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Inside living organisms, proteins are self-assembled into diverse 3D structures optimized for specific functions. This structure-function relationship can be exploited to synthesize functional materials through biotemplating and depositing functional materials onto protein structures. However, conventional biotemplating faces limitations due to the predominantly intracellular existence of proteins and associated challenges in achieving tunability while preserving functionality. In this study, Conversion to Advanced Materials via labeled Biostructures (CamBio), an integrated biotemplating platform that involves labeling target protein structures with antibodies followed by the growth of functional materials, ensuring outstanding nanostructure tunability is proposed. Protein-derived plasmonic nanostructures created by CamBio can serve as precise quantitative tools for assessing target species is demonstrated. The assessment is achieved through highly tunable and efficient surface-enhanced Raman spectroscopy (SERS). CamBio enables the formation of dense nanogap hot spots among metal nanoparticles, templated by diverse fibrous proteins comprising densely repeated monomers. Furthermore, iterative antibody labeling strategies to adjust the antibody density surrounding targets, amplifying the number of nanogaps and consequently improving SERS performance are employed. Finally, cell-patterned substrates and whole meat sections as SERS substrates, confirming their easily accessible, cost-effective, scalable preparation capabilities and dimensional tunability are incorporated., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

The agricultural sector plays a pivotal role in driving the economy of many developing countries. Any dent in this economical structure may have a severe impact on a country's population. With rising climate change and increasing pollution, the agricultural sector is experiencing significant damage. Over time this cumulative damage will affect the integrity of food crops and create food security issues around the world. Therefore, an early warning system is needed to detect possible stress on food crops. Here we present a review of the recent developments in nanomaterial-based Surface Enhanced Raman Spectroscopy (SERS) substrates which could be utilized to monitor agricultural crop responses to natural and anthropogenic stress. Initially, our review delves into diverse and cost-effective strategies for fabricating SERS substrates, emphasizing their intelligent utilization across various agricultural scenarios. In the second phase of our review, we spotlight the specific application of SERS in addressing critical food security issues. By detecting nutrients, hormones, and effector molecules in plants, SERS provides valuable insights into plant health. Furthermore, our exploration extends to the detection of contaminants, chemicals, and foodborne pathogens within plants, showcasing the versatility of SERS in ensuring food safety. The cumulative knowledge derived from these discussions illustrates the transformative potential of SERS in bolstering the agricultural economy. By enhancing precision in nutrient management, monitoring plant health, and enabling rapid detection of harmful substances, SERS emerges as a pivotal tool in promoting sustainable and secure agricultural practices. Its integration into agricultural processes not only augments productivity but also establishes a robust defence against potential threats to crop yield and food quality. As SERS continues to evolve, its role in shaping the future of agriculture becomes increasingly pronounced, promising a paradigm shift in how we approach and address challenges in food production and safety., Competing Interests: Declaration of competing interest The authors have no relevant financial or non-financial interests to disclose., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Avian influenza viruses (AIV) are capable of infecting a considerable proportion of the world's population each year, leading to severe epidemics with high rates of morbidity and mortality. The methods now used to diagnose influenza virus A include the Western blot test (WB), hemagglutination inhibition (HI), and enzyme-linked immunosorbent assays (ELISAs). But because of their labor-intensiveness, lengthy procedures, need for costly equipment, and inexperienced staff, these approaches are considered inappropriate. The present review elucidates the recent advancements in the field of avian influenza detection through the utilization of nanomaterials-based immunosensors between 2014 and 2024. The classification of detection techniques has been taken into account to provide a comprehensive overview of the literature. The review encompasses a detailed illustration of the commonly employed detection mechanisms in immunosensors, namely, colorimetry, fluorescence assay, surface plasmon resonance (SPR), surface-enhanced Raman spectroscopy (SERS), electrochemical detection, quartz crystal microbalance (QCM) piezoelectric, and field-effect transistor (FET). Furthermore, the challenges and future prospects for the immunosensors have been deliberated upon. The present review aims to enhance the understanding of immunosensors-based sensing platforms for virus detection and to stimulate the development of novel immunosensors by providing novel ideas and inspirations. Therefore, the aim of this paper is to provide an updated information about biosensors, as a recent detection technique of influenza with its details regarding the various types of biosensors, which can be used for this review., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Long-stranded non-coding RNAs (lncRNA) have important roles in disease as transcriptional regulators, mRNA processing regulators and protein synthesis factors. However, traditional methods for detecting lncRNA are time-consuming and labor-intensive, and the functions of lncRNA are still being explored. Here, we present a surface enhanced Raman spectroscopy (SERS) based biosensor for the detection of lncRNA associated with liver cancer (LC) as well as in situ cellular imaging. Using the dual SERS probes, quantitative detection of lncRNA (DAPK1-215) can be achieved with an ultra-low detection limit of 952 aM by the target-triggered assembly of core-satellite nanostructures. And the reliability of this assay can be further improved with the R 2 value of 0.9923 by an internal standard probe that enables the signal dynamic calibration. Meanwhile, the high expression of DAPK1-215 mainly distributed in the cytoplasm was observed in LC cells compared with the normal ones using the SERS imaging method. Moreover, results of cellular function assays showed that DAPK1-215 promoted the migration and invasion of LC by significantly reducing the expression of the structural domain of death associated protein kinase. The development of this biosensor based on SERS can provide a sensitive and specific method for exploring the expression of lncRNA that would be a potential biomarker for the screening of LC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Alzheimer's disease (AD) is a chronic and progressive neurodegenerative disorder that affects millions of individuals worldwide. Researchers have conducted numerous studies to find accurate biomarkers for early AD diagnosis and develop more effective treatments. The main pathological hallmarks of AD are amyloid beta and Tau proteins. Other biomarkers, such as DNA, RNA, and proteins, can also be helpful in early AD diagnosis. To diagnose and treat AD promptly, it is essential to accurately measure the concentration of biomarkers in the cerebrospinal fluid or blood. However, due to the low concentrations of these biomarkers in the body, highly sensitive analytical techniques are required. To date, sensors have become increasingly important due to their high sensitivity, swift detection, and adaptable manipulation features. These qualities make them an excellent substitute for conventional instruments. Nanomaterials are commonly employed in sensors to amplify signals and improve sensitivity. This review paper summarized the integration of nanomaterials in optical sensor systems, including colorimetric, fluorescent, and surface-enhanced Raman scattering sensors for AD biomarkers detection.

This work describes our recent PCB-based plasmonic nanostructured platform patent (US 11,828,747B2) for the detection of biomarkers in breast cancer serum (BCS). A 50 nm thin gold film (TGF) was immersion-coated on PCB (i.e., PCB-TGF) and immobilized covalently with gold nanourchin (GNU) via a 1,6-Hexanedithiol (HDT) linkage to produce a plasmonic activated nanostructured thin film (PANTF) platform. A label-free SERS immunosensor was fabricated by conjugating the platform with monoclonal HER-II antibodies (mAb) in a directional orientation via adipic acid dihydrazide (ADH) to provide higher accessibility to overexpressed HER-II biomarkers (i.e., 2+ (early), 3+ (locally advanced), and positive (meta) in BCS. An enhancement factor (EF) of 0.3 × 10 5 was achieved for PANTF using Rhodamine (R6G), and the morphology was studied by scanning electron microscopy (SEM) and atomic force microscope (AFM). UV-vis spectroscopy showed the peaks at 222, 231, and 213 nm corresponding to ADH, mAb, and HER-II biomarkers, respectively. The functionalization and conjugation were investigated by Fourier Transform Near Infrared (FT-NIR) where the most dominant overlapped spectra of 2+, 3+, and Pos correspond to OH-combination of carbohydrate, RNH 2 1st overtone, and aromatic CH 1st overtone of mAb, respectively. SERS data were filtered using the filtfilt filter from scipy.signals , baseline corrected using the Improved Asymmetric Least Squares ( isals ) function from the pybaselines.Whittaker library. The results showed the common peaks at 867, 1312, 2894, 3026, and 3258 cm -1 corresponding to glycine, alanine ν (C-N-C) assigned to the symmetric C-N-C stretch mode; tryptophan and α helix; C-H antisymmetric and symmetric stretching; NH 3 + in amino acids; and N-H stretch primary amide, respectively, with the intensity of Pos > 3 + > 2 + . This trend is justifiable considering the stage of each sample. Principal Component Analysis (PCA) and Linear Discrimination Analysis (LDA) were employed for the statistical analysis of data.

