The selection of circulating tumor cells (CTCs) directly from blood as a real-time liquid biopsy has received increasing attention over the past ten years, and further analysis of these cells may greatly aid in both research and clinical applications. CTC analysis could advance understandings of metastatic cascade, tumor evolution, and patient heterogeneity, as well as drug resistance. Until now, the rarity and heterogeneity of CTCs have been technical challenges to their wider use in clinical studies, but microfluidic-based isolation technologies have emerged as promising tools to address these limitations. This review provides a detailed overview of latest and leading microfluidic devices implemented for CTC isolation. In particular, this study details must-have device performances and highlights the tradeoff between recovery and purity. Finally, the review gives a report of CTC potential clinical applications that can be conducted after CTC isolation. Widespread microfluidic devices, which aim to support liquid-biopsy-based applications, will represent a paradigm shift for cancer clinical care in the near future.
Magnetophoresis offers many advantages for manipulating magnetic targets in microsystems. The integration of micro-flux concentrators and micro-magnets allows achieving large field gradients and therefore large reachable magnetic forces. However, the associated fabrication techniques are often complex and costly, and besides, they put specific constraints on the geometries. Magnetic composite polymers provide a promising alternative in terms of simplicity and fabrication costs, and they open new perspectives for the microstructuring, design, and integration of magnetic functions. In this review, we propose a state of the art of research works implementing magnetic polymers to trap or sort magnetic micro-beads or magnetically labeled cells in microfluidic devices.
Magnetophoresis-based microfluidic devices offer simple and reliable manipulation of micro-scale objects and provide a large panel of applications, from selective trapping to high-throughput sorting. However, the fabrication and integration of micro-scale magnets in microsystems involve complex and expensive processes. Here we report on an inexpensive and easy-to-handle fabrication process of micrometer-scale permanent magnets, based on the self-organization of NdFeB particles in a polymer matrix (polydimethylsiloxane, PDMS). A study of the inner structure by X-ray tomography revealed a chain-like organization of the particles leading to an array of hard magnetic microstructures with a mean diameter of 4 µm. The magnetic performance of the self-assembled micro-magnets was first estimated by COMSOL simulations. The micro-magnets were then integrated into a microfluidic device where they act as micro-traps. The magnetic forces exerted by the micro-magnets on superparamagnetic beads were measured by colloidal probe atomic force microscopy (AFM) and in operando in the microfluidic system. Forces as high as several nanonewtons were reached. Adding an external millimeter-sized magnet allowed target magnetization and the interaction range to be increased. Then, the integrated micro-magnets were used to study the magnetophoretic trapping efficiency of magnetic beads, providing efficiencies of 100% at 0.5 mL/h and 75% at 1 mL/h. Finally, the micro-magnets were implemented for cell sorting by performing white blood cell depletion.
Nd-Fe-B micrometer-size dots were prepared by optical lithography and sputtering. It is proposed to use such structures as model systems to study intergranular phase engineering in Nd-Fe-B permanent magnets. The influence of Ta, Nd, Dy, and Gd coatings on the magnetization reversal of such Nd-Fe-B dot arrays are compared, after different heat treatments. A very thin layer of Dy (tNdFeB/tDy = 120) was found to lead to a significant increase of the coercive field, up to 80% for a total equivalent Dy content of less than 5 at. % of all the Nd. A coercivity increase of up to 20% was found with Gd coating which is attributed to the so-called superferrimagnetic coupling phenomenon. Nd and Ta coating are neutral or detrimental to the magnetic hardness.
Size-selected FeRh clusters have been deposited at low energy and under ultra-high vacuum conditions, on a epitaxial thin film. Using x-ray diffraction in grazing incidence configuration, we have observed the chemical ordering of FeRh nanoparticles into the chemically ordered B2 phase after annealing, while a reciprocal space mapping indicates that particles, despite their random deposition, are finally adopting preferential orientations reflecting an atomic ordering with the crystal. In addition to the usual epitaxy relationship observed for FeRh thin films, an unexpected orientation is detected ( in-plane rotation, leading to a new cube-on-cube epitaxy relationship), which must be specific to nanosized FeRh particles.