Label-free Surface Enhanced Raman Scattering (SERS) on Centrifugal Silver Plasmonic Paper (CSPP): A Novel Methodology for Unprocessed Biofluids Sampling and Analysis

Abstract

Label-free SERS is a powerful bio-analytical technique in which molecular fingerprinting is combined with localized surface plasmons (LSPs) on metal surfaces to achieve high sensitivity. Silver and gold colloids are among the most common nanostructured substrates used in SERS, but since protein-rich samples such as serum or plasma can hinder the SERS effect due to protein–substrate interactions, they often require a deproteinization step. Moreover, SERS methods based on metal colloids often suffer from a poor reproducibility. Here, we propose a paper-based SERS sampling method in which unprocessed human serum samples are first soaked on paper strips (0.4 × 2 cm2), and then mixed with colloidal silver nanoparticles by centrifugation to obtain a Centrifugal Silver Plasmonic Paper (CSPP). The CSPP methodology has the potential to become a promising tool in bioanalytical SERS applications: it uses common colloidal substrates but without the need for sample deproteinization, while having a good reproducibility both in terms of overall spectral shape (r > 0.96) and absolute intensity (RSD < 10%). Moreover, this methodology allows SERS analysis more than one month after serum collection on the paper strip, facilitating storage and handling of clinical samples (including shipping from clinical sites to labs).

Label-Free SERS for Rapid Differentiation of SARS-CoV-2-Induced Serum Metabolic Profiles in Non-Hospitalized Adults

“…According to the CV loadings ( Figure S5a ), the major explanatory SERS vibrational modes attributed to the separations observed on CVA scores ( Figure 3 a) displayed intensity differences that corresponded to metabolites present in higher or lower relative levels in patient sera. The dominant peaks at 722, 1093, and 1331 cm –1 (ring modes in hypoxanthine/purines and analogues), 32 − 35 and bands at 1451 cm –1 (CH 2 deformations in lipids/proteins) and 1581 cm –1 (ring modes in amino acids), 36 , 37 as shown in Table S1 , were detected in higher quantities in the sera of COV– than COV+ patients group ( Figure 3 a), indicating metabolite downregulation in response to SARS-CoV-2 infection and recovery. On the other hand, the main characteristic bands detected at 630 cm –1 (uric acid) and 1250 cm –1 (amide III vibration), 34 , 36 were present in greater amounts in the sera of COV+ patients than COV– subjects ( Figure 2 a), suggesting upregulation of biomolecules in COV+ groups.…”

Surface-Enhanced Raman Analysis of Uric Acid and Hypoxanthine Analysis in Fractionated Bodily Fluids

“…For the liquid SERS analysis of purine metabolites from serum, proteins have to be removed since the relatively high concentration of serum proteins prevents the adsorption of metabolites [ 3 , 38 ]. Note, the use of centrifugal filtration to fractionate the biofluids is largely based on previous works [ 40 , 41 ]. Recently, Esposito and co-workers have proposed an alternative technique to spin gingival crevicular fluid on Periopaper ® filter paper to undergo SERs analysis [ 42 ].…”

“…The disease burden of hyperuricemia is increasing, especially in high-income countries and economically developing world with a Western lifestyle [ 2 ]. An in-crease of the serum uric acid and hypoxanthine concentration in patients with myocardial infarction indicates a significant metabolic involvement of xanthine oxidoreductase in this disease and therefore a possible role in the development of tissue damage in the postischaemic phase due to oxygen radicals generated by the oxidase activity of this enzyme [ 40 , 41 ]. Increased uric acid and hypoxanthine concentration is associated with cancer, HIV, gout, and hypertension.…”

Spectroscopic insights into peri-implant mucositis and peri-implantitis: unveiling peri-implant crevicular fluid profiles using surface enhanced Raman scattering

“…On the day of analysis, each strip was kept at room temperature, processed by adding a colloidal dispersion of citratedreduced silver nanoparticles (Ag-NPs), centrifuged (10 min, 4289g), and allowed to dry at room temperature for about 15 minutes, as described previously. 17,21 To facilitate handling, all dried strips were placed on a standard microscope slide (25 × 75 mm) that was fitted onto the portable microscope stage before measurement. SERS measurements were performed on 15 different days and over 3 different batches of Ag-NPs.…”

“…The rapid immobilization of Ag-NPs on the sampling paper surface induced by the centrifugation was accompanied with an almost complete reduction in interference from large proteins, as previously reported. 17,21 Furthermore, the presence of residual spectral contributions from vibrational bands associated with aminoacidic residues (927 cm −1 , ν(C-C), and 1005 cm −1 , Phe ring breathing) is not surprising given the high abundance of small proteins, especially pro-inflammatory cytokines, within the PICF, contributing to various physiological and pathological processes. 39 Despite the similarities, subtle differences reflecting selected small alterations in the overall biochemical composition of the PICF associated with the two considered pathological conditions can also be observed (Fig.…”