Research
High-throughput Microfluidic Devices for Cell and Gene Therapy Manufacturing
Cellular therapies are revolutionizing the treatment of a broad spectrum of hard-to-treat diseases, including sickle cell disease, autoimmune disorders, and cancer. Despite the enormous potential of cell therapies, manufacturing remains a critical bottleneck, leading to waitlist mortality. The current cell therapy manufacturing paradigm, built around conventional lab technology, is lossy and not optimal for scale-up. Supported by a K-25 NIH Career Award, we are developing high-throughput microfluidic cell isolation, manipulation, and washing tools to enable cellular engineering at scale.
Circulating Tumor Cells (CTCs) for Guiding Targeted Therapies
Recently, targeted therapies such as Antibody-drug conjugates (ADCs) and Bispecific T-cell Engagers (BiTEs) have shown remarkable efficacy in breast and small-cell lung cancer. ADCs target cell surface proteins such as TROP2 and HER2to deliver highly toxic payloads, whereas BiTEs use bispecific antibodies (e.g., DLL3-CD3) to engage T cells for tumor killing. Despite the remarkable efficacy of these treatments, a significant fraction of patients don't respond. Currently, there are no biomarkers available to optimize the selection and sequencing of the existing ADCs and BiTEs. Archival specimens do not fully address the spatial and temporal heterogeneity of the target marker. We are studying circulating tumor cells (CTCs) obtained from 10 to 20 mL blood samples to quantitatively measure dynamic target marker expression. Specifically, we are exploring the ability to predict who will respond to these therapies and the mechanisms of resistance.
Epitope Expression Persists in Circulating Tumor Cells as Breast Cancers Acquire Resistance to Antibody Drug Conjugates, A. Mishra et al., bioRxiv, 2025.
Tumor cell-based liquid biopsy using high-throughput microfluidic enrichment of entire leukapheresis product, A. Mishra et al., Nature Communications, 2025.
Ultrahigh-throughput magnetic sorting of large blood volumes for epitope-agnostic isolation of circulating tumor cells, A. Mishra et al., PNAS, 2020.
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