Proactive management of foodborne illness requires routine surveillance of foodborne pathogens, which requires developing simple, rapid, and sensitive detection methods. Here, a strategy is presented that enables the detection of multiple foodborne bacteria using a 3D nanostructure swab and deep learning-based Raman signal classification. The nanostructure swab efficiently captures foodborne pathogens, and the portable Raman instrument directly collects the Raman signals of captured bacteria. a deep learning algorithm has been demonstrated, 1D convolutional neural network with binary labeling, achieves superior performance in classifying individual bacterial species. This methodology has been extended to mixed bacterial populations, maintaining accuracy close to 100%. In addition, the gradient-weighted class activation mapping method is used to provide an investigation of the Raman bands for foodborne pathogens. For practical application, blind tests are conducted on contaminated kitchen utensils and foods. The proposed technique is validated by the successful detection of bacterial species from the contaminated surfaces. The use of a 3D nanostructure swab, portable Raman device, and deep learning-based classification provides a powerful tool for rapid identification (≈5 min) of foodborne bacterial species. The detection strategy shows significant potential for reliable food safety monitoring, making a meaningful contribution to public health and the food industry., (© 2024 The Authors. Small published by Wiley‐VCH GmbH.)

Recent advances in the use of stable isotopes necessitate novel synthesis techniques for isotope separation and enrichment that are scalable and offer high throughput. Stable-isotope-enriched nanostructures can offer unique advantages as nanomedicines, safe tracers, and labels and are critical for applications in various industrial processes, metabolic research, and medicine. So far, there exists no method to synthesize miniature isotope-enriched materials at the nanoscale. In this study, an ultrafast Laser-induced isotope enrichment at nanoscale (LIIEN) is put forward to synthesize isotope-enriched nanostructures, eliminating the need for large equipment and expenses, thereby demonstrating a lab-scale isotope enrichment process. A significant isotope enrichment for Carbon nanostructures is observed. The isotope enrichment can be attributed to the redistribution of isotope ions in the plasma plume explained by the plasma centrifuge model. The LIIEN synthesized structures exhibit excellent Surface-Enhanced Raman Scattering (SERS) signal enhancement and reproducibility, making them potential candidates for SERS-based biomolecule sensing. This technique is an efficient method to fabricate nanosized isotope-enriched structures of characteristic properties by carefully tuning laser parameters at ambient conditions., (© 2024 Wiley‐VCH GmbH.)

Sensing and characterizing water-soluble polypeptides are essential in various biological applications. However, detecting polypeptides using Surface-Enhanced Raman Scattering (SERS) remains a challenge due to the dominance of aromatic amino acid residues and backbones in the signal, which hinders the detection of non-aromatic amino acid residues. Herein, intra-nanoparticle plasmonic nanogap were designed by etching the Ag shell in Au@AgNPs (i.e., obtaining AuAg cores) with chlorauric acid under mild conditions, at the same time forming the outermost Au shell and the void between the AuAg cores and the Au shell (AuAg@void@Au). By varying the Ag to added chloroauric acid molar ratios, we pioneered a simple, controllable, and general synthetic strategy to form interlayer-free nanoparticles with tunable Au shell thickness, achieving precise regulation of electric field enhancement within the intra-nanogap. As validation, two polypeptide molecules, bacitracin and insulin B, were successfully synchronously encapsulated and spatial-confined in the intra-nanogap for sensing. Compared with concentrated 50 nm AuNPs and Au@AgNPs as SERS substrates, our simultaneous detection method improved the sensitivity of the assay while benefiting to obtain more comprehensive characteristic peaks of polypeptides. The synthetic strategy of confining analytes while fabricating plasmonic nanostructures enables the diffusion of target molecules into the nanogap in a highly specific and sensitive manner, providing the majority of the functionality required to achieve peptide detection or sequencing without the hassle of labeling., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The COVID-19 pandemic underlines the need for effective strategies for controlling virus spread and ensuring sensitive detection of SARS-CoV-2. This review presents the potential of nanomaterial-enabled optical biosensors for rapid and low-cost detection of SARS-CoV-2 biomarkers, demonstrating a comprehensive analysis including colorimetric, fluorescence, surface-enhanced Raman scattering, and surface plasmon resonance detection methods. Nanomaterials including metal-based nanomaterials, metal-organic frame-based nanoparticles, nanorods, nanoporous materials, nanoshell materials, and magnetic nanoparticles employed in the production of optical biosensors are presented in detail. This review also discusses the detection principles, fabrication methods, nanomaterial synthesis, and their applications for the detection of SARS-CoV-2 in four categories: antibody-based, antigen-based, nucleic acid-based, and aptamer-based biosensors. This critical review includes reports published in the literature between the years 2021 and 2024. In addition, the review offers critical insights into optical nanobiosensors for the diagnosis of COVID-19. The integration of artificial intelligence and machine learning technologies with optical nanomaterial-enabled biosensors is proposed to improve the efficiency of optical diagnostic systems for future pandemic scenarios., (© 2024. The Author(s).)

The implementation of low-cost and rapid technologies for the on-site detection of mycotoxin-contaminated crops is a promising solution to address the growing concerns of the agri-food industry. Recently, there have been significant developments in surface-enhanced Raman spectroscopy (SERS) for the direct detection of mycotoxins in food and feed. This review provides an overview of the most recent advancements in the utilization of SERS through the successful fabrication of novel nanostructured materials. Various bottom-up and top-down approaches have demonstrated their potential in improving sensitivity, while many applications exploit the immobilization of recognition elements and molecular imprinted polymers (MIPs) to enhance specificity and reproducibility in complex matrices. Therefore, the design and fabrication of nanomaterials is of utmost importance and are presented herein. This paper uncovers that limited studies establish detection limits or conduct validation using naturally contaminated samples. One decade on, SERS is still lacking significant progress and there is a disconnect between the technology, the European regulatory limits, and the intended end-user. Ongoing challenges and potential solutions are discussed including nanofabrication, molecular binders, and data analytics. Recommendations to assay design, portability, and substrate stability are made to help improve the potential and feasibility of SERS for future on-site agri-food applications., (© 2024 The Authors. Advanced Materials published by Wiley‐VCH GmbH.)

