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Parallel Selective Capture of Single Circulating Melanoma Cells and Integrated On-Chip Determination of Mutational Status

Award Number: R21EB028583
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 An unexpected response from a minority of cells can have a dramatic impact on the development, prognosis, and treatment of disease. For example, in the progression of cancer, a resistant minority of circulating tumor cells (CTCs) lead to the development of refractory metastases at relapse. We are only just beginning to uncover these phenomena and the underlying biological mechanisms because they are obscured at the bulk scale. Detection of a rare mutation can require the analysis of hundreds to thousands of individual cells. We have developed a dielectrophoresis (DEP)-based device with a high yield of selective single-cell capture in an array of microchambers arranged along the sides of branched microfluidic channels. An important point is that DEP-based selection is marker-independent, which critically, makes this approach especially relevant to the identification of CTCs in melanoma, for which there are no reliable biomarkers (cell surface antigens). We propose to integrate genetic assays into this platform for the identification of a mutation that is an indicator for a specific chemotherapeutic agent that is in widespread use. Specifically, we will create devices and methods to assess mutations by incorporating structures and custom materials that facilitate on-chip end-point polymerase chain reaction (PCR). An important feature of our technology is that the transfer of cells into reaction chambers (for genetic analysis) is accomplished using simple fluidic and electrokinetic components (no moving parts). This technological development is significant because 1) it addresses a need for integrated marker-free selection, isolation, and analysis of single cells, 2) the platform is sufficiently simple for broad application in clinical laboratories, thus enabling characterization of CTCs isolated from individual patients, and 3) it will enable future basic research into the molecular mechanisms of acquired resistance in melanoma. This innovative combination of a platform for marker-free selection with detection of mutations in melanoma will transform melanoma treatment and research because it will allow unparalleled access to information regarding the distribution of mutations related to susceptibility or resistance to therapeutic agents among individual CTCs.


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: 2024 ( Subtotal = $0 )
2024	2021	IOWA STATE UNIVERSITY OF SCIENCE AND TECHNOLOGY	1350 BEARDSHEAR HALL	AMES	IA	50011	STORY	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	3	2/15/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $171,459 )
2021	2021	IOWA STATE UNIVERSITY OF SCIENCE AND TECHNOLOGY	515 MORRILL RD, 1350 BEARDSHEAR HALL	AMES	IA	50011	STORY	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	3	6/24/2021	NON-COMPETING CONTINUATION	$171,459
														Subtotal = $171,459

Issue Date FY: 2020 ( Subtotal = $172,946 )
2020	2020	IOWA STATE UNIVERSITY OF SCIENCE AND TECHNOLOGY	515 MORRILL RD, 1350 BEARDSHEAR HALL	AMES	IA	50011	STORY	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	001	2	8/31/2020	NON-COMPETING CONTINUATION	$176,712
2020	2019	IOWA STATE UNIVERSITY OF SCIENCE AND TECHNOLOGY	515 MORRILL RD, 1350 BEARDSHEAR HALL	AMES	IA	50011	STORY	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	1	11/7/2019	NEW	-$3,766
														Subtotal = $172,946

Issue Date FY: 2019 ( Subtotal = $212,079 )
2019	2019	IOWA STATE UNIVERSITY OF SCIENCE AND TECHNOLOGY	515 MORRILL RD, 1350 BEARDSHEAR HALL	AMES	IA	50011	STORY	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	1	7/29/2019	NEW	$212,079
														Subtotal = $212,079

Grand Total All Awards = $556,484

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Parallel Selective Capture of Single Circulating Melanoma Cells and Integrated On-Chip Determination of Mutational Status

Award Number: R21EB028583

ORGANIZATION: NATIONAL INSTITUTE Of BIOMEDICAL IMAGING & BIOENGINEERING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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