A simple pyramid-shaped microchamber towards highly efficient isolation of circulating tumor cells from breast cancer patients

Abstract

Isolation and detection of circulating tumor cells (CTCs) has showed a great clinical impact for tumor diagnosis and treatment monitoring. Despite significant progresses of the existing technologies, feasible and cost-effective CTC isolation techniques are more desirable. In this study, a novel method was developed for highly efficient isolation of CTCs from breast cancer patients based on biophysical properties using a pyramid-shaped microchamber. Through optimization tests, the outlet height of 6 μm and the flow rate of 200 μL/min were chosen as the optimal conditions. The capture efficiencies of more than 85% were achieved for cancer cell lines (SKBR3, BGC823, PC3, and H1975) spiked in DMEM and healthy blood samples without clogging issue. In clinic assay, the platform identified CTCs in 13 of 20 breast cancer patients (65%) with an average of 4.25 ± 4.96 CTCs/2 mL, whereas only one cell was recognized as CTC in 1 of 15 healthy blood samples. The statistical analyses results demonstrated that both CTC positive rate and CTC counts were positive correlated with TNM stage (p < 0.001; p = 0.02, respectively). This microfluidic platform successfully demonstrated the clinical feasibility of CTC isolation and would hold great potential of clinical application in predicting and monitoring the prognosis of cancer patients.

Recent Advances in Microfluidic Platform for Physical and Immunological Detection and Capture of Circulating Tumor Cells

“…The parts that we do not want to etch are usually protected. Liu et al used wet etching and thermal bonding to create a pyramid-shaped microfluidic device with one inlet and six outlets [82]. The microchamber is a critical functional component of microfluidic devices for CTC separation.…”

“…However, the major drawback was its low throughput. Furthermore, Liu et al developed a simple pyramid-shaped microchamber that is feasible, cost-effective, and highly efficient for CTC separation from breast carcinoma patients [82]. With an optimised flow rate of 200 µL/min, the capture efficiency of the device was assessed with a fresh blood sample in five sequence concentrations of 25-200 cells/mL using four different cancer cell lines (BGC823, H1975, PC-3, and SKBR3) spiked into DMEM medium.…”

Consistency evaluation of lung adenocarcinoma tissue and circulating tumor cells related gene mutation detection based on multi-site immunomagnetic beads

“…For instance, Yin et al 24 reported that the average number of CTCs in patients with rectal cancer was 6.9/5 mL before surgery and 3.5/5 mL after surgery. Liu et al 25 found that the average number of CTCs in breast cancer patients was 4.25 ± 4.96/2 mL, and only one CTC was identified in 15 blood samples from healthy subjects. Yu et al 26 reported an average number of CTCs of 10.82/7.5 mL in patients with non-small cell lung tumors.…”

Sensitive and specific detection of circulating tumor cells promotes precision medicine for cancer

“…For example, a recent wedge-shaped microfluidic device [ Figure 2G] based on the difference in size, as well as rigidity and nuclear/cytoplasmic ratio between CTCs and normal blood cells, was fabricated to enhance CTC isolation, exhibiting excellent capture performance with ≥ 85% capture efficiency [52] . Similarly, benefiting from those multiple biophysical properties, Liu et al [53] [ Figure 2H] developed a pyramid-shaped microchamber to achieve a more than 85% capture efficiency and a 93% recovery yield. In addition, vortex technology has been exploited and validated for isolating CTCs based on differences in size, shape and deformability by inertial microfluidics and laminar micro-vortices.…”