In-Droplet Electromechanical Cell Lysis and Enhanced Enzymatic Assay Driven by Ion Concentration Polarization

Droplets enable the encapsulation of cells for their analysis in isolated domains. The study of molecular signatures (including genes, proteins, and metabolites) from a few or single cells is critical for identifying key subpopulations. However, dealing with biological analytes at low concentrations requires long incubation times and amplification to achieve the requisite signal strength. Further, cell lysis requires additional chemical lysing agents or heat, which can interfere with assays. Here, we leverage ion concentration polarization (ICP) in droplets to rapidly lyse breast cancer cells within 2 s under a DC voltage bias of 30 V. Numerical simulations attribute cell lysis to an ICP-based electric field and shear stress. We further achieve up to 19-fold concentration enrichment of an enzymatic assay product resulting from cell lysis and a 3.8-fold increase in the reaction rate during enrichment. Our technique for sensitive in-droplet cell analysis provides scope for rapid, high-throughput detection of low-abundance intracellular analytes.