Tunable Nano-Shearing: Some New Ideas for Capturing CTCs and Rare Molecules from Blood (#80)
Progression of cancer in patients is characterized by the invasion of cancer cells from the primary cancer site through the bloodstream, and results in metastatic colonies in different parts of the body. Detecting these circulating tumor cells (CTCs) is extremely challenging owing to their low relative abundance (e.g., as low as a few cells per mL of blood). While reaching this detection limit is challenging in itself, many of the non-CTCs tend to nonspecifically bind to solid electrodes. Herein we report a tuneable alternating current electro-hydrodynamic (ac-EHD) force which drives lateral fluid motion within a few nanometers of an electrode surface. Because the magnitude of this fluid shear force can be tuned externally (e.g., via the application of an ac electric field), it provides a new capability to physically displace weakly (nonspecifically) bound cellular and molecular analytes. To demonstrate the utility of this tuneable Nano-shearing phenomenon, we present data on purpose-built microfluidic devices that employ ac-EHD to capture rare CTCs and molecules1-5. This tuneable control of surface shear forces and concomitant fluid micromixing allows for two critical improvements to the traditional immunocapture of cellular targets: (i) enhanced capture efficiency due to an increased number of sensor-target collisions, which is a result of improved transport, and (ii) enhanced specificity resulting from the ability to tune nanoscopic fluid shear forces at the electrode interface, which serves to shear away loosely bound, nonspecific species present in biological samples. Here we show that an ac-EHD device containing asymmetric planar and microtip electrode pairs can capture whole breast cancer cells in complex fluids, with high efficiency (approximately 93%) and specificity. We therefore feel that this new capability of externally tuning and manipulating nanoscopic fluid flow could have wide applications as an innovative approach to enhance the specific capture of rare CTCs.
- 1) Vaidyanathan, Shiddiky, Rauf, Dray, Tay, Trau, 86 (4), 2042 Analytical Chem (2014)
- 2) Shiddiky, Vaidyanathan, Rauf, Tay, Trau, 4, 3716 Sci Reports (2014)
- 3) Vaidyanathan, Rauf, Dray, Shiddiky, Trau, 20 (13), 3724 Chem Euro J (2014)
- 4) Rauf, Shiddiky, Trau, Chem Comm 50 (37), 4813 (2014)
- 5) Vaidyanathan, Rauf, Shiddiky, Trau, 61, 184, Biosensors & Bioelectronics (2014)