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Fractionation and Profiling of Heterogeneous Circulating Tumor Cells Using a Hyperuniform- Structured Microchip

Award Number: R21CA240185
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/07/2020
PERIOD OF PERFORMANCE END DATE: 07/31/2025

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Fractionation and Profiling of Heterogeneous Circulating Tumor Cells Using a Hyperuniform- Structured Microchip - Title: Fractionation and Profiling of Heterogeneous Circulating Tumor Cells Using a Hyperuniform-structured Microchip Project Summary/Abstract Circulating tumor cells (CTCs) are highly heterogeneous, and specific CTC subpopulations, rather than the whole, are responsible for cancer metastasis. Current CTC technologies simply isolate all CTCs in a blood sample without resolving them into distinct subpopulations, preventing researchers from acquiring true insights into the metastatic potential of CTCs. As a consequence, correlation between CTC heterogeneity and tumor progression is largely unknown. In addition, existing CTC characterization methods often involve destructive fixation and permeabilization protocols, which limit the potential for subsequent phenotypic analysis of CTCs and other downstream applications. The goal of this proposal is to understand the metastatic potential of CTCs through effective fractionation and profiling of CTC subpopulations. I propose to isolate, in-situ identify, and selectively recover CTCs using a microchip with hyperuniform structure. Hyperuniformity (HU) is an emerging concept of a packing pattern which contains local heterogeneity or randomness and global regularity or homogeneity. My work, for the first time, will integrate the concept of hyperuniformity into affinity-based microfluidic devices for CTC isolation. I hypothesize that due to the controlled differences in local flow patterns induced by the hyperuniform structure, cell arrest in different locations on the microchip will require different adhesive strengths. Further, this adhesive strength is anticipated to be related to the types and densities of surface markers on the captured CTCs and therefore, their metastatic character. Specific aims include (1) Design and characterize HU structured microchip for CTC capture and analyze flow pattern and adhesion force in the device; (2) Capture and identify subpopulations of CTCs with variable expression of the surface marker using a HU microchip; and (3) Explore several key factors for potential incorporation of the HU microchip platform into clinical oncology settings. The HU microchip offers a simple and unique resolution for fractionation of CTCs, as its global homogeneity provides equal possibility of CTC adherence; and local heterogeneity allows simultaneous differentiation of subpopulations by analyzing adhesive strength required for individual CTCs. As a result, subpopulations of CTCs can be identified using only their capture locations on the HU chip without requiring additional post-capture immunofluorescence characterization. The most significant quantitative milestones are to achieve 80% accuracy on statistical correlation on: 1) the locations on a HU chip with strength of cell-post interaction, 2) predictions of location vs. cell type in a cancer cell mixture (PC3 and LNCaP), and 3) achieving 80% accuracy on identification of released EMT and non-EMT cells from their locations on a HU microchip, validated by immunostaining. If successfully developed, this HU microchip can be easily integrated into research laboratories to study fundamental cancer biology related to CTC heterogeneity, as well as into clinical settings to profile CTC subpopulations to assist cancer diagnosis, predict tumor progression, and monitor therapeutic efficacy.


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: 2026 ( Subtotal = $0 )
2026	2020	TEXAS TECH UNIVERSITY SYSTEM	2500 BROADWAY	LUBBOCK	TX	79409	LUBBOCK	USA	Cancer Biology Research	000	1	12/8/2025	NEW	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2022	TEXAS TECH UNIVERSITY SYSTEM	2500 BROADWAY	LUBBOCK	TX	79409	LUBBOCK	USA	Cancer Biology Research	001	1	7/25/2024	SUPPLEMENT FOR EXPANSION	$0
2024	2020	TEXAS TECH UNIVERSITY SYSTEM	2500 BROADWAY	LUBBOCK	TX	79409	LUBBOCK	USA	Cancer Biology Research	000	1	7/25/2024	NEW	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $0 )
2023	2020	TEXAS TECH UNIVERSITY SYSTEM	2500 BROADWAY	LUBBOCK	TX	79409	LUBBOCK	USA	Cancer Biology Research	000	1	6/13/2023	NEW	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $71,919 )
2022	2022	TEXAS TECH UNIVERSITY SYSTEM	2500 BROADWAY	LUBBOCK	TX	79409	LUBBOCK	USA	Cancer Biology Research	000	1	9/8/2022	SUPPLEMENT FOR EXPANSION	$71,919
														Subtotal = $71,919

Issue Date FY: 2020 ( Subtotal = $553,092 )
2020	2020	TEXAS TECH UNIVERSITY SYSTEM	2500 BROADWAY	LUBBOCK	TX	79409	LUBBOCK	USA	Cancer Biology Research	000	1	8/7/2020	NEW	$553,092
														Subtotal = $553,092

Grand Total All Awards = $625,011

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Fractionation and Profiling of Heterogeneous Circulating Tumor Cells Using a Hyperuniform- Structured Microchip

Award Number: R21CA240185

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 08/07/2020

PERIOD OF PERFORMANCE END DATE: 07/31/2025

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