title: Hyaluronic acid-functionalized electrospun PLGA nanofibers embedded in a microfluidic chip for cancer cell capture and culture.
abstract: Circulating tumor cells (CTCs) are important markers of metastatic cancer. The isolation and detection of CTCs from peripheral blood provides valuable information for cancer diagnosis and precision medicine. However, cost-efficient targeted separation of CTCs of different origins with clinically significant specificity and efficiency remains a major challenge. In this study, a facile approach was developed to fabricate a thin sheet of hyaluronic acid (HA)-functionalized PLGA nanofibrous membrane and integrate it into a microfluidic chamber. The HA was covalently conjugated onto polyethyleneimine (PEI)-modified electrospun poly(lactic-co-glycolic acid) (PLGA) nanofibers. Different techniques were employed to characterize the resulted nanofibers. The results show that the CD44+ carcinoma of various origins (HeLa, KB, A549, and MCF-7 cells) could be selectively captured by the PLGA-PEI-HA nanofibers in the microfluidic platform. Importantly, the PLGA-PEI-HA nanofibrous membrane was more efficient to capture HeLa cancer cells under flowing conditions than in static dishes, and at a really low density (20 cells per mL). Furthermore, with constant media perfusion, the captured HeLa cells could grow on the nanofibrous membrane in the microchip for days without compromised cell viability. This is the first trial of using HA-functionalized electrospun nanofibers in a lab-chip device for cancer cell capture and culture. Compared to conventional CTC capture methods, the integration of inexpensive functional electrospun nanofibers and microfluidic technologies may expand the frontiers of using advanced nanomaterials in portable diagnostic applications.
authors.affiliation: State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, People's Republic of China. xshi@dhu.edu.cn zhu@dhu.edu.cn.
authors.forename: Gangwei
authors.initials: G
authors.lastname: Xu
authors.affiliation: Department of Thoracic Surgery, Huashan Hospital, Fudan University, Shanghai 200040, P. R. China. hs_chenxiaofeng@126.com.
authors.forename: Yulong
authors.initials: Y
authors.lastname: Tan
authors.affiliation: State Key Laboratory of Transducer Technology, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Sciences, Shanghai 200050, People's Republic of China.
authors.forename: Tiegang
authors.initials: T
authors.lastname: Xu
authors.affiliation: State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, People's Republic of China. xshi@dhu.edu.cn zhu@dhu.edu.cn.
authors.forename: Di
authors.initials: D
authors.lastname: Yin
authors.affiliation: State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, People's Republic of China. xshi@dhu.edu.cn zhu@dhu.edu.cn.
authors.forename: Mengyuan
authors.initials: M
authors.lastname: Wang
authors.affiliation: State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, People's Republic of China. xshi@dhu.edu.cn zhu@dhu.edu.cn.
authors.forename: Mingwu
authors.initials: M
authors.lastname: Shen
authors.affiliation: Department of Thoracic Surgery, Huashan Hospital, Fudan University, Shanghai 200040, P. R. China. hs_chenxiaofeng@126.com.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Chen
authors.affiliation: State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, People's Republic of China. xshi@dhu.edu.cn zhu@dhu.edu.cn and Key Laboratory of Textile Science and Technology, Ministry of Education, Donghua University, Shanghai 201620, China.
authors.forename: Xiangyang
authors.identifier: http://orcid.org/0000-0001-6785-6645
authors.initials: X
authors.lastname: Shi
authors.affiliation: State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, People's Republic of China. xshi@dhu.edu.cn zhu@dhu.edu.cn.
authors.forename: Xiaoyue
authors.initials: X
authors.lastname: Zhu
mesh_terms: D000072283:A549 Cells; D018929:Cell Culture Techniques / Q000295:instrumentation*; D002469:Cell Separation / Q000295:instrumentation*; D004867:Equipment Design; D006367:HeLa Cells; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry*; D056656:Lab-On-A-Chip Devices; D019344:Lactic Acid / Q000737:chemistry*; D061986:MCF-7 Cells; D057139:Nanofibers / Q000737:chemistry*; D009369:Neoplasms / Q000473:pathology; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer
chemical_list: D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D006820:Hyaluronic Acid