Plasmonic optical biosensors for the analysis of nucleic acids have drawn a great deal of interest in nanomedicine because of their capability to overcome major limitations of conventional methods. Within this realm, surface-enhanced Raman scattering (SERS)-based sensing is progressively emerging as a powerful analytical tool beyond the basic grounds of academia to viable commercial products. SERS benefits from the synergistic combination between the intrinsic structural specificity and experimental flexibility of Raman spectroscopy, the extremely high sensitivity provided by plasmonic nanomaterials, and the tremendous advances in nanofabrication techniques and spectroscopic instrumentation. SERS application to nucleic acids analysis has been largely restricted to indirect sensing approaches, where a SERS reporter and oligonucleotide ligands are typically combined onto the nanomaterials to enable extrinsic detection of the target sequences. On the other hand, the acquisition of the intrinsic SERS vibrational fingerprint of nucleic acids (direct sensing) has traditionally suffered from major limitations. However, recent years have witnessed a burst of interest in this area, largely driven by the efforts to address key reproducibility and sensitivity issues. In this tutorial review, we summarize and discuss the most recent cutting-edge research in the field of direct SERS sensing of nucleic acids by coherently organising the diverse data reported in the literature in a structurally logical fashion.

Blood-based biomarkers (liquid biopsy) offer extremely valuable tools for the non-invasive diagnosis and monitoring of tumors. The protein c-MYC, a transcription factor that has been shown to be deregulated in up to 70% of human cancers, can be used as a robust proteomic signature for cancer. Herein, we developed a rapid, highly specific and sensitive SERS assay for the quantification of c-MYC in real blood samples. The sensing scheme relies on the use of specifically designed hybrid plasmonic materials and their bioderivatization with a selective peptidic receptor modified with a SERS transducer. Peptide/c-MYC recognition events translate into measurable alterations of the SERS spectra associated with a molecular orientation of the transducer, in agreement with the surface selection rules. The efficiency of the sensor is demonstrated in cellular lines, healthy donors and a cancer patient.

Exosomes are emerging as one of the most intriguing cancer biomarkers in modern oncology for early cancer diagnosis, prognosis and treatment monitoring. Concurrently, several nanoplasmonic methods have been applied and developed to tackle the challenging task of enabling the rapid, sensitive, affordable analysis of exosomes. In this review, we specifically focus our attention on the application of plasmonic devices exploiting surface-enhanced Raman spectroscopy (SERS) as the optosensing technique for the structural interrogation and characterization of the heterogeneous nature of exosomes. We summarized the current state-of-art of this field while illustrating the main strategic approaches and discuss their advantages and limitations.

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Staphylococcus aureus is a common cause of serious infections. One of the main drawbacks in its treatment is the time required for a positive diagnosis, over 24 h, as most methods are still based in bacterial culture. Herein, a microfluidic optical device for the rapid and ultrasensitive quantification of S. aureus in real human fluids is designed. In this approach, the surface‐enhanced Raman scattering (SERS)‐encoded particles, functionalized with either an antibody or an aptamer, form a dense collection of electromagnetic hot spots on the surface of S. aureus. This allows for an exponentially increase of the SERS signal when particles accumulate on the microorganism as compared to their free condition in bulk solution. Quantification is achieved by passing the sample through a microfluidic device with a collection window where a laser interrogates and classifies each of the induced bacteria–nanoparticle aggregates in real time. Further, the advantages of using aptamers versus antibodies as biorecognition elements are extensively investigated.

Point mutations in Ras oncogenes are routinely screened for diagnostics and treatment of tumors (especially in colorectal cancer). Here, we develop an optical approach based on direct SERS coupled with chemometrics for the study of the specific conformations that single-point mutations impose on a relatively large fragment of the K-Ras gene (141 nucleobases). Results obtained offer the unambiguous classification of different mutations providing a potentially useful insight for diagnostics and treatment of cancer in a sensitive, fast, direct and inexpensive manner.

Metastatic cancer patients require a continuous monitoring during the sequential treatment cycles to carefully evaluate their disease evolution. Repetition of biopsies is very invasive and not always feasible. Herein, we design and demonstrate a 3D-flow focusing microfluidic device, where all optics are integrated into the chip, for the fluorescence quantification of CTCs in real samples. To test the chip performance, two cell membrane targets, the epithelial cell adhesion molecule, EpCAM, and the receptor tyrosine-protein kinase, HER2, are selected. The efficiency of the platform is demonstrated on cell lines and in a variety of healthy donors and metastatic-breast cancer patients.

IntroductionThe aim of this study was to compare TOMOX versus FOLFOX4 as first-line treatment of advanced colorectal cancer (CRC).Materials and methods191 chemotherapy-naïve patients were randomized to receive TOMOX or FOLFOX4. Patients were evaluated every 3 months and chemotherapy was continued until disease progression or unacceptable toxicity. Overall response rate was the primary endpoint.Results183 patients were included in the intent-to-treat analysis (92 TOMOX and 91 FOLFOX4). Overall response rate was 45.6 and 36.3 % (p = 0.003) for TOMOX and FOLFOX4, respectively. No statistically significant differences were observed in overall survival (15.6 and 17.2 months; p = 0.475); progression-free survival (7.7 and 8.7 months; p = 0.292), and response duration (6.4 and 7.6 months; p = 0.372) for TOMOX and FOLFOX4, respectively. Grades 3 and 4 neutropenia (p < 0.0001) and leukopenia (p = 0.028) were more common with the FOLFOX4 regimen, while hepatic disorders and asthenia were higher in TOMOX group (p = ns). There were two treatment-related deaths in the FOLFOX4 arm and one in the TOMOX arm. Quality of life analysis based on the SF-36 revealed differences between the two regimens for physical and mental composite scores after 6 weeks, and for body pain and emotional role functioning after 6 and 12 weeks; all of these favored the FOLFOX4 arm (p ≤ 0.05).ConclusionsTOMOX and FOLFOX4 seem to have similar efficacy and are well tolerated in the first-line treatment for advanced CRC with different profiles of toxicity. The convenient TOMOX regimen may offer an alternative to fluoropyrimidine-based regimens.