High‑throughput and continuous flow isolation of rare circulating tumor cells and clusters in gastric cancer from human whole blood samples using electromagnetic vibration‑based filtration

Abstract

Circulating tumor cells (CTCs) or CTC clusters are considered as suitable and relevant targets for liquid biopsy as they more accurately indicate cancer progression, the therapeutic effects of treatment and allows for monitoring of cancer metastasis in real-time. Among the various methods for isolating CTCs, size-based filtration is one of the most convenient methods. However, cell clogging makes the filtration process less efficient. In the present study, an electromagnetic vibration-based filtration (eVBF) device was developed that efficiently isolated rare CTCs and CTC clusters from clinical blood samples of patients with gastric cancer. Using human blood samples spiked with human gastric cancer cells, the parameters of this device such as vibrating amplitude and flow rate were optimized. Putative CTCs were detected using a conventional filtration method and the eVBF device from the peripheral blood samples of patients with gastric cancer. Continuous flow isolation of CTCs was evaluated by a simulated blood flow system. The eVBF device utilized the electromagnetic force to generate a periodic vibration that prevented the cell clogging and improved the filtering efficiency. The optimized eVBF device with the high-amplitude vibration exhibited a recovery efficiency of 80-90% from whole blood samples spiked with 100 or 1,000 gastric cancer cells per ml. Using the eVBF device, CTCs were detected in 100% of patients (10/10) with gastric cancer, and the positive detection rate of the eVBF device was 30% higher compared with the conventional filtration method. Furthermore, CTC clusters were detected in 40% (4/10) of CTC-positive patient samples, and the integrity of CTC clusters was preserved using the eVBF device. The eVBF device allowed for high-throughput (1 ml/min) and continuous flow isolation of CTCs without the addition of any antibodies, any chemical reagents or any pretreatment processes. Thus, the eVBF device provides an efficient tool for isolating rare CTCs and CTC clusters from patients with cancer, highlighting its potential for use in cancer diagnosis, treatment and cancer biology research.

Advances in analytical microfluidic workflows for differential cancer diagnosis

“…An electromagnetic vibration‑based filtration setup (electromagnetic force driving the vertical filter to vibrate cyclically) has been developed to generate a periodic vibration for preventing the clogging and improving the efficiency (positive detection rate 30% higher) compared to the conventional filtration approaches. [ 108 ] The appropriate design of filtration chambers in µ‐chips reduces the clogging effect. For example, the use of a partial effect of cross‐flow and broad channel size during a continuous purification in the filtration µ‐chip showed an ability to provide higher rate of recovery and purity without clogging effects.…”

Detection of circulating tumor cells: Advances and critical concerns (Review)

“…Cell clogging reduces the efficiency of filtration ( 66 ). To resolve this problem, an electromagnetic vibration-based filtration (eVBF) device was developed ( 74 ). The eVBF device can be used to generate an electromagnetic force with a periodic vibration that prevents cells from clogging ( 74 ).…”

“…To resolve this problem, an electromagnetic vibration-based filtration (eVBF) device was developed ( 74 ). The eVBF device can be used to generate an electromagnetic force with a periodic vibration that prevents cells from clogging ( 74 ). High-throughput (1 ml/min) is achieved without the need for antibodies or chemical reagents in the continuous isolation of CTCs or pretreatment processes ( 74 ).…”

“…The eVBF device can be used to generate an electromagnetic force with a periodic vibration that prevents cells from clogging ( 74 ). High-throughput (1 ml/min) is achieved without the need for antibodies or chemical reagents in the continuous isolation of CTCs or pretreatment processes ( 74 ). In addition, the eVBF device has been optimized with a high-amplitude vibration, and its recovery rate has increased to 80–90% for whole blood sampled with 100 or 1,000 gastric cancer cells/ml ( 74 ).…”

Sorting Technology for Circulating Tumor Cells Based on Microfluidics

“…A large number of studies have shown that CTCs exist in peripheral blood in different forms, including a free single cell and clusters of cells . CTCs are transmitted from primary tumors through phenotypic changes that enable the cells to penetrate blood vessels .…”