Abstract
Circulating 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 of cancer cells with their associated stroma cells. Here, we present a microfluidic device for mL/min flow rate, continuous-flow capture of viable CTCs from blood using deterministic lateral displacement (DLD) arrays. We show here that a DLD array device can isolate CTCs from blood with capture efficiency greater than 85% CTCs at volumetric flow rates of up to 10 mL/min with no effect on cell viability.
Highlights
Circulating 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[2,3] and determine the eventual location of metastasic invasions for possible treatment.[4]
There is a critical need to isolate, propagate and characterize viable CTCs and clusters to expand on understanding of the biology of metastasis,[5,6] enable new methods for studying the emergence of drug resistance,[7] and aid in the development personalized treatments.[8,9]
We show that a Deterministic lateral displacement (DLD) array can be designed such that it will isolate CTCs from blood with efficiency greater than 85% CTCs over a large range in sizes from milliliter-volume blood samples in minutes, with no effect on cell viability so that further culturing and analysis of the cells can be carried out
Summary
Circulating tumor cells (CTCs) and circulating clusters of cancer and stromal cells (the latter forming the “seed and soil” hypothesis of metastasis1) 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[2,3] and determine the eventual location of metastasic invasions for possible treatment.[4]. We present a DLD array device for mL/min flow rate, continuous-flow capture of viable CTCs from blood using deterministic lateral displacement arrays.
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