Extravasation, as one of the key steps in cancer metastasis, refers to the process where tumor cells escape the bloodstream by crossing the vascular endothelium and invade the targeted tissue, which accounts for the low five-year survival rate of cancer patients. Understanding the mechanism of cancer metastasis and inhibiting extravasation are crucial to improve patient prognosis. Here, a 3D organotypic microfluidic chip combined with SERS-based protein imprinted nanomaterials (SPINs) was proposed to study the extravasation process in vitro. The chip consists of a collagen gel channel and a vascular channel where human vein endothelial cells (HUVECs) and breast cancer cells are injected sequentially to induce extravasation. By comparing two subtypes of breast cancer cells (MCF-7 and MDA-MB-231), we successfully observed the difference in extravasation capabilities between two kinds of cells through fluorescence imaging. Meanwhile, thanks to the high specificity of molecular imprinting technology and the high sensitivity of surface enhanced Raman scattering (SERS), SPINs were utilized to analyze the concentration of several cancer secretions (interleukin-6 and interleukin-8) in complex biological fluid in real-time. Further, our model showed that downregulation of secretions by therapeutic drugs can inhibit the extravasation of breast cancers. This microfluidic model may pave the way for the fundamental research of the cancer metastasis and evaluating the therapeutic efficacy of potential drugs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Micro- and nanopatterning of materials, one of the cornerstones of emerging technologies, has transformed research capabilities in lab-on-a-chip diagnostics. Herein, a micro- and nanolithographic method is developed, enabling structuring materials at the submicron scale, which can, in turn, accelerate the development of miniaturized platform technologies and biomedical sensors. Underpinning it is the advanced electro-hydrodynamic surface molecular lithography, via inducing interfacial instabilities produces micro- and nanostructured substrates, uniquely integrated with synthetic surface recognition. This approach enables the manufacture of design patterns with tuneable feature sizes, which are functionalized via synthetic nanochemistry for highly sensitive, selective, rapid molecular sensing. The development of a high-precision piezoelectric lithographic rig enables reproducible substrate fabrication with optimum signal enhancement optimized for functionalization with capture molecules on each micro- and nanostructured array. This facilitates spatial separation, which during the spectroscopic sensing, enables multiplexed measurement of target molecules, establishing the detection at minute concentrations. Subsequently, this nano-plasmonic lab-on-a-chip combined with the unconventional computational classification algorithm and surface enhanced Raman spectroscopy, aimed to address the challenges associated with timely point-of-care detection of disease-indicative biomarkers, is utilized in validation assay for multiplex detection of traumatic brain injury indicative glycan biomarkers, demonstrating straightforward and cost-effective micro- and nanoplatforms for accurate detection., (© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

Optical imaging and spectroscopic modalities are of considerable current interest for in vivo cancer detection and image-guided surgery, but the turbid or scattering nature of biomedical tissues has severely limited their abilities to detect buried or occluded tumor lesions. Here we report the development of a dual-modality plasmonic nanostructure based on colloidal gold nanostars (AuNSs) for simultaneous surface-enhanced Raman scattering (SERS) and photoacoustic (PA) detection of tumor phantoms embedded (hidden) in ex vivo animal tissues. By using red blood cell membranes as a naturally derived biomimetic coating, we show that this class of dual-modality contrast agents can provide both Raman spectroscopic and PA signals for the detection and differentiation of hidden solid tumors with greatly improved depths of tissue penetration. Compared to previous polymer-coated AuNSs, the biomimetic coatings are also able to minimize protein adsorption and cellular uptake when exposed to human plasma without compromising their SERS or PA signals. We further show that tumor-targeting peptides (such as cyclic RGD) can be noncovalently inserted for targeting the ανβ 3 -integrin receptors expressed on metastatic cancer cells and tracked via both SERS and PA imaging (PAI). Finally, we demonstrate image-guided resections of tumor-mimicking phantoms comprising metastatic tumor cells buried under layers of skin and fat tissues (6 mm in thickness). Specifically, PAI was used to determine the precise tumor location, while SERS spectroscopic signals were used for tumor identification and differentiation. This work opens the possibility of using these biomimetic dual-modality nanoparticles with superior signal and biological stability for intraoperative cancer detection and resection.

A label-free detection method for noninvasive biofluids enables rapid on-site disease screening and early-stage cancer diagnosis by analyzing metabolic alterations. Herein, we develop three-dimensional plasmonic hexaplex nanostructures coated on a paper substrate (3D-PHP). This flexible and highly absorptive 3D-PHP sensor is integrated with commercial saliva collection tube to create an efficient on-site sensing platform for lung cancer screening via surface-enhanced Raman scattering (SERS) measurement of human saliva. The multispike hexaplex-shaped gold nanostructure enhances contact with saliva viscosity, enabling effective sampling and SERS enhancement. Through testing patient salivary samples, the 3D-PHP sensor demonstrates successful lung cancer detection and diagnosis. A logistic regression-based machine learning model successfully classifies benign and malignant patients, exhibiting high clinical sensitivity and specificity. Additionally, important Raman peak positions related to different lung cancer stages are investigated, suggesting insights for early-stage cancer diagnosis. Integrating 3D-PHP senor with the conventional saliva collection tube platform is expected to offer promising practicality for rapid on-site disease screening and diagnosis, and significant advancements in cancer detection and patient care., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

The organization of geometrically diverse metal nanoparticles into a core/satellite structure at a large scale is a promising strategy for improve SERS performance due to hot spots localized enrichment and signal increase. However, due to the lack of extensional frames and strong electrostatic repulsion between plasma NPs, the fabrication of such 3D architectures with a high-density periodic hotspot in the focus volume has proven exceedingly difficult. Herein, we demonstrate a facile large-scale assembly of geometrically diverse metal nanoparticles strategy for constructing spatially extended 3D plasmonic nanostructures resembling "signal towers" based on RCA-mediated periodic organization of gold nanospheres (GNS) surrounding gold nanorods (GNRs). Using cancer cell T4 PNK as a model, a padlock probe with 5'- hydroxyl (P-circle) was designed as the T4 PNK substrate. The center Au nanorod was coated with P 1 and served as a "pedestal" to allow substantial loading of P-circle after target phosphorylation to initiate the rolling ring amplification reaction (RCA). The resultant DNA nanowire serves as an "antenna" to successively lock numerous Raman reporter P 2 (Cy3-P 2 -SH) through base pairing at regular intervals. Finally, the 3D plasma DNA nanostructures that resemble "signal towers" could be obtained by placing a large number of GNS with a strong affinity for Au-S. The proposed 3D SERS sensor exhibited a sensitivity of LOD as low as 0.274 mU/mL, which was attributed to a substantial electromagnetic field enhancement at the inter-nanoparticle gaps between the adjacent pedestal and antenna. Moreover, by exploiting the synergistic effect of the periodically extended DNA scaffold generated by RCA amplification and the co-assembly of thiol ligand, the loaded GNS can be extended to three-dimensional space, forming a high-density periodic hotspot in the focal volume, thereby ensuring high enhancement and high reproducibility of Raman signals. In addition, this method can be used to quantify T4 PNK in HeLa cells, demonstrating its applicability in diagnosing and estimating PNK-related diseases in complex fluids., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

In this work, nanostructures comprising silver nanoparticles supported on a wrinkled chitosan matrix (Ag@Ch) were successfully synthesized by a simple aging process at room temperature for four days through self-assembly. Chitosan, a natural polysaccharide was used as a support as well as a reducing agent for the formation of Ag nanostructures and the creation of hotspots for SERS activity. The fabricated Ag@Ch nanostructures were characterized by several spectroscopic techniques and were used as a surface-enhanced Raman scattering (SERS) substrate. The effect of wet, dry, and liquid samples on the SERS enhancement has been studied and was found to be effective for sensing Methylene blue, Crystal Violet, and p-Nitrophenol with detection limits of 3.8, 8.1, and 8.2 ppb respectively. The SERS enhancement of the Ag@Ch was attributed to the combination of both electromagnetic (EM) and chemical effects (CE). Density functional theory (DFT) calculations were used to explain the observed surface enhancement. Good agreement was observed between the experimental and simulated spectra., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

We developed petal-like plasmonic nanoparticle (PLNP) clusters-based colloidal SERS method for enrofloxacin (EnFX) detection. PLNPs were synthesized by the regulation of single-stranded DNA composed of homo-cytosine deoxynucleotides (hC) catalyzed by terminal deoxynucleotidyl transferase. SERS hot spots were created via the agglomeration process of PLNPs by adding an inorganic salt potassium iodide solution, in which EnFX molecules were attached to the negatively charged PLNPs surface by electrostatic interactions. This approach enabled direct in situ detection of antibiotic residues, achieving a limit of detection (LOD) of 1.15 μg/kg for EnFX. The spiked recoveries of the SERS method were approximately 92.7% to 107.2% and the RSDs ranged from 1.05% to 7.8%, indicating that the method can be applied to actual sample detection. This colloidal SERS measurement platform would be very promising in various applications, especially in real-time and on-site food safety screening owing to its rapidness, simplicity, and sensitivity., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The detection and identification of clinical biomarkers with related sensitivity have become a source of considerable concern for biomedical analysis. There have been increasing efforts toward the development of single-molecule analytical platforms to overcome this concern. The latest developments in plasmonic nanomaterials include fascinating advances in energy, catalyst chemistry, optics, biotechnology, and medicine. Nanomaterials can be successfully applied to biomolecule and drug detection in plasmonic nanosensors for pharmaceutical and biomedical analysis. Plasmonic-based sensing technology exhibits high sensitivity and selectivity depending on surface plasmon resonance (SPR) or localized surface plasmon resonance (LSPR) phenomena. In this critical paper, we offer an overview of the methodology of the SPR, LSPR, surface-enhanced Raman scattering (SERS), surface-enhanced infrared absorption (SEIRA), surface-enhanced fluorescence (SEF), and plasmonic nanoplatforms advanced for pharmaceutical and biomedical applications. First of all, we present here a brief discussion of the above trends. We have devoted the last section to the explanation of SPR, LSPR, SERS, SEIRA, and SEF platforms, which have found a wide range of applications, and reviewed recent advances for biomedical and pharmaceutical analysis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Surface-enhanced Raman spectroscopy (SERS) has been extensively used in biomedical and food safety detection due to its advantages of label-free, in situ and fingerprint spectrum. However, it is challenging to develop an excellent SERS substrate that possesses all three of these characteristics including sensitivity, repeatability and stability., Results: In this work, a specific sodium alginate hydrogel flexible SERS substrate encapsulated gold-silver core-shell nanoparticles (Au@Ag NPs) was developed to address the aforementioned issue. The Au@Ag NPs with SERS "hot spot" structure were evenly dispersed in the hydrogel, which achieved the direct and high efficiency detection of the pesticide residues from complex sample matrix. Taking thiram as objective, this SERS substrates exhibit high sensitivity (detection limit of approximately 1 × 10 -10  mol/L), excellent stability (maintain above 78.35 % of SERS activity after 7 weeks) and outstanding repeatability (RSD in one substrate as low as 3.56 %). Furthermore, the flexible hydrogel SERS substrates can be used to analyze a variety of small molecules in real samples (juices, vegetables and fruits), without the need for a laborious pretreatment process., Significance: In light of the aforementioned benefits, the functional flexible hydrogel SERS substrates present a reliable platform for the accurate and on-site measurement of chemical contaminants from complex samples., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Surface-enhanced Raman scattering (SERS) is of growing interest for a wide range of applications, especially for biomedical analysis, thanks to its sensitivity, specificity, and multiplexing capabilities. A crucial role for successful applications of SERS is played by the development of reproducible, efficient, and facile procedures for the fabrication of metal nanostructures (SERS substrates). Even more challenging is to extend the fabrication techniques of plasmonic nano-textures to atomic force microscope (AFM) probes to carry out tip-enhanced Raman spectroscopy (TERS) experiments, in which spatial resolution below the diffraction limit is added to the peculiarities of SERS. In this short review, we describe recent studies performed by our group during the last ten years in which novel nanofabrication techniques have been successfully applied to SERS and TERS experiments for studying bio-systems and molecular species of environmental interest.

The abuse of benzodiazepines is a serious health hazard that can cause damage to the central nervous system.Trace monitoring of benzodiazepines in serum can effectively prevent the damage caused by these drugs. Therefore, in this study, a Fe 3 O 4 @PDA@Au core-shell satellite nanomaterial SERS(Surface-Enhanced Raman Scattering) probe that integrates magnetic separation techniques and a multi-hotspot structure was synthetized by in situ growth of gold nanoparticles on the surface of PDA(Polymerized dopamine)-coated Fe 3 O 4 . The size and gap of Au nanoparticles on the surface of the SERS probe can be modulated by regulating the amount of HAuCl 4 to create 3D multi-hotspot structures. The good dispersion and superparamagnetic properties of this SERS probe enable it to fully contact and load the target molecules in the serum, and the applied magnetic field facilitates separation and enrichment.This process increases the molecular density and number of SERS hotspots, thereby enhancing detection sensitivity. Based on the above considerations, this SERS probe can detect traces of eszopiclone and diazepam in serum at concentrations as low as 1 μg/ml with good linearity, offering promising applications in clinical monitoring of drug concentrations in blood., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Surface-enhanced Raman scattering (SERS) is an ultra-sensitive vibration spectroscopy technology, with the advantages of multi-index and non-destructive quantitative detection, has attracted much attention in the joint detection of biomarkers. A novel SERS biosensor with multisite capture and interference-free quantification was designed for the joint detection of the sepsis biomarker interleukin-6 (IL-6) and procalcitonin (PCT). This biosensor had two interference-free core-shell SERS probes with highly efficient electromagnetic enhancement and a multisite functionalized magnetic nanomaterial with high adsorption capacity. They formed sandwich structure with the targets through boronic affinity and immunoreaction, and the multi-target quantitative analysis of biomarkers in serum was performed using a portable Raman spectrometer in the Raman-silent region. The SERS biosensor was exhibited highly sensitive with detection limits of 0.584 and 2.99 pg/mL for IL-6 and PCT, respectively. In addition, it exhibited excellent selectivity and specificity even with the interference of other proteins. As this SERS method showed excellent performance in the detection of sepsis, it has great potential for multi-index detection in clinical diagnosis of major diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Flexible biochips that enable sensitive detection and simultaneous quantification of biomarkers are of great importance in the field of point-of-care testing. Recently, surface-enhanced Raman scattering (SERS)-based flexible biochips have attracted a great deal of research attention for disease detection due to their rapid, sensitive, and noninvasive sensing abilities. Phenomenal progress in the synthesis of structure-controlled plasmonic nanomaterials has made SERS a powerful sensing platform for disease diagnosis and trace detection. Here, we demonstrate flexible plasmonic biochips for the SERS-based detection of uric acid (UA). Flexible strips exhibited excellent sensing performance with a detection limit of around 10 μM of UA, which is lower than the average level of UA in tears. This rapid and sensitive detection method enables the noninvasive diagnosis of gouty arthritis.

