Optical detection techniques based on surface enhanced Raman spectroscopy (SERS) and capable of providing relevant information on molecular and protein composition of biological samples, are gaining rising attention in clinical research as alternatives to traditional detection assays. Meanwhile, due to the technological advances in compact instrumentation as well as in nanofabrication processes, SERS probes based on portable guided-wave systems, have been implemented thus providing for easier accessibility into complex environments and enabling for real-time in situ detection of low concentrated target analytes. In the present study, low-cost fabrication processes were successfully combined with surface functionalization strategies for the fabrication of disposable SERS-active substrates, engineered to tightly fit the distal end of portable Raman instruments. Being based on a polymer casting fabrication process, the overall design of the substrates can be easily adapted to the varied geometry of the probes to be fit, thus guaranteeing high design versatility. SERS-functionality was achieved by immobilization of gold nanoparticles whose size and shape directly affect the plasmonic properties of the substrates. Moreover, SERS substrates can be further modified by covalently binding molecules acting as baits to selectively fish target biomarkers within heterogeneous samples thereby increasing the specificity of SERS signals. Finally, these sensors represent a powerful tool potentially implementable for the early diagnosis of widespread pathologies by real-time SERS analysis of liquid biopsy.
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