Microfluidic Devices for Isolating and Releasing Disseminated Tumor Cells in Bone Marrow

Triple-negative breast cancer (TNBC) is a highly aggressive and lethal subtype of breast cancer. Many TNBC patients have significant risks of developing life-threatening metastases even after receiving successful neoadjuvant treatment. One reason for this high treatment failure rate is the presence of treatment-resisting disseminated tumor cells (DTCs) in the bone marrow (BM). DTCs have an extremely low occurrence of 1 per 106−107 nucleated BM cells. Hence, one challenge in studying DTCs is to enrich for these rare cells while retaining their viability for further molecular analysis. Microfluidic technology has become a promising solution by offering high detection sensitivity, low reagent consumption, and simple operation. Our project demonstrates the use of the immunoaffinity-based geometrically enhanced mixing (GEM) microfluidic device to efficiently capture TNBC cells in BM aspirates and safely release them for future single-cell ribonucleic acid (RNA) sequencing. Using anti-EGFR (epidermal growth factor receptor) antibodies as the capture agent, the GEM offers a capture efficiency of ∼70%. By combining the cell-dissociation chemical trypsin with mechanical impulses, the release efficiency reaches ∼95% while maintaining viability and morphology similar to that of TNBC cells in culture. This work has the potential to contribute towards the future identification of TNBC therapeutic targets.