Development of microfluidic flow cytometry capable of characterization of single-cell intrinsic structural and electrical parameters

Although single-cell intrinsic structural and electrical parameters (e.g. D (c) of cell diameter, D (n) of nuclear diameter, sigma (cy) of cytoplasmic conductivity and C (sm) of specific membrane capacitance) are promising for cell-type classification, they cannot be obtained simultaneously due to structural limitations of previously reported flow cytometry. This paper presented a microfluidic flow cytometry made of a double T-type constriction channel plus a predefined fluorescence detection domain, capable of high-throughput characterizing single-cell D (c), D (n), sigma (cy) and C (sm) leveraging a home-developed impedance-fluorescence model. As a demonstration, the microfluidic platform quantified D (c), D (n), sigma (cy) and C (sm) from similar to 10 000 individual cells of three well-established tumor cell lines of A549, SW620 and HeLa where successful rates of cell-type classification were estimated as 54.5 +/- 1.3% (D (c)), 68.9 +/- 6.8% (D (c) + D (n)) and 84.8 +/- 4.4% (D (c), D (n), sigma (cy) + C (sm)) based on neural pattern recognition. Then D (c), D (n), sigma (cy) and C (sm) derived from similar to 10 000 single cells of K562 vs Jurkat of leukemia and SACC-LM vs CAL 27 of oral tumor were quantified and compared, where successful rates of cell-type classification were estimated as 87.3% (K562 vs Jurkat) and 79.5% (SACC-LM vs CAL 27), respectively. In summary, the microfluidic platform reported in this study could quantify single-cell intrinsic structural and electrical parameters simultaneously, leading to significant increases in successful rates of cell-type classification.