Efficient Capture and Separation of Cancer Cells Using Hyaluronic Acid-Modified Magnetic Beads in a Microfluidic Chip

Abstract

The efficient isolation and specific discrimination of circulating tumor cells (CTCs) is expected to provide valuable information for understanding tumor metastasis and play an important role in the treatment of cancer patients. In this study, we developed a novel and rapid method for efficient capture and specific identification of cancer cells using hyaluronic acid (HA)-modified SiO2-coated magnetic beads in a microfluidic chip. First, polyacrylamide-surfaced SiO2-coated magnetic beads (SiO2@MBs) were covalently conjugated with HA, and the created HA-modified SiO2@MBs (HA-SiO2@MBs) display binding specificity to HeLa cells (a human cervical carcinoma cell line) overexpressing CD44 receptors. After incubating the HA-SiO2@MBs with cancer cells for 1 h, the mixture of MBs and cells was drawn into a designed microfluidic channel with two inlets and outlets. Through the formation of lamellar flow, cells specifically bound with the HA-SiO2@MBs can be separated under an external magnetic field with a capture efficiency of up to 92.0%. The developed method is simple, fast, and promising for CTC separation and cancer diagnostics applications.

Recent progress of nanostructure-based enrichment of circulating tumor cells and downstream analysis

“…Yin et al designed the HA-functionalized silica coated magnetic beads HA-SiO 2 @MBs, and combined it with a microfluidic chip to achieve the efficient capture and separation of CD44-overexpression cells. 92 The magnetic beads are specific to HeLa cells-overexpressing CD44 receptors, and the capture efficiency is as high as 92.0%. Melanie Schmidt et al designed HA-functionalized double-response poly ( N -isopropylacrylamide) (PNIPAM) microgel coating for CTC capture and release, as shown in Fig.…”

Trapping of a Single Microparticle Using AC Dielectrophoresis Forces in a Microfluidic Chip

“…Magnetic capture enables the capture and manipulation of cells by combining them with nanoscale immunomagnetic beads. This method has high specificity and is a commonly used method for cell trapping [ 25 , 26 ]. However, this method requires the pretreatment of cells to bind magnetic nanoparticles to targeted cells, which is complicated and costly and may cause damage to the biological activity of the cells.…”

Composite Microfluidic Petri Dish-Chip (MPD-Chip) without Protein Coating for 2D Cell Culture

“…Microfluidic chips provide a microenvironment conducive to cell growth, closely emulating physiological conditions within the human body. This characteristic renders them invaluable for advancing research in the realm of cellular science. − Microfluidic chips are comprised of a cover and a substrate, with the prevailing choice for the material of both the cover and substrate being poly­(dimethylsiloxane) (PDMS) due to its advantageous characteristics: biocompatibility, gas permeability, optical transparency, facile microstructure molding, ease of bonding, notable chemical resistance, and cost-effectiveness. − However, the inherent hydrophobic nature of PDMS has been demonstrated as a factor contributing to compromised cell adhesion. − The amelioration of hydrophobicity within microchannels of PDMS chip can be achieved through modification with extracellular matrix proteins, such as fibronectin, collagen, and laminin. − However, in the context of long-term culture, the dissociation of these proteins may occur, resulting in the aggregation and detachment of cells. , Furthermore, hydrophilic treatments by this method tend to lose effectiveness within a few days, thus limiting their utility for extended culture periods or devices requiring prestorage before use. Coating procedures also escalated the experimental costs. − …”