Abstract
Circulating tumor cells (CTCs) are essential biomarkers for cancer diagnosis. Although various devices have been designed to detect, enumerate, and isolate CTCs from blood, some of these devices could have some drawbacks, such as the requirement of labeling, long process time, and high cost. Here, we present a microfluidic device based on the concept of "hydrodynamic cavitation-on-chip (HCOC)", which can detect CTCs in the order of minutes. The working principle relies on the difference of the required inlet pressure for cavitation inception of working fluids when they pass through the microfluidic device. The interface among the solid/floating particles, liquid, and vapor phases plays an important role in the strength of the fluid to withstand the rupture and cavitation formation. To this end, four experimental groups, including the "cell culture medium", "medium + Jurkat cells", "medium + Jurkat cells + CTCs", and "medium + CTCs", were tested as a proof of concept with two sets of fabricated microfluidic chips with the same geometrical dimensions, in which one set contained structural sidewall roughness elements. Jurkat cells were used to mimic white blood cells, and MDA-MB-231 cells were spiked into the medium as CTCs. Accordingly, the group with CTCs led to detectable earlier cavitation inception. Additionally, the effect of the CTC concentration on cavitation inception and the effect of the presence of sidewall roughness elements on the earlier inception were evaluated. Furthermore, CTC detection tests were performed with cancer cell lines spiked in blood samples from healthy donors. The results showed that this approach, HCOC, could be a potential approach to detect the presence of CTCs based on cavitation phenomenon and offer a cheap, user-friendly, and rapid tool with no requirement for any biomarker or extensive films acting as a biosensor. This approach also possesses straightforward application procedures to be employed for detection of CTCs.