Figure 1. The concept for high-throughput cell deformation cytometry, in which a cell (A) flows through the optical stretching region (B) in a microchannel, and its dimensions before (A) and after (C) stretching can be used to characterize its deformability.
Cellular elastic parameters are sensitive to physiological and pathological events occurring during the life cycle. Studies employing a variety of techniques suggest that healthy, malignant, and metastatic cells can be distinguished on the basis of their differing elastic properties. Parasitic infection also influences cell mechanics. For example, infection of red blood cells (RBCs) by Plasmodium falciparum decreases the elastic modulus 10-fold. These examples suggest that cellular mechanics may provide a biomarker for detecting disease or assessing its progression. For clinical applications cell elasticity measurements, it is necessary to resolve the distribution of elastic parameters at the single-cell level for statistically significant numbers.
Optical trapping provides an advantageous approach for non-contact, high-speed measurement. Deformability induced by divergent counter-propagating beams has been used to trap and elongate individual cells along the beam axis. In this technique however, each cell is sequentially trapped and then stretched, resulting in very low throughput. To screen significantly larger numbers of cells, we replaced the divergent Gaussian beam with a focused beam from a single-emitter diode laser focused parallel to the direction of flow in a microfluidic channel. In this approach, anisotropic optical forces stretch the cells without stopping or slowing them. We recently presented both experimental results on red blood cells, and computational results illustrating how the elastic modulus of each cell is determined from the equilibrium deformation. We measured deformability of 1275 RBCs in 18 minutes at a rate of 1.2 cells/s, which is ~100-fold faster than previous methods. Currently, we are extending this method to even higher speeds and to diverse cell types.