A micropillar‐integrated smart microfluidic device for specific capture and sorting of cells

Abstract

An integrated smart microfluidic device consisting of nickel micropillars, microvalves, and microchannels was developed for specific capture and sorting of cells. A regular hexagonal array of nickel micropillars was integrated on the bottom of a microchannel by standard photolithography, which can generate strong induced magnetic field gradients under an external magnetic field to efficiently trap superparamagnetic beads (SPMBs) in a flowing stream, forming a bed with sufficient magnetic beads as a capture zone. Fluids could be manipulated by programmed controlling the integrated air-pressure-actuated microvalves, based on which in situ bio-functionalization of SPMBs trapped in the capture zone was realized by covalent attachment of specific proteins directly to their surface on the integrated microfluidic device. In this case, only small volumes of protein solutions (62.5 nL in the capture zone; 375 nL in total volume needed to fill the device from inlet A to the intersection of outlet channels F and G) can meet the need for protein! The newly designed microfluidic device reduced greatly chemical and biological reagent consumption and simplified drastically tedious manual handling. Based on the specific interaction between wheat germ agglutinin (WGA) and N-acetylglucosamine on the cell membrane, A549 cancer cells were effectively captured and sorted on the microfluidic device. Capture efficiency ranged from 62 to 74%. The integrated microfluidic device provides a reliable technique for cell sorting.

An efficient microfluidic sorter: implementation of double meandering micro striplines for magnetic particles switching

“…The beads are commercially available and can be functionalized by tagging with desired bio-molecules such as DNA, antibody, and protein (Pamme 2005;Gijs et al 2010). Recently, extensive works have been carried out in understanding the trapping (Lee et al 2001(Lee et al , 2004Liu et al 2007b), transport (Rida et al 2003;Speetjens and de Boeck 2004), manipulation (Smistrup et al 2006;Shikida et al 2009;Wang et al 2006), and separation (Choi et al 2001;Deng et al 2002) behaviors of magnetic beads.…”

Fundamentals and application of magnetic particles in cell isolation and enrichment: a review

“…Along similar lines, microfluidic devices containing magnetic micropillar structures can be used to capture specific target cells (Liu et al, 2009c). One example is a microfluidic device that featured a strong induced magnetic field derived from an array of hexagonal nickel micropillars captured target cancer cells for subsequent on-chip sample preparations (Liu et al, 2007). While it is true that in-situ analysis can be performed with high sensitivity using small sample volumes in a complex manner in lab-on-a-chip devices that employ magnetic cell separation, this technology is still limited by time-consuming and labor-intensive procedures such as magnetic bead labeling (Whitesides, 2006).…”

“…Another type of microfluidic device has been developed that generates a strong induced magnetic field mediated by an array of hexagonal nickel micro-pillars in the flow path. This device can capture target cancer cells by using on-chip sample preparation (Liu et al, 2007). …”

Polymer monolith‐integrated multilayer poly(dimethylsiloxane) microchip for online microextraction and capillary electrophoresis

“…Multilayer PDMS microfluidic chip was fabricated with standard soft photolithography similar to the process Electrophoresis 2010, 31, 3028-3034 described previously [32]. Briefly, masks for making microfluidic units were obtained by printing a specific pattern onto a transparency film with a high-resolution (3600 dpi) printer.…”