pH-Responsive Carbon Nanotube Film-Based Microfluidic Chip for Efficient Capture and Release of Cancer Cells
Kuang Hong Neoh, Kok Suen Cheng, Huaisheng Wu, Anqi Chen, Yukun Sun, Binglin Li, Anyuan Cao, Ray P. S. Han
Abstract
Advances in microfluidic technologies have fast-tracked the development of efficient assaying of circulating tumor cells (CTCs), but the release of the captured cells that are still biologically viable remains a challenge. In this work, a glass/polydimethylsiloxane (PDMS) microfluidic pH-responsive carbon nanotube (CNT) chip is presented for the efficient capture and release of cancer cells in spiked blood samples. This chip is made up of two components: (i) a bottom-layer glass slide coated with a CNT film functionalized with pH-responsive poly-l-lysine (PLL) connected to anti-epithelial cell adhesion molecule (EpCAM) antibodies and (ii) a top-layer PDMS cover with herringbone channels. Adopting an optimized staggered symmetrical herringbone design in our chip, the collision frequency of cells with the functionalized CNT film is significantly intensified and this generated a capture efficiency of 86.7 ± 9.3%. By elevating the pH value to create a conformational change in PLL, we attained a release efficiency of 84.7 ± 12.2%. Furthermore, our data showed that the biological viability of released cells is 84.6 ± 5.5%. The released cells can be cultured for up to 7 days with no changes in the morphology and EpCAM expression. If fast and accurate assaying of CTCs is desired over cell viability, our chip, which uses a high optical transparency CNT film, allows on-chip immunofluorescence staining to be carried out. Overall, the CNT chip constitutes a promising microfluidic technology for the capture and release of biologically viable CTCs for downstream molecular and functional analyses.