A Switchable Interface with Stimuli-Responsive Polymer Brushes for Rare Cell Isolation and Cell Detachment

Polymer interface science is broadening its area to nanotechnologies, medicine, and biotechnology. The well-defined and controlled polymeric interfaces have been developed and provided a variety of surface properties by varying molecular characteristics of the polymer brushes¹.  However, affinity-based sorting of colloidal particulates, such as cells and viruses, from a mixture of different particles is limited due to the quasi-irreversible adsorption having a high energy barrier to detach particles from the surface.^{2, 3} This limitation can be overcome by utilizing local oscillating repulsive forces generated at the microstructured stimuli-responsive polymer interface. The particle adhesion force is balanced by the repulsion force. In this study, a microstructured polymer interface consisting of poly(N-isopropylacrylamide) (PNIPAM) and RGD (Arg-Gly-Asp) conjugated polyacrylic acid (PAA) was prepared. PNIPAM is known for a stimuli-responsive polymer that changes its conformation responding to the lower critical solution temperature (LCST)⁴, so repulsive force is generated by changing its conformation responding to temperature change. PAA is used for the conjugation of adhesive motifs for affinity-based interactions with particles. Such a dynamic regime enables competitive adsorption-desorption of different particles and sorting of colloidal mixtures based on the strength of particle-polymer adhesion. The developed interface was successfully proved its ability to sort the specific particles through the isolation of U-87 MG cancer cells from whole blood cells with one out of billions cells ratio based on the composition of their membrane proteins, integrins.

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(2)Housmans, C.; Sferrazza, M.; Napolitano, S., Kinetics of irreversible chain adsorption. Macromolecules 2014, 47 (10), 3390-3393

(3) Yu, C.; Granick, S., Revisiting Polymer Surface Diffusion in the Extreme Case of Strong Adsorption. Langmuir 2014, 30 (48), 14538-14544.

(4) Tsai, Hsin-Yi, et al. "Two-Dimensional Micropatterns of Self-Assembled Poly (N-isopropylacrylamide) Microgels for Patterned Adhesion and Temperature-Responsive Detachment of Fibroblasts." Langmuir: the ACS journal of surfaces and colloids 29.39 (2013).