Microfluidic technologies for circulating tumor cell isolation

Abstract

Metastasis is the main cause of tumor-related death, and the dispersal of tumor cells through the circulatory system is a critical step in the metastatic process. Early detection and analysis of circulating tumor cells (CTCs) is therefore important for early diagnosis, prognosis, and effective treatment of cancer, enabling favorable clinical outcomes in cancer patients. Accurate and reliable methods for isolating and detecting CTCs are necessary to obtain this clinical information. Over the past two decades, microfluidic technologies have demonstrated great potential for isolating and detecting CTCs from blood. The present paper reviews current advanced microfluidic technologies for isolating CTCs based on various biological and physical principles, and discusses their fundamental advantages and drawbacks for subsequent cellular and molecular assays. Owing to significant genetic heterogeneity among CTCs, microfluidic technologies for isolating individual CTCs have recently been developed. We discuss these single-cell isolation methods, as well as approaches to overcoming the limitations of current microfluidic CTC isolation technologies. Finally, we provide an overview of future innovative microfluidic platforms.

Tracking cancer progression: from circulating tumor cells to metastasis

“…For this reason, antigen-independent technologies have been developed to deplete red blood cells and WBCs from a blood sample, leaving a CTCenriched, antigen-agnostic product for subsequent downstream analysis. These technologies include sizebased filtration of CTCs (taking advantage of their larger diameter when compared to blood cells), CTC enrichment based on other physical parameters, and immunomagnetic depletion of WBCs [9]. A comprehensive list of CTC isolation technologies is beyond the scope of this short review, but it is important to recognize that each technology may favor the enrichment of a particular CTC subtype (e.g., high antigen-expressing CTCs in the case of positive selection methods, larger CTCs in the case of size-based filtration methods, among others) and that possible technology-driven biases should be recognized and considered when interpreting downstream molecular results.…”

Tumor Cell Dormancy: Threat or Opportunity in the Fight against Cancer

“…Also, inherent difficulties in detecting and characterizing micrometastatic lesions/individual cells in the patient is another hurdle to assess the relative contribution of various mechanisms of dormancy in the clinical setting [23]. However, the new emerging methodologies, namely microfluidics based on analyzing microliters of serum samples may enable detection of single cells, as wells as DTCs and may aid to capture dormancy dynamics at a single-cell resolution (reviewed in [24][25][26][27]). A full discussion of dormancy-related experimental models is recently reviewed [28][29][30].…”

Microfluidic techniques for tumor cell detection

“…These microfluidic chips are simpler and easier to obtain high throughput. In detail, passive methods consist of mechanical filtering, hydrodynamics, and inertial microfluidics . Most of the researches concentrate in mechanical filtering and inertial microfluidics.…”