While high-throughput combinatorial sample generation plays a critical role in drug discovery and cell-based assays, standard methods have encountered challenges of time or cost-effectiveness when using manual preparation or serial-dispensing liquid handlers. To address these challenges, we introduce a novel parallel combinatorial microfluidic (PCM) system that applies the design of hydraulic-resistance networks to simultaneously generate a prespecified combinatorial map. Unlike conventional serial dispensing, PCM devices integrated superhydrophobic outlets for parallel contactless dispensing, thereby minimizing contamination, reducing processing time, and ensuring an identical reaction time across all samples. Regardless of the number of target samples, the PCM system demonstrated rapid operation by completing all processes within 5 min. Devices fabricated for multiple combinatorial maps validated the PCM design principle and high-throughput scalability by reliably producing the predefined maps with droplet sizes of 3.5 μl. A proof-of-concept study of antibiotic cell assays confirmed the biocompatibility of the system and its ability to produce results comparable to those of standard methods, as demonstrated by good overlapping ranges of the half maximal inhibitory concentration (IC50). This work establishes a novel, cost-effective, high-throughput technology for combinatorial screenings in drug development with future improvements targeting sub-3.5 μl to enhance accuracy.
Wongwiset et al. (Sun,) studied this question.