Signal Reproducibility Research Articles

Recent Developments in SERS Microfluidic Chips: From Fundamentals to Biosensing Applications.

This paper reviews the latest research progress of surface-enhanced Raman spectroscopy (SERS) microfluidic chips in the field of biosensing. Due to its single-molecule sensitivity, selectivity, minimal or no preprocessing, and immediacy, SERS is considered a promising biosensing technology. However, the nondirectional interactions between biological samples and the substrate, as well as fluctuations in the sample environment temperature during signal acquisition, can affect the stability and reproducibility of SERS signals. Integrating SERS spectroscopy with microfluidic chips not only leverages the continuous sample flow, high reaction efficiency, high throughput, and multifunctionality of microfluidic chips to address challenges in biosensing applications but also expands the scope of microfluidic technology by providing a novel on-chip optical detection method. The combination of SERS and microfluidic chips not only enables the complementary advantages of both technologies but also offers a highly promising "combined technology" for the field of biosensing. This paper starts by introducing the enhancement mechanisms of SERS and presents both labeled and label-free SERS strategies. Based on the differences in substrate properties, we broadly categorize SERS microfluidic chips into colloidal nanoparticle-based SERS microfluidic chips and fixed substrate-based SERS microfluidic chips. Finally, we review the latest research progress on SERS microfluidic chips for biosensing biological targets such as nucleic acids, proteins, small biomolecules, and live cells. In the conclusion and outlook section, we summarize the challenges faced by SERS microfluidic chips in biosensing and propose feasible solutions. To better leverage the role of SERS microfluidic chips in biosensing, we also present an outlook on the future development of this combined technology.

Microfluidic synthesis of gold nanoparticle-doped microspherical photonic crystal as SERS substrate for methylene blue detection.

Anovel microfluidic approach is presentedfor the one-step synthesis of gold nanoparticle-doped microspherical photonic crystal (AuNP-MPC) for ultrasensitive surface-enhanced Raman spectroscopy(SERS) detection of methylene blue (MB), a common environmental pollutant. The AuNP-MPC microspheres exhibited excellent SERS activity due to the surface plasmon resonance of Au nanoparticles. And the SERS signal was significantly enhanced by strategically manipulating the photonic band gap (PBG) of the AuNP-MPC microspheres to achieve optimal overlap with the excitation laser wavelength. The SERS signal of MB was significantly enhanced by this, reaching an EF as high as 3.03 × 106. The AuNP-MPC microspheres demonstrated rapid adsorption of MB within just 5min, making them suitable for rapid detection applications. Notably, the limit of quantification was as low as 1 × 10-8mol/L, highlighting the exceptional sensitivity of this approach. Furthermore, the AuNP-MPC microspheres exhibited excellent homogeneity, reproducibility, and stability of SERS signals, which are crucial qualities for practical SERS applications. This work presents a promising avenue for developing SERS-active microfluidic platforms for the rapid detection of trace organic pollutants in environmental monitoring.

Design and Engineering of Silver Nanomushroom Arrays as a Universal Solid-State SERS Platform for the Label-Free, Sensitive, and Quantitative Detection of Trace Proteins.

Surface-enhanced Raman scattering (SERS) is an ultrasensitive optical technique that is critical for protein detection and essential for identifying protein structure and concentrations in various biomedical and diagnostic applications. However, achieving highly sensitive and reproducible SERS signals for label-free proteins remains challenging due to their weak Raman signals and structural complexity. In this study, silver nanomushroom arrays (Ag NMAs) as SERS substrates were readily prepared and surface-engineered using a facile template-assisted micro- and nanofabrication approach. The surface of the substrate exhibits nanoscale roughness, long-range order, and hydrophilicity, enabling rapid and uniform dispersion of protein molecules. These molecules are anchored through Ag-S bonds, resulting in ultrasensitive Raman signals driven by strong electromagnetic enhancement effects. The highly ordered array structure improves signal repeatability, achieving a relative standard deviation of as low as 4.32%. Additionally, utilizing the silicon characteristic peak of the SERS substrate as an internal standard significantly reduces measurement errors, allowing for reliable and precise quantitative detection of protein molecules, with a linear correlation coefficient (R2) exceeding 0.96. Ultrasensitive SERS detection and effective protein discrimination via principal component analysis further validate the Ag NMA substrate's potential for universal trace protein detection. This study presents an advanced SERS platform for the sensitive and rapid detection of trace proteins, showcasing significant potential in pharmaceutical research, metabolic studies, diagnostic medicine, and protein engineering.

