Abstract
Circulating tumor cells (CTCs) are important clinical markers for both cancer early diagnosis and prognosis. Various techniques have been developed in the past decade to isolate and quantify these cells from the blood while microfluidic technology attracts significant attention due to better controlled microenvironment. When combined with advanced nanotechnologies, CTC isolation performance in microfluidic devices can be further improved. In this article, by extending the wavy-herringbone concept developed earlier in our team, we prepared a hierarchical microfluidic chip by introducing a uniform coating of nanoparticles with anti-epithelial cell adhesion molecule (EpCAM) on wavy microgrooves. This hierarchical structured platform not only maintains the capture purity of the wavy-herringbone structure but improves the capture efficiency thanks to the larger surface area to volume ratio brought by nanoparticles. Our results demonstrated a capture efficiency of almost 100% at a low shear rate of 60/s. Even at a higher shear rate of 400/s, the hierarchical micro/nanostructures demonstrated an enhancement of up to ~3-fold for capture efficiency (i.e., 70%) and ~1.5-fold for capture purity (i.e., 68%), compared to wavy-herringbone structures without nanoparticle coating. With these promising results, this hierarchical structured platform represents a technological advancement for CTC isolation and cancer care.
Highlights
Tumors are among the leading causes of deaths across the world
Various derivatives of the HB chip [20,23,24] were developed subsequently, for example, by incorporation of nanostructures, including nanopillars [25] and nanovelcro [26], into microfluidics to increase the overall surface area and enhance the cell-surface interactions. These hierarchical structures presented a better capture efficiency and their clinical utilities were demonstrated on patients of various cancer phenotypes [26,27,28]
We have recently developed a wavy-HB chip where the smooth groove edges eliminate regions with extremely low shear stress
Summary
Tumors are among the leading causes of deaths across the world. Tumor detection, especially in the early stage, is of great interest to both researchers and clinicians. Various derivatives of the HB chip [20,23,24] were developed subsequently, for example, by incorporation of nanostructures, including nanopillars [25] and nanovelcro [26], into microfluidics to increase the overall surface area and enhance the cell-surface interactions These hierarchical structures presented a better capture efficiency and their clinical utilities were demonstrated on patients of various cancer phenotypes [26,27,28]. Leveraging our success with the wavy-HB chips and knowledge that nanostructures with a diameter of 100 nm enhance CTC capture [30], here we combined the two features by coating the wavy-HB microstructure with nanoparticles (NPs) in this study This hierarchical structure reflects advantages from both microscale and nanoscale: by constructing the wavy-HB microstructures, the chip preserves a high purity by eliminating the extremely low-shear regions (demonstrated in an earlier study [31]), by integrating NPs, the chip presents a high capture efficiency due to both HB induced vortex effect and NP induced enhanced cell-surface interactions. The tumor cell capture tests were performed and the results were compared with other designs reported in literature
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