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Clusterin plays an important role in carcinogenesis and serves as an important diagnostic biomarker of various clinical conditions. This work describes an application of a surface-enhanced Raman scattering (SERS)-based immunoassay using Al foil substrate that has the potential for the detection of clusterin. We first optimized the parameters of the assay using anti-human IgG/human IgG (hIgG) as a model antibody/antigen system using various substrates based on Au film, Si, Al tape and Al foil. Among the tested substrates, Al foil exhibited better performance, when assay of human IgG on Al foil demonstrated a detection limit of 2 pM and a semi logarithmic trend range from 10 pM to 1000 pM. Afterwards, the same SERS immunoassay method was implemented for detection of clusterin and resulted in a good semi-logarithmic calibration line with a high R2 value of 0.99, which was obtained in the range from 1 ng/mL to 1000 ng/mL. The low detection limit for clusterin antigen was found to be 3 ng/mL, which is better than most LODs for clusterin reported in the literature and also nearly 4 orders of magnitude lower than possible concentrations of clusterin in human blood. Moreover, the assay requires a relatively low volume of sample (10 μL). Overall, the assay performance demonstrates the significant potential of SERS on Al foil as a low-cost/high-availability substrate for sensing and biosensing, including detection of cancer biomarkers.

Human saliva is a heterogeneous bodily fluid with a complex composition, which contains antibodies, proteins, and viruses, making it applicable in clinical diagnosis. There are several advantages of the analysis of saliva samples over other biofluids, including a non-invasive and simple collection procedure for extraoral detection. Biomarker or pathogen detection in saliva can be performed with various methods: mass spectrometry, PCR, ELISA, electrochemical, and optical methods such as fluorescence, SPR, and SERS. The early detection of cancer and other disease biomarkers, as well as infectious agents, can be crucial for effective treatment and minimization of mortality from those diseases. The following paper reviews extraoral detection techniques to identify the most sensitive methods for diagnosing early and asymptomatic patients. The LODs collected and tabulated from 149 analytical papers, alongside the sensitivity, specificity, and sometimes the area under the curve (AUC) tabulated from 118 clinical studies, have all become parameters for the comparative quantitative analysis. Based on the limited but substantial number of analytical studies on the detection of cortisol in saliva (29), the electrochemical platforms demonstrated the highest sensitivity, with a geometric mean LOD of 11 pM. Within these methods, voltametric ones showed the best performance with 6 pM geometric mean LOD. Electrochemical techniques are then followed by immunoassay- and mass spectrometry-based platforms, with corresponding geometric average LOD values of 39.1 and 171 pM, respectively. However, clinical outcomes are at least as meaningful as LOD values. In terms of clinical analysis, ELISA and direct-SERS outperformed other methods, achieving balanced accuracy of approximately 87% and AUC values of 0.96 for direct SERS and 0.86 for ELISA. MS and PCR followed closely, with balanced accuracies around 84%. While the direct SERS is not yet widespread in clinical applications, its potential can be forged if the standardization issue is addressed.

Quantum Dots (QDs) are small semiconductor nanoparticles (<10 nm) with strong, relatively stable, and tunable luminescent properties, which are increasingly applied in the sensing and detection of various analytes, including metal ions, biomarkers, explosives, proteins, RNA/DNA fragments, pesticides, drugs, and pollutants. In this review, we critically assess recent developments and advancements in luminescent QD-based sensors from an analytical perspective. We collected, tabulated, and analyzed relevant data reported in 124 peer-reviewed articles. The key analytical figures of merit, including the limit of detection (LOD), excitation and emission wavelengths, and size of the particles were extracted, tabulated, and analyzed with graphical representations. We calculated the geometric mean and median LODs from those tabulated publications. We found the following geometric mean LODs: 38 nM for QD-fluorescent-based sensors, 26 nM for QD-phosphorescent-based sensors, and an impressively low 0.109 pM for QD-chemiluminescent-based sensors, which demonstrate by far the best sensitivity in QD-based detection. Moreover, AI-based sensing methods, including the ATTBeadNet model, optimized principal component analysis(OPCA) model, and Support Vector Machine (SVM)-based system, were reviewed as they enhance the analytical performance of the detection. Despite these advances, there are still challenges that include improvements in recovery values, biocompatibility, stability, and overall performance. This review highlights trends to guide the future design of robust, high-performance, QD-based luminescent sensors.