A simple, low-cost implant for reliable diaphragm EMG recordings in awake, freely behaving rats.

Breathing is a complex neuromuscular process vital to sustain life. In pre-clinical animal models, the study of respiratory motor control is primarily accomplished through neurophysiologic recordings and functional measurements of respiratory output. Neurophysiologic recordings that target neural or muscular output via direct nerve recordings or respiratory muscle electromyography (EMG) are commonly collected during anesthetized conditions. While offering tight control of experimental preparations, the use of anesthesia results in respiratory depression, may impact cardiovascular control, eliminates the potential to record volitional non-ventilatory behaviors, and can limit translation. Since the diaphragm is a unique muscle which is rhythmically active and difficult to access, placing diaphragm EMGs to collect chronic recordings in awake animals is technically challenging. Here, we describe methods for fabricating and implanting indwelling diaphragm EMG electrodes to enable recordings from awake rodents for longitudinal studies. These electrodes are relatively easy and quick to produce (∼1 hour), are affordable, and provide high quality and reproducible diaphragm signals using a tethered system that allows animals to freely behave. This system is also designed to work in conjunction with whole body plethysmography to facilitate simultaneous recordings of diaphragm EMG and ventilation. We include detailed instructions and considerations for electrode fabrication and surgical implantation. We also provide a brief discussion on data acquisition, material considerations for implant fabrication, and the physiological implications of the diaphragm electromyography signal.Significance Statement Investigations of respiratory neuromuscular output have frequently involved the diaphragm muscle, given its role as the main inspiratory muscle in mammals. While anesthetized preparations are fundamental to our understanding of respiratory neuromuscular control, using awake, freely behaving models enhances translatability, particularly when developing and evaluating therapeutic strategies in conditions that result in respiratory pathology and impaired breathing. Here, we describe an affordable and easy-to-produce electromyography implant that enables stable recordings of diaphragm output in awake, behaving rodents over long-term experimental protocols and offer a brief commentary on data acquisition and analysis of these signals.

Immobilized Saccharomyces cerevisiae viable cells for electrochemical biosensing of Cu(II)

Electrodes functionalised with weak electroactive microorganisms offer a viable alternative to conventional chemical sensors for detecting priority pollutants in bioremediation processes. Biofilm-based biosensors have been proposed for this purpose. However, biofilm formation and maturation require 24–48 h, and the microstructure and coverage of the electrode surface cannot be controlled, leading to poorly reproducible signal and sensitivity. Alternatively, semiconductive biocompatible coatings can be used for viable cell immobilization, achieving reproducible coverage and resulting in a stable biosensor response. In this work, we use a polydopamine (PDA)-based coating to immobilize Saccharomyces cerevisiae yeast viable cells on carbon screen printed electrodes (SPE) for Cu(II) detection, with potassium ferricyanide (K3[Fe (CN)6]) as a redox mediator. Under these conditions, the current output correlates with Cu (II) concentration, reaching a limit of detection of 2.2 µM, as calculated from the chronoamperometric response. The bioelectrochemical results are supported by standard viability assays, microscopy, and electrochemical impedance spectroscopy. The PDA coatings can be functionalised with different mutant strains, thus expanding the toolbox for biosensor design in bioremediation.

Plug-In Design of the Microneedle Electrode Array for Multi-Parameter Biochemical Sensing in Gouty Arthritis.

Gouty arthritis is one of the most common forms of inflammatory arthritis and has brought a significant burden on patients and society. Current strategies for managing gout primarily focus on long-term urate-lowering therapy. With the rapid advancement of point-of-care testing (POCT) technology, continuous monitoring of gout-related biomarkers like uric acid (UA) or inflammatory cytokines can provide rapid and personalized diagnosis for gout management. In this study, a plug-in design of a microneedle electrode array (PIMNA) was developed and integrated into a multi-parameter sensing portable system in combination with embedded circuits and a mobile application. The system enabled real-time, in situ, and dynamic monitoring of biomarkers, including UA, reactive oxygen species (ROS), and pH at gouty joints. The multi-parameter monitoring system demonstrated a wide linear response range, excellent selectivity, stability, reproducibility, and reliable signal transmission performance. In vivo experiments demonstrated the real-time monitoring capability of PIMNA for UA, ROS, and pH, showing the potential to facilitate urate-lowering management and inflammation assessment. Prospectively, the system enables quantitative analysis of the complexity and diversity of gout, presenting promising applications in clinical practice. This work provides a unique strategy with potential for broader applications in gout management and arthritic disease treatment.

