3D printing of multifunctional optofluidic systems for high-sensitive detection of pathological biomarkers in liquid biopsies

Liquid biopsies represent a minimally invasive tool for the precocious diagnosis of widespread diseases as well as for routinely patients monitoring by tracking selective biomarkers. Optical detection techniques based on surface enhanced Raman spectroscopy (SERS) are capable of providing information on the molecular content of analyzed samples thus representing one of the most promising analytical method in clinical research, as alternative to traditional bioassays. With the attempt to realize point-of-impact diagnostic devices, in the present study 3D printing and soft-lithography processes were combined with plasmonic nanoparticles (NPs) synthesis for the development of multifunctional lab-onchips (LOCs) integrating SERS sensors for liquid probing. As a matter of fact, LOCs enable to easily handle small volumes of samples as well as to perform multifunctional analyses. This is crucial for pathologies whose diagnosis relies on the ratio of more than one biomarker. To this end, being based on a 3D printing process, the overall design of the devices was rapidly prototyped to integrate channels and detection chambers aligned with optical fibers and portable Raman probes for signal delivering and collection. SERS functionality was achieved by immobilization of gold NPs whose chemistry was modified to enhance NPs deposition and stability. Finally, we are exploring direct laser writing for the integration of mechanical and optical microcomponents needed for liquids control and signal delivering and collection, respectively. The final devices collecting multiple functions and detection configurations will provide high sensitivity, speed of analysis, low sample and reagent consumption, measurement automation and standardization on a highly integrated dynamic platform that will revolutionize liquid biopsy making it costless, on-chip, handy and easy to use.