISF chronically in vivo. The device will consist of a nanofluidic pump (nanopump) coupled to micro-
scale probes (microprobes), with fluid flow characteristics optimized in vitro prior to translation to a stand-alone
in vivo device. 2) Optimize the storage and processing of small volumes of sampled ISF, withdrawn via
nanopump, for analysis via liquid chromatography-tandem mass spectrometry (LC-MS/MS). 3) Determine the
detection limits for the dynorphin neuropeptide family in ISF in vitro prior to detection of these neurochemicals in
in vivo samples at physiological and pathological concentrations. 4) Perform short-term monitoring of dynorphin
at baseline and in acute stress to demonstrate the efficacy of this tool in tracking these large neuropeptides in
real-time. 5) Track the dynorphin family of neuropeptides in a rodent model of cocaine SUD, lending greater
insight into the biochemical basis of substance withdrawal and relapse. Our aim is to demonstrate the failsafe
function of this sampling platform in vivo and establish its ability to monitor neuropeptide dynamics with precise
spatiotemporal control. We aim to provide neuroscientists with a new tool for investigating the biochemical basis
of neural pathology in well-established animal models, enabling more accurate diagnosis and treatment of neural
disorders in humans in the future.

## Key facts

- **NIH application ID:** 10090597
- **Project number:** 5R01EB027717-02
- **Recipient organization:** MASSACHUSETTS INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** Michael J Cima
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $614,927
- **Award type:** 5
- **Project period:** 2020-02-01 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10090597

## Citation

> US National Institutes of Health, RePORTER application 10090597, Micro-invasive biochemical sampling of brain interstitial fluid for investigating neural pathology (5R01EB027717-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10090597. Licensed CC0.

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