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Ultra-Rare Cell In Vivo Flow Cytometry

Award Number: R01HL124315
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/15/2015
PERIOD OF PERFORMANCE END DATE: 05/31/2021

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Ultra-Rare Cell In Vivo Flow Cytometry - DESCRIPTION: There are many areas of biomedical research where the study of rare circulating cells is important. Examples include cancer metastasis, hematological malignancies, organ transplant biology, immunology, and reproductive medicine and stem-cell therapies. In this project we will develop a new high-throughput optical scanner with unprecedented capabilities for studying rare circulating cells in small animals in vivo. Circulating cells are normally quantified by drawing small blood samples which are purified and analyzed with hemocytometry or flow cytometry. However, it is known that handling and purifying blood samples can affect cell viability, and that rare cells can escape detection due to the small sampling volume. More recently, `in vivo flow cytometry' (IVFC) methods have been developed that allow enumeration of cells without drawing samples. While extremely useful, these generally rely on interrogation of microscopic blood vessels with small flow rates, so that rare cells are undetectable. New high-sensitivity and high-accuracy tools for studying circulating cells are therefore greatly needed by the research community. In this proposal we will develop a miniaturized optical scanner that will use diffuse photons to interrogate circulating blood in the limb of a mouse. The technology - termed "ultra-rare cell IVFC" (UR-IVFC) - will employ a number of unique design elements including, i) multiple tomographic optical rings with fiber-coupled lasers and fluorescence detectors, ii) efficient geometric light collection, iii) frequency encoded lasers and detector channels, and, iv) advanced signal processing algorithms for accurate counting and tracking of cells. In combination, UR-IVFC will allow single-cell sensitivity in a 10 minute scan and with a false alarm rate less than 0.001 per minute. We anticipate that the unique capabilities of UR-IVFC will have immediate impact in many research fields. We will first use UR-IVFC to study treatment of multiple myeloma (MM), a hematological malignancy for which there is currently no cure. We will study "cell mobilization therapy", which is an emerging treatment strategy for MM. MM cells are chemically forced from the protective bone marrow niche into circulation where they are vulnerable to chemotherapy. We will use UR-IVFC to study whether specific clonal sub-populations of MM cells are resistant to mobilization, and we will test the efficacy of mobilizing agents for minimal residual disease (MRD). In addition to illuminating molecular mechanisms of MM biology and treatment resistance, these studies could yield new therapeutic strategies for patients suffering from MM. Moreover they are extremely difficult (or outright infeasible) to perform with existing technology.


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: 2022 ( Subtotal = $0 )
2022	2018	NORTHEASTERN UNIVERSITY	360 HUNTINGTON AVE	BOSTON	MA	02115	SUFFOLK	USA	Blood Diseases and Resources Research	000	4	11/20/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2020 ( Subtotal = $0 )
2020	2018	NORTHEASTERN UNIVERSITY	360 HUNTINGTON AVE	BOSTON	MA	02115	SUFFOLK	USA	Blood Diseases and Resources Research	000	4	8/12/2020	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2018 ( Subtotal = $405,166 )
2018	2018	NORTHEASTERN UNIVERSITY	360 HUNTINGTON AVE	BOSTON	MA	02115	SUFFOLK	USA	Blood Diseases and Resources Research	000	4	5/12/2018	NON-COMPETING CONTINUATION	$405,166
														Subtotal = $405,166

Issue Date FY: 2017 ( Subtotal = $406,018 )
2017	2017	NORTHEASTERN UNIVERSITY	360 HUNTINGTON AVE	BOSTON	MA	02115	SUFFOLK	USA	Blood Diseases and Resources Research	000	3	6/14/2017	NON-COMPETING CONTINUATION	$406,018
														Subtotal = $406,018

Issue Date FY: 2016 ( Subtotal = $353,550 )
2016	2016	NORTHEASTERN UNIVERSITY	360 HUNTINGTON AVENUE	BOSTON	MA	02115	SUFFOLK	USA	Blood Diseases and Resources Research	000	2	5/16/2016	NON-COMPETING CONTINUATION	$353,550
														Subtotal = $353,550

Issue Date FY: 2015 ( Subtotal = $348,100 )
2015	2015	NORTHEASTERN UNIVERSITY	360 HUNTINGTON AVENUE	BOSTON	MA	02115	SUFFOLK	USA	Cardiovascular Diseases Research	000	1	8/14/2015	NEW	$348,100
														Subtotal = $348,100

Grand Total All Awards = $1,512,834

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Ultra-Rare Cell In Vivo Flow Cytometry

Award Number: R01HL124315

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 08/15/2015

PERIOD OF PERFORMANCE END DATE: 05/31/2021

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