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.

The isolation of circulating tumor cells (CTCs) directly from blood, as a liquid biopsy, could lead to a paradigm shift in cancer care. The MagPure chip provides a powerful tool for subsequent purification of CTCs and dissection of their clinical information.

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.

The concept of the lab-on-a-chip, at the core of many point-of-care or point-of use environmental or human diagnostic products, is intricately linked to the idea of single-use. The need for decentralisation, convenient diagnostic solutions has led to the design and production of centimeter scale, disposable devices, used once, then discarded. This approach has increased the amount of generated waste beyond laboratories and into the communities where adequate disposal maybe is inadequate. Have we unwittingly created a "technological trap" resulting in unintended, additional, and potentially avoidable, waste [1]? Thus, a legitimate question is "are we part of the solution or part of the problem?" How can we ensure that the social benefits of such solutions are not delivered at the expense of an environmental impact that might take years to be fully appreciated? How big of a problem does the lab-on-a-chip waste represent? Can a single-use approach be reversible, or can it be alleviated through materials or methods choices? Most of the environmental sustainability of a single-use device is locked at the design stage and material choice is one of the many contributing factors to the environmental impact of the device. Can we identify applications where single use can be avoided, or can the impact of single use devices be minimized through material and design choices? Importantly, a transition to alternative materials and reagents is not just an engineering problem. Beyond the functional aspects, there are significant economic and regulatory implications to consider. We are calling for engineers, economists, healthcare professionals, manufacturers, regulators and policy makers to join forces and work together to answer this Grand Challenge: how do we reduce the amount of waste created by the lab-on-achip and point-of-care devices industry?The environmental impact of lab-on-a-chip devices in the point-of-care or point-of-need industry is arguably difficult to assert, as no studies have been conducted to quantify this yet.At the inception of the lab-on-chip field, a microfluidic approach was touted as the possibility to reduce reagents and solvent consumption. However, how much of this, still hold true? To yield meaningful results microfluidic devices often need similar amounts of sample and reagents than would be used in a bench assay. That is certainly the case when comparing to the use of liquid handling robots capable of handling microvolumes, with arguably less paraphernalia than most microfluidic-based devices.The majority of point-of-need and point-of-care industry uses petroleum-based plastics [2], [3], [4]. We also know that the industry is in full expansion to the need for decentralized healthcare. According to various reports, the microfluidic market sits at an estimated $11 billion and is projected to grow at an average rate of 10% CAGR. Meanwhile the point-of-care market is worth $32 billion with a CAGR of 11.5%. Whilst the exact production volumes have not been reported, it is clear the production equates waste at the end of the life cycle. An open question is how much of the industry produce single-use versus re-usable products. Similarly, the distribution of different end-of-life processes (incineration, landfill or recycling) for point-of-care and point-of-use devices are unknown, however, the toxic effect of plastic incineration or landfill on environmental, human and animal health is well documented [5], [6], [7]. Preventing the use of petrochemical plastics has the potential of significant carbon savings in the industry, but also reduces toxic effects on human, animal and environmental health. Plastic pollution from the diagnostic industry is also a social justice issue, which affects predominantly the Global South. Manufacturers (predominantly from western or global north) have shied away from responsible practice and distribute products with unclear disposal indications [6].Over the last five years, awareness of environmental sustainability in the medical sector has risen, partly due to the pandemic, which highlighted the impact of medical waste as the broader public observed the widespread disposal of masks, other PPE, and diagnostic kits [8], [9]. There has been several attempts to raise awareness about end-of-use issues and waste specifically in the sector of lab-on-a-chip and point-of-care diagnostics [3], [4], [6]. However as commented elsewhere, there is a reluctance particularly from the global health field, to acknowledge the issue of pollution [7]. Developing green processes means questioning our own laboratory practices. What is the carbon footprint of research activities in academic laboratories related to these activities and the amount of waste generated? Purchases and travel are the two main sources of CO2e emissions in laboratories, and the carbon footprint can reach 10 t CO2e per researcher in the fields of physics, biology or engineering. How can we reduce it? Several initiatives, such as mygreenlab.org, Labo 1.5 in France, or LEAF (Laboratory Efficiency Assessment Framework) in the UK are schemes proposing methods for assessing the carbon footprint and actions that lab users can take to save plastics, water, energy and other resources. What would it mean in practice for a microfluidic lab? What are the waste streams like for our sector of activity? Several editors have also launched new journals or manuscripts collection focusing on sustainability: example, the American Chemical Society launched "Sustainable Chemistry & Engineering" in 2013, Nature created "Nature Sustainability" in 2018, and Taylor and Francis have created the "International Journal of Sustainable Engineering", in 2024. In the meantime, the Royal Society of Chemistry (RSC) has launched a new cross-journals collection called "Sustainable Laboratories". These activities, while laudable, remain niche, and the same big questions are still there and more work is needed to understand the...