This article compares the applications of traditional gold and silver-based SERS substrates and less conventional (Pd/Pt, Cu, Al, Si-based) SERS substrates, focusing on sensing, biosensing, and clinical analysis. In recent decades plethora of new biosensing and clinical SERS applications have fueled the search for more cost-effective, scalable, and stable substrates since traditional gold and silver-based substrates are quite expensive, prone to corrosion, contamination and non-specific binding, particularly by S-containing compounds. Following that, we briefly described our experimental experience with Si and Al-based SERS substrates and systematically analyzed the literature on SERS on substrate materials such as Pd/Pt, Cu, Al, and Si. We tabulated and discussed figures of merit such as enhancement factor (EF) and limit of detection (LOD) from analytical applications of these substrates. The results of the comparison showed that Pd/Pt substrates are not practical due to their high cost; Cu-based substrates are less stable and produce lower signal enhancement. Si and Al-based substrates showed promising results, particularly in combination with gold and silver nanostructures since they could produce comparable EFs and LODs as conventional substrates. In addition, their stability and relatively low cost make them viable alternatives for gold and silver-based substrates. Finally, this review highlighted and compared the clinical performance of non-traditional SERS substrates and traditional gold and silver SERS substrates. We discovered that if we take the average sensitivity, specificity, and accuracy of clinical SERS assays reported in the literature, those parameters, particularly accuracy (93–94%), are similar for SERS bioassays on AgNP@Al, Si-based, Au-based, and Ag-based substrates. We hope that this review will encourage research into SERS biosensing on aluminum, silicon, and some other substrates. These Al and Si based substrates may respond efficiently to the major challenges to the SERS practical application. For instance, they may be not only less expensive, e.g., Al foil, but also in some cases more selective and sometimes more reproducible, when compared to gold-only or silver-only based SERS substrates. Overall, it may result in a greater diversity of applicable SERS substrates, allowing for better optimization and selection of the SERS substrate for a specific sensing/biosensing or clinical application.

Gliomas are intracranial tumors characterized by limited diagnostics and treatment approaches. Blood-circulating miRNAs represent a regulatory class of molecules that change their expression under pathological conditions and can relatively easily be detected. The present study evaluates the diagnostic potential of blood-circulating miRNAs in glioma. All grades of gliomas are included in the analysis. The articles were retrieved from the PubMed, Web of Science and Scopus databases up to October 2025. The studies were considered to be eligible if they used glioma patients and healthy controls and compared their miRNA levels, indicating sensitivity and specificity values. Risk of bias was assessed using the QUADAS-2 tool. The collected data was pooled by the STATA 19.0 MP bivariate random effects model and indicated heterogeneity using the I2 statistic value. To identify possible reasons for heterogeneity, we utilized subgroup analysis and meta-regression. Publication bias was assessed with Deeks’ funnel plot, and the test diagnostic potential was evaluated with Fagan’s nomogram. We analyzed 31 original reports covering 2299 glioma patients and 1719 healthy controls. A meta-analysis on 59 data points extracted from the analyzed papers was conducted. The combined pooled sensitivity was found to be equal to 0.83 (95%CI: 0.80–0.86), the specificity 0.88 (95%CI: 0.85–0.90), the positive likelihood ratio 6.7 (95%CI: 5.4–8.5), the negative likelihood ratio 0.19 (95%CI: 0.16–0.23), and the diagnostic odds ratio 35 (95%CI: 25–50). An SROC analysis revealed an AUC equal to 0.92 (95%CI: 0.90–0.94). The reported diagnostic parameters imply that blood-circulating miRNAs hold the potential to be developed into diagnostic biomarkers for glioma identification. However, the high heterogeneity in the analyzed studies suggests that the results should be considered as exploratory only.

Excessive protein excretion in human urine is an early and sensitive marker of diabetic nephropathy and primary and secondary renal disease. Kidney problems, particularly chronic kidney disease, remain among the few growing causes of mortality in the world. Therefore, it is important to develop an efficient, expressive, and low-cost method for protein determination. Surface enhanced Raman spectroscopy (SERS) methods are potential candidates to achieve these criteria. In this paper, a SERS method was developed to distinguish patients with proteinuria from the healthy group. Commercial gold nanoparticles (AuNPs) with diameters of 60 nm and 100 nm, and silver nanoparticles (AgNPs) with a diameter of 100 nm were tested on the surface of four different substrates including silver and gold films, silicon, and aluminum tape. SERS spectra were acquired from 111 unique human urine samples prepared and measured for each of the seven different nanoparticle plus substrate combinations. Data analysis by the PCA-LDA algorithm and the ROC curves gave results for the diagnostic figures of merits. The best sensitivity, specificity, accuracy, and AUC were 0.91, 0.84, 0.88, and 0.94 for the set with 100 nm Au NPs on the silver substrate, respectively. Among the three metal substrates, the substrate with AuNPs and Al tape performed slightly worse than the other three substrates, and 100 nm gold nanoparticles on average produced better results than 60 nm gold nanoparticles. The 60 nm diameter AuNPs and silicon, which is about one order of magnitude more cost-effective than AuNPs and gold film, showed a relative performance close to the performance of 60 nm AuNPs and Au film (average AUC 0.88 (Si) vs. 0.89 (Au)). This is likely the first reported application of unmodified silicon in SERS substrates applied for direct detection of proteins in any biofluid, particularly in urine. These results position silicon and AuNPs@Si in particular as a perspective SERS substrate for direct urine analysis, including clinical diagnostics of proteinuria.

