Microfluidic-Enabled Print-to-Screen Platform for High-Throughput Screening of Combinatorial Chemotherapy.
Since the 1960s, combination chemotherapy has been widely utilized as a standard method to treat cancer. However, because of the potentially enormous number of drug candidates and combinations, conventional identification methods of the effective drug combinations are usually associated with significantly high operational costs, low throughput screening, laborious and time-consuming procedures, and ethical concerns. In this paper, we present a low-cost, high-efficiency microfluidic print-to-screen (P2S) platform, which integrates combinatorial screening with biomolecular printing for high-throughput screening of anticancer drug combinations. This P2S platform provides several distinct advantages and features, including automatic combinatorial printing, high-throughput parallel drug screening, modular disposable cartridge, and biocompatibility, which can potentially speed up the entire discovery cycle of potent drug combinations. Microfluidic impact printing utilizing plug-and-play microfluidic cartridges is experimentally characterized with controllable droplet volume and accurate positioning. Furthermore, the combinatorial print-to-screen assay is demonstrated in a proof-of-concept biological experiment which can identify the positive hits among the entire drug combination library in a parallel and rapid manner. Overall, this microfluidic print-to-screen platform offers a simple, low-cost, high-efficiency solution for high-throughput large-scale combinatorial screening and can be applicable for various emerging applications in drug cocktail discovery.
Micro-Nano Innovations (MiNI) Laboratory, Biomedical Engineering, University of California , Davis, California 95616, United States.
Yuzhe
Y
Ding
Micro-Nano Innovations (MiNI) Laboratory, Biomedical Engineering, University of California , Davis, California 95616, United States.
Jiannan
J
Li
Department of Biochemistry and Molecular Medicine, Division of Hematology and Oncology, UC Davis Cancer Center, University of California , Davis, California 95817, United States.
Wenwu
W
Xiao
Department of Biochemistry and Molecular Medicine, Division of Hematology and Oncology, UC Davis Cancer Center, University of California , Davis, California 95817, United States.
Kai
K
Xiao
Department of Biochemistry and Molecular Medicine, Division of Hematology and Oncology, UC Davis Cancer Center, University of California , Davis, California 95817, United States.
Joyce
J
Lee
Department of Biochemistry and Molecular Medicine, Division of Hematology and Oncology, UC Davis Cancer Center, University of California , Davis, California 95817, United States.
Urvashi
U
Bhardwaj
Micro-Nano Innovations (MiNI) Laboratory, Biomedical Engineering, University of California , Davis, California 95616, United States.
Zijie
Z
Zhu
Micro-Nano Innovations (MiNI) Laboratory, Biomedical Engineering, University of California , Davis, California 95616, United States.
Philip
P
Digiglio
Micro-Nano Innovations (MiNI) Laboratory, Biomedical Engineering, University of California , Davis, California 95616, United States.
Gaomai
G
Yang
Department of Biochemistry and Molecular Medicine, Division of Hematology and Oncology, UC Davis Cancer Center, University of California , Davis, California 95817, United States.
Kit S
KS
Lam
Micro-Nano Innovations (MiNI) Laboratory, Biomedical Engineering, University of California , Davis, California 95616, United States.
Tingrui
T
Pan
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000032:analysis* / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D020650:Combinatorial Chemistry Techniques; D004353:Drug Evaluation, Preclinical; D057166:High-Throughput Screening Assays / Q000295:instrumentation; D006801:Humans; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation; D011327:Printing / Q000295:instrumentation; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured