Biosensors, Volume 14, Issue 2 (February 2024) – 54 articles

This article presents the design of a low-power, low-noise neural signal amplifier for neural recording. The structure reduces the current consumption of the amplifier through current scaling technology and lowers the input-referred noise of the amplifier by combining a source degeneration resistor and current reuse technologies. The amplifier was fabricated using a 0.18 μm CMOS MS RF G process. The results show the front-end amplifier exhibits a measured mid-band gain of 40 dB/46 dB and a bandwidth ranging from 0.54 Hz to 6.1 kHz; the amplifier’s input-referred noise was measured to be 3.1 μVrms, consuming a current of 3.8 μA at a supply voltage of 1.8 V, with a Noise Efficiency Factor (NEF) of 2.97. The single amplifier’s active silicon area is 0.082 mm². Full article

Lead poses severe effects on living organisms, and since Pb²⁺ ions tend to accumulate in different organs, it is crucial to monitor Pb²⁺ concentration in samples such as water and soil. One of the approaches is the utilization of biosensors combined with aptamer-based layers for the electrochemical detection of lead ions. Herein, we present the studies of applying miniaturized screen-printed transducers as solid surfaces to fabricate aptamer layers. As the research is the direct continuation of our previous studies regarding the use of gold disk electrodes, the working parameters of elaborated aptasensors were defined, including the range of linear response (10–100 nM), selectivity as well as stability, regeneration, and feasibility of application for the analysis of real samples. This was achieved using voltammetric techniques including cyclic and square-wave voltammetry in the presence of methylene blue redox indicator. Full article

Reflection-type photoplethysmography (PPG) pulse sensors used in wearable smart watches, true wireless stereo, etc., have been recently considered a key component for monitoring biological signals such as heart rate, SPO₃, and blood pressure. Typically, the optical front end (OFE) of these PPG sensors is heterogeneously configured and packaged with light sources and receiver chips. In this paper, a novel quarter-annulus photodetector (NQAPD) with identical inner and outer radii of curvature has been developed using a plasma dicing process to realize a ring-type OFE receiver, which maximizes manufacturing efficiency and increases the detector collection area by 36.7% compared to the rectangular PD. The fabricated NQAPD exhibits a high quantum efficiency of over 90% in the wavelength of 500 nm to 740 nm and the highest quantum efficiency of 95% with a responsivity of 0.41 A/W at the wavelength of 530 nm. Also, the NQAPD is shown to increase the SNR of the PPG signal by 5 to 7.6 dB compared to the eight rectangular PDs. Thus, reflective PPG sensors constructed with NQAPD can be applied to various wearable devices requiring low power consumption, high performance, and cost-effectiveness. Full article

Nanostructures have played a key role in the development of different techniques to attack severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Some applications include masks, vaccines, and biosensors. The latter are of great interest for detecting diseases since some of their features allowed us to find specific markers in secretion samples such as saliva, blood, and even tears. Herein, we highlight how hierarchical nanoparticles integrated into two or more low-dimensional materials present outstanding advantages that are attractive for photonic biosensing using their nanoscale functions. The potential of nanohybrids with their superlative mechanical characteristics together with their optical and optoelectronic properties is discussed. The progress in the scientific research focused on using nanoparticles for biosensing a variety of viruses has become a medical milestone in recent years, and has laid the groundwork for future disease treatments. This perspective analyzes the crucial information about the use of hierarchical nanostructures in biosensing for the prevention, treatment, and mitigation of SARS-CoV-2 effects. Full article

Due to advances in additive manufacturing and prototyping, affordable and rapid microfluidic sensor-integrated assays can be fabricated using additive manufacturing, xurography and electrode shadow masking to create versatile platform technologies aimed toward qualitative assessment of acute cytotoxic or cytolytic events using stand-alone biochip platforms in the context of environmental risk assessment. In the current study, we established a nasal mucosa biosensing platform using RPMI2650 mucosa cells inside a membrane-integrated impedance-sensing biochip using exclusively rapid prototyping technologies. In a final proof-of-concept, we applied this biosensing platform to create human cell models of nasal mucosa for monitoring the acute cytotoxic effect of zinc oxide reference nanoparticles. Our data generated with the biochip platform successfully monitored the acute toxicity and cytolytic activity of 6 mM zinc oxide nanoparticles, which was non-invasively monitored as a negative impedance slope on nasal epithelial models, demonstrating the feasibility of rapid prototyping technologies such as additive manufacturing and xurography for cell-based platform development. Full article

