Numerical modeling of microfluidic devices for circulating tumor cell detection

Christopher  Michael Landry

doi:10.7273/000004103

Throughout the world, cancer is a primary health concern due its high mortality rate. The typical cause of death from cancer is metastasis, which is the spreading of a primary tumor to distant organs. Currently, cancer metastasis is attributed to Circulating Tumor Cells (CTCs). A CTC is a cancer cell that has dislodged from the primary tumor and entered the blood stream. In order to achieve early cancer detection and improve patient prognosis, CTCs must be separated from whole blood samples. One of the most promising ways to achieve this separation is through microfluidic devices. Unfortunately, experimental testing of microfluidic devices is expensive, time-consuming, and lacks the ability to demonstrate underlying physics. To help resolve the issues associated with experimental testing, numerical modeling is employed. Here, two types of label-free microfluidic devices are modeled and tested. First, a microfiltration device is modeled and the effects of a non-axisymmetric approach are tested. From the results, critical pressure was found to be a robust design criterion for microfiltration devices regardless of CTC approach condition. CTC transit time on the other hand was determined to have a dependence on approach condition; therefore, should not be used in designing microfiltration devices. The other type of label-free microfiltration device tested was a Deterministic Lateral Displacement (DLD) device. Here, underlying causes of experimental observations for a symmetric airfoil shaped pillar design were achieved through numerical modeling of flow fields and array anisotropy. Results show that array anisotropy is responsible for creating a lateral shift in the flow field. Critical size of the DLD device is reduced when the flow field shifts toward the direction of bumped motion, and increases when shifting occurs away from bumped motion. Additionally, an equation is proposed that relates migration angle to anisotropy via pseudoperiodicity. Lastly, a working limit for symmetric airfoil shaped pillar DLD devices was found to be between -25° and -35° angle of attack. These findings will aid in future design work and open the possibility of new applications for micro fabricated DLD devices by achieving smaller critical sizes than previously possible.

Numerical modeling of microfluidic devices for circulating tumor cell detection

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