Nanomaterials and clinical SERS technology: broad applications in disease diagnosis.

The critical need for rapid cancer diagnosis and related illnesses is growing alongside the current healthcare challenges, unfavorable prognosis, and constraints in diagnostic timing. As a result, emphasis on surface-enhanced Raman spectroscopy (SERS) diagnostic methods, including both label-free and labelled approaches, holds significant promise in fields such as analytical chemistry, biomedical science, and physics, due to the user-friendly nature of SERS. Over time, the SERS detection sensitivity and specificity with nanostructured materials for SERS applications (NMs-SERS) in different media have been remarkable. An investigation into electronic dynamics and interactions has revealed a seemingly fair result regarding the complementary effects of electromagnetic (EM) and chemical enhancements (CM), underscoring the operational principles of SERS. Nevertheless, the focus on translational SERS applications, especially beyond preliminary proof-of-concept research, remains limited. This review focuses on the advancements made in clinical SERS diagnostics and the essential role of NMs-SERS, ranging from plasmonic to non-plasmonic materials and other related advancements. Furthermore, it outlines the significant achievements of biomedical SERS in tumor diagnosis, particularly in identifying circulating tumor cells (CTCs), alongside a clear focus on NMs-SERS characteristics such as surface charge, shape, size, detection sensitivity, specificity, signal reproducibility, and recyclability. Finally, it underscores the use of microfluidic chips within the labelled SERS strategy for isolating CTCs, the concept of Ramanomics, and the integration of artificial intelligence (AI) to strengthen SERS data analysis. We hope that this review will help guide and expedite the potential for precise SERS diagnosis of key chronic diseases.

Gold nanorod in silver tetrahedron: Cysteamine mediated synthesis of SERS probes with embedded internal markers for AFP detection.

Plasmonic core-shell nanostructures with embedded internal markers used as Raman probes have attracted great attention in surface-enhanced Raman scattering (SERS) immunoassay for cancer biomarkers due to their excellent uniform enhancement. However, current core-shell nanostructures typically exhibit a spherical shape and are coated with a gold shell, resulting in constrained local field enhancement. In this work, we prepared a core-shell AuNR@BDT@Ag structure by depositing silver on the surface of Raman reporter-modified gold nanorods (AuNR). With cysteamine-driven specific deposition of Ag atoms, the internal standard nanoprobes with an ortho-tetrahedral morphology were obtained. Owing to its tetrahedral morphology and the effective plasmon coupling at the Ag-Au interface, this internal standard Raman probe exhibited excellent Raman enhancement. Also, with embedded Raman reporter, the probes of Au nanorod in Ag tetrahedron avoided the desorption of Raman reporter and competitive adsorption of interfering molecule, which greatly improved the stability and reproducibility of SERS signal and addressed the drawbacks of low reproducibility existing in SERS immunoassay. The feasibility of the AuNR@BDT@Ag probe was demonstrated by the sensitive detection of the liver cancer biomarker alpha-fetoprotein (AFP) in Eppendorf (EP) tubes and microfluidic chips. The results in EP tubes revealed a linear range of 1 fg/mL-1 ng/mL and a detection limit of 0.631fg/mL. When the detection was performed in microfluidic chips, the linear range was 10pg/mL to 0.1μg/mL, with a limit detection of 8.29pg/mL. The performance of AFP detection in EP tubes and microfluidic chips demonstrates that the tetrahedral core-shell AuNR@BDT@Ag nanostructures used as internal standard Raman probes have the potential to detect biomarkers in blood samples for cancer screening.

