Compact Micropatterned Chip Empowers Undisturbed and Programmable Drug Addition in High-Throughput Cell Screening.

Abstract

Simultaneously adding multiple drugs and other chemical reagents to individual droplets at specific time points presents a significant challenge, particularly when dealing with tiny droplets in high-throughput screening applications. In this study, a micropatterned polymer chip is developed as a miniaturized platform for light-induced programmable drug addition in cell-based screening. This chip incorporates a porous superhydrophobic polymer film with atom transfer radical polymerization reactivity, facilitating the efficient grafting of azobenzene methacrylate, a photoconformationally changeable group, onto the hydrophilic regions of polymer matrix at targeted locations and with precise densities. By employing light irradiation, the cyclodextrin-azobenzene host-guest complexes formed on the polymer chip can switch from an "associated" to a "dissociated" state, granting precise photochemical control over the supramolecular coding system and its surface patterning ability. Significantly, the exceptional spatial and temporal control offered by these chemical transitions empowers to utilize digital light processing systems for simultaneous regulation and release of cyclodextrin-bearing drugs across numerous droplets containing suspended or adhered cells. This approach minimizes mechanical disruption while achieving precise control over the timing of addition, dosage, and integration varieties of released drugs in high-throughput screening, all programmable to meet specific requirements.