Precise DNA quantification and nuclear imaging are pivotal for clinical testing, pathological diagnosis, and drug development. The detection and localization of mitochondrial DNA serve as crucial indicators of cellular health. We introduce a novel conjugated oligoelectrolyte (COE) molecule, COE-S3, featuring a planar backbone composed of three benzene rings and terminal side chains. This unique amphiphilic structure endows COE-S3 with exceptional water solubility, a high quantum yield of 0.79, and a significant fluorescence Stokes shift (λ_ex = 366 nm, λ_em = 476 nm), alongside a specific fluorescence response to DNA. The fluorescence intensity correlates proportionally with DNA concentration. COE-S3 interacts with double-stranded DNA (dsDNA) through an intercalation binding mode, exhibiting a binding constant (K) of 1.32 × 10⁶ M⁻¹. Its amphiphilic nature and strong DNA affinity facilitate its localization within mitochondria in living cells and nuclei in apoptotic cells. Remarkably, within 30 min of COE-S3 staining, cell vitality can be discerned through real-time nuclear fluorescence imaging of apoptotic cells. COE-S3’s high DNA selectivity enables quantitative intracellular DNA analysis, providing insights into cell proliferation, differentiation, and growth. Our findings underscore COE-S3, with its strategically designed, shortened planar backbone, as a promising intercalative probe for DNA quantification and nuclear imaging. Full article

The needless use of tetracyclines (TCs) in foodstuffs is a huge health concern in low- and middle-income and Arab countries. Herein, a sensitive and faster monitoring system for H₂O₂ and TCs is proposed, utilizing the large surface-to-volume ratio of a non-spherical gold nanoparticle/black phosphorus nanocomposite (BP-nsAu NPs) for the first time. BP-nsAu NPs were synthesized through a single-step method that presented nanozymatic activity through 3,3′,5,5′-Tetramethylbenzidine (TMB) oxidation while H₂O₂ was present and obeyed the Michaelis–Menten equation. The nanozymatic activity of the BP-nsAu NPs was enhanced 12-fold and their detection time was decreased 83-fold compared to conventional nanozymatic reactions. The proposed method enabled us to quantify H₂O₂ with a limit of detection (LOD) value of 60 nM. Moreover, target-specific aptamer-conjugated BP-nsAu NPs helped us detect TCs with an LOD value of 90 nM. The present strategy provides a proficient route for low-level TC monitoring in real samples. Full article

The design of a porous silicon (PSi) biosensor is not often documented, but is of the upmost importance to optimize its performance. In this work, the motivation behind the design choices of a PSi-based optical biosensor for the indirect detection of bacteria via their lysis is detailed. The transducer, based on a PSi membrane, was characterized and models were built to simulate the analyte diffusion, depending on the porous nanostructures, and to optimize the optical properties. Once all performances and properties were analyzed and optimized, a theoretical response was calculated. The theoretical limit of detection was computed as 10⁴ CFU/mL, based on the noise levels of the optical setup. The experimental response was measured using 10⁶ CFU/mL of Bacillus cereus as model strain, lysed by bacteriophage-coded endolysins PlyB221. The obtained signal matched the expected response, demonstrating the validity of our design and models. Full article

Respiratory pathogens pose a huge threat to public health, especially the highly mutant RNA viruses. Therefore, reliable, on-site, rapid diagnosis of such pathogens is an urgent need. Traditional assays such as nucleic acid amplification tests (NAATs) have good sensitivity and specificity, but these assays require complex sample pre-treatment and a long test time. Herein, we present an on-site biosensor for rapid and multiplex detection of RNA pathogens. Samples with viruses are first lysed in a lysis buffer containing carrier RNA to release the target RNAs. Then, the lysate is used for amplification by one-step reverse transcription and single-direction isothermal strand displacement amplification (SDA). The yield single-strand DNAs (ssDNAs) are visually detected by a lateral flow biosensor. With a secondary signal amplification system, as low as 20 copies/μL of virus can be detected in this study. This assay avoids the process of nucleic acid purification, making it equipment-independent and easier to operate, so it is more suitable for on-site molecular diagnostic applications. Full article

Single-entity electrochemistry, which employs electrolysis during the collision of single particles on ultramicroelectrodes, has witnessed significant advancements in recent years, enabling the observation and characterization of individual particles. Information on a single aqueous droplet (e.g., size) can also be studied based on the redox species contained therein. Dopamine, a redox-active neurotransmitter, is usually present in intracellular vesicles. Similarly, in the current study, the electrochemical properties of neurotransmitters in submicron droplets were investigated. Because dopamine oxidation is accompanied by proton transfer, unique electrochemical properties of dopamine were observed in the droplet. We also investigated the electrochemical properties of the adsorbed droplets containing DA and the detection of oxidized dopamine by the recollision phenomenon. Full article

Here, we present the results of our the electrochemical aptasensing strategy for retinol binding protein-4 (RBP-4) detection based on a thiolated aptamer against RBP-4 and 6-mercaptohexanol (MCH) directly immobilized on a gold electrode surface. The most important parameters affecting the magnitude of the analytical signal generated were optimized: (i) the presence of magnesium ions in the immobilization and measurement buffer, (ii) the concentration of aptamer in the immobilization solution and (iii) its folding procedure. In this work, a systematic assessment of the electrochemical parameters related to the optimization of the sensing layer of the aptasensor was carried out (electron transfer coefficients (α), electron transfer rate constants (k⁰) and surface coverage of the thiolated aptamer probe (Γ_Apt)). Then, under the optimized conditions, the analytical response towards RBP-4 protein, in the presence of an Fe(CN)₆^3−/4− redox couple in the supporting solution was assessed. The proposed electrochemical strategy allowed for RBP-4 detection in the concentration range between 100 and 1000 ng/mL with a limit of detection equal to 44 ng/mL based on electrochemical impedance spectroscopy (EIS). The specificity studies against other diabetes biomarkers, including vaspin and adiponectin, proved the selectivity of the proposed platform. These preliminary results will be used in the next step to miniaturize and test the sensor in real samples. Full article

Cancers of unknown primary (CUP) exhibit significant cellular heterogeneity and malignancy, which poses significant challenges for diagnosis and treatment. Recent years have seen deeper insights into the imaging, pathology, and genetic characteristics of CUP, driven by interdisciplinary collaboration and the evolution of diagnostic and therapeutic strategies. However, due to their insidious onset, lack of evidence-based medicine, and limited clinical understanding, diagnosing and treating CUP remain a significant challenge. To inspire more creative and fantastic research, herein, we report and highlight recent advances in the diagnosis and therapeutic strategies of CUP. Specifically, we discuss advanced diagnostic technologies, including 12-deoxy-2-[fluorine-18]fluoro-D-glucose integrated with computed tomography (18F-FDG PET/CT) or ⁶⁸Ga-FAPI (fibroblast activation protein inhibitor) PET/CT, liquid biopsy, molecular diagnostics, self-assembling nanotechnology, and artificial intelligence (AI). In particular, the discussion will extend to the effective treatment techniques currently available, such as targeted therapies, immunotherapies, and bio-nanotechnology-based therapeutics. Finally, a novel perspective on the challenges and directions for future CUP diagnostic and therapeutic strategies is discussed. Full article

Surface Plasmon Resonance (SPR) technology is known to be a powerful tool for studying biomolecular interactions because it offers real-time and label-free multiparameter analysis with high sensitivity. This article summarizes the results that have been obtained from the use of SPR technology in studying the dynamics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mutations. This paper will begin by introducing the working principle of SPR and the kinetic parameters of the sensorgram, which include the association rate constant (k_a), dissociation rate constant (k_d), equilibrium association constant (K_A), and equilibrium dissociation constant (K_D). At the end of the paper, we will summarize the kinetic data on the interaction between angiotensin-converting enzyme 2 (ACE2) and SARS-CoV-2 obtained from the results of SPR signal analysis. ACE2 is a material that mediates virus entry. Therefore, understanding the kinetic changes between ACE2 and SARS-CoV-2 caused by the mutation will provide beneficial information for drug discovery, vaccine development, and other therapeutic purposes. Full article

The goal of this study is to develop a rapid diagnostic test for rheumatic disease and systemic lupus erythematosus (SLE) screening. A novel rapid vertical flow assay (VFA) was engineered and used to assay anti-nuclear (ANA) and anti-dsDNA (αDNA) autoantibodies from systemic lupus erythematosus (SLE) patients and healthy controls (HCs). Observer scores and absolute signal intensities from the VFA were validated via ELISA. The rapid point-of-care VFA test that was engineered demonstrated a limit of detection of 0.5 IU/mL for ANA and αDNA autoantibodies in human plasma with an inter-operator CV of 19% for ANA and 12% for αDNA. Storage stability was verified over a three-month period. When testing anti-dsDNA and ANA levels in SLE and HC serum samples, the duplex VFA revealed 95% sensitivity, 72% specificity and an 84% ROC AUC value in discriminating disease groups, comparable to the gold standard, ELISA. The rapid αDNA/ANA duplex VFA can potentially be used in primary care clinics for evaluating patients or at-risk subjects for rheumatic diseases and for planning follow-up testing. Given its low cost, ease, and rapid turnaround, it can also be used to assess SLE prevalence estimates. Full article

Ribonucleic acid (RNA) viruses are one of the major classes of pathogens that cause human diseases. The conventional method to detect RNA viruses is real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR), but it has some limitations. It is expensive and time-consuming, with infrastructure and trained personnel requirements. Its high throughput requires sophisticated automation and large-scale infrastructure. Isothermal amplification methods have been explored as an alternative to address these challenges. These methods are rapid, user-friendly, low-cost, can be performed in less specialized settings, and are highly accurate for detecting RNA viruses. Microfluidic technology provides an ideal platform for performing virus diagnostic tests, including sample preparation, immunoassays, and nucleic acid-based assays. Among these techniques, nucleic acid isothermal amplification methods have been widely integrated with microfluidic platforms for RNA virus detection owing to their simplicity, sensitivity, selectivity, and short analysis time. This review summarizes some common isothermal amplification methods for RNA viruses. It also describes commercialized devices and kits that use isothermal amplification techniques for SARS-CoV-2 detection. Furthermore, the most recent applications of isothermal amplification-based microfluidic platforms for RNA virus detection are discussed in this article. Full article

Oxygen consumption has been used to evaluate various cellular activities. In addition, three-dimensional (3D) spheroids have been broadly exploited as advanced in vitro cell models for various biomedical studies due to their capability of mimicking 3D in vivo microenvironments and cell arrangements. However, monitoring the oxygen consumption of live 3D spheroids poses challenges because existing invasive methods cause structural and cell damage. In contrast, optical methods using fluorescence labeling and microscopy are non-invasive, but they suffer from technical limitations like high cost, tedious procedures, and poor signal-to-noise ratios. To address these challenges, we developed a microfluidic platform for uniform-sized spheroid formation, handling, and culture. The platform is further integrated with widefield frequency domain fluorescence lifetime imaging microscopy (FD-FLIM) to efficiently characterize the lifetime of an oxygen-sensitive dye filling the platform for oxygen consumption characterization. In the experiments, osteosarcoma (MG-63) cells are exploited as the spheroid model and for the oxygen consumption analysis. The results demonstrate the functionality of the developed approach and show the accurate characterization of the oxygen consumption of the spheroids in response to drug treatments. The developed approach possesses great potential to advance spheroid metabolism studies with single-spheroid resolution and high sensitivity. Full article

A taste sensor employs various lipid/polymer membranes with specific physicochemical properties for taste classification and evaluation. However, phosphoric acid di(2-ethylhexyl) ester (PAEE), employed as one of the lipids for the taste sensors, exhibits insufficient selectivity for umami substances. The pH of sample solutions impacts the dissociation of lipids to influence the membrane potential, and the response to astringent substances makes accurate measurement of umami taste difficult. This study aims to develop a novel taste sensor for detecting umami substances like monosodium L-glutamate (MSG) through surface modification, i.e., a methodology previously applied to taste sensors for non-charged bitter substance measurement. Four kinds of modifiers were tested as membrane-modifying materials. By comparing the results obtained from these modifiers, the modifier structure suitable for measuring umami substances was identified. The findings revealed that the presence of carboxyl groups at para-position of the benzene ring, as well as intramolecular H-bonds between the carboxyl group and hydroxyl group, significantly affect the effectiveness of a modifier in the umami substance measurement. The taste sensor treated with this type of modifier showed excellent selectivity for umami substances. Full article

