Microfluidic sorting of mammalian cells by optical force switching

Abstract

Microfluidic-based devices have allowed miniaturization and increased parallelism of many common functions in biological assays; however, development of a practical technology for microfluidic-based fluorescence-activated cell sorting has proved challenging. Although a variety of different physical on-chip switch mechanisms have been proposed, none has satisfied simultaneously the requirements of high throughput, purity, and recovery of live, unstressed mammalian cells. Here we show that optical forces can be used for the rapid (2-4 ms), active control of cell routing on a microfluidic chip. Optical switch controls reduce the complexity of the chip and simplify connectivity. Using all-optical switching, we have implemented a fluorescence-activated microfluidic cell sorter and evaluated its performance on live, stably transfected HeLa cells expressing a fused histone-green fluorescent protein. Recovered populations were verified to be both viable and unstressed by evaluation of the transcriptional expression of two genes, HSPA6 and FOS, known indicators of cellular stress.

Label-free, microfluidic separation and enrichment of human breast cancer cells by adhesion difference

“…7 These cell sorting systems have been miniaturized to microfluidic devices, demonstrating the possibility of being integrated into lab-on-a-chip devices. 8,9 In contrast, label-free methods typically utilize differences in physical properties such as cell size, 10 density, 11 cell adhesion, [12][13][14][15] and dielectric properties. [16][17][18] One potential drawback in label-free methods is that the physical difference is not high enough for efficient separation in many cases, which limits the widespread use of the label-free methods.…”

Size-Based Separation of Particles and Cells Utilizing Viscoelastic Effects in Straight Microchannels

“…[4][5][6] Microfluidic systems have been proven to be promising tools for particle/cell manipulation with higher sensitivity and accuracy than their macroscale counterparts. The last decade has seen extensive development of microfluidic approaches for particle/cell manipulation that resort to immunocapture, 7 externally applied physical fields, [8][9][10][11][12][13][14][15][16][17][18] microfiltration, 19,20 gravitational sedimentation, 21 or deterministic lateral migration. 22,23 More recently, cross-streamline migration induced by the hydrodynamic effects of carrier media, such as inertia 24,25 and viscoelasticity, 26,27 has shown its promise for effective particle/cell manipulation without need of labeling and external force fields.…”

Controlling Drop Size and Polydispersity Using Chemically Patterned Surfaces

“…[17,18,19,20,21,22,23,24,25,26,27,28,29,30] and the references therein. We explore numerically two ways in which this might be possible.…”