Enrichment of Circulating Tumor Cells from Whole Blood Using a Microfluidic Device for Sequential Physical and Magnetophoretic Separations

Based on their high clinical potential, the isolation and enrichment of rare circulating tumor cells (CTCs) from peripheral blood cells has been widely investigated. There have been technical challenges with CTC separation methods using solely cancer-specific surface molecules or just using physical properties of CTCs, as they may suffer from heterogeneity or lack of specificity from overlapping physical characteristics with leukocytes. Here, we integrated an immunomagnetic-based negative enrichment method that utilizes magnetic beads attached to leukocyte-specific surface antigens, with a physical separation method that utilizes the distinct size and deformability of CTCs. By manipulating the pressure distribution throughout the device and balancing the drag and magnetic forces acting on the magnetically labeled white blood cells (WBCs), the sequential physical and magnetophoretic separations were optimized to isolate intact cancer cells, regardless of heterogeneity from whole blood. Using a breast cancer cell line in whole blood, we achieved 100% separation efficiency for cancer cells and an average of 97.2% for WBCs, which resulted in a 93.3% average separation purity. The experimental results demonstrated that our microfluidic device can be a promising candidate for liquid biopsy and can be a vital tool for aiding future cancer research

Deterministic Capture of Individual Circulating Tumor Cells Using a Flow-Restricted Microfluidic Trap Array

Circulating tumor cells (CTCs) are regarded as a strong biomarker which includes clinically valuable information. However, CTCs are very rare and require precise separation and detection for effective clinical applications. Furthermore, downstream analysis has become necessary to identify the distinct sub-population of CTCs that causes metastasis. Here, we report a flow-restricted microfluidic trap array capable of deterministic single-cell capture of CTCs. The extent of flow restriction, correlating with the device geometry, was then optimized using a highly invasive breast cancer cell line (LM2 MDA-MB-231) to achieve 97% capture efficiency with a single-cell capture rate of 99%. Single-cell capture of CTCs from mice with full-blown metastasis was also demonstrated. The single-CTC capturing ability of the flow-restricted trap array not only showed cell enumerating ability but also high prospects for application in future automated downstream analysis

Highly Sensitive Tactile Shear Sensor Using Spatially Digitized Contact Electrodes

In this article, we report on a highly sensitive tactile shear sensor that was able to detect minute levels of shear and surface slip. The sensor consists of a suspended elastomer diaphragm with a top ridge structure, a graphene layer underneath, and a bottom substrate with multiple spatially digitized contact electrodes. When shear is applied to the top ridge structure, it creates torque and deflects the elastomer downwards. Then, the graphene electrode makes contact with the bottom spatially digitized electrodes completing a circuit producing output currents depending on the number of electrodes making contact. The tactile shear sensor was able to detect shear forces as small as 6 μN, detect shear direction, and also distinguish surface friction and roughness differences of shearing objects. We also succeeded in detecting the contact slip motion of a single thread demonstrating possible applications in future robotic fingers and remote surgical tools

Continuous Separation of Circulating Tumor Cells from Whole Blood Using a Slanted Weir Microfluidic Device

The separation of circulating tumor cells (CTCs) from the peripheral blood is an important issue that has been highlighted because of their high clinical potential. However, techniques that depend solely on tumor-specific surface molecules or just the larger size of CTCs are limited by tumor heterogeneity. Here, we present a slanted weir microfluidic device that utilizes the size and deformability of CTCs to separate them from the unprocessed whole blood. By testing its ability using a highly invasive breast cancer cell line, our device achieved a 97% separation efficiency, while showing an 8-log depletion of erythrocytes and 5.6-log depletion of leukocytes. We also developed an image analysis tool that was able to characterize the various morphologies and differing deformability of the separating cells. From the results, we believe our system possesses a high potential for liquid biopsy, aiding future cancer research