Microfluidics in Biomedical Engineering

2D combinatorial device for drug screening. High-throughput preparation of multi-component solutions is an integral process in biology, chemistry and materials science for screening, diagnostics and analysis. Here we present a microfluidic device that incorporates two gradient generators, a tree-like generator and a new microfluidic active injection system, interfaced by intermediate solution reservoirs to generate diluted combinations of input solutions within an 8 × 8 or 10 × 10 array of isolated test chambers. By appropriate choice of the two-component input solutions, test chamber concentrations that span any triangle in 2D concentration space may be obtained. In particular, explicit inputs are given for a coarse screening of a large region in concentration space followed by a more refined screening of a smaller region, including alternate inputs that span the same concentration region but with different distributions.

Jang YH†, Hancock MJ†, Kim SB, Selimović S, Sim WY, Bae H, Khademhosseini A. An integrated microfluidic device for two-dimensional combinatorial dilution. Lab Chip, 2011, 11 : 3277 – 3286. [pdf]

Directed assembly of cell-laden microgels. Solid particles floating on the surface of a dense liquid can deform the liquid surface, thereby generating lateral capillary forces, which may be repulsive or attractive depending on the particle weight, geometry, and wetting properties. We reported a rapid method for creating centimeter-scale, cell-laden tissue-like hydrogels through the directed assembly of shape-controlled microgels on a liquid–air interface. In addition, a hierarchical approach created complex multigel building blocks, which then assembled into tissues with precise spatial control over the cell distribution.

Zamanian B†, Masaeli M†, Nichol JW, Khabiry M, Hancock MJ, Bae H, Khademhosseini A. Interface directed self assembly of cell-laden microgels. Small, 2010, 6: 937 – 944 (PMC2858261) [pdf]

Cell docking and patterning in microchannels. Microstructures that generate shear-protected regions in microchannels can rapidly immobilize cells for cell-based biosensing and drug screening. By altering microstructure geometry, flow circuation in the microstructures force cells the align in specified patterns. Computational flow simulations link the groove geometry and bottom shear stress to the experimental cell docking patterns. Currently, single and double rectangular grooves are being used to align cells along corners. Past work has demonstrated the cell alignment and retention and their dependence on groove geometry. Current work is exploring chemical transport and delivery to the alighned cells, to realize a prototype biosensor.

Khabiry M†, Chung BG†, Hancock MJ†, Soundararajan HC, Du Y, Cropek DM, Lee WG and Khademhosseini A. Cell Docking in Double Grooves in a Microfluidic Channel. Small, 2009, 5:1186-1194 (PMC2683980) [pdf]

High-throughput cell seeding and patterning in microassays. A simple wiping technique is used to localize cells in large arrays of polymeric microwells. This robust method produces cell seeding densities that vary consistently with microwell geometry and cell concentration. A simple theoretical model accurately predicts cell seeding density and seeding efficiency in terms of the design parameters of the microwell array and the cell density. The technique seeded cells uniformly in 20x20 and 33x33 microarrays.

Kang L, Hancock MJ, Brigham MD and Khademhosseini A. Cell Confinement in Patterned Nanoliter Droplets in a Microwell Array. J. Biomed. Mater. Res. A 2010, 93A : 547 – 557 (PMC284573) [pdf]

A hollow sphere soft lithography fabrication approach. The study involves applications of a hollow sphere (HS) soft lithography method to create spherical chambers. The first application is long-term HD assays which employ the HS as a media reservoir to maintain prolonged and more consistent culture media conditions than conventional hanging drop (HD) assays. ESC aggregates grew for at least 12 days to achieve sizes that were twice as those achieved in conventional HD assays. The geometries of the HDs attached to the rim of HSs were analyzed and shown to agree with existing theory. Future work considers phenomena observed in the fabrication process and also the dynamics of flow and transport within a HS microenvironment.

Lee WG†, Ortmann D†, Hancock MJ and Khademhosseini A. A hollow sphere soft lithography approach for long-term hanging drop assays. Tissue Eng. C 2010, 16 : 249-259 (PMC2946882) [pdf]