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

Award Number: R01EB027717
ORGANIZATION: NATIONAL INSTITUTE Of BIOMEDICAL IMAGING & BIOENGINEERING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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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to translation to a stand-alone in vivo device. 2) Optimize the storage and processing of small volumes of sampled ISF, withdrawn via nanopump, for analysis via liquid chromatography-tandem mass spectrometry (LC-MS/MS). 3) Determine the detection limits for the dynorphin neuropeptide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.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2023 ( Subtotal = $624,325 )
2023	2023	MASSACHUSETTS INSTITUTE OF TECHNOLOGY	77 MASSACHUSETTS AVE	CAMBRIDGE	MA	02139	MIDDLESEX	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	001	4	1/30/2023	NON-COMPETING CONTINUATION	$62,432
2023	2023	MASSACHUSETTS INSTITUTE OF TECHNOLOGY	77 MASSACHUSETTS AVE	CAMBRIDGE	MA	02139	MIDDLESEX	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	4	11/30/2022	NON-COMPETING CONTINUATION	$561,893
														Subtotal = $624,325

Issue Date FY: 2022 ( Subtotal = $625,925 )
2022	2022	MASSACHUSETTS INSTITUTE OF TECHNOLOGY	77 MASSACHUSETTS AVE	CAMBRIDGE	MA	02139	MIDDLESEX	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	001	3	6/27/2022	NON-COMPETING CONTINUATION	$62,593
2022	2022	MASSACHUSETTS INSTITUTE OF TECHNOLOGY	77 MASSACHUSETTS AVE	CAMBRIDGE	MA	02139	MIDDLESEX	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	3	11/1/2021	NON-COMPETING CONTINUATION	$563,332
														Subtotal = $625,925

Issue Date FY: 2021 ( Subtotal = $614,927 )
2021	2021	MASSACHUSETTS INSTITUTE OF TECHNOLOGY	77 MASSACHUSETTS AVE	CAMBRIDGE	MA	02139	MIDDLESEX	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	2	11/17/2020	NON-COMPETING CONTINUATION	$564,729
2021	2021	MASSACHUSETTS INSTITUTE OF TECHNOLOGY	77 MASSACHUSETTS AVE	CAMBRIDGE	MA	02139	MIDDLESEX	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	001	2	3/18/2021	NON-COMPETING CONTINUATION	$50,198
2021	2021	MASSACHUSETTS INSTITUTE OF TECHNOLOGY	77 MASSACHUSETTS AVE	CAMBRIDGE	MA	02139	MIDDLESEX	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	002	2	5/26/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $614,927

Issue Date FY: 2020 ( Subtotal = $628,550 )
2020	2020	MASSACHUSETTS INSTITUTE OF TECHNOLOGY	77 MASSACHUSETTS AVE	CAMBRIDGE	MA	02139	MIDDLESEX	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	1	1/28/2020	NEW	$628,550
														Subtotal = $628,550

Grand Total All Awards = $2,493,727

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

Award Number: R01EB027717

ORGANIZATION: NATIONAL INSTITUTE Of BIOMEDICAL IMAGING & BIOENGINEERING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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