TY - JOUR
T1 - Live circulating tumour cells selection on digitized self-assembled cell array (Digi-saca) chip by in-parallel/in-situ image analysis, cell capture, and cultivation
AU - Goudar, Venkanagouda S.
AU - Yeh, Ping Hao
AU - Wu, Shin Yao
AU - Chu, Cheng Hsuan
AU - Lu, Long Sheng
AU - Yang, Chien Hui
AU - Chiou, Tzeon Jye
AU - Tseng, Fan Gang
N1 - Funding Information:
Dr. Long-Sheng Lu is currently a practicing radiation oncologist and an assistant professor in Biomedical Materials and Tissue Engineering in Taipei Medical University, Taipei, Taiwan. He obtained his M.D. and pH.D. (pharmacology) from National Taiwan University, Taipei, Taiwan, and did postdoctoral training in M.D. Anderson Cancer Center and Texas Heart Institute, Houston, Texas, USA. He then joined Taipei Medical University for a physician scientist career. His research interests are applications of circulating tumor cells in personalized medicine and cardiovascular protection during radiotherapy. His work was recognized by Taiwan Merit Scholarship from Taiwan National Science Council, Excellent mention in Innovation and Startup Award (FITI) from Ministry of Science and Technology, and Junior Faculty Development Award from Taiwan Society for Therapeutic Radiology and Oncology. Overall, he is the author of more than 30 research articles with more than 1100 citations.
Funding Information:
We would like to thank the financial support from Veterans General Hospitals and University System of Taiwan Joint Research Program [VGHUST109-V6-1-1, VGHUST107-G6-1-1, VGHUST105-G6-1-1] and Ministry of Science and Technology (MOST), Taiwan by the projects [107-2221-E-007 -012 -MY3, 107-2622-E-007 -006 -CC2, 108 3017-F-007-0032, 108-2638-E-007-001-MY2]. Frontier Research Center on Fundamental and Applied Sciences of Matters, from The Featured Areas Research Center Programm within the frame work of the Higher Education Sprout Project by the Ministry of Education [MOE 108QR001I5]. Special thanks to Mr. Suei-Shen Wang for microneedle drawing, and to Mr. Manohar Prasad Koduri for helping in manuscript correction.
Funding Information:
We would like to thank the financial support from Veterans General Hospitals and University System of Taiwan Joint Research Program [VGHUST109-V6-1-1, VGHUST107-G6-1-1 , VGHUST105-G6-1-1 ] and Ministry of Science and Technology (MOST), Taiwan by the projects [ 107-2221-E-007 -012 -MY3 , 107-2622-E-007 -006 -CC2 , 108 3017-F-007-0032, 108-2638-E-007-001-MY2 ]. Frontier Research Center on Fundamental and Applied Sciences of Matters, from The Featured Areas Research Center Programm within the frame work of the Higher Education Sprout Project by the Ministry of Education [MOE 108QR001I5]. Special thanks to Mr. Suei-Shen Wang for microneedle drawing, and to Mr. Manohar Prasad Koduri for helping in manuscript correction.
Publisher Copyright:
© 2020 Elsevier B.V.
PY - 2020/8/1
Y1 - 2020/8/1
N2 - Cancer is one of the major and most deadly diseases of mankind. With present technologies, early detection and prevention of cancer disease is still a major bottleneck. Circulating Tumor Cells (CTC) is one of the cancer biomarkers for the diagnosis of metastasis. However, there is an urgent need to improve the turn around time of CTC detection from a small sample volume in order to promote its clinical implications. This paper highlights Digi-SACA, an automated workflow to capture CTCs from the whole blood on self-assembled cell array chips. The gravity force and lateral driving force based microfluidic chip drive the mononuclear blood cells from 4 ml of samples to form a monolayer without any external fluid control equipment. The subsequent immunostaining and automated image acquisition, image processing, CTC enumeration, and CTC harvest can be completed within 4 h. The sensitivity of Digi-SACA chip is 1 in ten million leukocytes which is very promising for early detection of the CTC. In a small pilot study series, the Digi-SACA chip is able to detect of the mean of 14.4 CTCs from 4 ml of blood in 10 clinical samples from patients with breast cancer, while mean of 17.6 CTCs were measured from the same sample set with IsoFlux™ platform from 4 ml of blood. We have also demonstrated the efficiency of our technique to pick CTC with glass micropipettes for standard cell culture growth up to 11–15 days. Overall, our study represents the liability of the Digi-SACA system in CTCs enumeration, detection, and isolation against the state-of-the-art.
AB - Cancer is one of the major and most deadly diseases of mankind. With present technologies, early detection and prevention of cancer disease is still a major bottleneck. Circulating Tumor Cells (CTC) is one of the cancer biomarkers for the diagnosis of metastasis. However, there is an urgent need to improve the turn around time of CTC detection from a small sample volume in order to promote its clinical implications. This paper highlights Digi-SACA, an automated workflow to capture CTCs from the whole blood on self-assembled cell array chips. The gravity force and lateral driving force based microfluidic chip drive the mononuclear blood cells from 4 ml of samples to form a monolayer without any external fluid control equipment. The subsequent immunostaining and automated image acquisition, image processing, CTC enumeration, and CTC harvest can be completed within 4 h. The sensitivity of Digi-SACA chip is 1 in ten million leukocytes which is very promising for early detection of the CTC. In a small pilot study series, the Digi-SACA chip is able to detect of the mean of 14.4 CTCs from 4 ml of blood in 10 clinical samples from patients with breast cancer, while mean of 17.6 CTCs were measured from the same sample set with IsoFlux™ platform from 4 ml of blood. We have also demonstrated the efficiency of our technique to pick CTC with glass micropipettes for standard cell culture growth up to 11–15 days. Overall, our study represents the liability of the Digi-SACA system in CTCs enumeration, detection, and isolation against the state-of-the-art.
KW - Breast cancer
KW - Circulating tumor cells (CTC)
KW - Digi-SACA chip
KW - Single-cell picking
UR - http://www.scopus.com/inward/record.url?scp=85084223501&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85084223501&partnerID=8YFLogxK
U2 - 10.1016/j.snb.2020.128002
DO - 10.1016/j.snb.2020.128002
M3 - Article
AN - SCOPUS:85084223501
SN - 0925-4005
VL - 316
JO - Sensors and Actuators, B: Chemical
JF - Sensors and Actuators, B: Chemical
M1 - 128002
ER -