Selective Capture, Fluidic Isolation and Electrical Lysis of Tumor Cells at a Wireless Electrode Array for a Single-Cell Enzymatic Assay

Joseph Banovetz^a, Robbyn Anand^a, Darshna Pagariya^a

^aIowa State University, 1605 Gilman Hall, 2415 Osborn Driv, Ames, United States

Proceedings of Emerging Investigators in Microfluidics Conference (EIMC)

Online, Spain, 2021 July 20th - October 6th

Organizers: Adrian Nightingale, Darius Rackus and Claire Stanley

Pending, Joseph Banovetz, presentation 010
Publication date: 5th July 2021

While cancer mortality has declined significantly with the development of targeted therapies, genetic and functional differences among cells allow certain subpopulations to evade treatment. Such heterogeneity has been implicated in drug resistance, metastasis, and poor patient prognosis. Cellular senescence, a state of cell-cycle arrest, in tumor cells is a desirable therapeutic outcome and is linked to the expression of the enzyme β-galactosidase. Therefore, assessment of β-galactosidase activity in individual cells provides a measure of the therapeutic response with single-cell resolution. Herein, we report a microfluidic device designed to study enzyme activity in single cancer cells. The device accomplishes selective capture of cancer cells by dielectrophoresis (DEP) at an array of wireless bipolar electrodes (BPEs). Following capture, cells are transferred into picoliter-scale reaction chambers. At a second capture point, inside the chambers, the cells are held in place during the introduction of reagents for the enzymatic assay. The chambers are subsequently isolated with an immiscible phase – a conductive, hydrophobic ionic liquid. Finally, the cells are electrically lysed to release intracellular β-galactosidase, which cleaves a fluorogenic substrate. Single-cell enzymatic activity is evaluated by following the accumulation of the fluorescent product over time. Our results demonstrate that cancer cells can be selectively captured, isolated and lysed with a high efficiency that is independent of chamber diameter – making this feature of the device tunable. We further report the distribution of β-galactosidase activity in a breast adenocarcinoma cell line (MDA-MB-231) and confirm that the population average β-galactosidase activity for individual cells assayed in parallel aligns with that obtained for ensemble measurements.

References:

[1] Li, M.; Anand, R. K. High-Throughput Selective Capture of Single Circulating Tumor Cells by Dielectrophoresis at a Wireless Electrode Array. J. Am. Chem. Soc. 2017, 139 (26), 8950–8959. https://doi.org/10.1021/jacs.7b03288.

[2] Li, M.; Anand, R. K. Integration of Marker-Free Selection of Single Cells at a Wireless Electrode Array with Parallel Fluidic Isolation and Electrical Lysis. Chem. Sci. 2019, 10 (5), 1506–1513. https://doi.org/10.1039/C8SC04804E.

[3] Kim, S. H.; Fujii, T. Efficient Analysis of a Small Number of Cancer Cells at the Single-Cell Level Using an Electroactive Double-Well Array. Lab Chip 2016, 16 (13), 2440–2449. https://doi.org/10.1039/c6lc00241b.

nanoGe is a prestigious brand of successful science conferences that are developed along the year in different areas of the world since 2009. Our worldwide conferences cover cutting-edge materials topics like perovskite solar cells, photovoltaics, optoelectronics, solar fuel conversion, surface science, catalysis and two-dimensional materials, among many others.

MATSUS

Previously nanoGe Spring Meeting (NSM) and nanoGe Fall Meeting (NFM), MATSUS is a multiple symposia conference focused on a broad set of topics of advanced materials preparation, their fundamental properties, and their applications, in fields such as renewable energy, photovoltaics, lighting, semiconductor quantum dots, 2-D materials synthesis, charge carriers dynamics, microscopy and spectroscopy semiconductors fundamentals, etc.

International Conference on Hybrid and Organic Photovoltaics

International Conference on Hybrid and Organic Photovoltaics (HOPV) is celebrated yearly in May. The main topics are the development, function and modeling of materials and devices for hybrid and organic solar cells. The field is now dominated by perovskite solar cells but also other hybrid technologies, as organic solar cells, quantum dot solar cells, and dye-sensitized solar cells and their integration into devices for photoelectrochemical solar fuel production.

Asia-Pacific International Conference on Perovskite, Organic Photovoltaics and Optoelectronics

The main topics of the Asia-Pacific International Conference on Perovskite, Organic Photovoltaics and Optoelectronics (IPEROP) are discussed every year in Asia-Pacific for gathering the recent advances in the fields of material preparation, modeling and fabrication of perovskite and hybrid and organic materials. Photovoltaic devices are analyzed from fundamental physics and materials properties to a broad set of applications. The conference also covers the developments of perovskite optoelectronics, including light-emitting diodes, lasers, optical devices, nanophotonics, nonlinear optical properties, colloidal nanostructures, photophysics and light-matter coupling.

International Conference on Perovskite Thin Film Photovoltaics Perovskite Photonics and Optoelectronics

The International Conference on Perovskite Thin Film Photovoltaics Perovskite Photonics and Optoelectronics (NIPHO) is the best place to hear the latest developments in perovskite solar cells as well as on recent advances in the fields of perovskite light-emitting diodes, lasers, optical devices, nanophotonics, nonlinear optical properties, colloidal nanostructures, photophysics and light-matter coupling.