Novel Microfluidic Approaches to Circulating Tumor Cell Separation and Sorting of Blood Cells: A Review

Abstract The separation of circulating tumor cells (CTCs) that originate from tumor or cancer tissue plays an important role in cancer diagnostics, progression analyses, and treatment proficiency. Cancer metastasis occurs when CTCs spread throughout the body and invade healthy tissues, which leads to new tumors in that area. Although a dramatic rate of death begins from CTCs spreading around the body, valuable measures can be taken to control their development. A first step is separating these harmful cells from the bloodstream and then investigating their features to introduce complementary treatments that can affect the cancerous cells without damaging healthy cells. Numerous techniques have been developed for continuous and fast separation of CTCs. Over the last two decades, the reduction in reagent demand, sample volume, analysis time, and patient safety are just a few of the motivations that encourage researchers to study microfluidic instruments for CTC separation from other blood cells. Among them, inertial microfluidic devices are promising due to their simple structure and setup. However, one shortcoming of this technique is the need for pumps to drive fluid flow, a low ability to control cell movement, and the possibility of clogging the channel. One technique that may potentially overcome these shortcomings is the so-called rotational micro-fluidic platform. However, this technique alone is still not enough. In this paper, a detailed analysis of each technique that emphasizes both strengths and shortcomings is presented. Subsequently, a new approach that combines microfluidics with magnetic nanoparticles and is based on the antibody binding principle is proposed. The feasibility of implementing this combined technique will also be discussed.