MP46: Centrifuge-on-a-Chip: Rapid and Automated Sample Preparation for Cell Suspensions

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Albert J. Mach, Armin Arshi, Jaehyun Kim, Dino Di Carlo
University of California, Los Angeles

Labeling and washing target cells are common protocols for many cell biology assays. Typically, this time-consuming process requires multiple centrifugation steps for sample preparation. Additionally, the standard benchtop centrifuge is a bulky instrument that limits many diagnostics assays performed in remote settings. Here, we have developed a miniaturized system that replicates the function of a centrifuge without moving parts. The system can concentrate and resuspend cells to low liquid volumes from dilute and concentrated samples at rates of milliliters per minute. Operating using purely fluid dynamic phenomenon, the centrifuge-on-a-chip consists of a microchip with straight channels followed by expansion-contraction arrays to create microscale vortices with recirculating fluid that can be used to trap and exchange fluid around cells.

We investigate this novel phenomenon of cell trapping by identifying the hydrodynamic forces responsible for cell trapping, determining the critical particle size required for trapping in specific geometries, and presenting potential biological applications. Using polydisperse polymer beads, we demonstrate that particles larger than the critical particle size migrate laterally through fluid streamlines and orbit within the vortex while smaller particles follow fluid streamlines and travel out of the device. As a proof of concept, we injected blood spiked with MCF-7 breast cancer cells and demonstrated selective trapping of MCF-7 cells (~20 micron) spiked within blood (cell sizes 2-15 micron). Once the blood sample was completely loaded, we flushed out blood cells via rapid solution exchange and collected the trapped cancer cells for analysis.

In another application, we demonstrate on-chip cell fluorescent labeling techniques using rapid solution exchange, including cell fixation, permeabilization and labeling of intracellular antigens. We performed all operations of cell labeling within the microchip without the need for manual input and washing steps. Since the cell traps can be deactivated by lowering the flow rate, we retrieved these cells for downstream assays. We envision this system to be used in-line with downstream cell-based assays performed by flow cytometry, and may critically address the need for low cost centrifugation steps for point-of-care or resource poor settings.

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