Abstract 3480: High-throughput size and deformability-based cancer cell separation
Authors: Yip Gordon , Ionescu Daniel , Johnson Edwin , Dick Mikael , Fang Zecong , Harb Wael A. , Hong Bin , Xu Jie 
Published: May 2015

Cancer cells are ultra-rare in the peripheral blood of cancer patients, with numbers as low as a few in 10^6-10^7 leukocytes. Separation and enrichment of these cancer cells has historically been extremely difficult, often akin to pinpointing a needle in a haystack. Microfluidic devices, which are capable of sorting and detecting cells by structural constraint and immuno-identity, have been working well in isolating subpopulations of the cells with desired physical characteristics and phenotype from blood. However, it is not a new matter that the use of microdevices is often subject to low throughput, and therefore, there has been an assumption for the trade-off between the sample processing time and the purity of the cells to be collected. Size exclusion-based microdevices, e.g., the microfilter and the microsieve chip, provide a significantly shorter processing time than other microdevices, but fail to enrich cancer cells at a higher purity. Adding a second enriching parameter by means of cell deformability, in addition to cell size, has improved the purity. The effort of this paper is to develop a new type of microfluidic device, the spiral flow microfilter (SFF), which incorporates a third parameter of differential migration for the clog-free processing of large volume of blood. A spiral microchannel was constructed as the main flow pathway for the whole blood with high flow speed. It employs inertial lift and drag forces within the channel due to the radius of the bend to force the whole blood toward the outer wall of the inner channel. This outer wall is composed of small slits which, while allowing the normal blood cells through, deflects the large cancer cells, leaving them in the inner section. The slits are spaced ∼5µm apart, forming a “comb.” This “comb” is formed from millions of micro-scale pillars, with the assumption that a cancer cell is larger and stiffer than a normal blood cell, and will not pass between the pillars as normal cells do. To enhance the filtration process through slits, a minor vacuum is supplied through the outlet of the outer section of the spiral channel for the quick removal of normal cells. Simultaneously, cancer cells are retrieved from the outlet of the inner section. The SFF was made via soft lithography and Polydimethylsiloxane (PDMS) casting. Using photolithography, the master of the SFF geometry is made. The SFF is then cast using the master from PDMS. In testing, breast cancer cells (MDA-MB-231 and MDA-MB-453) or a mixture with human leukocytes were guided through the SFF. The flow rates and pressure drop were monitored. The deformation of the cells inside the channel was visualized using a high-speed camera. Our results concluded that cancer cells can be quickly separated from normal cells in minutes with purity and recovery greater than 90%. This device could be a useful tool for point-of-care analysis of circulating tumor cells in patients as a promise of personalized treatment planning and monitoring.

Citation Format: Gordon Yip, Daniel Ionescu, Edwin Johnson, Mikael Dick, Zecong Fang, Wael A. Harb, Bin Hong, Jie Xu. High-throughput size and deformability-based cancer cell separation. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3480. doi:10.1158/1538-7445.AM2014-3480