Single cell biology has offered a new path to obtain biological insight that has been masked by the ensemble average from a large cell population. Studying biology at the single-cell level will not only enhance our understanding of the complicated biological mechanisms but also help produce new therapy and drugs to cure human diseases. To support single cell analysis, new tools of extraordinary precision, flexibility, and capability have to be developed. Although microfluidic device has been demonstrated as a highly promising platform for investigating single cells, one serious limit of today's microfluidic single-cell device is that cells in microfluidic environment is very different from cells in standad culture environment and even more different from cells in physiological environment. We propose to develop a universal microfluidic single-cell dispensing and conditioning device to addresses this important limitation. The device has an innovative architecture that integrates different functions, including single cell detection, capturing, conditioning, and release, on a microfluidic platform. The proposed device will operate in a close-loop fashion, requiring no user intervention once the user application is specified, due to the field-programmable-gate-array (FPGA) control and coordination of all the functions together. Besides these unique features, the proposed device can be manufactured at very low cost, fully automated, compatible with industrial standards, and expanded into array format for ultrahigh throughput. The proposed device is intended to become a tool that will be widely used on a daily base by researchers performing fundamental and clinical research benefiting from single cell studies. Since single-cell biology prevails in many areas of biology and medicine, the proposed device is anticipated to satisfy a major need in biomedicine with increasing demands in the future. If developed successfully, the device will facilitate and accelerate discoveries in cancer and stem cell research, new cell therapy, drug screening and testing, infectious and genetic diseases, cell-cell interactions, and cell signaling. The device will also become an invaluable tool for the development of medical devices and assays dealing with rare cell populations such as assays for circulating tumor cells (CTCs), cancer stem cells and personalized medicine.

Public Health Relevance

We propose to develop a universal tool to facilitate and enhance single cell research. Employing an innovative device architecture that integrates the functions of single cell detection, capture, conditioning, and release, the device not only offers the much needed precision and flexibility for single cell research but also keeps single cells in the environments closest to the physiological environment. The proposed project aims at demonstrating the concept and viability of the technology with functional device prototypes for single cell research.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21GM107977-01
Application #
8576156
Study Section
Special Emphasis Panel (ZGM1-BBCB-A (BT))
Program Officer
Friedman, Fred K
Project Start
2013-08-01
Project End
2016-04-30
Budget Start
2013-08-01
Budget End
2014-04-30
Support Year
1
Fiscal Year
2013
Total Cost
$178,534
Indirect Cost
$53,534
Name
University of California San Diego
Department
Engineering (All Types)
Type
Schools of Arts and Sciences
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
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Chiu, Yu-Jui; Cai, Wei; Shih, Yu-Ru V et al. (2016) A Single-Cell Assay for Time Lapse Studies of Exosome Secretion and Cell Behaviors. Small 12:3658-66
Han, Yuanyuan; Lo, Yu-Hwa (2015) Imaging Cells in Flow Cytometer Using Spatial-Temporal Transformation. Sci Rep 5:13267