Assistant Professor Hong Kong Polytechnic University, Hong Kong
Phagocytic cells recognize and phagocytose pathogens for elimination. After being internalized by immune cells, bacterial pathogens can remain hidden at low levels or replicate intracellularly. This may pose significant challenges in research and clinical settings, where phagocytosis-detection approaches involve flow cytometry or microscopic search often have difficulties detecting rare bacteria-internalized phagocytes among large populations of uninfected cells. Hence it is important to develop a rapid, non-disruptive, and label-free phagocytosis detection approach. Using deformability assays and microscopic imaging, we have demonstrated for the first time that phagocytes with internalized bacteria display more aberrant physical properties, including stiffer surface and larger size, compared to uninfected monocytes. Taking advantage of these physical differences, a novel microfluidics-based biosensor platform for phagocytosis detection was developed to passively sort, concentrate and quantify rare monocytes with internalized pathogens (MIP) from uninfected monocyte populations. The clinical utility of the MIP platform was demonstrated by enriching and detecting bacteria-internalized monocytes from human blood samples rapidly (1.5 h). Patient-derived bacterial isolates were further used to validate the clinical utility of the MIP platform. In conclusion, our proof-of-concept platform could be used to rapidly diagnose microbial infections via detection of phagocytosis, thereby improving the clinical outcomes for point-of-care management of early infections.