High performance isolation of circulating tumor cells by acoustofluidic chip coupled with ultrasonic concentrated energy transducer.

ABSTRACT

The isolation of circulating tumor cells (CTCs) from whole blood is a challenging task. Although various studies on the separation of CTCs by acoustofluidic devices have been reported, difficulties still persist, such as the complicated equipment, high cost, and difficult operation. Those problems should be resolved urgently. Herein, we developed an acoustofluidic chip separation system coupled with an ultrasonic concentrated energy transducer (UCET) system for efficient separation of CTCs. In the separation system, the acoustically sensitive particles were pre-focused by inertial forces of the PDMS chip channel structure. Then, the particles with different sizes were separated by acoustic radiation forces (ARF). In this study, the circulating tumor cells was simulated (CTCs-like particles) by aminated mesoporous acoustically sensitive particles (MSN@AM) encapsulated carboxylate polystyrene microspheres (PS-COOH). Subsequently, efficient CTCs-like particles separation was achieved by the acoustofluidic chip coupling system. This study effectively separated polystyrene microspheres carrying acoustically sensitive particles (MSN@AM@PS-COOH). However, the MSNs agglomerates and PS microspheres without acoustically sensitive particles did not show phenomenon of separation. This method allows to efficiently separate 2 µm MSNs agglomerates，8.0-8.9 µm PS microspheres and 10-10.5 µm MSN@AM@PS-COOH particles. It is demonstrated that the CTCs-like particles show more sensitive response, longer moving distance, and more obvious separation effect at the condition of the low frequency traveling wave sound field (20 kHz from UCET). This system can maintain the same separation with reduced amount of reagents used for cancer detection. It may provide a reliable basis for sorting out CTCs efficiently from the whole blood of cancer patients.