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Integration of Hierarchical Micro-/Nanostructures in a Microfluidic Chip for Efficient and Selective Isolation of Rare Tumor Cells.

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.

SUBMITTER: Wang S

PROVIDER: S-EPMC6843196 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Integration of Hierarchical Micro-/Nanostructures in a Microfluidic Chip for Efficient and Selective Isolation of Rare Tumor Cells.

Wang Shunqiang S Cho Younghyun Y Cheng Xuanhong X Yang Shu S Liu Yi Y Liu Yaling Y

Micromachines 20191014 10

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 concep ...[more]

PMID: 31615080

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Project description:BackgroundCirculating tumor cells (CTCs) existing in peripheral blood can be used to predict the prognosis and survival of cancer patients. The study was designed to detect circulating tumor cells and circulating tumor single cell genes by applying microfluidic chip technology. It was used to explore the clinical application value in breast cancer.MethodsWe have developed a size-based CTCs sorting microfluidic chip, which contains a hexagonal array and a micro-pipe channel array to isolate and confirm both single CTCs and CTCs clusters. The sorting performance of the as-fabricated chip was tested by analyzing the clinical samples collected from 129 breast cancer patients and 50 healthy persons.ResultsIn this study, the chip can detect different immunophenotypes of CTCs in breast cancer patients. It was found that the new microfluidic device had high sensitivity (73.6%) and specificity (82.0%) in detecting CTCs. By detecting the blood samples of 129 breast cancer patients and 50 healthy blood donors, it was found that the number of CTCs was not associated with clinical factors such as age, gender, pathological type, and tumor size of breast cancer patients (P > 0.05), but was associated with TNM staging of breast cancer, with or without metastasis (P < 0.005). There was a statistically significant difference in the number of CTCs between luminal A (ER+/PR+/HER2-) and HER-2+ (ER-/PR-/HER2+) (P < 0.05). The best cut-off level distinguished by CTC between the breast cancer patients and the healthy persons was 3.5 cells/mL, with 0.845 for AUC-ROC, 0.790-0.901 for 95% CI, 73.6% for sensitivity, and 82% for specificity (P = 0.000). The combination of CTC, CEA, CA125 and CA153 can provide more effective breast cancer screening.ConclusionsThe CTCs analysis method presented here doesn't rely on the specific antibody, such as anti-EpCAM, which would avoid the missed inspection caused by antibody-relied methods and offer more comprehensive biological information for clinical breast cancer diagnosis and treatment.

Dataset Information

Integration of Hierarchical Micro-/Nanostructures in a Microfluidic Chip for Efficient and Selective Isolation of Rare Tumor Cells.

Publications

Integration of Hierarchical Micro-/Nanostructures in a Microfluidic Chip for Efficient and Selective Isolation of Rare Tumor Cells.

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