Breast cancer (BC) affects millions of women worldwide, causing over 500,000 deaths annually. It is the leading cause of cancer mortality in women, with 70% of deaths occurring in developing countries. Elastography, which evaluates tissue stiffness, is a promising real-time minimally invasive technique for BC diagnosis. This study assessed strain elastography (SE) and the fat-to-lesion (F/L) index for BC diagnosis. This prospective study included 216 women who underwent SE, ultrasound, mammography, and breast biopsy (108 malignant, 108 benign). Three expert radiologists performed imaging and biopsies. Mean F/L index was 3.70 ± 2.57 for benign biopsies and 18.10 ± 17.01 for malignant. We developed two predictive models: a logistic regression model with AUC 0.893, 79.63% sensitivity, 87.62% specificity, 86.9% positive predictive value (+PV), and 80.7% negative predictive value (−PV); and a neural network with AUC 0.902, 80.56% sensitivity, 88.57% specificity, 87.9% +PV, and 81.6% −PV. The optimal Youden F/L index cutoff was >5.76, with 84.26% sensitivity and specificity. The F/L index positively correlated with BI-RADS (Spearman’s r = 0.073, p < 0.001) and differed among molecular subtypes (Kruskal-Wallis, p = 0.002). SE complements mammography for BC diagnosis. With adequate predictive capacity, SE is fast, minimally invasive, and useful when mammography is contraindicated. Full article

Neurodegenerative diseases and Alzheimer’s disease (AD), as one of the most common causes of dementia, result in progressive losses of cholinergic neurons and a reduction in the presynaptic markers of the cholinergic system. These consequences can be compensated by the inhibition of acetylcholinesterase (AChE) followed by a decrease in the rate of acetylcholine hydrolysis. For this reason, anticholinesterase drugs with reversible inhibition effects are applied for the administration of neurodegenerative diseases. Their overdosage, variation in efficiency and recommendation of an individual daily dose require simple and reliable measurement devices capable of the assessment of the drug concentration in biological fluids and medications. In this review, the performance of electrochemical biosensors utilizing immobilized cholinesterases is considered to show their advantages and drawbacks in the determination of anticholinesterase drugs. In addition, common drugs applied in treating neurodegenerative diseases are briefly characterized. The immobilization of enzymes, nature of the signal recorded and its dependence on the transducer modification are considered and the analytical characteristics of appropriate biosensors are summarized for donepezil, huperzine A, rivastigmine, eserine and galantamine as common anti-dementia drugs. Finally, the prospects for the application of AChE-based biosensors in clinical practice are discussed. Full article

Pulse Wave Velocity (PWV) analysis is valuable for assessing arterial stiffness and cardiovascular health and potentially for estimating blood pressure cufflessly. However, conventional PWV analysis from two transducers spaced closely poses challenges in data management, battery life, and developing the device for continuous real-time applications together along an artery, which typically need data to be recorded at high sampling rates. Specifically, although a pulse signal consists of low-frequency components when used for applications such as determining heart rate, the pulse transit time for transducers near each other along an artery takes place in the millisecond range, typically needing a high sampling rate. To overcome this issue, in this study, we present a novel approach that leverages the Nyquist–Shannon sampling theorem and reconstruction techniques for signals produced by bioimpedance transducers closely spaced along a radial artery. Specifically, we recorded bioimpedance artery pulse signals at a low sampling rate, reducing the data size and subsequently algorithmically reconstructing these signals at a higher sampling rate. We were able to retain vital transit time information and achieved enhanced precision that is comparable to the traditional high-rate sampling method. Our research demonstrates the viability of the algorithmic method for enabling PWV analysis from low-sampling-rate data, overcoming the constraints of conventional approaches. This technique has the potential to contribute to the development of cardiovascular health monitoring and diagnosis using closely spaced wearable devices for real-time and low-resource PWV assessment, enhancing patient care and cardiovascular disease management. Full article