Silica nanoparticles surface-decorated with Au-Ag alloy nanoparticles as highly sensitive, reproducible, and stable surface-enhanced Raman scattering (SERS) substrates

The optical properties of metal nanoparticles (NPs) are heavily influenced by their structure and composition, making them useful in surface-enhanced Raman scattering (SERS) applications. In addition, metal-embedded silica NPs have excellent plasmonic characteristics and high reproducibility that further enhance SERS measurements. Although silica NPs have been encapsulated in various metals and alloys, practical applications require strong, stable, and reproducible optical signals. Herein, we synthesized Silica nanoparticles surface-decorated with Au-Ag alloy nanoparticles (SiO2@AuAg NPs) to perform as excellent SERS substrates. SiO2@AuAg NPs were synthesized by introducing seed Au NPs onto a spherical SiO2 NP core, followed by the addition of Au and Ag ions. From the NP characterization results, we also elucidate the growth mechanism for AuAg alloy NPs depending on the ratio of added Au to Ag ions. SiO2@AuAg NPs synthesized under optimized conditions exhibited a strong SERS signal with high stability, sensitivity, and reproducibility. Finally, SiO2@AuAg NPs successfully detected crystal violet (CV), thiram, and carbaryl at levels of 6.95 ×10-7M, 5.56 ×10-7M, and 7.14 ×10-6M, respectively, which are lower than the pesticide residue limits set by the U.S. Environmental Protection Agency (EPA). The detection reproducibility was also high, with an approximate relative standard deviation (RSD) of only 8.4% even after 3 days. The SERS substrate not only has high SERS activity and stability but can also be used to detect trace amounts of chemicals, enabling accurate SERS-based applications.

Miniaturization and characterization of patient derived hepatocellular carcinoma tumor organoid cultures for cancer drug discovery applications.

Patient derived tumor organoid (PDTO) models retain the structural, morphological, genetic, and clonal heterogeneity of the original tumors. The ability to efficiently generate, expand, and biobank PDTOs has the potential to make the clinical diversity of cancer accessible for personalized medicine assay guided therapeutic drug selection and drug discovery. We describe the miniaturization and growth in 96- and 384-well formats of a single non-tumor liver and two Hepatocellular carcinoma (HCC) organoids derived from cryopreserved PDTO cells and the application of high content imaging (HCI) to characterize the models and enhance drug sensitivity testing. Non-invasive sequentially acquired transmitted light images showed that seeding cryopreserved cells from non-tumoral and HCC PDTOs into 96- or 384-well plates in reduced growth factor Matrigel (rgf-MG) that were fed with growth medium every 3 days supported organoid growth up to 15 days. The number and sizes of organoids increased with longer times in culture. HCC PDTO's had more heterogeneous morphologies than non-tumor organoids with respect to size, shape, and optical density. Organoids cultured in rgf-MG could be stained in situ with HCI reagents without mechanical, chemical or enzymatic disruption of the hydrogel matrices and quantitative data extracted by image analysis. Hoechst and live/dead reagents provided organoid numbers and viability comparisons. HCC PDTO's stained with phalloidin or immuno-stained with α-tubulin antibodies revealed F-actin and microtubule cytoskeleton organization. HCC PDTO's stained with antibodies to signaling pathway proteins and their phosphorylation status allowed comparisons of relative expression levels and inference of pathway activation. Images of HCC PDTO's exposed to ellipticine showed that drugs penetrate Matrigel hydrogels and accumulate in organoid cells. 9-day 384-well HCC organoid cultures exhibited robust and reproducible growth signals suitable for cancer drug testing. Complimenting cell viability readouts with multiple HCI parameters including morphological features and dead cell staining improved the analysis of drug impact and enhanced the value that could be extracted from these more physiologically relevant three-dimensional HCC organoid cultures.

Study on the SERS Effect and Mechanism of Vertically Oriented MoS<sub>2</sub> Nanosheet Composite with Ag Substrate

