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Streamlined and comprehensive circulating tumor exosome profiling by microfluidic arrayed nanoplasmonic sensors and actuators

Award Number: R01EB030623
ORGANIZATION: NATIONAL INSTITUTE Of BIOMEDICAL IMAGING & BIOENGINEERING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 06/15/2021
PERIOD OF PERFORMANCE END DATE: 03/31/2026

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Streamlined and comprehensive circulating tumor exosome profiling by microfluidic arrayed nanoplasmonic sensors and actuators - PROJECT SUMMARY Detection of cancer biomarkers in the blood, known as “liquid biopsy”, can in principle improve the accuracy of measuring nearly invisible “minimal residual disease (MRD)”. Exosomes are cell- excreted extracellular vesicles that contain surface proteins and genetic materials (DNA and RNA) that reflect the characteristics and make-up of the parental cell. Analyzing exosomes would therefore provide direct insight into the state of the cancerous cell. For cancer diagnostics in particular, recent evidences have shown that several micro-RNAs are differentially expressed in CTE. Therefore, unlocking the wealth of information in CTE can potentially cause a paradigm shift. However, current barriers for profiling CTE are the following: (1) all existing technologies require blood withdrawal; (2) involve sophisticated protocols; (3) label-free sizing/counting lacks molecular specificity; (4) provide highly averaged results with high background from normal exosomes, thus leading to poor sensitivity. (5) provide “partial” information: either surface antigen or cargo DNA/RNA, but not both. All of the above has led to a simplistic binary outcome that lacks dynamic range and cannot be used frequently with high sensitivity. We propose a multi-pronged solution on a microfluidic arrayed nanoplasmonic sensor & actuator (MANSA) platform for: (1) streamlined isolation, concentration, and profiling. (2) improve sensitivity by monitoring individual unlabeled exosome binding events with dynamic imaging technology complemented by spectroscopic imaging. (3) improve specificity by profiling both surface antigen and internal D/RNA biomarkers at single exosome level. (4) eliminate blood withdrawal using an integrated needle device. (5) benchmark performance with various sample complexity from cancer cell line extracts to cancer patient blood samples. Our goal is to obtain a high-resolution, digital exosome map with both multiplex surface protein and cargo D/RNA biomarker profiles to facilitate high dynamic range enumeration and boost sensitivity. The proposed technology will become a cost- effective, point-of-care-friendly, translational platform that will address a critical need in early cancer and MRD detection to improve cancer healthcare outcomes. The technology can also be broadly applied to exosome-based diagnostics of non-cancer diseases and basic biomedical research.


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: 2025 ( Subtotal = $647,192 )
2025	2025	UNIVERSITY OF HOUSTON SYSTEM	4300 MARTIN LUTHER KING BLVD	HOUSTON	TX	77204	HARRIS	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	5	6/17/2025	NON-COMPETING CONTINUATION	$647,192
														Subtotal = $647,192

Issue Date FY: 2024 ( Subtotal = $1 )
2024	2024	UNIVERSITY OF HOUSTON SYSTEM	4300 MARTIN LUTHER KING BLVD	HOUSTON	TX	77204	HARRIS	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	4	6/27/2024	NON-COMPETING CONTINUATION	$1
														Subtotal = $1

Issue Date FY: 2023 ( Subtotal = $816,857 )
2023	2023	UNIVERSITY OF HOUSTON SYSTEM	4300 MARTIN LUTHER KING BLVD	HOUSTON	TX	77204	HARRIS	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	001	3	7/7/2023	SUPPLEMENT FOR EXPANSION	$155,000
2023	2023	UNIVERSITY OF HOUSTON SYSTEM	4300 MARTIN LUTHER KING BLVD	HOUSTON	TX	77204	HARRIS	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	3	7/6/2023	NON-COMPETING CONTINUATION	$661,857
														Subtotal = $816,857

Issue Date FY: 2022 ( Subtotal = $910,316 )
2022	2022	UNIVERSITY OF HOUSTON SYSTEM	4800 W CALHOUN ST STE 316	HOUSTON	TX	77004	HARRIS	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	001	2	7/21/2022	SUPPLEMENT FOR EXPANSION	$247,033
2022	2022	UNIVERSITY OF HOUSTON SYSTEM	4800 W CALHOUN ST STE 316	HOUSTON	TX	77004	HARRIS	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	2	4/8/2022	NON-COMPETING CONTINUATION	$663,283
														Subtotal = $910,316

Issue Date FY: 2021 ( Subtotal = $678,432 )
2021	2021	UNIVERSITY OF HOUSTON SYSTEM	4800 W CALHOUN ST STE 316	HOUSTON	TX	77004	HARRIS	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	1	6/10/2021	NEW	$678,432
														Subtotal = $678,432

Grand Total All Awards = $3,052,798

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Streamlined and comprehensive circulating tumor exosome profiling by microfluidic arrayed nanoplasmonic sensors and actuators

Award Number: R01EB030623

ORGANIZATION: NATIONAL INSTITUTE Of BIOMEDICAL IMAGING & BIOENGINEERING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 06/15/2021

PERIOD OF PERFORMANCE END DATE: 03/31/2026

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