Microfluidic System for Studying the Interaction of Nanoparticles and Microparticles with Cells

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Abstract
Nanoparticles and microparticles have many potential biomedical applications ranging from imaging to drug delivery. Therefore, in vitro systems that can analyze and optimize the interaction of such particles with cells may be beneficial. Here, we report a microfluidic system that can be used to study these interactions. As a model system, we evaluated the interaction of polymeric nanoparticles and microparticles and similar particles conjugated to aptamers that recognize the transmembrane prostate specific membrane antigen (PSMA), with cells seeded in microchannels. The binding of particles to cells that expressed or did not express the PSMA (LNCaP or PC3, respectively) were evaluated with respect to changes in fluid shear stress, PSMA expression on target cells, and particle size. Nanoparticle−aptamer bioconjugates selectively adhered to LNCaP but not PC3 cells at static and low shear (2) but not higher shear (∼4.5 dyn/cm2) conditions. Control nanoparticles and microparticles lacking aptamers and microparticle−aptamer bioconjugates did not adhere to LNCaP cells, even under very low shear conditions (∼0.28 dyn/cm2). These results demonstrate that the interaction of particles with cells can be studied under controlled conditions, which may aid in the engineering of desired particle characteristics. The scalability, low cost, reproducibility, and high-throughput capability of this technology is potentially beneficial to examining and optimizing a wide array of cell−particle systems prior to in vivo experiments.