Chronic kidney disease is a global public health concern, representing a critical global public health challenge with increasing morbidity and mortality rates. The disease is a long-term condition characterized by the progressive loss of renal function. Early detection of declining kidney health and timely intervention are crucial to slow disease progression and improve prognosis, mitigating complications, including cardiovascular events. Current diagnostic standards are unable to detect early stages of kidney disease, reflecting early signs of glomerular and tubular damage. This creates an urgent need to identify reliable biomarkers for early detection, prognosis and therapeutic monitoring of kidney diseases. Novel biomarkers, including urinary microRNA, exosomal components, proteomic signatures and integrated multi-omics profiles, facilitated by up-to-date technologies offer strong promise for enhancing early diagnosis, risk assessment and monitoring of the disease. We focus on the fundamental biological significance and clinical application of these markers, discussing a critical evaluation of novel methodologies and clinical evidence supporting their potential for earlier and more precise diagnosis. This review summarizes innovative urinary biomarkers and advanced analytical technologies that can provide a more comprehensive and accurate assessment of the kidney status towards early diagnosis, better prognosis and better quality of life for patients with chronic kidney disease.

Cancer is the disease found to be the reason for the largest portion of deaths in the world annually and these mortality values are expected to increase in the future. Early detection of cancer biomarkers may help save millions of lives, particularly by implementing non-invasive and economical detection methods. In this review, we tabulated and quantitatively compared the data collected in 173 rows from 124 publications, which describe the clinical application of various methods in detection of cancer biomarkers. Those methods include mass spectrometry (MS), immunoassays (IAs), enzyme-linked immunosorbent assay (ELISA), polymerase chain reaction (PCR), surface-enhanced Raman spectroscopy (SERS), and Fourier-transform infrared spectroscopy (FTIR). We found that direct methods may have an advantage over indirect methods. Direct SERS reported in clinical applications can also achieve a higher area under the curve, higher sensitivity, and specificity than those parameters for ELISA, PCR, MS, and FTIR applications. Based on the average area under the curve (AUC) values reported in the last 6-7 years for each method, the performance of the analytical methods for the clinical cancer detection increases from IAs (0.76), ELISA (0.83), MS (0.87), and PCR (0.89) to FTIR (0.95) and SERS (0.97).

Proteinuria poses a substantial risk for the progression of chronic kidney disease (CKD) and its related complications. Kidneys excrete hundreds of individual proteins, some with a potential impact on CKD progression or as a marker of the disease. However, the available data on specific urinary proteins and their relationship with CKD severity remain limited. Therefore, we aimed to investigate the urinary proteome and its association with kidney function in CKD patients and healthy controls. The proteomic analysis of urine samples showed CKD stage-specific differences in the number of detected proteins and the exponentially modified protein abundance index for total protein (p = 0.007). Notably, specific urinary proteins such as B2MG, FETUA, VTDB, and AMBP exhibited robust negative associations with kidney function in CKD patients compared to controls. Also, A1AG2, CD44, CD59, CERU, KNG1, LV39, OSTP, RNAS1, SH3L3, and UROM proteins showed positive associations with kidney function in the entire cohort, while LV39, A1BG, and CERU consistently displayed positive associations in patients compared to controls. This study suggests that specific urinary proteins, which were found to be negatively or positively associated with the kidney function of CKD patients, can serve as markers of dysfunctional or functional kidneys, respectively.

Surface enhanced fluorescence (SEF) is observed with very high contrast (100–200) from single E. coli bacteria cells labeled with Carbon nanodots (CDs), on aluminum foil and aluminum film. Likely, it is the first application of organic CDs in SEF. SEF with 633 nm excitation delivered a much higher contrast than SEF with 532 nm excitation. Contrast is the ratio of the fluorescent intensities of labeled CDs to unlabeled (control) cells. High contrast with CDs is also observed on the gold film, silicon, and glass. Enhancement factor (EF) is the ratio of the signal on the metal substrate to the signal on the glass. Single E. coli cells, labeled with commercial graphene quantum dots (GCDs), demonstrated higher EFs (44 on gold, 35 on Al film), but at least one order of magnitude lower contrast (7–10 on aluminum and gold) than cells labeled with organic CDs. Therefore, organic CDs can be a good choice for cell imaging/labeling, capable of achieving a signal to noise (standard deviation of the control) as high as 700 on Al film. Overall, aluminum foil and film are highlighted as inexpensive but efficient substrates for Metal Enhanced Fluorescence, particularly MEF of bacterial cells stained with CDs.