Despite a substantial increase in testing facilities during the pandemic, access remains a major obstacle, particularly in low-resource and remote areas. This constraint emphasizes the need for high-throughput potential point-of-care diagnostic tools in environments with limited resources. Loop-mediated isothermal amplification (LAMP) is a promising technique, but improvements in sensitivity are needed for accurate detection, especially in scenarios where the virus is present in low quantities. To achieve this objective, we present a highly sensitive detection approach of a dual-mode graphene-based field-effect transistor (G-FET) biosensor with LAMP. The G-FET biosensor, which has a transparent graphene microelectrode array on a glass substrate, detects LAMP products in less than 30 min using both observable color changes and Dirac point voltage measurements, even in samples with low viral concentrations. This dual-mode G-FET biosensor emerges as a potential alternative to conventional RT-PCR for severe acute respiratory syndrome-associated coronavirus (SARS-CoV)-2 detection or point-of-care testing, particularly in resource-constrained scenarios such as developing countries. Moreover, its capacity for colorimetric detection with the naked eye enhances its applicability in diverse settings. Full article

This article explores the importance of wearable and remote technologies in healthcare. The focus highlights its potential in continuous monitoring, examines the specificity of the issue, and offers a view of proactive healthcare. Our research describes a wide range of device types and scientific methodologies, starting from traditional chest belts to their modern alternatives and cutting-edge bioamplifiers that distinguish breathing from chest impedance variations. We also investigated innovative technologies such as the monitoring of thorax micromovements based on the principles of seismocardiography, ballistocardiography, remote camera recordings, deployment of integrated optical fibers, or extraction of respiration from cardiovascular variables. Our review is extended to include acoustic methods and breath and blood gas analysis, providing a comprehensive overview of different approaches to respiratory monitoring. The topic of monitoring respiration with wearable and remote electronics is currently the center of attention of researchers, which is also reflected by the growing number of publications. In our manuscript, we offer an overview of the most interesting ones. Full article

Bacterial infections, increasingly resistant to common antibiotics, pose a global health challenge. Traditional diagnostics often depend on slow cell culturing, leading to empirical treatments that accelerate antibiotic resistance. We present a novel large-volume microscopy (LVM) system for rapid, point-of-care bacterial detection. This system, using low magnification (1–2×), visualizes sufficient sample volumes, eliminating the need for culture-based enrichment. Employing deep neural networks, our model demonstrates superior accuracy in detecting uropathogenic Escherichia coli compared to traditional machine learning methods. Future endeavors will focus on enriching our datasets with mixed samples and a broader spectrum of uropathogens, aiming to extend the applicability of our model to clinical samples. Full article

We report a three-dimensional (3D) SERS substrate consisting of a silver nanoparticle (AgNP) coating on the skeleton-fiber surfaces of a polytetrafluoroethylene (PTFE) membrane. Simple thermal evaporation was employed to deposit Ag onto the PTFE membrane to produce grape-shaped AgNPs. The 3D-distributed AgNPs exhibit not only strong localized surface plasmon resonance (LSPR) but also strong hydrophobic performance. High-density hotspots via silver nano-grape structures and nanogaps, the large 3D interaction volume, and the large total surface area, in combination with the hydrophobic enrichment of the specimen, facilitate high-sensitivity sensing performance of such a SERS substrate for the direct detection of low-concentration molecules in water. An enhancement factor of up to 1.97 × 10¹⁰ was achieved in the direct detection of R6G molecules in water with a concentration of 10⁻¹³ mol/L. The lowest detection limit of 100 ppt was reached in the detection of melamine in water. Such a SERS sensor may have potential applications in food-safety control, environmental water pollution monitoring, and biomedical analysis. Full article

Mechanical strain has been shown to be a versatile and tunable means to control various properties of nanomaterials. In this work, we investigate how strain applied to individual ZnO nanorods (NRs) can affect the fluorescence signals originated from external sources of bioanalytes, which are subsequently coupled and guided onto the NRs. Specifically, we determine how factors such as the NR length and protein concentration can influence the strain-induced changes in the waveguided fluorescence intensity along the NRs. We employ a protein of tumor necrosis factor-α (TNF-α) and a fluorophore-labeled antibody in a model immunoassay reaction, after which Alexa488-TNF-α immunocomplex is formed on ZnO NRs. We elucidate the relationships between the types as well as amounts of strain on the NRs and the fluorescence intensity originated from the Alexa488-TNF-α immunocomplexes. We show that tensile (compressive) strain applied to the NR leads to an increase (decrease) in the waveguided fluorescence signals. By assessing important optical phenomena such as fluorescence intensification on nanorod ends (FINE) and degree of FINE (DoF), we confirm their linear dependence with both the types and amounts of strain. Furthermore, the strain-induced changes in both FINE and DoF are found to be independent of protein concentration. We determine that NR length plays a critical role in obtaining high strain-dependence of the measured fluorescence signals. Particularly, we ascertain that longer NRs yield larger changes in both FINE and DoF in response to the applied strain, relative to shorter ones. In addition, longer NRs permit higher linear correlation between the protein concentration and the waveguided fluorescence intensity. These outcomes provide valuable insight into exploiting strain to enhance the detection of optical signals from bioanalytes, thus enabling their quantifications even at ultra-trace levels. Coupled with the use of individual ZnO NRs demonstrated in our measurements, this work may contribute to the development of a miniaturized, highly sensitive biosensor whose signal transduction is best optimized by the application of strain. Full article

