Drug screening on digital microfluidics for cancer precision medicine

Jiao Zhai, Yingying Liu, Weiqing Ji, Xinru Huang, Ping Wang, Yunyi Li, Haoran Li, Ada Hang-Heng Wong, Xiong Zhou, Ping Chen, Lianhong Wang, Ning Yang, Chi Chen, Haitian Chen, Pui-In Mak, Chu-Xia Deng, Rui Martins, Mengsu Yang, Tsung-Yi Ho, Shuhong Yi (), Hailong Yao () and Yanwei Jia ()
Additional contact information
Jiao Zhai: University of Macau
Yingying Liu: University of Macau
Weiqing Ji: University of Science and Technology Beijing
Xinru Huang: Sun Yat-Sen University
Ping Wang: The First Affiliated Hospital of Guangzhou Medical University
Yunyi Li: University of Macau
Haoran Li: University of Macau
Ada Hang-Heng Wong: University of Macau
Xiong Zhou: University of Macau
Ping Chen: University of Macau
Lianhong Wang: Hunan University
Ning Yang: University of Macau
Chi Chen: Sun Yat-Sen University
Haitian Chen: Sun Yat-Sen University
Pui-In Mak: University of Macau
Chu-Xia Deng: University of Macau
Rui Martins: University of Macau
Mengsu Yang: City University of Hong Kong
Tsung-Yi Ho: The Chinese University of Hong Kong
Shuhong Yi: Sun Yat-Sen University
Hailong Yao: University of Science and Technology Beijing
Yanwei Jia: University of Macau

Nature Communications, 2024, vol. 15, issue 1, 1-16

Abstract: Abstract Drug screening based on in-vitro primary tumor cell culture has demonstrated potential in personalized cancer diagnosis. However, the limited number of tumor cells, especially from patients with early stage cancer, has hindered the widespread application of this technique. Hence, we developed a digital microfluidic system for drug screening using primary tumor cells and established a working protocol for precision medicine. Smart control logic was developed to increase the throughput of the system and decrease its footprint to parallelly screen three drugs on a 4 × 4 cm2 chip in a device measuring 23 × 16 × 3.5 cm3. We validated this method in an MDA-MB-231 breast cancer xenograft mouse model and liver cancer specimens from patients, demonstrating tumor suppression in mice/patients treated with drugs that were screened to be effective on individual primary tumor cells. Mice treated with drugs screened on-chip as ineffective exhibited similar results to those in the control groups. The effective drug identified through on-chip screening demonstrated consistency with the absence of mutations in their related genes determined via exome sequencing of individual tumors, further validating this protocol. Therefore, this technique and system may promote advances in precision medicine for cancer treatment and, eventually, for any disease.

Date: 2024
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DOI: 10.1038/s41467-024-48616-3

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