Lab on chips for liquid biopsy: a flexible and customized approach through microfabrication.

Cancer early detection is one of the most challenging purposes of preventive medicine. Liquid biopsy represents a revolutionary approach, fostering access to early screening and increasing patients' compliance, two crucial issues in reaching the largest possible audience in prevention campaigns. To facilitate this approach, the deployment of innovative methods for easy manipulation of biological fluids and the availability of devices for the rapid and low-cost detection of biomarkers is essential. The aim of this study was the optimization of multifunctional Lab-On-Chips with the final aim of realizing a platform for oral carcinoma cells trapping from a complex biological fluid as saliva and for specific subcellular components like extracellular vesicles (EVs) from the neuroblastoma cell model. A set of different microfluidic building blocks was realized through poly-methyl methacrylate (PMMA) micromilling, microfabricated and functionalized to optimize surface chemistry for capturing tumor cells or EVs in multiple channels, assess working concentration for biological fluids and combine sample preparation with detection modules all in the same chip. After optimization, a proof-of-concept device was realized mimicking liquid biopsy analysis from saliva, a biological fluid readily available and with a high compliance from patients, useful for the early diagnosis of cancer.