A Silicon-based Coral-like Nanostructured Microfluidics to Isolate Rare Cells in Human Circulation: Validation by SK-BR-3 Cancer Cell Line and Its Utility in Circulating Fetal Nucleated Red Blood Cells
Gwo-Chin Ma,
Wen-Hsiang Lin,
Chung-Er Huang,
Ting-Yu Chang,
Jia-Yun Liu,
Ya-Jun Yang,
Mei-Hui Lee,
Wan-Ju Wu,
Yun-Shiang Chang,
Ming Chen
Affiliations
Gwo-Chin Ma
Department of Genomic Medicine and Center for Medical Genetics, Changhua Christian Hospital; and Department of Genomic Science and Technology, Changhua Christian Hospital Healthcare System, Changhua 50046, Taiwan
Wen-Hsiang Lin
Department of Genomic Medicine and Center for Medical Genetics, Changhua Christian Hospital; and Department of Genomic Science and Technology, Changhua Christian Hospital Healthcare System, Changhua 50046, Taiwan
Chung-Er Huang
International College of Semiconductor Technology, National Chiao Tung University, Hsinchu 30010, Taiwan
Ting-Yu Chang
Department of Genomic Medicine and Center for Medical Genetics, Changhua Christian Hospital; and Department of Genomic Science and Technology, Changhua Christian Hospital Healthcare System, Changhua 50046, Taiwan
Jia-Yun Liu
Department of Genomic Medicine and Center for Medical Genetics, Changhua Christian Hospital; and Department of Genomic Science and Technology, Changhua Christian Hospital Healthcare System, Changhua 50046, Taiwan
Ya-Jun Yang
Department of Genomic Medicine and Center for Medical Genetics, Changhua Christian Hospital; and Department of Genomic Science and Technology, Changhua Christian Hospital Healthcare System, Changhua 50046, Taiwan
Mei-Hui Lee
Department of Genomic Medicine and Center for Medical Genetics, Changhua Christian Hospital; and Department of Genomic Science and Technology, Changhua Christian Hospital Healthcare System, Changhua 50046, Taiwan
Wan-Ju Wu
Department of Obstetrics and Gynecology, Changhua Christian Hospital, Changhua 50006, Taiwan
Yun-Shiang Chang
Department of Molecular Biotechnology, Da-Yeh University, Changhua 51591, Taiwan
Ming Chen
Department of Genomic Medicine and Center for Medical Genetics, Changhua Christian Hospital; and Department of Genomic Science and Technology, Changhua Christian Hospital Healthcare System, Changhua 50046, Taiwan
Circulating fetal cells (CFCs) in maternal blood are rare but have a strong potential to be the target for noninvasive prenatal diagnosis (NIPD). “Cell RevealTM system„ is a silicon-based microfluidic platform capable to capture rare cell populations in human circulation. The platform is recently optimized to enhance the capture efficiency and system automation. In this study, spiking tests of SK-BR-3 breast cancer cells were used for the evaluation of capture efficiency. Then, peripheral bloods from 14 pregnant women whose fetuses have evidenced non-maternal genomic markers (e.g., de novo pathogenic copy number changes) were tested for the capture of circulating fetal nucleated red blood cells (fnRBCs). Captured cells were subjected to fluorescent in situ hybridization (FISH) on chip or recovered by an automated cell picker for molecular genetic analyses. The capture rate for the spiking tests is estimated as 88.1%. For the prenatal study, 2⁻71 fnRBCs were successfully captured from 2 mL of maternal blood in all pregnant women. The captured fnRBCs were verified to be from fetal origin. Our results demonstrated that the Cell RevealTM system has a high capture efficiency and can be used for fnRBC capture that is feasible for the genetic diagnosis of fetuses without invasive procedures.
