An Automated Digital Microfluidic System Based on Inkjet Printing

Cellular interactions, such as intercellular communication and signal transduction, can be enhanced within three-dimensional cell spheroids, contributing significantly to cellular viability and proliferation. This is crucial for advancements in cancer research, drug testing, and personalized medicine. The dimensions of the cell spheroids play a pivotal role in their functionality, affecting cell proliferation and differentiation, intercellular interactions, gene expression, protein synthesis, drug penetration, and metabolism. Consequently, different spheroid sizes may be required for various drug sensitivity experiments. However, conventional 3D cell spheroid cultures suffer from challenges such as size inconsistency, poor uniformity, and low throughput. To address these issues, we have developed an automated, intelligent system based on inkjet printing. This system allows for precise control of droplet volume by adjusting algorithms, thereby enabling the formation of spheroids of varying sizes. For spheroids of a single size, the printing pattern can be modified to achieve a coefficient of variation within 10% through a bidirectional compensation method. Furthermore, the system is equipped with an automatic pipetting module, which facilitates the high-throughput preparation of cell spheroids. We have implemented a 3 × 3 spheroid array in a 24-well plate, printing a total of 216 spheroids in just 11 min. Last, we attempted to print mouse small intestinal organoids and cultured them for 7 days, followed by immunofluorescent staining experiments. The results indicate that our equipment is capable of supporting the culture of organoids, which is of great significance for high-throughput drug screening and personalized medicine.