Blood cell separation with magnetic techniques: a critical review

Blood cell separation is a critical process for many clinical and research applications. Among the various techniques employed for blood cell isolation, magnetic techniques are very attractive due to their multiple benefits, i.e. high efficiency, simplicity, low-cost, and no need for expensive equipment or trained operators. Microfluidic devices integrating magnetophoresis have demonstrated promising results for high-throughput separation, with some achieving separation rates of over 10⁸ cells per hour. However, there are many different approaches that can be used for blood magnetic separations, with the selection depending on the sample properties, target cells and purpose of the isolated fractions. This critical review examines recent advances (2014-2025) in magnetic techniques for separating blood cells. Both labeled and label-free approaches are analyzed, with a focus on their performance and impact on cellular function, highlighting their strengths, limitations, and potential for future development in clinical research applications. Among the labeled approaches, positive selection methods have been shown to achieve high purities for various cell types; nevertheless, these techniques might affect cell functionality after separation. Therefore, negative selection can be used for the separation of cells when cellular functionality needs to be preserved. Moreover, label-free techniques, primarily focused on red blood cells (RBCs) separation, can be used for blood cell isolation by leveraging the cells' intrinsic magnetic properties. These methods showed potential for continuous, high-purity RBCs separation, with some devices achieving over 95% recovery and purity. This work aims to provide valuable guidelines for the appropriate selection of magnetic technologies for blood separations to accomplish the successful implementation of magnetophoresis in clinical practice.