Surface plasmon resonance (SPR) is a powerful tool for determining molecular interactions quantitatively. SPR imaging (SPRi) further improves the throughput of SPR technology and provides the spatially resolved capability for observing the molecular interaction dynamics in detail. SPRi is becoming more and more popular in biological and chemical sensing and imaging. However, SPRi suffers from low spatial resolution due to the imperfect optical components and delocalized features of propagating surface plasmonic waves along the surface. Diverse kinds of approaches have been developed to improve the spatial resolution of SPRi, which have enormously impelled the development of the methodology and further extended its possible applications. In this minireview, we introduce the mechanisms for building a high-spatial-resolution SPRi system and present its experimental schemes from prism-coupled SPRi and SPR microscopy (SPRM) to surface plasmonic scattering microscopy (SPSM); summarize its exciting applications, including molecular interaction analysis, molecular imaging and profiling, tracking of single entities, and analysis of single cells; and discuss its challenges in recent decade as well as the promising future. Full article

Hemoglobin (Hb) disorders are among the most common monogenic diseases affecting nearly 7% of the world population. Among various Hb disorders, approximately 1.5% of the world population carries β-thalassemia (β-Thal), affecting 40,000 newborns every year. Early screening and a timely diagnosis are essential for β-thalassemia patients for the prevention and management of later clinical complications. However, in Africa, Southern Europe, the Middle East, and Southeast Asia, where β-thalassemia is most prevalent, the diagnosis and screening for β-thalassemia are still challenging due to the cost and logistical burden of laboratory diagnostic tests. Here, we present Gazelle, which is a paper-based microchip electrophoresis platform that enables the first point-of-care diagnostic test for β-thalassemia. We evaluated the accuracy of Gazelle for the β-Thal screening across 372 subjects in the age range of 4–63 years at Apple Diagnostics lab in Mumbai, India. Additionally, 30 blood samples were prepared to mimic β-Thal intermediate and β-Thal major samples. Gazelle-detected levels of Hb A, Hb F, and Hb A₂ demonstrated high levels of correlation with the results reported through laboratory gold standard high-performance liquid chromatography (HPLC), yielding a Pearson correlation coefficient = 0.99. This ability to obtain rapid and accurate results suggests that Gazelle may be suitable for the large-scale screening and diagnosis of β-Thal. Full article

Tuna is an excellent food product, relatively low in calories, that is recommended for a balanced diet. The continuously increasing demand, especially for bluefin-tuna-based food preparations, and its relatively high market price make adulteration by intentionally mixing with other lower-priced tunas more prospective. The development of rapid methods to detect tuna adulteration is a great challenge in food analytical science. We have thus developed a simple, fast, and low-cost molecular rapid test for the visual detection of tuna adulteration. It is the first sensor developed for tuna authenticity testing. The three species studied were Thunnus thynnus (BFT), Thunnus albacares, and Katsuwonus pelamis. DNA was isolated from fresh and heat-treated cooked fish samples followed by PCR. The PCR products were hybridized (10 min) to specific probes and applied to the rapid sensing device. The signal was observed visually in 10–15 min using gold nanoparticle reporters. The method was evaluated employing binary mixtures of PCR products from fresh tissues and mixtures of DNA isolates from heat-treated tissues (canned products) at adulteration percentages of 1–100%. The results showed that the method was reproducible and specific for each tuna species. As low as 1% of tuna adulteration was detected with the naked eye. Full article