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-by-one in a continuous flow would find applications in cell-mechanotyping studies such as correlational studies of the cell mechanical phenotype and molecular mechanism.
Highlights
Abnormalities in cell deformability are associated with disease pathogenesis and progression
Compared with existing deformability-based sorting techniques, the demonstrated microfluidic device measures the deformability and immediately sorts the particles one-by-one in real time
We studied the factors affecting the sorting dynamics in a continuous flow by carrying out both modeling and experiments
Summary
Abnormalities in cell deformability are associated with disease pathogenesis and progression. The device seamlessly integrates single-particle deformability sensing and active hydrodynamic sorting into a single microfluidic chip. The deformability is measured by evaluating the transit time during which an individual particle squeezes through a microscale constriction[10], while the active particle sorting is implemented by hydrodynamic flow control.
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