Surface enhanced Raman spectroscopy (SERS) is meeting the requirements in biomedical science being a highly sensitive and specific analytical tool. By employing portable Raman systems in combination with customized sample pre-treatment, point-of-care-testing (POCT) becomes feasible. Powerful SERS-active sensing surfaces with high stability and modification layers if required are available for testing and application in complex biological matrices such as body fluids, cells or tissues. This review summarizes the current state in sample collection and pretreatment in SERS detection protocols, SERS detection schemes, i.e. direct and indirect SERS as well as targeted and non-targeted SERS, and SERS-active sensing surfaces. Moreover, the recent developments and advances of SERS in biomedical application scenarios, such as infectious diseases, cancer diagnostics and therapeutic drug monitoring is given, which enables the readers to identify the sample collection and preparation protocols, SERS substrates and detection strategies that are best-suited for their specific applications in biomedicine.

Background: The current diagnosis of Alzheimer’s disease (AD) is based on a series of analyses which involve clinical, instrumental and laboratory findings. However, signs, symptoms and biomarker alterations observed in AD might overlap with other dementias, resulting in misdiagnosis. Methods: Here we describe a new diagnostic approach for AD which takes advantage of the boosted sensitivity in biomolecular detection, as allowed by seed amplification assay (SAA), combined with the unique specificity in biomolecular recognition, as provided by surface-enhanced Raman spectroscopy (SERS). Results: The SAA-SERS approach supported by machine learning data analysis allowed efficient identification of pathological Aβ oligomers in the cerebrospinal fluid of patients with a clinical diagnosis of AD or mild cognitive impairment due to AD. Conclusions: Such analytical approach can be used to recognize disease features, thus allowing early stratification and selection of patients, which is fundamental in clinical treatments and pharmacological trials.

For the progress of point-of-care medicine, where individual health status can be easily and quickly monitored using a handheld sensor, saliva serves as one of the best-suited body fluids thanks to its availability and abundance of physiological indicators. Salivary biomarkers, combined with rapid and highly sensitive detection tools, may pave the way to new real-time health monitoring and personalized preventative therapy branches using saliva as a target matrix. Saliva is increasing in importance in liquid biopsy, a non-invasive approach that helps physicians diagnose and characterize specific diseases in patients. Here, we propose a proof-of-concept study combining the unique specificity in biomolecular recognition provided by surface-enhanced Raman spectroscopy (SERS) in combination with molecular dynamics (MD) simulations, which give leave to explore the biomolecular absorption mechanism on nanoparticle surfaces, in order to verify the traceability of two validated salivary indicators, i.e., interleukin-8 (IL-8) and lysozyme (LYZ), implicated in oropharyngeal squamous cell carcinoma (OSCC) and oral infection. This strategy simultaneously assures the detection and interpretation of protein biomarkers in saliva, ultimately opening a new route for the evolution of fast and accurate point-of-care SERS-based sensors of interest in precision medicine diagnostics.

The study demonstrates the potential of advanced vibrational spectroscopy to reveal the complex molecular composition of cerumen, suggesting its promising application as a non-invasive diagnostic tool for identifying disease-related biomarkers.

Accurate detection of antibiotics in biological samples is essential for clinical diagnoses and therapeutic drug monitoring. This research examines how proteins and other substances in blood plasma affect the detection of the antibiotic ceftriaxone using surface-enhanced Raman spectroscopy (SERS). We detected ceftriaxone spiked in blood plasma without sample preparation within the range of 1 mg/mL to 50 µg/mL. By employing a pretreatment approach involving methanol-based protein precipitation to eliminate interfering substances from a spiked blood plasma solution, we could detect ceftriaxone down to 20 µg/mL. The comparative analysis demonstrates that the protein precipitation step enhances the sensitivity of SERS-based detection of drugs in the matrix blood plasma. The insights derived from this study are highly beneficial and can prove advantageous in developing new antibiotic detection methods that are both sensitive and selective in complex biological matrices. These methods can have important implications for clinical treatments.