Surface enhanced Raman spectroscopy (SERS) can provide rich molecular structure information with ultra-sensitive, non-destructive, and rapid detection down to the single-molecule level. It has been widely applied in physics, chemistry, biomedicine, environmental science, material science and other fields. Combining the advantages of metals and 2D nanomaterials, various 2D/metal composite structures have been proposed for SERS. However, the contribution of 2D nanomaterials in Raman enhancement is often limited. In this work, vertically aligned MoS<sub>2</sub> nanosheet composite with silver nanoparticles (Ag NPs) was proposed for SERS detection. Large-area vertically aligned MoS<sub>2</sub> nanosheets, which were grown directly on molybdenum (Mo) foil using hydrothermal method, can effectively enhance molecular adsorption, light absorption, and provide dual electromagnetic and chemical enhancement. Furthermore, annealing treatment of the MoS<sub>2</sub> nanosheets significantly improves the efficiency of charge transfer between Ag NPs and MoS<sub>2</sub>, thereby increasing the chemical contribution to SERS. The results demonstrate that the annealed MoS<sub>2</sub>/Ag substrate exhibits outstanding SERS performance, with a detection limit for R6G molecules as low as 10<sup>-12</sup> M, which is four orders of magnitude lower than that of the unannealed substrate. The enhancement factor (EF) is calculated to be approximately 1.08×10<sup>9</sup>, approaching the sensitivity required for single-molecule detection. Additionally, the substrate performs high signal reproducibility at low concentrations, enabling ultra-sensitive detection of pesticide residues in aquatic products.

Advances in Surface-Enhanced Raman Spectroscopy for Therapeutic Drug Monitoring.

Therapeutic drug monitoring (TDM) is pivotal for optimizing drug dosage regimens in individual patients, particularly for drugs with a narrow therapeutic index. Surface-enhanced Raman spectroscopy (SERS) has shown great potential in TDM due to high sensitivity, non-destructive analysis, specific fingerprint spectrum, low sample consumption, simple operation, and low ongoing costs. Due to the rapid development of SERS for TDM, a review focusing on the analytical method is presented to better understand the trends. This review examines the latest advancements in SERS substrates and their applications in TDM, highlighting the innovations in substrate design that enhance detection sensitivity and selectivity. We discuss the challenges faced by SERS for TDM, such as substrate signal reproducibility and matrix interference from complex biological samples, and explore solutions like digital colloid-enhanced Raman spectroscopy, enrichment detection strategies, microfluidic SERS, tandem instrument technologies, and machine learning-enabled SERS. These advancements address the limitations of traditional SERS applications and improve analytical efficiency in TDM. Finally, conclusions and perspectives on future research directions are presented. The integration of SERS with emerging technologies presents a transformative approach to TDM, with the potential to significantly enhance personalized medicine and improve patient outcomes.

Surfing beta burst waveforms to improve motor imagery-based BCI

Abstract Our understanding of motor-related, macroscale brain processes has been significantly shaped by the description of the event-related desynchronization (ERD) and synchronization (ERS) phenomena in the mu and beta frequency bands prior to, during, and following movement. The demonstration of reproducible, spatially- and band-limited signal power changes has, consequently, attracted the interest of non-invasive brain-computer interface (BCI) research for a long time. BCIs often rely on motor imagery (MI) experimental paradigms that are expected to generate brain signal modulations analogous to movement-related ERD and ERS. However, a number of recent neuroscience studies has questioned the nature of these phenomena. Beta band activity has been shown to occur, on a single-trial level, in short, transient, and heterogeneous events termed bursts rather than sustained oscillations. In a previous study, we established that an analysis of hand MI binary classification tasks based on beta bursts can be superior to beta power in terms of classification score. In this article, we elaborate on this idea, proposing a signal processing algorithm that is comparable to- and compatible with state-of-the-art techniques. Our pipeline filters brain recordings by convolving them with kernels extracted from beta bursts and then applies spatial filtering before classification. This data-driven filtering allowed for a simple and efficient analysis of signals from multiple sensors, thus being suitable for online applications. By adopting a time-resolved decoding approach, we explored MI dynamics and showed the specificity of the new classification features. In accordance with previous results, beta bursts improved classification performance compared to beta band power, while often increasing information transfer rate compared to state-of-the-art approaches.

Massive Screening of Food Extracts for Quality Assessment and Standardization of Allergenic Activity.

