Blood-based liquid biopsies provide a minimally invasive alternative to identify cellular and molecular signatures that can be used as biomarkers to detect early-stage cancer, predict disease progression, longitudinally monitor response to chemotherapeutic drugs, and provide personalized treatment options. Specific targets in blood that can be used for detailed molecular analysis to develop highly specific and sensitive biomarkers include circulating tumor cells (CTCs), exosomes shed from tumor cells, cell-free circulating tumor DNA (cfDNA), and circulating RNA. Given the low abundance of CTCs and other tumor-derived products in blood, clinical evaluation of liquid biopsies is extremely challenging. Microfluidics technologies for cellular and molecular separations have great potential to either outperform conventional methods or enable completely new approaches for efficient separation of targets from complex samples like blood. Researchers from the University of Alabama at Birmingham provide a comprehensive overview of blood-based targets that can be used for analysis of cancer, review microfluidic technologies that are currently used for isolation of CTCs, tumor derived exosomes, cfDNA, and circulating RNA, and provide a detailed discussion regarding potential opportunities for microfluidics-based approaches in cancer diagnostics.
Examples of microfluidic devices for label-free capture of CTCs
(A) Filtration: Exploiting size differences to ensure separation of CTCs based on differences in size and deformability. (A1) Microscopic images of flexible spring microarrays that are used for exosome capture, and (A2) Actual setup including a schematic of the various components of the capture system. (B) Spiral Devices: Demonstration of the use of inertial focusing within microfluidic channels to enable size based separation of cancer cell lines from other blood cells. (B1) Design and mechanism of separation of cells and particles using spiral microchannels, and (B2) Actual devices and workflow for processing of samples for CTC isolation. (C) Surface Energy: Using differences in cell surface energy to enable initial phase partitioning and the initial separation is enhanced via inertial forces. (C1) Schematic of the device for inertia enhanced phase partitioning, (C2) Actual fabricated device and (C3) Setup for operation of the device.