Highly efficient and selective isolation of rare tumor cells using a microfluidic chip with wavy-herringbone micro-patterned surfaces

Abstract

Circulating tumor cells (CTCs) in peripheral blood have been recognized as a general biomarker for diagnosing cancer and providing guidance for personalized treatments. Yet due to their rarity, the challenge for their clinical utility lies in the efficient isolation while avoiding the capture of other non-targeted white blood cells (WBCs). In this paper, a wavy-herringbone (HB) microfluidic chip coated with antibody directly against epithelial cell adhesion molecule (anti-EpCAM) was developed for highly efficient and selective isolation of tumor cells from tumor cell-spiked whole blood samples. By extending the concept of the hallmark HB-Chip in literature, the wavy-HB chip not only achieves high capture efficiency (up to 85.0%) by micro-vortexes induced by HB structures, but also achieves high purity (up to 39.4%) due to the smooth wavy microstructures. These smooth wavy-HB structures eliminate the ultra-low shear rate regions in the traditional grooved-HB structures that lead to non-specific trapping of cells. Compared with the grooved-HB chip with sharp corners, the 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.

Inertia based microfluidic capture and characterisation of circulating tumour cells for the diagnosis of lung cancer

“…Various studies have shown the ability to isolate and capture CTCs in lung cancer patients, using a range of platforms, from antibody based (14,15) to filtration based techniques (4,5), with varying levels of performance and success.…”

Materials and microfluidics: enabling the efficient isolation and analysis of circulating tumour cells

“…65 This WBC background could be attributed to low shear stagnate regions of fluid within the crevices of the herringbone grooves. 143,144 The herringbone chip has been used in numerous clinical demonstrations (Table 1) with high median CTC counts, especially for prostate cancer, and clinical sensitivities ranging between 56% – 93%. 28,41,65,75,141,142,145 …”

Circulating tumor microemboli: Progress in molecular understanding and enrichment technologies

“…Moreover, it has been observed that CTM containing up to 20 cells may adopt reversible single-file chain-like geometries which helps them traverse through 5-10 µm constrictions, a striking observation which may have implications in the usage of filtration based devices for CTM enrichment (Au et al, 2016). (Wang et al, 2016). Marker dependent isolation of CTM, whether by macroscale approaches or microfluidic platforms, faces another challenge.…”