Research
(under construction)
Ultrahigh-throughput sorting of rare circulating tumor cells (CTCs)
CTC-based liquid biopsies have emerged as a promising tool for cancer diagnostics, treatment selection, and response monitoring. However, despite impressive technological gains, the presence of only a few CTCs in the standard 10 mL blood samples has severely limited their clinical utility. Leukapheresis products (leukopaks) obtained by screening whole human blood (~5 liters) can enhance the number of isolated CTCs to thousands of cells (100-fold). Even though leukopaks provide a path to isolating a large number of CTCs, owing to their large volume (~120 mL) and the presence of 100-fold more nucleated cells than in a 10 mL blood sample, current state-of-the-art cell sorting techniques can only process 3-5% of the sample. We developed an ultrahigh-throughput LPCTC-iChip cell sorting platform to process the full leukopak volume and recover thousands of viable CTCs.
Ultrahigh-throughput magnetic sorting of large blood volumes for epitope-agnostic isolation of circulating tumor cells, A. Mishra, T. Dubash et al., PNAS, 2020. https://doi.org/10.1073/pnas.2006388117.
Microfluidic concentration and separation of circulating tumor cell clusters from large blood volumes, J. F. Edd, A. Mishra et al., Lab on a Chip, 2020. https://doi.org/10.1039/C9LC01122F
High-throughput Microfluidic Devices for Cell and Gene Therapy Manufacturing
Boosted by a 5-year K-25 career award from NIH (2023-2028), we will develop an efficient microfluidic technology for stem cell isolation from blood products of patients with Sickle Cell Disease (SCD). SCD is a genetic disorder that affects ~100,000 Americans in the United States alone. Obtaining a sufficient number of blood stem cells is paramount to the success of stem cell gene therapy. However, the higher numbers of sickled RBCs adversely hamper the yield of CD34+ stem cells during purification, leading to the loss of ~50% of highly valuable stem cell dose. There is, therefore, an immediate need to develop an isolation technology that can recover stem cells from full leukopaks with high yield. We will develop a microfluidic stem cell isolation technology (HSPC-iChip) that can recover CD34+ cells from full apheresis products while depleting contaminating cells.
Optoelectrical Tweezers: Rapid Electrokinetic Patterning (REP)
For more information on REP, please read "Optoelectrical microfluidics as a promising tool in biology," A. Mishra, J.-S. Kwon, R. Thakur and S. Wereley, Trends in Biotechnology, Cell Press, 2014 (*Cover Article). http://dx.doi.org/10.1016/j.tibtech.2014.06.002
REP research highlighted on the cover of the Trends in Biotechnology Journal (Cell Press)