Centrifugal microfluidic systems for cancer cell separation: Advances, challenges, and applications

• Recent progress in centrifugal microfluidic platforms for CTC separation reviewed. • Comparative analysis of size-, density-, and affinity-based separation strategies. • Integration of biocompatible nanoparticles enhances capture efficiency and viability. • Advances in automation, throughput, and clinical translation are emphasized. • Future prospects for point-of-care cancer diagnostics using Lab-on-a-Disc systems. Cancer remains a leading global health challenge, with circulating tumor cells (CTCs) playing a pivotal role in metastasis and disease progression. Efficient detection and isolation of CTCs are essential for early diagnosis, therapeutic monitoring, and the advancement of personalized treatment strategies. However, their extreme rarity in peripheral blood presents significant technical challenges for reliable enrichment and analysis. Centrifugal microfluidic systems, or lab-on-a-disc (LOCD) platforms, offer a promising solution by enabling automated, high-throughput, and cost-effective separation of rare cancer cells with minimal manual intervention. This review provides a comprehensive analysis of recent advances in centrifugal microfluidic technologies, with a focus on cancer cell separation for diagnostics and the challenges of clinical translation. Particular attention is given to the optimization of separation techniques, improvements in microchannel design, and strategies to minimize contamination and cell damage while enhancing purity and yield. We critically compare label-free, affinity-based, and hybrid separation approaches, and examine how material selection, surface functionalization, automation, and integrated detection modules in-fluence device performance. Clinical relevance is emphasized throughout, including examples of real patient applications, regulatory challenges, and translational barriers. Furthermore, we propose future directions to address persistent limitations such as clogging, limited specificity, and standardization. While routine clinical implementation remains complex, recent innovations have significantly improved system robustness, reproducibility, and accessibility. This review serves as a resource for researchers and clinicians, summarizing the current state of the field and outlining the path forward for the next generation of centrifugal microfluidic systems tailored for cancer cell separation.