1. Academic Validation
  2. High Throughput Confined Migration Microfluidic Device for Drug Screening

High Throughput Confined Migration Microfluidic Device for Drug Screening

  • Small. 2023 Jan 12;e2207194. doi: 10.1002/smll.202207194.
Zihan Yang 1 2 Zhihang Zhou 1 3 Tongxu Si 1 2 Zhengdong Zhou 1 2 Li Zhou 1 3 Y Rebecca Chin 1 Liang Zhang 1 Xinyuan Guan 4 Mengsu Yang 1 2
Affiliations

Affiliations

  • 1 Department of Biomedical Sciences, and Tung Biomedical Sciences Centre City University of Hong Kong, 83 Tat Chee Avenue, Kowloon, Hong Kong SAR, 999077, P. R. China.
  • 2 Department of Precision Diagnostic and Therapeutic Technology, City University of Hong Kong Futian Research Institute, Shenzhen, Guangdong, 518000, P. R. China.
  • 3 Department of Gastroenterology, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, P. R. China.
  • 4 Department of Clinical Oncology, the University of Hong Kong, Hong Kong, Hong Kong SAR, 999077, P. R. China.
Abstract

Cancer metastasis is the major cause of cancer-related death. Excessive extracellular matrix deposition and increased stiffness are typical features of solid tumors, creating confined spaces for tumor cell migration and metastasis. Confined migration is involved in all metastasis steps. However, confined and unconfined migration inhibitors are different and drugs available to inhibit confined migration are rare. The main challenges are the modeling of confined migration, the suffering of low throughput, and Others. Microfluidic device has the advantage to reduce reagent consumption and enhance throughput. Here, a microfluidic chip that can achieve multi-function drug screening against the collective migration of Cancer cells under confined environment is designed. This device is applied to screen out effective drugs on confined migration among a novel mechanoreceptors compound library (166 compounds) in hepatocellular carcinoma, non-small lung Cancer, breast Cancer, and pancreatic ductal adenocarcinoma cells. Three compounds that can significantly inhibit confined migration in pan-cancer: mitochonic acid 5 (MA-5), SB-705498, and diphenyleneiodonium chloride are found. Finally, it is elucidated that these drugs targeted mitochondria, actin polymerization, and cell viability, respectively. In sum, a high-throughput microfluidic platform for screening drugs targeting confined migration is established and three novel inhibitors of confined migration in multiple Cancer types are identified.

Keywords

cancer metastasis; confined migration; drug screening; microfluidics.

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