Magnetic particles assisted capture and release of rare circulating tumor cells using wavy-herringbone structured microfluidic devices

Abstract

A wavy-herringbone (wavy-HB) structured microfluidic device was used to effectively and selectively capture and release circulating tumor cells (CTCs) by using immunoaffinity and magnetic force. This device was designed to create passive turbulence and increase the possibility of tumor cells colliding with the device wall. Under an external magnetic field, magnetic particles (MPs) coated with anti-EpCAM against a tumor cell surface protein (EpCAM) were immobilized over the wavy-HB surface to capture tumor cells. After removing the magnetic field, the captured cells with surplus MPs were released from the device and collected; thus, these cells could be re-cultured for further analysis. Under optimized conditions, the capture efficiency of the tumor cells can be as high as 92% ± 2.8%. Capture experiments were also performed on whole blood samples, and the capture efficiency was in a high range of 81-95%, at different tumor cell concentrations. Such a method can potentially be used for CTC sorting from patient blood samples, CTC concentration monitoring, therapeutic guidance and drug dosage choice, and further study of tumors, such as drug screening and tumor mutations.

Gelatin Nanoparticle-Coated Silicon Beads for Density-Selective Capture and Release of Heterogeneous Circulating Tumor Cells with High Purity

“…Compared with traditional EpCAM-based capturing methods, this novel method showed significantly superior capture efficiency (>80%) and purity (>85%). In addition, with the gelatin coating, the captured CTCs can be released with up to 94% efficiency and 92.5% viability, which is comparable to other CTC release methods 31 , 32 . This simple method also benefits from ease of instrumentation in the clinical setting since it requires only standard centrifuge equipment, which is common in clinical diagnostics labs.…”

Detection of Rare Objects by Flow Cytometry: Imaging, Cell Sorting, and Deep Learning Approaches

“…Furthermore, these systems were shown to be effective for the isolation of magnetically labeled cells including rare circulating cells from blood samples. As a recent example, Shi et al successfully isolated HCT-116 human colorectal cancer CTCs selectively labeled with magnetic nanoparticles from the whole blood samples by a wavy-herringbone structured microfluidic device with a capture efficiency of 81%-95% [241]. The specific wave structure of the microchannels creates turbulence in the liquid flow increasing the colliding probability with the channel walls and improving the effectiveness of the cells capturing.…”

Nanotechnology-Assisted Isolation and Analysis of Circulating Tumor Cells on Microfluidic Devices

“…In order to avoid the effect of red blood cell (RBC) sedimentation on the capture purity, an automated motion-controlled microfluidic system was designed in which magnets were put on top of the microchannel (inverted channel) [ 65 ]. Based on a similar mechanism, a series of microfluidic devices and methods for CTC isolation was developed, such as microfluidic magnetic activated cell sorting (μ-MACS) [ 66 ], a microfluidic mixing/magnetic-activated cell sorting (μ-MixMACS) device [ 67 ] and a wavy-herringbone (wavy-HB)-structured microfluidic device [ 68 ]. Lee et al ( Figure 2 B) reported a μ-MixMACS device for one-step negative enrichment [ 67 ].…”

“…After specifically removing WBCs, more than 85% of the MCF-7 cells were obtained from leukocyte samples. Shi et al developed a wavy-herringbone (wavy-HB)-structured microfluidic device in which anti-EpCAM coated MNPs were immobilized over the wavy-HB surface under an external magnetic field [ 68 ]. A high yield (92%) and a high range of CTC capture efficiency (81–95%) in whole blood samples were obtained using this wavy-HB structured device.…”