Marrying chemistry with biology by combining on-chip solution-based combinatorial synthesis and cellular screening

Abstract

Drug development often relies on high-throughput cell-based screening of large compound libraries. However, the lack of miniaturized and parallelized methodologies in chemistry as well as strict separation and incompatibility of the synthesis of bioactive compounds from their biological screenings makes this process expensive and inefficient. Here, we demonstrate an on-chip platform that combines solution-based synthesis of compound libraries with high-throughput biological screenings (chemBIOS). The chemBIOS platform is compatible with both organic solvents required for the synthesis and aqueous solutions necessary for biological screenings. We use the chemBIOS platform to perform 75 parallel, three-component reactions to synthesize a library of lipidoids, followed by characterization via MALDI-MS, on-chip formation of lipoplexes, and on-chip cell screening. The entire process from the library synthesis to cell screening takes only 3 days and about 1 mL of total solutions, demonstrating the potential of the chemBIOS technology to increase efficiency and accelerate screenings and drug development.

Tyrosine Kinase Inhibitors in Cancer: Breakthrough and Challenges of Targeted Therapy

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Droplet Precise Self‐Splitting on Patterned Adhesive Surfaces for Simultaneous Multidetection

“…Microdroplets provide excellent platforms for microreactions and have elicited enormous research interest for their potential application in biological assays, [1][2][3][4] combinatorial analysis, [5][6][7][8][9][10] and drug discovery, [11,12] for which it is crucial to separate microdroplets and deposit them into desired locations with as pecific arrangement and morphology.S of ar, various methods have been developed and employed to distribute microdroplets,s uch as inkjet printing,d ispensing, discontinuous dewetting, and microfluidics. [13][14][15][16] Forexample, biosample suspensions were separated into microdroplet arrays and used for incubation and screening, [17] and microdroplets of ac olloidal nanoparticle solution were dispensed and assembled for fluorescence-based metal-ion recognition.…”

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