Microfluidic deformability-activated sorting of single particles

Abstract

Mechanical properties have emerged as a significant label-free marker for characterizing deformable particles such as cells. Here, we demonstrated the first single-particle-resolved, cytometry-like deformability-activated sorting in the continuous flow on a microfluidic chip. Compared with existing deformability-based sorting techniques, the microfluidic device presented in this work measures the deformability and immediately sorts the particles one-by-one in real time. It integrates the transit-time-based deformability measurement and active hydrodynamic sorting onto a single chip. We identified the critical factors that affect the sorting dynamics by modeling and experimental approaches. We found that the device throughput is determined by the summation of the sensing, buffering, and sorting time. A total time of~100 ms is used for analyzing and sorting a single particle, leading to a throughput of 600 particles/min. We synthesized poly(ethylene glycol) diacrylate (PEGDA) hydrogel beads as the deformability model for device validation and performance evaluation. A deformability-activated sorting purity of 88% and an average efficiency of 73% were achieved. We anticipate that the ability to actively measure and sort individual particles one-byone in a continuous flow would find applications in cell-mechanotyping studies such as correlational studies of the cell mechanical phenotype and molecular mechanism.

Pressure-Biased Nanopores for Excluded Volume Metrology, Lipid Biomechanics, and Cell-Adhesion Rupturing

“…The forces acting on a lipid particle include both electrically derived and hydrodynamic-derived forces as shown in Figure a. Both deformation mechanisms have been reported previously with electrodeformation being studied using nanopores and hydrodynamic deformations being studied using microfluidic chips ( e.g ., deformation cytometry). , An important distinction is that nanoscale entities such as nanoliposomes cannot be measured using microfluidic chips due to the inability to observe them under a microscope. Regarding electrodeformation, differences in conductivity (σ) and permittivity (ε) of the media internal and external to the liposome are responsible for the forces acting on the membrane .…”

Image-based cell sorting using focused travelling surface acoustic waves

“…The authors proposed that this parameter can be used in a high throughput system to distinguish between different cell types, but this has not yet been demonstrated. 20 Other active approaches have been developed to increase the sorting rate, but they showed sorting mostly on a heterogeneous mixture of cells 8,19 or beads 75 with distinct mechanical properties. Recently, using a SSAW actuator we demonstrated deformation-based sorting of RBCs.…”

Microfluidics Used as a Tool to Understand and Optimize Membrane Filtration Processes

“…Soft particles are mostly chosen as models for cells and protein aggregates, and often microgels are used due to their ease of production, and tunable properties. Soft particles are able to modify size and shape during filtration, therefore making their filtration behavior much more complex [19,59], e.g., leading to added flow resistance when pressurized in a filtration cake layer [60].…”