Controllable self-assembly of the DNA-linked gold nanoparticle (AuNP) architecture for in vivo biomedical applications remains a key challenge. Here, we describe the use of the programmed DNA tetrahedral structure to control the assembly of three different types of AuNPs (∼20, 10, and 5 nm) by organizing them into defined positioning and arrangement. A DNA-assembled "core-satellite" architecture is built by DNA sequencing where satellite AuNPs (10 and 5 nm) surround a central core AuNP (20 nm). The density and arrangement of the AuNP satellites around the core AuNP were controlled by tuning the size and amount of the DNA tetrahedron functionalized on the core AuNPs, resulting in strong electromagnetic field enhancement derived from hybridized plasmonic coupling effects. By conjugating with the Raman molecule, strong surface-enhanced Raman scattering photoacoustic imaging signals could be generated, which were able to image microRNA-21 and tumor tissues in vivo . These results provided an efficient strategy to build precision plasmonic superstructures in plasmonic-based bioanalysis and imaging.

Purpose: A novel CYPA-targeted, SiO 2 encapsulated Au star@AgAu yolk-shell nanostructure (YSNS) was synthesized and used for ovarian cancer early diagnosis and therapy., Methods: Diverse spectroscopic and microscopic methods were utilized to investigate the pattern of the yolk-shell nanostructure. In addition, in vitro and in vivo experiments were carried out., Results: It can be found that the ratio of HAuCl 4 and AgNO 3 played a critical role in the constitution of the yolk-shell nanostructure. The as-prepared yolk-shell nanostructure showed excellent SERS performance, which could be utilized as SERS substrate for specific sensitivity analysis of ovarian cancer markers cyclophilin A (CYPA) with detectable limit of 7.76*10 -10 μg/mL. In addition, the as-prepared yolk-shell nanostructure possessed outstanding photothermal performance, which could be used as photothermal agent for ovarian cancer therapy. Experiments in vitro and in vivo proved that the as-prepared yolk-shell nanostructures are ideal candidate for early diagnosis and therapy for ovarian cancer in one platform., Conclusion: This work holds promise to offer a new method for the detection and therapy of ovarian cancer in the early stage., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 Lan et al.)

The technique of ultrafast laser ablation in liquids has evolved and matured over the past decade, with several impending applications in various fields such as sensing, catalysis, and medicine. The exceptional feature of this technique is the formation of nanoparticles (colloids) and nanostructures (solids) in a single experiment with ultrashort laser pulses. We have been working on this technique for the past few years, investigating its potential using the surface-enhanced Raman scattering (SERS) technique in hazardous materials sensing applications. Ultrafast laser-ablated substrates (solids and colloids) could detect several analyte molecules at the trace levels/mixture form, including dyes, explosives, pesticides, and biomolecules. Here, we present some of the results achieved using the targets of Ag, Au, Ag-Au, and Si. We have optimized the nanostructures (NSs) and nanoparticles (NPs) obtained (in liquids and air) using different pulse durations, wavelengths, energies, pulse shapes, and writing geometries. Thus, various NSs and NPs were tested for their efficiency in sensing numerous analyte molecules using a simple, portable Raman spectrometer. This methodology, once optimized, paves the way for on-field sensing applications. We discuss the protocols in (a) synthesizing the NPs/NSs via laser ablation, (b) characterization of NPs/NSs, and (c) their utilization in the SERS-based sensing studies.

Surface-enhanced Raman scattering (SERS) technology has attracted more and more attention in the biomedical field due to its ability to provide molecular fingerprint information of biological samples, as well as its potential in single-cell analysis. This work aims to establish a simple strategy for label-free SERS bioanalysis based on Au@carbon dot nanoprobes (Au@CDs). Here, polyphenol-derived CDs are utilized as the reductant to rapidly synthesize core-shell Au@CD nanostructures, which allows powerful SERS performance even when the concentration of methylene blue (MB) is as low as 10 -9 M, due to the cooperative Raman enhancement mechanism. For bioanalysis, Au@CDs can serve as a unique SERS nanosensor to identify the cellular components of biosamples (e.g., cancer cells and bacteria). The molecular fingerprints from different species can be further distinguished after combination with the principal component analysis. In addition, Au@CDs also enable label-free SERS imaging to analyze intracellular composition profiles. This strategy offers a feasible, label-free SERS bioanalysis, opening up a new prospect for nanodiagnosis.

Here, surface-enhanced Raman scattering (SERS) and tip-enhanced Raman scattering (TERS) were used to characterize the selective adsorption of N-substituted 4-[(NH-R)(phosphono)-S-methyl]phenylboronic acids on the surface of platinum nanoparticles (PtNPs) from an aqueous solution and from air. The nature of the interaction of the studied compounds with the PtNPs/H 2 O and PtNPs/air interfaces was discussed and compared. For this purpose, 4-[(N-anilino)(phosphono)-S-methyl]phenylboronic acid (1-PBA-PA) and its two analogs (2-PBA-PA and bis{1-PBA-PA}) as well as the PtNPs were synthesized in surfactant/ion-free solution via a synthetic route that allows control of the size and morphology of the NPs. The positively charged PtNPs with a size of ~12 nm were characterized by ultraviolet-visible spectroscopy (UV-Vis), dynamic light scattering (DLS), scanning electron microscopy (SEM), and X-ray powder diffraction (XRD)., (© 2023 Wiley Periodicals LLC.)

We report on efficient surface-enhanced Raman spectroscopy (SERS) supporting substrates, which are based on deoxyribonucleic acid (DNA)-assisted lithography (DALI) and a layered configuration of materials. In detail, we used nanoscopic DNA origami bowtie templates to form hybrid nanostructures consisting of aligned silver bowtie-shaped particles and apertures of similar shape in a silver film. We hypothesized that this particular geometry could facilitate a four-fold advantage in Raman enhancement compared to common particle-based SERS substrates, and further, we verified these hypotheses experimentally and by finite difference time domain simulations. In summary, our DALI-fabricated hybrid structures suppress the background emission, allow emission predominantly from the areas of high field enhancement, and support additional resonances associated with the nanoscopic apertures. Finally, these nanoapertures also enhance the fields associated with the resonances of the underlying bowtie particles. The versatility and parallel nature of our DNA origami-based nanofabrication scheme and all of the above-mentioned features of the hybrid structures therefore make our optically resonant substrates attractive for various SERS-based applications.

Surface-Enhanced Raman Scattering (SERS) technology, as a powerful tool to identify molecular species by collecting molecular spectral signals at the single-molecule level, has achieved substantial progresses in the fields of environmental science, medical diagnosis, food safety, and biological analysis. As deepening research is delved into SERS sensing, more and more high-performance or multifunctional SERS substrate materials emerge, which are expected to push Raman sensing into more application fields. Especially in the field of biological analysis, intrinsic and extrinsic SERS sensing schemes have been widely used and explored due to their fast, sensitive and reliable advantages. Herein, recent developments of SERS substrates and their applications in biomolecular detection (SARS-CoV-2 virus, tumor etc.), biological imaging and pesticide detection are summarized. The SERS concepts (including its basic theory and sensing mechanism) and the important strategies (extending from nanomaterials with tunable shapes and nanostructures to surface bio-functionalization by modifying affinity groups or specific biomolecules) for improving SERS biosensing performance are comprehensively discussed. For data analysis and identification, the applications of machine learning methods and software acquisition sources in SERS biosensing and diagnosing are discussed in detail. In conclusion, the challenges and perspectives of SERS biosensing in the future are presented., (© 2023. The Author(s).)

Surface-enhanced Raman scattering (SERS) with the advantages of high sensitivity, nondestructive analysis, and a unique fingerprint effect shows great potential in point-of-care testing (POCT). However, SERS faces challenges in rapidly constructing a substrate with high repeatability, homogeneity, and sensitivity, which are the key factors that restrict its practical applications. In this study, we propose a one-step chemical printing strategy for synthesizing a three-dimensional (3D) plasmon-coupled silver nanocoral (AgNC) substrate (only need about 5 min) without any pretreatments and complex instruments. The galvanic replacement between AgNO 3 and Cu sheets will provide both Ag 0 for the formation of silver nanostructures and Cu 2+ for the polymerization of fish sperm DNA (FSDNA). The protection of AgNCs is facilitated by the crosslinked FSDNA, which can improve the stability of the substrate and promote the control of its coral-like morphology. The obtained substrate displays excellent capacity of signal enhancement due to the 3D plasmon coupling both between nanocoral tentacles and between nanocorals and Cu sheets as well. Therefore, the AgNC substrates display high activity (enhancement factor = 1.96 × 10 8 ) and uniformity (RSD < 6%). Food colorants have been widely used in various foods to improve their color, but the inevitable toxicity of colorants seriously threatens food safety. Therefore, the proposed AgNC substrates were used to directly quantify three kinds of weak-affinity food colorant molecules including Brilliant Blue, Allura Red, and Sunset Yellow assisted by the capture by cysteamine hydrochloride (CA), showing the detection limits ( S / N = 3) of 0.053, 0.087, and 0.089 ppm, respectively. The SERS method has been further applied in the detection of the three kinds of food colorants in both complex food samples and urine with recoveries of 91-119%. The satisfactory detection results suggest that the facile preparation strategy of AgNC substrates will be widely used in SERS-based POCT to promote the development of food safety and on-site healthcare.

Scalp hairs are readily present at most crime scenes because an average person sheds around 100 hairs a day. Forensic experts analyze hair found at crime scenes to identify suspects involved in a crime. Many people color their hair on a regular basis. Therefore, confirmatory analysis of hair colorants can be extremely useful in forensic investigation of hair evidence. However, most currently available methods for analysis of hair colorants are invasive, destructive, or not reliable. Surface enhanced Raman spectroscopy (SERS) is a minimally invasive, fast, and highly accurate technique that can be used to identify colorants present on hair. SERS is based on 106-108 enhancement of Raman scattering from molecules present in the close proximity to noble metal nanostructures. In this study, we investigate the extent to which SERS can be used to reveal coloration history of hair. We found that SERS enables nearly 100% identification of dyes of different color if those were applied on hair in the sequential order. The same accuracy was observed for colorants of different brand and type. Furthermore, SERS was capable of revealing the order in which two colorants were applied on hair. Finally, we demonstrated that SERS could be used to reveal hair coloration history if two randomly selected dyes of different color, brand and type were used to color the hair. These findings facilitate the need for forensic experts to account for hair that has been redyed and can be identified against a library of the same colorant combinations., (© 2023. The Author(s).)

Raman nanoparticle probes are a potent class of optical labels for the interrogation of pathological and physiological processes in cells, bioassays, and tissues. Herein, we review the recent advancements in fluorescent and Raman imaging using oligodeoxyribonucleotide (ODN)-based nanoparticles and nanostructures, which show promise as effective tools for live-cell analysis. These nanodevices can be used to investigate a vast number of biological processes occurring at various levels, starting from those involving organelles, cells, tissues, and whole living organisms. ODN-based fluorescent and Raman probes have contributed to the achievement of significant advancements in the comprehension of the role played by specific analytes in pathological processes and have inaugurated new possibilities for diagnosing health conditions. The technological implications that have emerged from the studies herein described could open new avenues for innovative diagnostics aimed at identifying socially relevant diseases like cancer through the utilization of intracellular markers and/or guide surgical procedures based on fluorescent or Raman imaging. Particularly complex probe structures have been developed within the past five years, creating a versatile toolbox for live-cell analysis, with each tool possessing its own strengths and limitations for specific studies. Analyzing the literature reports in the field, we predict that the development of ODN-based fluorescent and Raman probes will continue in the near future, disclosing novel ideas on their application in therapeutic and diagnostic strategies.

The SERS intensity of analytes is primarily influenced by the density and distribution of hotspots, which are often difficult to manipulate or regulate. In this study, cucurbit[8]uril (CB[8]), a kind of rigid macrocyclic molecule, was introduced to achieve ~ 1-nm nanogap between gold nanoparticles to increase the density of SERS hotspots. Three kinds of estrogens (estrone (E1), bisphenol A (BPA), and hexestrol (DES)) which are molecules with weak SERS signals were targeted in the hotspots by CB[8] to further improve the sensitivity and selectivity of SERS. It was demonstrated that CB[8] can link gold nanoparticles together through carbonyl groups. In addition, the host-guest interaction of CB[8] and estrogens was proved from the nuclear magnetic resonance hydrogen and infrared spectra. In the presence of CB[8], the SERS intensities of E1, BPA, and DES were increased to 19-fold, 74-fold, and 4-fold, respectively, and the LOD is 3.75 µM, 1.19 µM, and 8.26 µM, respectively. Furthermore, the proposed SERS method was applied to actual milk sample analysis with recoveries of E1 (85.0 ~ 112.8%), BPA (83.0 ~ 103.7%), and DES (62.6 ~ 132.0%). It is expected that the proposed signal enlarging strategy can be applied to  other analytes after further development., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Metal nanostructures with a tunable plasmonic gap are useful for photonics, surface-enhanced spectroscopy, biosensing, and bioimaging applications. The use of these structures as chemical and biological sensing/imaging probes typically requires an ultra-precise synthesis of the targeted nanostructure in a high yield, with Raman dye-labeling and complex assay components and procedures. Here, a plasmonic nanostructure with tunable dual nanogaps, Au dual-gap nanodumbbells (AuDGNs), is designed and synthesized via the anisotropic adsorption of polyethyleneimine on Au nanorods to facilitate tip-selective Au growths on nanorod tips for forming mushroom-shaped dumbbell-head structures at both tips and results in dual gaps (intra-head and inter-head gaps) within a single particle. AuDGNs are synthesized in a high yield (>90%) while controlling the inter-head gap size, and the average surface-enhanced Raman scattering (SERS) enhancement factor (EF) value is 7.5 × 10 8 with a very narrow EF distribution from 1.5 × 10 8 to 1.5 × 10 9 for >90% of analyzed particles. Importantly, AuDGNs enable label-free on-particle SERS detection assays through the diffusion of target molecules into the intraparticle gap for different DNA sequences with varying ATGC combinations in a highly specific and sensitive manner without a need for Raman dyes., (© 2023 Wiley-VCH GmbH.)

Plasmonic nanostructures have a desirable surface-enhanced Raman scattering (SERS) response related to particle spacing. However, precisely controlling the distance of plasmonic nanostructures is still a challenge. DNA has the merit of specific recognition, and flexible modification of functional groups, which can be used to flexibly adjust the gaps between plasmonic nanostructures for improving the stability of SERS. In this paper, DNA-guided gold nanoparticles formed one-dimensional ordered structures and they were self-assembled at the water-oil interface by a bottom-up approach. Notably, an output switching strategy successfully transfers a small amount of target into a large amount of reporter DNA; thereby, Raman probes are captured on the sensing interface and achieve the SERS assay of microRNA 155 (miRNA-155). This study is an exciting strategy for obtaining ordered plasmonic structures and providing surveillance, which is important for the clinical diagnosis of early-stage cancer.

