An Integrated Microfluid Device for Simultaneous Capture and Spectroscopic Characterization of Live Cells

Cornell University Background
The invention describes an integrated system for rapid attraction of live cells onto a plasmonic metasurface, and collection and analysis of their vibrational fingerprints. A microfluidic device is integrated with the dielectrophoresis (DEP) attraction method and Metasurface-Enhanced Infrared Reflection Spectroscopy (MEIRS) spectral characterization method described in another Cornell University invention, to enable high-throughput detection of cell types and subtle effects of drugs on the live cells.
Technology Overview
The system provides a new approach to cytopathology, based on spectroscopic data obtained from coupling mid-infrared light to vibrational modes of the constituent molecules (e.g. proteins, lipids, phospholipids, etc.). It incorporates a microfluidic device to provide high-throughput delivery of live cells in their natural aqueous environment to a meta-electrode comprised of a plasmonic meta-surface and metallic cell-capturing wires. When voltage is applied, the cells (including cancerous and normal cells as well as adherent and non-adherent cell types) are collected within seconds. During collection the live cells are simultaneously measured using MEIRS, and then analyzed and characterized through statistical multivariate statistical methods such as principal components analysis (PCA).
The inventors fabricated microfluidic devices with pixel-sized channels using standard lithography processes, and demonstrated effective delivery, collection and characterization of colon cancer, skin cancer, and leukaemia cells (HCT116, A431 and Jurkat cell lines).
In addition, the distinct effects of primary tumor cells’ treatment by salinomycin and doxorubicin drugs were measured both separately and combined, and related to the results of MTT cell viability assays, demonstrating the ability of MEIRS to spectroscopically detect the delicate effects of a cell sensitizing drug.

Further Details:

Glen Kelp, Joy Li, Junlan Lu, Nicholas DiNapoli, Robert Delgado, Chao Liu, Donglei Fan, Shourya Dutta-Gupta and Gennady Shvets, “Infrared spectroscopy of live cells from a flowing solution using electrically-biased plasmonic metasurfaces.“ Lab Chip, 2020,20, 2136-2153.
S. Gupta, G. Kelp, N. Arju, S. Emelianov, G. Shvets; “Metasurface-enhanced infrared spectroscopy: From protein detection to cells differentiation.” CLEO/Europe-EQEC, 2017 Conference on Lasers and Electro-Optics Europe & European Quantum Electronics Conference; Oct 2017.
G. Shvets, G. Kelp, S. Gupta, N. DiNapoli; “Circulating tumor cells enrichment and phenotyping by combining dielectrophoresis and metasurface-enhanced infrared spectroscopy (Conference Presentation)”, Proc. SPIE 10489, Optical Biopsy XVI: Toward Real-Time Spectroscopic Imaging and Diagnosis, 1048903 (14 March 2018);
G. Kelp, N. Arju, A. Lee, E. Esquivel, R. Delgado, Y. Yu, S. Dutta-Gupta, K. Sokolov and G. Shvets, “Application of metasurface-enhanced infra-red spectroscopy to distinguish between normal and cancerous cell types.“ Analyst, 2019,144, 1115-1127.
Steven H. Huang, Robert Delgado, Gennady B. Shvets, “Metasurface-enhanced infrared spectroscopy for continuously monitoring the effect of cholesterol depletion in live cells.“ Proceedings Volume 11236, Biomedical Vibrational Spectroscopy 2020: Advances in Research and Industry; 112360P (2020)

Benefits

Rapid collection and analysis of cells in their natural aqueous environment
High throughput method
Works with non-adherent as well as adherent cells
Requires only a small sample
Simple and inexpensive device fabrication

Applications

Diagnostic tool to detect cancers
Drug efficacy studies
Biomedical research

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