Recent advances and perspectives on capture and concentration of label-free rare cells for biomedical science and engineering research

Capture and concentration of the rare cells from a heterogeneous population plays an important role in the development of disease diagnostics, therapeutics, and biomedical research/applications. Phenotypic and genetic characterization of these rare cells can provide important information to guide cancer therapy and regenerative medicine. Large-scale supply of the rare cells at high purity and viability is essential, especially on stem cells, cancer stem cells (CSCs), and circulating tumor cells (CTCs). Conventional capture and concentration methods providing efficient and high throughput isolations are introduced; however, most of them require well-defined biochemical markers and immunolabeling procedures which are complicated, uneconomical, and often unreliable. In contrast, the emerging label-free cell capture methods based on biophysical and biomechanical properties of the desired cell population are growing. In this review, we aim to describe the status of label-free rare cell capture and concentration techniques and to highlight exciting new approaches in this field. Label-free rare cell isolation methods using intrinsic biophysical properties such as filtration, size, electrical polarizability, dielectrophoresis, optical dielectrophoresis, and hydrodynamic chromatography are introduced. Moreover, the microfluidic systems adopted to precisely handle cells and interface with other tools have been described earlier; thus, new approaches dealing with merging label-free selection methods and microfluidic systems are merely summarized. Furthermore, the capture and concentration methods using biochemical and materials properties such as cell-materials interaction, spheroid formation, and stem cells/CSCs niche mimicking are highlighted particularly. Advancing cell isolation technique provides the opportunity to avoid the shortcoming of using biochemical labels and presents better flexibility for subsequent characterization, such as on site screening, high throughput screening, and personalized medicine.