Jae Jung Kim

Synthesis of Cell-Adhesive Anisotropic Multifunctional Particles by Stop Flow Lithography and Streptavidin–Biotin Interactions

Cell-adhesive particles are of significant interest in biotechnology, the bioengineering of complex tissues, and biomedical research. Their applications range from platforms to increase the efficiency of anchorage-dependent cell culture to building blocks to loading cells in heterogeneous structures to clonal-population growth monitoring to cell sorting. Although useful, currently available cell-adhesive particles can accommodate only homogeneous cell culture. Here, we report the design of anisotropic hydrogel microparticles with tunable cell-adhesive regions as first step toward micropatterned cell cultures on particles. We employed stop flow lithography (SFL), the coupling reaction between amine and N-hydroxysuccinimide (NHS) and streptavidin-biotin chemistry to adjust the localization of conjugated collagen and poly-L-lysine on the surface of microscale particles. Using the new particles, we demonstrate the attachment and formation of tight junctions between brain endothelial cells. We also demonstrate the geometric patterning of breast cancer cells on particles with heterogeneous collagen coatings. This new approach avoids the exposure of cells to potentially toxic photoinitiators and ultraviolet light and decouples in time the microparticle synthesis and the cell culture steps to take advantage of the most recent advances in cell patterning available for traditional culture substrates.

Governing Principles of Alginate Microparticle Synthesis with Centrifugal Forces

A controlled synthesis of polymeric particles is becoming increasingly important because of emerging applications ranging from medical diagnostics to self-assembly. Centrifugal synthesis of hydrogel microparticles is a promising method, combining rapid particle synthesis and the ease of manufacturing with readily available laboratory equipment. This method utilizes centrifugal forces to extrude an aqueous polymer solution, sodium alginate (NaALG) through a nozzle. The extruded solution forms droplets that quickly cross-link upon contact with aqueous calcium chloride (CaCl2) solution to form hydrogel particles. The size distribution of hydrogel particles is dictated by the pinch-off behavior of the extruded solution through a balance of inertial, viscous, and surface tension stresses. We identify the parameters dictating the particle size and provide a numerical correlation predicting the average particle size. Furthermore, we create a phase map identifying different pinch-off regimes (dripping without satellites, dripping with satellites, and jetting), explaining the corresponding particle size distributions, and present scaling arguments predicting the transition between regimes. By shedding light on the underlying physics, this study enables the rational design and operation of particle synthesis by centrifugal forces.

Microfluidic platform for selective microparticle parking and paired particle isolation in droplet arrays

Immobilizing microscale objects (e.g., cells, spheroids, and microparticles) in arrays for direct observation and analysis is a critical step of many biological and chemical assays; however, existing techniques are often limited in their ability to precisely capture, arrange, isolate, and recollect objects of interest. In this work, we present a microfluidic platform that selectively parks microparticles in hydrodynamic traps based on particle physical characteristics (size, stiffness, and internal structure). We present an accompanying scaling analysis for the particle parking process to enable rational design of microfluidic traps and selection of operating conditions for successful parking of desired particles with specific size and elastic modulus. Our platform also enables parking of encoded particle pairs in defined spatial arrangements and subsequent isolation of these pairs in aqueous droplets, creating distinct microenvironments with no cross-contamination. In addition, we demonstrate the ability to recollect objects of interest (i.e., one particle from each pair) after observation within the channel. This integrated device is ideal for multiplexed assays or microenvironment fabrication for controlled biological studies.