Integrated microflow cytometry for portable immunophenotypic cell analysis

Abstract

Flow cytometry is a powerful tool for analyzing cellular phenotypes in a large population of cells, and it is commonly used in many applications from basic research to clinical practice. A major challenge facing miniaturization of flow cytometry is the dichotomous trade-off between performance and portability. To decouple the competing performance parameters, we propose a comprehensive approach for development of integrated microflow (IM) cytometry by (i) replacing a conventional sheath-based fluidic system with a microfluidic device capable of on-chip flow-rate regulation and sheathless cell focusing and (ii) adopting fluorescent nanocrystal labelling that allows multicolor detection with a single excitation source and an emission filter. The IM cytometer consists simply of a laser diode, an optical filter, an objective lens, a CMOS sensor and the microfluidic device, effectively miniaturizing flow cytometry into a portable device with a footprint of 398.4 cm3 and a weight of 613.9 g. We applied the IM cytometer to detect an immunophenotypic difference between two different types of breast cancer cells simply by dropping a sample solution onto the inlet reservoir of the microfluidic device. The IM cytometric operation was performed within 0.8 min of sample dropping, and the cytometric analysis results showed excellent agreement with those of conventional flow cytometry, providing a new direction in miniaturization of flow cytometry while maintaining its functionalities.