The surface-enhanced Raman scattering (SERS) bioprobe's strategy for identifying tumor cells always depended on the intensity difference of the Raman signal compared with that of normal cells. Hence, exploring novel SERS nanostructure with excellent spectra stability, a high enhancement factor (EF), and good biocompatibility is a primary premise for boosting SERS signal reliability and accuracy of tumor cells. Here, high SERS EF (5.52 × 10 6 ) is acquired by developing novel amorphous nitrogen-doped carbon (NDC) nanocages (NCs), whose EF value was in a leading position among carbon-based SERS substrates. In addition, a uniform SERS signal was obtained on NDC NCs due to homogeneous morphology and size. The delocalized carbon-conjugated systems of graphitic-N, pyrrole-N, and pyridine-N with lone pair electrons increase the electronic density of states and reduce the electron localization function of NDC NCs, thereby promoting the charge transfer process. The electron-donor platform of the NDC NCs facilitates the thermodynamic process of charge transfer, resulting in multimode vibrational coupling in the surface complexes, which greatly amplifies the molecular polarizability. Importantly, the good biocompatibility and signal stability endow these NDC NC SERS bioprobes unique superiority in distinguishing tumor cells, and quantitative recognition of two triple-negative breast cancer cells based on SERS detection mode has been successfully realized.

Bacteria cause many common infections and are the culprit of many outbreaks throughout history that have led to the loss of millions of lives. Contamination of inanimate surfaces in clinics, the food chain, and the environment poses a significant threat to humanity, with the increase in antimicrobial resistance exacerbating the issue. Two key strategies to address this issue are antibacterial coatings and effective detection of bacterial contamination. In this study, we present the formation of antimicrobial and plasmonic surfaces based on Ag-Cu x O nanostructures using green synthesis methods and low-cost paper substrates. The fabricated nanostructured surfaces exhibit excellent bactericidal efficiency and high surface-enhanced Raman scattering (SERS) activity. The Cu x O ensures outstanding and rapid antibacterial activity within 30 min, with a rate of >99.99% against typical Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus bacteria. The plasmonic Ag nanoparticles facilitate the electromagnetic enhancement of Raman scattering and enables rapid, label-free, and sensitive identification of bacteria at a concentration as low as 10 3 cfu/mL. The detection of different strains at this low concentration is attributed to the leaching of the intracellular components of the bacteria caused by the nanostructures. Additionally, SERS is coupled with machine learning algorithms for the automated identification of bacteria with an accuracy that exceeds 96%. The proposed strategy achieves effective prevention of bacterial contamination and accurate identification of the bacteria on the same material platform by using sustainable and low-cost materials.

We describe the fabrication of plasmonic-active nanostructured thin film substrate as a label-free surface-enhanced Raman scattering (SERS)-based biosensor immobilized covalently with monoclonal HER-II antibody (mAb) to detect overexpressed HER-II as a biomarker in breast cancer serum (BCS). Oriented conjugation of mAb via hydrazone linkage to provide higher mAb accessibility was characterized by UV-vis and reflective Fourier transform near-infrared (FT-NIR) spectroscopic techniques. The interaction of BCS with mAb was studied by FT-NIR and nonresonant SERS at 637 nm. The results showed detection of glycoprotein content at different laser powers including a rise in amino acid and glycan content with varying results at higher power. With nonresonant SERS we observed nonlinear behavior of peak intensity. Analysis of variance was implemented to determine the effect of laser power which was found not to be a contributing factor. However, at the nanoscale, factors including the heating effect and aggregation of molecules can contribute to the nonlinearity of peak intensity., (© 2022 Wiley-VCH GmbH.)

Integration of plasmonic nanostructures with fiber-optics-based neural probes enables label-free detection of molecular fingerprints via surface-enhanced Raman spectroscopy (SERS), and it represents a fascinating technological horizon to investigate brain function. However, developing neuroplasmonic probes that can interface with deep brain regions with minimal invasiveness while providing the sensitivity to detect biomolecular signatures in a physiological environment is challenging, in particular because the same waveguide must be employed for both delivering excitation light and collecting the resulting scattered photons. Here, a SERS-active neural probe based on a tapered optical fiber (TF) decorated with gold nanoislands (NIs) that can detect neurotransmitters down to the micromolar range is presented. To do this, a novel, nonplanar repeated dewetting technique to fabricate gold NIs with sub-10 nm gaps, uniformly distributed on the wide (square millimeter scale in surface area), highly curved surface of TF is developed. It is experimentally and numerically shown that the amplified broadband near-field enhancement of the high-density NIs layer allows for achieving a limit of detection in aqueous solution of 10 -7  m for rhodamine 6G and 10 -5  m for serotonin and dopamine through SERS at near-infrared wavelengths. The NIs-TF technology is envisioned as a first step toward the unexplored frontier of in vivo label-free plasmonic neural interfaces., (© 2023 The Authors. Advanced Materials published by Wiley-VCH GmbH.)

Plasmonic nanoparticles that self-assemble into highly ordered superlattice nanostructures hold substantial promise for facilitating ultra-trace surface-enhanced Raman scattering (SERS) detection. Herein, we propose a boiling-point evaporation method to synthesize ordered monocrystal-like superlattice Au nanostructures (OML-Au NTs) with a polyhedral morphology. Combined with thermal nanoimprint technology, OML-Au NTs were directly transferred to impact-resistant polystyrene (IPS) flexible SERS substrates, the obtained flexible substrates (donated as OML-Au NTs/IPS) detection limit for R6G molecules as low as 10 -13 M. These results were confirmed by simulating the electromagnetic field distribution of ordered/unordered two-dimensional single-layer and three-dimensional aggregated gold nanostructures. The OML-Au NTs/IPS substrates were successfully used to detect and quantify three commonly-used agricultural pesticides, achieving detection limits as low as 10 -11 M and 10 -12 M, and in situ real-time detection limit reached 0.24 pg/cm 2 for thiram on apple peels, which was 3 orders of magnitude lower than the current detection limit. In addition, the Raman intensity from multiple locations showed a relative standard deviation lower than 7 %, exhibiting the reliability necessary for practical applications. As a result, this research demonstrates a highly reproducible method to enable the development of plasmonic nanomaterials with flexible superstructures., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Epidemiological control and public health monitoring during the outbreaks of infectious viral diseases rely on the ability to detect viral pathogens. Here we demonstrate a rapid, sensitive, and selective nanotechnology-enhanced severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection based on the surface-enhanced Raman scattering (SERS) responses from the plasma-engineered, variant-specific antibody-functionalized silver microplasma-engineered nanoassemblies (AgMEN) interacting with the SARS-CoV-2 spike (S) and nucleocapsid (N) proteins. The three-dimensional (3D) porous AgMEN with plasmonic-active nanostructures provide a high sensitivity to virus detection via the remarkable SERS signal collection. Moreover, the variant-specific antibody-functionalization on the SERS-active AgMEN enabled the high selectivity of the SARS-CoV-2 S variants, including wild-type, Alpha, Delta, and Omicron, under the simulated human saliva conditions. The exceptional ultrahigh sensitivity of our SERS biosensor was demonstrated via SARS-CoV-2 S and N proteins at the detection limit of 1 fg mL -1 and 0.1 pg mL -1 , respectively. Our work demonstrates a versatile SERS-based detection platform can be applied for the ultrasensitive detection of virus variants, infectious diseases, and cancer biomarkers., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Two-dimensional nanostructures (2DNS) attract tremendous interest and have emerged as potential materials for a variety of applications, including biomolecule sensing, due to their high surface-to-volume ratio, tuneable optical and electronic properties. Advancements in the engineering of 2DNS and associated technologies have opened up new opportunities. Surface-enhanced Raman scattering (SERS) is a rapid, highly sensitive, non-destructive analytical technique with exceptional signal amplification potential. Several structurally and chemically engineered 2DNS with added advantages (e.g., π-π* interaction), over plasmonic SERS substrates, have been developed specifically towards biomolecule sensing in a complex matrix, such as biological fluids. This review focuses on the recent developments of 2DNS-SERS substrates for biomolecule sensor applications. The recent advancements in engineered 2DNS, particularly for SERS substrates, have been systematically surveyed. In SERS substrates, 2DNS are used as either a standalone signal enhancer or as support for the dispersion of plasmonic nanostructures. The current challenges and future opportunities in this synergetic combination have also been discussed. Given the prospects in the design and preparation of newer 2DNS, this review can give a critical view on the current status, challenges and opportunities to extrapolate their applications in biomolecule detection.