(1) Background: In drug discovery and pharmaceutical quality control, a challenge is to assess protein extracts used for allergy therapy and in vivo diagnosis, such as prick tests. Indeed, there are significant differences between the features of marketed products due to variations in raw materials, purification processes, and formulation techniques. (2) Methods: A protein array technology has been developed to provide comprehensive information on protein-biomarker interactions on a large scale to support the pharmaceutical industry and clinical research. The biosensing method is based on immobilizing low volumes of protein extracts (40 nL) on thermoplastic chips in array format. The biological activity was estimated by incubating with serum from representative food allergy patients. (3) Results: The reproducible optical signals were registered (deviation lower than 10%) using low-cost technologies such as a smartphone and a reader of digital versatile discs. The method was applied to pharmaceutical products to diagnose ten common food allergies, including barley, kiwi, milk, prawn, egg, peanut, wheat, peach, walnut, and squid. Quality indicators were established from spot intensities, enabling an effective comparison of manufacturers. (4) Conclusions: A biosensing-based strategy for screening pharmaceutical products emerges as a reliable and advantageous alternative to traditional approaches such as electrophoresis, fluorescence chips, and ELISA assays. This high-throughput method can contribute to understanding complex biological processes and evaluate the performance of pharmaceutical products.

Au Ordered Array Substrate for Rapid Detection and Precise Identification of Etomidate in E-Liquid Through Surface-Enhanced Raman Spectroscopy.

Etomidate (ET), a medical anesthetic, is increasingly being incorporated into e-liquids for consumption and abuse as a new psychoactive substance (NPS), leading to significant social issues. In this work, large-area Au micro- and nano-structured ordered arrays were engineered as surface-enhanced Raman spectroscopy (SERS) substrates for fast detection and precise identification of ET and its metabolites. This ordered array, characterized by abundant electromagnetic enhancement hotspots and structural uniformity, imparts unique properties to the SERS substrate, including ultra-sensitivity, spectral signal reproducibility, and precise quantitative capabilities. Furthermore, it effectively mitigates interference from the complex matrix of e-liquids, facilitating the rapid detection of trace amounts of ET molecules. This SERS rapid detection technology can act as a preliminary screening method for gold-standard spectroscopic analysis, facilitating the on-site rapid screening of suspicious samples and thereby enabling efficient detection and precise verification.

Laser Desorption/Ionization on Au@TiO2 Core@Shell Nanostars for Mass Spectrometric Analysis of Small Molecules.

The core@shell nanostars composed of star-like Au nanocores with TiO2 shells (Au@TiO2 NSs) are synthesized in a one-pot reaction without any reducing or surface-controlling agents. The Au@TiO2 NSs exhibit strong absorption in the UV region based on the interaction between the Au nanocore and the TiO2 shell, and this optochemical property leads to the efficient laser desorption/ionization time-of-flight mass spectrometry (LDI-TOF-MS) analysis of small molecules with low background interference and high reproducible mass signals compared with spherical Au nanoparticles (NPs). The limit of detection and dynamic range values of various analytes also improved with Au@TiO2 NSs compared with those obtained with spherical Au NPs. Our findings successfully demonstrate that Au@TiO2 NSs are a promising matrix for the LDI-TOF-MS analysis of various small molecules as well as synthetic polymers.

Digital SERS immunoassay of Interleukin-6 based on Au@Ag-Au nanotags

Interleukin-6 (IL-6) is a crucial cytokine involved in inflammation and immune regulation. However, the detection of IL-6 with ultrasensitivity and high specificity remains a significant challenge due to the inherent complexity of biofluids. Herein, we present a digital surface enhanced Raman scattering (SERS) immunoassay using core-shell Au@Ag-Au nanotags for IL-6 detection with ultrasensitivity and high reliability. A low-cost silicon chip was functionalized as capture substrates, employing novel SERS nanotags that exhibit strong, robust and reproducible signals at single-nanoparticle resolution as the amplification element. We proposed two analytical methods to validate single-molecule events follow a Poisson distribution and to quantify protein biomarkers over a broad linear dynamic range, respectively. The strong alignment between theoretical and experimental results enhances the method's reliability. Our assay provides two readouts: colorimetric analysis by naked eyes for high concentrations (>1 ng/mL) and digital SERS analysis for low concentrations. Following method optimization, we obtained a linear range from 100 fg/mL to 1 ng/mL (R2 = 0.994) with a limit of detection (LOD) of 12.4 fg/mL, suitable for clinical applications. The method was tested for IL-6 quantification in healthy human serum and saliva, with recoveries from 92.4% to 105.3%. Finally, the immunoassay demonstrated strong consistency with the standard clinical laboratory method when tested with clinical serum samples. Thus, our proposed the digital SERS immunoassay is a promising tool for the precision clinical diagnosis of IL-6-related diseases or other conditions.

