High-throughput and label-free cell cluster monitoring based on light scattering imaging and microfluidic technique

Efficient detection of cell clusters is of paramount importance in the production and packaging processes of single-cell suspensions, as it can significantly impact cell density uniformity, induce apoptosis, and compromise the accuracy of cell sorting outcomes. This study introduces a novel, high-throughput and label-free method for monitoring cell clusters, leveraging light scattering imaging and microfluidic technologies. Two-dimensional (2D) light scattering, as a vital label free analytical approach, proves effective in detecting and analyzing biological particles with intricate structures. Through optical microscopy coupled with a high-speed camera, this study examines the 2D light scattering patterns produced by cell clusters, facilitating the discrimination between single cells and clustered cells. This label-free methodology offers distinct advantages over traditional labeling techniques, as it preserves cellular integrity without invasive disruptions. Furthermore, innovative microfluidic chip design enables continuous real-time monitoring of cell clusters, empowering rapid and high-throughput detection. Experimental validation involved monitoring silicon oxide (SiO₂) microsphere suspensions, demonstrating the method's capacity for high-throughput and high-sensitivity cell cluster monitoring. This research presents a promising tool for efficiently handling and monitoring the production of single-cell suspensions, with potential applications in various fields of cell biology and biotechnology.