Abstract
AbstractCirculating tumor cells (CTCs) and circulating clusters of cancer and stromal cells have been identified in the blood of patients with malignant cancer and can be used as a diagnostic for disease severity, assess the efficacy of different treatment strategies and possibly determine the eventual location of metastatic invasions for possible treatment. There is thus a critical need to isolate, propagate and characterize viable CTCs and clusters. Here, we present a microfluidic device for mL/min flow rate, continuous-flow capture of viable CTCs from blood using deterministic lateral displacement arrays. We show here that a deterministic bump array can be designed such that it will isolate with efficiency greater than 85% CTCs over a large range in sizes from millimeter volume clinical blood samples in minutes, with no effect on cell vitality so that further culturing and analysis of the cells can be carried out.
Highlights
Much of the recent work in this area has focused on capturing cells on epithelial antibodycoated surfaces in microfluidic flow channels[11,12], but these devices must be operated slowly (∼ mL/hr) to maintain capture efficiency and viable cell recover is difficult because cells are strongly bound to the surface once they attach
Deterministic lateral displacement is a microfluidic size-based particle sorting method with excellent size selectivity which does not depend on first order on the rate of flow since it does not rely on diffusion, adaptability to sorting multiple particle sizes[19 ], and dynamic control of critical particle sizes[20]
According the operating principles of DLD, large particles above a designed critical size will flow along this tilted axis of the array, while the fluid and small particles flow in the horizontal direction defined by the array sidewalls
Summary
Much of the recent work in this area has focused on capturing cells on epithelial antibodycoated surfaces in microfluidic flow channels[11,12], but these devices must be operated slowly (∼ mL/hr) to maintain capture efficiency and viable cell recover is difficult because cells are strongly bound to the surface once they attach. According the operating principles of DLD, large particles above a designed critical size (e.g. the cancer cells) will flow along this tilted axis of the array, while the fluid and small particles flow in the horizontal direction defined by the array sidewalls. Large particles are concentrated towards the center of the flow chamber and collected at a narrow collection output while all other fluid is directed to a waste outlet.
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