Highly Sensitive Trimetazidine Determination Using Composite Yttria-Stabilized Zirconia Doped with Titanium Oxide-Carbon Black Biosensor.

A novel composite voltammetric biosensor has been developed for the first time, utilizing a glassy carbon electrode modified with yttria-stabilized zirconia doped with titanium dioxide and carbon black (YSZTiO2-CB/GCE), specifically designed for the detection of trimetazidine (TMZ). The measurement conditions, including both the supporting electrolyte and instrumental settings, were optimized to enhance performance. In the concentration range of 0.5 to 7 µM, it is not necessary to use preconcentration time for the determination of TMZ. The limit of detection (for 60 s of preconcentration time) was equal to 5.5 nM (1.87 ng mL-1), outperforming other voltammetric methods in terms of sensitivity. The reproducibility of the trimetazidine signal (with a concentration of 0.05 µM) exhibited a relative standard deviation (RSD) of 3.3% over 10 measurements. Additionally, our biosensor is characterized by excellent stability, ease of use, and straightforward preparation. The proposed biosensor and method have proven effective in analyzing TMZ in a variety of matrices, including urine, blood plasma, pharmaceutical formulations, as well as gastric and intestinal fluids, yielding recovery rates ranging from 97.7 to 102.3%.

Direct detection of melamine in milk via surface-enhanced Raman scattering using gold-silver anisotropic nanostructures

As the degree of anisotropy in nanoparticle morphology increases, the resulting electromagnetic enhancement can be significantly intensified. Herein, we have attempted to develop anisotropic gold-silver (a-AuAg) nanoparticles deposited on a titanium sheet (a-AuAg@Ti) as a highly efficient Surface-enhanced Raman Spectroscopy (SERS) sensor for rapid detection of health-hazardous milk adulterants like melamine. Hierarchical a-AuAg nanoparticles have been synthesized via a facile seed and growth-mediated method, followed by immobilization on a titanium sheet using a drop-casting technique. The structural, morphological, chemical, and optical properties of a-AuAg@Ti sensors have been systematically investigated and correlated with their respective SERS performance. Morphological analysis revealed the occurrence of triangular, hexagonal, and pentagonal-shaped nanoparticles with an average particle size of ∼ 23 to 26 nm. Preliminary SERS analysis using Rhodamine 6G (R6G) probe molecule revealed significantly higher SERS activity for a-AuAg nanoparticles compared to their spherical counterparts. This could be attributed to the lightning rod effect associated with the synthesized anisotropic nanostructures. An enhancement factor of 1.7 x 108 has been estimated for a-AuAg@Ti sensor with excellent signal reproducibility. Further, the efficacy of melamine detection has been investigated by spiking it into water and milk samples. The estimated lower detection limit (LDL) near picomolar and nanomolar concentrations have been obtained for melamine-spiked samples in water and milk, respectively. High-performance liquid chromatography analysis for melamine revealed an LDL of only 0.1 µM, indicating the higher sensitivity of a-AuAg@Ti SERS sensor. Moreover, we have also analyzed commercial milk products to verify the melamine contents, but none of them showed melamine-specific fingerprint bands. Our findings highlight the superior sensitivity of a-AuAg@Ti substrates for real-time melamine detection, making them excellent optical sensing tools for food safety analysis.

Physiological signal analysis and open science using the Julia language and associated software.

In this mini review, we propose the use of the Julia programming language and its software as a strong candidate for reproducible, efficient, and sustainable physiological signal analysis. First, we highlight available software and Julia communities that provide top-of-the-class algorithms for all aspects of physiological signal processing despite the language's relatively young age. Julia can significantly accelerate both research and software development due to its high-level interactive language and high-performance code generation. It is also particularly suited for open and reproducible science. Openness is supported and welcomed because the overwhelming majority of Julia software programs are open source and developed openly on public platforms, primarily through individual contributions. Such an environment increases the likelihood that an individual not (originally) associated with a software program would still be willing to contribute their code, further promoting code sharing and reuse. On the other hand, Julia's exceptionally strong package manager and surrounding ecosystem make it easy to create self-contained, reproducible projects that can be instantly installed and run, irrespective of processor architecture or operating system.