Stiffness based enrichment of leukemia cells using microfluidics.

• Type of Material: Article
• Authors: Muhymin Islam, Georgia Institute of Technology; Abhishek Raj, Georgia Institute of Technology; Brynn McFarland, Georgia Institute of Technology; Hannah Maxine Brink, Georgia Institute of Technology; Jordan Ciciliano, Georgia Institute of Technology; Meredith Fay, Georgia Institute of Technology; David R Myers, Emory University; Christopher R Flowers, Emory University; Edmund K Waller, Emory University; Wilbur Lam, Emory University; Alexander Alexeev, Georgia Institute of Technology; Todd Sulchek, Georgia Institute of Technology
• Language: English
• Date: 2020-09
• Publisher: AIP Publishing LLC
• Publication Version: Final Published Version
• Copyright Statement: © 2020 Author(s).
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1063/1.5143436
• Title of Journal or Parent Work: APL Bioengineering
• ISSN: 2473-2877
• Volume: 4
• Issue: 3
• Start Page: 036101
• End Page: 036101
• Grant/Funding Information: This work was performed in part at the Georgia Tech Institute for Electronics and Nanotechnology, a member of the National Nanotechnology Coordinated Infrastructure, which was supported by the National Science Foundation.; This research was supported by the National Institutes of Health (Nos. NIH/NIBIB 1R21EB020977-01 and NIH/NCI R21CA191243).
• Keywords: detection; survival; label-free microfluid; leukemia; cancer; cell biophysics
• Research Categories: Biology, Cell; Health Sciences, Oncology

Abstract

To improve the survival rate of cancer patients, new diagnosis strategies are necessary to detect lower levels of cancer cells before and after treatment regimens. The scarcity of diseased cells, particularly in residual disease after treatment, demands highly sensitive detection approaches or the ability to enrich the diseased cells in relation to normal cells. We report a label-free microfluidic approach to enrich leukemia cells from healthy cells using inherent differences in cell biophysical properties. The microfluidic device consists of a channel with an array of diagonal ridges that recurrently compress and translate flowing cells in proportion to cell stiffness. Using devices optimized for acute T cell leukemia model Jurkat, the stiffer white blood cells were translated orthogonally to the channel length, while softer leukemia cells followed hydrodynamic flow. The device enriched Jurkat leukemia cells from white blood cells with an enrichment factor of over 760. The sensitivity, specificity, and accuracy of the device were found to be >0.8. The values of sensitivity and specificity could be adjusted by selecting one or multiple outlets for analysis. We demonstrate that low levels of Jurkat leukemia cells (1 in 10^4 white blood cells) could be more quickly detected using flow cytometry by using the stiffness sorting pre-enrichment. In a second mode of operation, the device was implemented to sort resistive leukemia cells from both drug-sensitive leukemia cells and normal white blood cells. Therefore, microfluidic biomechanical sorting can be a useful tool to enrich leukemia cells that may improve downstream analyses.