Microfluidic Sorting Technology
Cell sorting is critical for many applications ranging from stem cell research to cancer therapy. The current benchmark technologies that perform this function, fluorescence-activated cell sorting (FACS) and magnetic-activated cell sorting (MACS), are unable to meet the growing demands in purity, throughput, and recovery. Microfluidics offers a potential solution to this challenge in a disposable format, through precise control of separation forces and parallel/serial system architectures. The goal of our work in this area is to utilize the unique features of microfluidics to create new cell-sorting technologies with enhanced performance and novel functionalities.
Surface-marker specific sorting of rare cells using dielectrophoresis
We developed an electrokinetic sorting methodology that exploits dielectrophoresis (DEP) to efficiently isolate rare cells from complex mixtures in microfluidic channels. In this approach, the dielectrophoretic amplitude response of rare target cells is modulated by labeling cells with particles that differ in their polarizability. Labeled cells experience a larger DEP force and are therefore deflected into the collection outlet, while unlabeled cells remain undeflected. To demonstrate the efficiency of marker-specific cell separation, the DEP-activated cell sorter (DACS) was applied for affinity-based enrichment of rare bacteria expressing a specific surface marker from an excess of nontarget bacteria that do not express this marker. Rare target cells were enriched by > 200-fold in a single round of sorting at a single-channel throughput of 10,000 cells per second.
For more information, refer to our paper:
X. Hu, P. H. Bessette, J. Qian, C. D. Meinhart, P. S. Daugherty, and H. T. Soh. Marker Specific Sorting of Rare Cells Using Dielectrophoresis. Proceedings of the National Academy of Sciences, USA, 102, 44 , 15757-15761, (2005) .
Illustration of the DACS concept
Multi-target rare cell separation using dielectrophoresis and magnetophoresis
Microfluidics provides a platform for precise control over separation forces, be they fluidic, magnetic, electric, acoustic, or other. This controllability has allowed us to extend surface marker-specific sorting in a number of different ways in order to increase the functionality and throughput of this technique.
By differentially labeling multiple target cells with different sized magnetic or polystyrene particles, we have demonstrated simultaneous separation of two target cells from a complex mixture with high purity and high throughput. The concept is similar to DACS, in that a force balance causes labeled cells to deflect into the collection stream. Because the deflection force depends on the volume of the label, and the fluidic drag depends on the effective radius of the cell-label complex, cells labeled with large labels are deflected more easily. By controlling the geometry of the deflecting elements, cells labeled with large particles can be deflected into a different outlet than cells labeled with smaller particles. We have demonstrated this concept using both dielectrophoretic forces and magnet forces. In both cases, we were able to achieve simultaneous final purities of over 90% from starting concentrations of less than 0.5%, corresponding to enrichment values of over 500-fold, at throughputs ranging from ~107 to ~109 cells/hr.
For more information, refer to our papers:
U. Kim, J. Qian, S. A. Kenrick, P. S. Daugherty, and H. T. Soh. Multi-Target Dielectrophoresis Activated Cell Sorter (MT-DACS), Analytical
Chemistry, (80) 8656-8661 (2008)
J. D. Adams, U. Kim, and H. T. Soh, Multi-Target Magnetic Activated Cell Sorter (MT-MACS), Proceedings of the National Academy of Sciences, USA, (105) 18165-18170 (2008).
Illustration of the multitarget DACS concept
Overview of the multitarget magnetic cell separation concept