title: Biodegradable nano-films for capture and non-invasive release of circulating tumor cells.
abstract: Selective isolation and purification of circulating tumor cells (CTCs) from whole blood is an important capability for both clinical medicine and biological research. Current techniques to perform this task place the isolated cells under excessive stresses that reduce cell viability, and potentially induce phenotype change, therefore losing valuable information about the isolated cells. We present a biodegradable nano-film coating on the surface of a microfluidic chip, which can be used to effectively capture as well as non-invasively release cancer cell lines such as PC-3, LNCaP, DU 145, H1650 and H1975. We have applied layer-by-layer (LbL) assembly to create a library of ultrathin coatings using a broad range of materials through complementary interactions. By developing an LbL nano-film coating with an affinity-based cell-capture surface that is capable of selectively isolating cancer cells from whole blood, and that can be rapidly degraded on command, we are able to gently isolate cancer cells and recover them without compromising cell viability or proliferative potential. Our approach has the capability to overcome practical hurdles and provide viable cancer cells for downstream analyses, such as live cell imaging, single cell genomics, and in vitro cell culture of recovered cells. Furthermore, CTCs from cancer patients were also captured, identified, and successfully released using the LbL-modified microchips.
authors.affiliation: Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.|Department of Chemical Engineering, Texas Tech University, Lubbock, TX, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Surgery, Harvard Medical School, Boston, MA, USA.|Center for Engineering in Medicine, Harvard Medical School, Boston, MA, USA.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Reátegui
authors.affiliation: Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
authors.forename: Myoung-Hwan
authors.initials: MH
authors.lastname: Park
authors.affiliation: Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
authors.forename: Steven
authors.initials: S
authors.lastname: Castleberry
authors.affiliation: Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.|David H. Koch Institute of Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
authors.forename: Jason Z
authors.initials: JZ
authors.lastname: Deng
authors.affiliation: Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
authors.forename: Bryan
authors.initials: B
authors.lastname: Hsu
authors.affiliation: Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
authors.forename: Sarah
authors.initials: S
authors.lastname: Mayner
authors.affiliation: Center for Engineering in Medicine, Harvard Medical School, Boston, MA, USA.
authors.forename: Anne E
authors.initials: AE
authors.lastname: Jensen
authors.affiliation: Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA.|Department of Medicine, Harvard Medical School, Boston, MA, USA.
authors.forename: Lecia V
authors.initials: LV
authors.lastname: Sequist
authors.affiliation: Department of Surgery, Harvard Medical School, Boston, MA, USA.|Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA.
authors.forename: Shyamala
authors.initials: S
authors.lastname: Maheswaran
authors.affiliation: Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA.|Howard Hughes Medical Institute, Chevy Chase, MD, USA.|Department of Medicine, Harvard Medical School, Boston, MA, USA.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Haber
authors.affiliation: Department of Surgery, Harvard Medical School, Boston, MA, USA.|Center for Engineering in Medicine, Harvard Medical School, Boston, MA, USA.
authors.forename: Mehmet
authors.initials: M
authors.lastname: Toner
authors.affiliation: Center for Engineering in Medicine, Harvard Medical School, Boston, MA, USA.|Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA.|Department of Medicine, Harvard Medical School, Boston, MA, USA.
authors.forename: Shannon L
authors.initials: SL
authors.lastname: Stott
authors.affiliation: Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.|David H. Koch Institute of Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
authors.forename: Paula T
authors.initials: PT
authors.lastname: Hammond
mesh_terms: D000464:Alginates / Q000737:chemistry*; D001672:Biocompatible Materials / Q000737:chemistry*; D002452:Cell Count; D045744:Cell Line, Tumor; D002469:Cell Separation / Q000379:methods*; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D006801:Humans; D046210:Microfluidic Analytical Techniques / Q000379:methods*; D049329:Nanostructures / Q000737:chemistry* / Q000648:ultrastructure; D009369:Neoplasms / Q000097:blood* / Q000175:diagnosis; D009360:Neoplastic Cells, Circulating / Q000473:pathology*; D011073:Polyamines / Q000737:chemistry; D013499:Surface Properties
chemical_list: D000464:Alginates; D001672:Biocompatible Materials; D006603:Hexuronic Acids; D011073:Polyamines; C063994:polyallylamine; D020723:Glucuronic Acid
keywords: Alginate; Biodegradable; Circulating tumor cells; Layer-by-layer; Nano-film; Surface modification