Tissue biopsy, the sampling of human cells using surgery, constitutes a significant barrier to easy and frequent monitoring of cancer patients. In liquid biopsy, the blood of cancer patients is instead sampled to monitor the level of cancer biomarkers. Detecting nucleic acid biomarkers for cancer diagnosis requires the enzymatic amplification of sequences to be identified to achieve the needed level of sensitivity. Such a step introduces constraints and drawbacks in the assays, and efforts have been made to identify innovative amplification-free protocols for DNA detection. The possibilities offered by nanoparticle-enhanced surface plasmon resonance imaging in detecting non-amplified DNA circulating in cancer patients’ blood will be discussed in the context of applications to cancer diagnosis based on liquid biopsy. The role played by the proper design of the plasmonic sensor surface will also be discussed with specific emphasis on a new dual-functional low-fouling poly-L-lysine-based surface layer.
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