Circulating tumor cells (CTCs) in peripheral blood have been recognized as
Circulating tumor cells (CTCs) in peripheral blood have been recognized as a general biomarker for diagnosing cancer and providing guidance for personalized treatments. wavy-HB chip shows a significantly higher purity while maintaining similarly high capture efficiency. Furthermore, the wavy-HB chip has up to 11% higher captured cell viability over the grooved-HB chip. The distributions of tumor cells and WBCs along the grooves and waves are investigated to help understand the mechanisms behind the better performance of the wavy-HB chip. The wavy-HB chip may serve as a promising platform for CTC capture and cancer diagnosis. Graphical Abstract We present a microfluidic chip with wavy-herringbone micro-patterned surfaces for highly efficient and selective isolation of viable rare tumor cells. Introduction In the past few decades, microfluidic devices have been extensively employed in the fields of chemical, biomedical and environmental engineering, summarized in a few review articles.1C3 The device miniaturization using microfluidics leads to low reagent cost, low waste, fast reaction process and the predictable laminar flow pattern in microscale fluid flow.2,4C6 One exciting application is the early-stage detection of circulating tumor cells (CTCs),7,8 which are rare cells originally shed from a solid primary tumor and ultimately form a secondary tumor site in the course of blood circulation. Increasing studies have also shown strong clinical relevance of CTC amount for early cancer diagnostics,9 metastasis progress10,11 and therapy response12,13. In various common cancers, including breast cancer, pancreatic cancer and colorectal Rabbit polyclonal to ZNF624.Zinc-finger proteins contain DNA-binding domains and have a wide variety of functions, mostof which encompass some form of transcriptional activation or repression. The majority ofzinc-finger proteins contain a Krppel-type DNA binding domain and a KRAB domain, which isthought to interact with KAP1, thereby recruiting histone modifying proteins. Zinc finger protein624 (ZNF624) is a 739 amino acid member of the Krppel C2H2-type zinc-finger protein family.Localized to the nucleus, ZNF624 contains 21 C2H2-type zinc fingers through which it is thought tobe involved in DNA-binding and transcriptional regulation cancer, CTCs have been found to overexpress epithelial cell adhesion molecules (EpCAMs), which are not found in normal cells. Given the EpCAM expression difference, researchers have designed various microfluidic channels coated with anti-EpCAM for immuno-affinity based CTC detections.8,14C16 However, the challenge still lies in the efficiency of detection due to the scarce amount of CTCs, typically 1C10 cells vs. ~ 4 billion red blood cells E 2012 (RBCs) and ~ 4 million white blood cells (WBCs) per 1 mL of patient blood. The typical laminar flow in a microfluidic device will not be able to address the challenge, especially for limited time and channel length. Passive mixing within microfluidic devices has been proposed to induce increased collisions between cells and anti-EpCAM coated channel surfaces, thus enhancing the cell capture.17,18 One hallmark micro-mixer, first introduced by Stroock clinical utilities have been demonstrated with a capture efficiency of up to 79% under low shear rates of ~ 13/s. The cell dynamics in the micro-vortex flow induced by grooved-HB structures have also been studied extensively,21,22 which provide design guidelines for specific applications. Moreover, the structure simplicity of the grooved-HB structure allows for its wide integration into various platforms to enhance the E 2012 cell-surface interactions. Wang tests with whole blood spiked with CTCs were performed in both grooved-HB chips and wavy-HB chips. The results show that similar capture efficiency is obtained in both chips, while the wavy-HB chip showed a 39.4% purity, significantly higher than the 25.7% in the grooved-HB chip under the same shear rate of 400/s. In the high shear rate range (200/s to 400/s), the wavy-HB chip showed up to two-fold higher purity than the grooved-HB chip. Figure 1 Working mechanism of the wavy-HB microfluidic chip for highly efficient and selective CTC capture. (a) Schematic figure of a single unit of the wavy-HB pattern. (b) Flow velocity components in the cross-section illustrate E 2012 the micro-vortex. (c) Integral … In the following sections, the working principle for the proposed wavy-HB chip is first introduced. The capture performance was simulated numerically and compared with the grooved-HB chip. Then the fabrication method of wavy-HB chip is described followed by its morphology characterization. tests in both grooved-HB chips and wavy-HB chips were investigated and the test results were compared E 2012 side-by-side in both chips. Cell distribution profiles were also studied to help understand the performance differences between the grooved-HB chip and the wavy-HB chip. Materials and Methods Microfluidic Chip Design, Fabrication and Assembly Both grooved-HB chip and wavy-HB chip consist of a patterned polydimethylsiloxane (PDMS) layer at bottom and a PDMS channel layer on top,.