Sensor-integrated microfluidic approaches for liquid biopsies applications in early detection of cancer

Cancer represents one of the conditions with the most causes of death worldwide. Common methods for its diagnosis are based on tissue biopsies-the extraction of tissue from the primary tumor, which is used for its histological analysis. However, this technique represents a risk for the patient, along with being expensive and time-consuming and so it cannot be frequently used to follow the progress of the disease. Liquid biopsy is a new cancer diagnostic alternative, which allows the analysis of the molecular information of the solid tumors via a body fluid draw. This fluid-based diagnostic method displays relevant advantages, including its minimal invasiveness, lower risk, use as often as required, it can be analyzed with the use of microfluidic-based platforms with low consumption of reagent, and it does not require specialized personnel and expensive equipment for the diagnosis. In recent years, the integration of sensors in microfluidics lab-on-a-chip devices was performed for liquid biopsies applications, granting significant advantages in the separation and detection of circulating tumor nucleic acids (ctNAs), circulating tumor cells (CTCs) and exosomes. The improvements in isolation and detection technologies offer increasingly sensitive and selective equipment’s, and the integration in microfluidic devices provides a better characterization and analysis of these biomarkers. These fully integrated systems will facilitate the generation of fully automatized platforms at low-cost for compact cancer diagnosis systems at an early stage and for the prediction and prognosis of cancer treatment through the biomarkers for personalized tumor analysis.

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(A) The HB-Chip is composed by a collection of microfluidic channels with a single fluid entrance to multiple channels to move again to a single channel to exit, which allows uniform blood flow inside the device. (B) Herringbone chip with microstructures in a double-sided channel. The chip was validated with real blood samples from lung cancer detection. CTCs were capture and stained inside the chip with antibodies against CK in red, DAPI in blue, and CD45 in green. (C) Microfluidic platform for highly efficient retention of CTCs based on a physical variation on cell deformation and diameter. The chip is composed by micro-ellipse filters which were able to detect CTCs from the detection of colon, breast and non-small-cell lung (NSCLC) cancer. (D) Tumor cells captured by a microfluidic platform for high capture efficiency of CTCs (Green), where the CTCs pass through the ellipse filters (Scale bar = 50 μm) (E) Nanopillar arrays with a diameter of 650 nm with cell membrane details of the capture cells into the device. (F) OncoBean Chip with micropost structures inside the device. The device allows the cell separation by affinity at high flow rates, applying a radial flow, which produces a variation of the shear profile across the device. (G) Microfluidic device based on the separation of CTCs clusters by Size and Asymmetry. The device was tested with whole blood (red) and colored PBS buffer (blue).

Sierra J, Marrugo-Ramirez J, Rodríguez-Trujillo R, Mir M, Samitier J. (2020) Sensor-Integrated Microfluidic Approaches for Liquid Biopsies Applications in Early Detection of Cancer. Sensors (Basel) 20(5). [abstract]

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