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Development and validation of nanoparticle-mediated microfluidic profiling approach for rare cell analysis

Award Number: R33CA204574
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 03/15/2017
PERIOD OF PERFORMANCE END DATE: 02/28/2021

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Development and validation of nanoparticle-mediated microfluidic profiling approach for rare cell analysis - Project Summary: Circulating tumour cells (CTC) are shed into the vasculature from primary tumours, and have been shown to contribute to the formation of metastatic lesions in model systems. Monitoring these circulating cells therefore presents, in principle, a means to monitor a tumour's metastatic potential in real time. Similar to the heterogeneity of cellular subpopulations within an individual tumour, CTCs within an individual also exhibit heterogeneity, containing subpopulations having varying relevance to the development of metastatic disease. Recent studies show that specific subpopulations of CTCs possess metastatic potential, while other subpopulations of circulating epithelial cells may be relatively benign. Similarly, the levels of surface proteins on CTCs are heterogeneous and dynamic: they are observed to change as a function of disease stage and response to therapy. In particular, the epithelial-mesenchymal transition (EMT) appears to be a dynamic process in CTCs, and the markers that correspond to these two states vary and contribute to the phenotypic heterogeneity of CTCs. Using a microfluidic device, the velocity valley (VV) chip, that was developed in our group, we now have the ability to profile a CTC population from blood samples and by sorting these cells based on expression of surface markers. This novel technology has enabled us to capture and study CTCs within various ranges of EMT. In this proposal, our goal is to fully develop the VV chip technology into a fully integrated device for CTC population profiling, CTC detection, and molecular analysis. This will be accomplished through integration of companion technologies allowing for sensitive on-chip electrochemical detection and genetic analysis of CTCs. Manufacturing methods for the device will be investigated for production at high-scale. In addition, automation for sample analysis and detection will be developed enabling the full realization of the device in a clinical or research setting. Finally the device will be validated with clinical samples from prostate and breast cancer patients. This project will include the collaboration of a multidisciplinary team of six researchers and clinicians for device development, manufacturing, and clinical testing. As a team, the researchers will work to develop and validate this diagnostic platform. At the completion of this project a clinical research tool will be produced capable of profiling a patient's CTC population and providing molecular and genetic information on the EMT for that population in a single automated device with capture, profiling, and detection capabilities.


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 = $1,760 )
2022	2019	GOVERNING COUNCIL OF THE UNIVERSITY OF TORONTO	27 KING'S COLLEGE CIR	TORONTO	ON			CAN	Cancer Detection and Diagnosis Research	000	3	9/26/2022	NON-COMPETING CONTINUATION	$1,760
														Subtotal = $1,760

Issue Date FY: 2021 ( Subtotal = -$9,277 )
2021	2019	GOVERNING COUNCIL OF THE UNIVERSITY OF TORONTO	27 KING'S COLLEGE CIR	TORONTO	ON			CAN	Cancer Detection and Diagnosis Research	000	3	8/12/2021	NON-COMPETING CONTINUATION	-$9,277
														Subtotal = -$9,277

Issue Date FY: 2019 ( Subtotal = $305,702 )
2019	2019	GOVERNING COUNCIL OF THE UNIVERSITY OF TORONTO	27 KING'S COLLEGE CIR	TORONTO	ON	M5S 1A1		CAN	Cancer Detection and Diagnosis Research	000	3	2/13/2019	NON-COMPETING CONTINUATION	$251,182
2019	2019	GOVERNING COUNCIL OF THE UNIVERSITY OF TORONTO	27 KING'S COLLEGE CIR	TORONTO	ON	M5S 1A1		CAN	Cancer Detection and Diagnosis Research	001	3	5/15/2019	NON-COMPETING CONTINUATION	$54,520
														Subtotal = $305,702

Issue Date FY: 2018 ( Subtotal = $258,952 )
2018	2018	GOVERNING COUNCIL OF THE UNIVERSITY OF TORONTO	27 KING'S COLLEGE CIR	TORONTO	ON	M5S 1A1		CAN	Cancer Detection and Diagnosis Research	001	2	5/23/2018	NON-COMPETING CONTINUATION	$25,894
2018	2018	GOVERNING COUNCIL OF THE UNIVERSITY OF TORONTO	27 KING'S COLLEGE CIR	TORONTO	ON	M5S 1A1		CAN	Cancer Detection and Diagnosis Research	000	2	1/19/2018	NON-COMPETING CONTINUATION	$233,058
														Subtotal = $258,952

Issue Date FY: 2017 ( Subtotal = $258,952 )
2017	2017	UNIVERSITY OF TORONTO	27 KING'S COLLEGE CIR	TORONTO	ON	M5S 1A1		CAN	Cancer Detection and Diagnosis Research	000	1	3/13/2017	NEW	$258,952
														Subtotal = $258,952

Grand Total All Awards = $816,089

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Development and validation of nanoparticle-mediated microfluidic profiling approach for rare cell analysis

Award Number: R33CA204574

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 03/15/2017

PERIOD OF PERFORMANCE END DATE: 02/28/2021

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