title: Scaffold-integrated microchips for end-to-endin vitrotumor cell attachment and xenograft formation.
abstract: Microfluidic technologies have substantially advanced cancer research by enabling the isolation of rare circulating tumor cells (CTCs) for diagnostic and prognostic purposes. The characterization of isolated CTCs has been limited due to the difficulty in recovering and growing isolated cells with high fidelity. Here, we present a strategy that uses a 3D scaffold, integrated into a microfludic device, as a transferable substrate that can be readily isolated after device operation for serial usein vivoas a transplanted tissue bed. Hydrogel scaffolds were incorporated into a PDMS fluidic chamber prior to bonding and were rehydrated in the chamber after fluid contact. The hydrogel matrix completely filled the fluid chamber, significantly increasing the surface area to volume ratio, and could be directly visualized under a microscope. Computational modeling defined different flow and pressure regimes that guided the conditions used to operate the chip. As a proof of concept using a model cell line, we confirmed human prostate tumor cell attachment in the microfluidic scaffold chip, retrieval of the scaffold en masse, and serial implantation of the scaffold to a mouse model with preserved xenograft development. With further improvement in capture efficiency, this approach can offer an end-to-end platform for the continuous study of isolated cancer cells from a biological fluid to a xenograft in mice.
authors.affiliation: Center for Engineering in Medicine, Massachusetts General Hospital & Harvard Medical School and Shriners Hospital for Children, Boston, MA 02114, USA ; Department of Chemical Engineering, University of Massachusetts, Amherst, MA 01003, USA.
authors.forename: Jungwoo
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Scientific Computing, Florida State University, Tallahassee, FL 32306, USA.
authors.forename: Nathaniel
authors.initials: N
authors.lastname: Kohl
authors.affiliation: Department of Scientific Computing, Florida State University, Tallahassee, FL 32306, USA.
authors.forename: Sachin
authors.initials: S
authors.lastname: Shanbhang
authors.affiliation: Center for Engineering in Medicine, Massachusetts General Hospital & Harvard Medical School and Shriners Hospital for Children, Boston, MA 02114, USA ; Harvard Stem Cell Institute, Boston, MA 02138, USA.
authors.forename: Biju
authors.initials: B
authors.lastname: Parekkadan