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.

从异质群体中捕获和浓缩稀有细胞在疾病诊断，治疗和生物医学研究/应用的发展中起着重要作用。这些稀有细胞的表型和遗传特征可提供重要信息，以指导癌症治疗和再生医学。以高纯度和活力大规模供应稀有细胞至关重要，尤其是在干细胞，癌症干细胞（CSC）和循环肿瘤细胞（CTC）上。介绍了提供有效和高通量隔离的常规捕获和浓缩方法；但是，它们中的大多数都需要定义明确的生化标记和免疫标记程序，这些程序复杂，不经济且通常不可靠。相比之下，基于所需细胞群的生物物理和生物力学特性的新兴无标记细胞捕获方法正在不断发展。在这篇综述中，我们旨在描述无标签稀有细胞捕获和浓缩技术的现状，并重点介绍该领域令人兴奋的新方法。介绍了使用固有生物物理特性（如过滤，尺寸，电极化率，介电电泳，光学介电电泳和流体动力学色谱法）的无标记稀有细胞分离方法。此外，前面已经描述了用于精确处理细胞并与其他工具连接的微流体系统。因此，仅总结了涉及合并无标记选择方法和微流体系统的新方法。此外，特别强调了利用生化和材料特性（例如细胞与材料的相互作用，球体形成以及干细胞/ CSC的小生境模拟）的捕获和浓缩方法。先进的细胞分离技术为避免使用生化标记的缺点提供了机会，并为后续表征（例如现场筛选，高通量筛选和个性化药物）提供了更好的灵活性。