title: Sensitive and Specific Biomimetic Lipid Coated Microfluidics to Isolate Viable Circulating Tumor Cells and Microemboli for Cancer Detection.
abstract: Here we presented a simple and effective membrane mimetic microfluidic device with antibody conjugated supported lipid bilayer (SLB) "smart coating" to capture viable circulating tumor cells (CTCs) and circulating tumor microemboli (CTM) directly from whole blood of all stage clinical cancer patients. The non-covalently bound SLB was able to promote dynamic clustering of lipid-tethered antibodies to CTC antigens and minimized non-specific blood cells retention through its non-fouling nature. A gentle flow further flushed away loosely-bound blood cells to achieve high purity of CTCs, and a stream of air foam injected disintegrate the SLB assemblies to release intact and viable CTCs from the chip. Human blood spiked cancer cell line test showed the ~95% overall efficiency to recover both CTCs and CTMs. Live/dead assay showed that at least 86% of recovered cells maintain viability. By using 2 mL of peripheral blood, the CTCs and CTMs counts of 63 healthy and colorectal cancer donors were positively correlated with the cancer progression. In summary, a simple and effective strategy utilizing biomimetic principle was developed to retrieve viable CTCs for enumeration, molecular analysis, as well as ex vivo culture over weeks. Due to the high sensitivity and specificity, it is the first time to show the high detection rates and quantity of CTCs in non-metastatic cancer patients. This work offers the values in both early cancer detection and prognosis of CTC and provides an accurate non-invasive strategy for routine clinical investigation on CTCs.
authors.affiliation: Genomics Research Center, Academia Sinica, Nankang, Taipei, Taiwan.
authors.forename: Jia-Yang
authors.initials: JY
authors.lastname: Chen
authors.affiliation: Division of Colon and Rectal Surgery, Chang Gung Memorial Hospital, Kueishan, Taoyuan, Linkou, Taiwan.|Graduate Institute of Clinical Medical Science, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Wen-Sy
authors.initials: WS
authors.lastname: Tsai
authors.affiliation: Genomics Research Center, Academia Sinica, Nankang, Taipei, Taiwan.
authors.forename: Hung-Jen
authors.initials: HJ
authors.lastname: Shao
authors.affiliation: Genomics Research Center, Academia Sinica, Nankang, Taipei, Taiwan.
authors.forename: Jen-Chia
authors.initials: JC
authors.lastname: Wu
authors.affiliation: Genomics Research Center, Academia Sinica, Nankang, Taipei, Taiwan.
authors.forename: Jr-Ming
authors.initials: JM
authors.lastname: Lai
authors.affiliation: Genomics Research Center, Academia Sinica, Nankang, Taipei, Taiwan.|Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Si-Hong
authors.initials: SH
authors.lastname: Lu
authors.affiliation: Genomics Research Center, Academia Sinica, Nankang, Taipei, Taiwan.
authors.forename: Tsung-Fu
authors.initials: TF
authors.lastname: Hung
authors.affiliation: Genomics Research Center, Academia Sinica, Nankang, Taipei, Taiwan.
authors.forename: Chih-Tsung
authors.initials: CT
authors.lastname: Yang
authors.affiliation: Genomics Research Center, Academia Sinica, Nankang, Taipei, Taiwan.
authors.forename: Liang-Chun
authors.initials: LC
authors.lastname: Wu
authors.affiliation: Division of Colon and Rectal Surgery, Chang Gung Memorial Hospital, Kueishan, Taoyuan, Linkou, Taiwan.|Graduate Institute of Clinical Medical Science, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Jinn-Shiun
authors.initials: JS
authors.lastname: Chen
authors.affiliation: Genomics Research Center, Academia Sinica, Nankang, Taipei, Taiwan.|Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan.
authors.forename: Wen-Hwa
authors.initials: WH
authors.lastname: Lee
authors.affiliation: Genomics Research Center, Academia Sinica, Nankang, Taipei, Taiwan.|Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Ying-Chih
authors.initials: YC
authors.lastname: Chang
mesh_terms: D000328:Adult; D000906:Antibodies / Q000276:immunology; D000951:Antigens, Neoplasm / Q000097:blood* / Q000276:immunology / Q000302:isolation & purification; D015179:Colorectal Neoplasms / Q000097:blood* / Q000276:immunology; D055088:Early Detection of Cancer; D005260:Female; D045325:HCT116 Cells; D006801:Humans; D056656:Lab-On-A-Chip Devices; D008055:Lipids / Q000737:chemistry; D008297:Male; D008875:Middle Aged; D009360:Neoplastic Cells, Circulating / Q000276:immunology* / Q000473:pathology
chemical_list: D000906:Antibodies; D000951:Antigens, Neoplasm; D008055:Lipids