Suspension arrays are a critical components of next generation multiplexed detection technologies. Current fluorescence suspension arrays are limited by a multiplexed coding ceiling and difficulties with ultrasensitive detection. Raman mode is a promising substitute, but the complex spectral peak distributions and extremely weak intrinsic signal intensity severely diminish Raman signal performance in suspension arrays. To address these limitations, we constructed a Raman suspension array system using plasmonic microbeads as barcode substrates and Au nanoflowers as reporter carriers. The well-designed shell morphology and plasmonic microbead composition enabled significant surface enhancement Raman scattering (SERS) such that we were able to adjust silent region Raman-coding intensity levels. Due to synergistic SERS effects from the plasmonic shell and the multi-branched Au nanoflower nanostructure, the reporting signal was greatly improved, enabling ultrasensitive detection of 5-plexed lung cancer markers. Detection in patient serum samples demonstrated good consistency with the standard electrochemiluminescence method. Thus, this silent region SERS barcode-based suspension array is a developmental advance for modern multiplexed biodetection, potentially providing a powerful early disease screening and diagnosis tool., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The most relevant technique for portable (on-chip) sensors is Surface Enhanced Raman Scattering (SERS). This strategy crashes in the case of large (biorelevant) molecules and nano-objects, whose SERS spectra are irreproducible for "homeopathic" concentrations. We suggested solving this problem by SERS-mapping. We analyzed the distributions of SERS parameters for relatively "small" (malachite green (MG)) and "large" (phthalocyanine, H 2 Pc*) molecules. While fluctuations of spectra for "small" MG were negligible, noticeable distribution of spectra was observed for "large" H 2 Pc*. We show that the latter is due to a random arrangement of molecules with respect to "hot spot" areas, which have limited sizes, thus amplifying the lines corresponding to vibrations of different molecule parts. We have developed a method for engineering low-cost SERS substrates optimized for the best enhancement efficiency and a measurement protocol to obtain a reliable Raman spectrum, even for a countable number of large molecules randomly distributed over the substrate.

Surface-enhanced Raman scattering (SERS) is a very promising tool for the direct detection of biomarkers for the diagnosis of i.e., cancer and pathogens. Yet, current SERS strategies are hampered by non-specific interactions with co-existing substances in the biological matrices and the difficulties of obtaining molecular fingerprint information from the complex vibrational spectrum. Raman signal enhancement is necessary, along with convenient surface modification and machine-based learning to address the former issues. This review aims to describe recent advances and prospects in SERS-based approaches for cancer and pathogens diagnosis. First, direct SERS strategies for key biomarker sensing, including the use of substrates such as plasmonic, semiconductor structures, and 3D order nanostructures for signal enhancement will be discussed. Secondly, we will illustrate recent advances for indirect diagnosis using active nanomaterials, Raman reporters, and specific capture elements as SERS tags. Thirdly, critical challenges for translating the potential of the SERS sensing techniques into clinical applications via machine learning and portable instrumentation will be described. The unique nature and integrated sensing capabilities of SERS provide great promise for early cancer diagnosis or fast pathogens detection, reducing sanitary costs but most importantly allowing disease prevention and decreasing mortality rates., (© 2022. The Author(s).)

Concentrating a trace amount of molecules from liquids, solid objects, or the gas phase and delivering them to a localized area are crucial for almost any trace analyte detection device. Analytes within a liquid droplet resting on micro/nanostructured surfaces with liquid-repellent coatings can be concentrated during solvent evaporation. However, these coatings suffer from complex manufacturing procedures, poor versatility, and limited analyte enrichment efficiency. Here, we report on the use of an acoustic levitation platform to losslessly concentrate the analyte molecules dissolved in any volatile liquid, attached to solid objects, or spread in air. Gold nanoparticles can be simultaneously concentrated with the analytes in different phases, realizing sensitive, surface-enhanced Raman scattering detection even at attomolar (10 -18  mol/L) concentration levels. The acoustic levitation platform-enabled, lossless analyte enrichment can significantly increase the analytical performance of many conventional microsensing techniques., (© 2022. The Author(s).)

In this Letter, a method for the rapid and efficient preparation of ultrasensitive detection substrates by assembling gold nanorod suspensions with the application of an alternating current (AC) field is proposed, and it is found that frequency and voltage are the effective means of regulation. A sandwich structure (parallel SiO 2 plate) not only effectively slows down the evaporation rate, but also visually reveals the changes in the assembly process. Under the optimal assembly conditions, the sensitivity and uniformity of the substrate to different probe molecules are tested. The Raman detection results experimentally show that the detection limits of Rhodamine 6G (Rh6G), crystal violet (CV), and Aspartame (APM) molecular solutions are 10 -14  M, 10 -10  M, and 62.5 mg/L, respectively, and the mixed dye molecular solutions can also be effectively distinguished. Furthermore, Rh6G and CV characteristic peaks at 1647 cm -1 and 1619 cm -1 were measured at randomly selected positions, and their relative standard deviations (RSDs) were 5.63% and 8.45%, respectively, indicating that the substrate has good uniformity. The effective regulation of the self-assembly results of nanoparticles will further enhance the practical application effect of surface-enhanced Raman technology and expand the application prospects of this technology.

Surface-enhanced Raman scattering (SERS) provides significantly enhanced Raman scattering signals from molecules adsorbed on plasmonic nanostructures, as well as the molecules' vibrational fingerprints. Plasmonic nanoparticle systems are particularly powerful for SERS substrates as they provide a wide range of structural features and plasmonic couplings to boost the enhancement, often up to >10 8 -10 10 . Nevertheless, nanoparticle-based SERS is not widely utilized as a means for reliable quantitative measurement of molecules largely due to limited controllability, uniformity, and scalability of plasmonic nanoparticles, poor molecular modification chemistry, and a lack of widely used analytical protocols for SERS. Furthermore, multiscale issues with plasmonic nanoparticle systems that range from atomic and molecular scales to assembled nanostructure scale are difficult to simultaneously control, analyze, and address. In this perspective, we introduce and discuss the design principles and key issues in preparing SERS nanoparticle substrates and the recent studies on the uniform and controllable synthesis and newly emerging machine learning-based analysis of plasmonic nanoparticle systems for quantitative SERS. Specifically, the multiscale point of view with plasmonic nanoparticle systems toward quantitative SERS is provided throughout this perspective. Furthermore, issues with correctly estimating and comparing SERS enhancement factors are discussed, and newly emerging statistical and artificial intelligence approaches for analyzing complex SERS systems are introduced and scrutinized to address challenges that cannot be fully resolved through synthetic improvements.