Immunomagnetic nanoscreening of circulating tumor cells with a motion controlled microfluidic system

Abstract

Combining the power of immunomagnetic assay and microfluidic microchip operations, we successfully detected rare CTCs from clinical blood samples. The microfluidic system is operated in a flip-flop mode, where a computer-controlled rotational holder with an array of microfluidic chips inverts the microchannels. We have demonstrated both theoretically and experimentally that the direction of red blood cell (RBC) sedimentation with regards to the magnetic force required for cell separation is important for capture efficiency, throughput, and purity. The flip-flop operation reduces the stagnation of RBCs and non-specific binding on the capture surface by alternating the direction of the magnetic field with respect to gravity. The developed immunomagnetic microchip-based screening system exhibits high capture rates (more than 90%) for SkBr3, PC3, and Colo205 cell lines in spiked screening experiments and successfully isolates CTCs from patient blood samples. The proposed motion controlled microchip-based immunomagnetic system shows great promise as a clinical tool for cancer diagnosis and prognosis.

Inkjet-Print Micromagnet Array on Glass Slides for Immunomagnetic Enrichment of Circulating Tumor Cells

“…They are very weakly magnetized 1mm thick elastic sheets (AFG-13346 Magnet Sheets, ProMAG Products, Marietta, OH ). In our previous study, we measured the magnetic field induced by the spacer to be small enough to be neglected and they can be treated as simple distance offset [28]. It is noteworthy that the spacers only cover the front part of the channel so that the strong magnetic field in the later part of the channel can prevent potential CTCs loss.…”

Skeletal stem cell isolation: A review on the state-of-the-art microfluidic label-free sorting techniques

“…When an antibody with high specificity is used, high recovery efficiencies are possible with excellent depletion of contaminating cells at high throughput. The work of Plouffe et al (Plouffe et al, 2012) and Huang et al (Huang et al, 2012) are two good examples in which the throughput was of the order of hundreds of millions to a billion cells per minute. Plouffe et al (Plouffe et al, 2012) reported recovery of spiked CTCs or primary haematopoietic stem cells (HSCs) from whole blood with efficiencies of 88% and 97%, whilst Huang et al (Huang et al, 2012) successfully detected CTCs from cancer patients with recovery efficiencies rounding 60% to 70%.…”

Targeted nanotechnology for cancer imaging

“…Depending on whether a nanoparticle seeks a vascular, a deep tissue or a blood-circulating target, the design of a nanoparticle requires different considerations and features. For example, ligand-functionalized magnetic iron oxide nanoparticles can bind to CTCs, which can be captured using immunomagnetic separation [33, 34]. In the case targeting metastasis, vascular targeting may be more effective than deep tissue targeting (which requires the EPR effect).…”