Use Of Biosensors Research Articles

Highly sensitive and robust refractometric sensing by magnetic dipole of Si nanodisks

Silicon metasurfaces have been attracting interest in the sensing field because of their ability to support magnetic Mie resonance, low optical heating, and CMOS-compatible fabrication processes. Herein, we demonstrate that the sensitivity of the magnetic dipole (MD) mode for nanodisk Mie resonators (as high as 385 nm/RIU) is similar to the sensitivity of plasmonic metasurfaces and greater than that of the electric dipole (ED) mode of nanodisk Mie resonators. We also engineer the thickness of Mie resonators to achieve an MD-mode linewidth as small as 0.56 nm and a figure of merit greater than 160 RIU−1. The measured sensitivity of the MD mode is more accurate than that of the ED mode, which is more prone than the MD mode to measurement errors arising from the partial filling of the liquid. Our study paves the way for the development of MD-mode-based dielectric biosensors for use in personal healthcare and medical diagnosis.

A review on the contamination of SARS-CoV-2 in water bodies: Transmission route, virus recovery and recent biosensor detection techniques

The discovery of SARS-CoV-2 virus in the water bodies has been reported, and the risk of virus transmission to human via the water route due to poor wastewater management cannot be disregarded. The main source of the virus in water bodies is the sewage network systems which connects to the surface water. Wastewater-based epidemiology has been applied as an early surveillance tool to sense SARS-CoV-2 virus in the sewage network. This review discussed possible transmission routes of the SARS-CoV-2 virus and the challenges of the existing method in detecting the virus in wastewater. One significant challenge for the detection of the virus is that the high virus loading is diluted by the sheer volume of the wastewater. Hence, virus preconcentration from water samples prior to the application of virus assay is essential to accurately detect traceable virus loading. The preparation time, materials and conditions, virus type, recovery percentage, and various virus recovery techniques are comprehensively discussed in this review. The practicability of molecular methods such as Polymer-Chain-Reaction (PCR) for the detection of SARS-CoV-2 in wastewater will be revealed. The conventional virus detection techniques have several shortcomings and the potential of biosensors as an alternative is also considered. Biosensing techniques have also been proposed as an alternative to PCR and have reported detection limits of 10pg/μl. This review serves to guide the reader on the future designs and development of highly sensitive, robust and, cost effective SARS-CoV-2 lab-on-a-chip biosensors for use in complex wastewater.

Analogue of electromagnetically induced transparency in square slotted silicon metasurfaces supporting bound states in the continuum.

In this work, a silicon metasurface designed to support electromagnetically induced transparency (EIT) based on quasi-bound states in the continuum (qBIC) is proposed and theoretically demonstrated in the near-infrared spectrum. The metasurface consists of a periodic array of square slot rings etched in a silicon layer. The interruption of the slot rings by a silicon bridge breaks the symmetry of the structure producing qBIC stemming from symmetry-protected states, as rigorously demonstrated by a group theory analysis. One of the qBIC is found to behave as a resonance-trapped mode in the perturbed metasurface, which obtains very high quality factor values at certain dimensions of the silicon bridge. Thanks to the interaction of the sharp qBIC resonances with a broadband bright background mode, sharp high-transmittance peaks are observed within a low-transmittance spectral window, thus producing a photonic analogue of EIT. Moreover, the resonator possesses a simple bulk geometry with channels that facilitate the use in biosensing. The sensitivity of the resonant qBIC on the refractive index of the surrounding material is calculated in the context of refractometric sensing. The sharp EIT-effect of the proposed metasurface, along with the associated strong energy confinement may find direct use in emerging applications based on strong light-matter interactions, such as non-linear devices, lasing, biological sensors, optical trapping, and optical communications.

Periodic Nanohole Arrays with Enhanced Lasing and Spontaneous Emissions for Low-Cost Plasmonic Devices

Periodic arrays of air nanoholes in thin metal films that support surface plasmon resonances can provide an alternative approach for boosting the light–matter interactions at the nanoscale. Nanohole arrays have garnered great interest in recent years for their use in biosensing, light emission enhancement, and spectroscopy. Here, we employ a simple technique to fabricate nanohole arrays and examine their photonic applications including enhanced lasing and spontaneous emission of novel nanomaterials. In contrast to the complicated and most commonly used electron-beam lithography technique, hexagonal arrays of nanoholes are fabricated by using a simple combination of shadowing nanosphere lithography technique and electron-beam deposition. Through spectral and temporal characterizations, it was shown that these arrays offer an enhancement in the lasing emission of an organic dye liquid gain medium with a quality factor above 150 as well as an accelerated decay rate for CdSe quantum dots. The simple fabrication of nanohole arrays together with their excellent optical responses can therefore offer a great potential in the industrialization of plasmonic devices for use in various realms of emerging technologies such as gas sensing, biomedical imaging, and ultrafast on-chip coherent light sources.

Synthetic Biology Approaches to Hydrocarbon Biosensors: A Review.

Monooxygenases are a class of enzymes that facilitate the bacterial degradation of alkanes and alkenes. The regulatory components associated with monooxygenases are nature’s own hydrocarbon sensors, and once functionally characterised, these components can be used to create rapid, inexpensive and sensitive biosensors for use in applications such as bioremediation and metabolic engineering. Many bacterial monooxygenases have been identified, yet the regulation of only a few of these have been investigated in detail. A wealth of genetic and functional diversity of regulatory enzymes and promoter elements still remains unexplored and unexploited, both in published genome sequences and in yet-to-be-cultured bacteria. In this review we examine in detail the current state of research on monooxygenase gene regulation, and on the development of transcription-factor-based microbial biosensors for detection of alkanes and alkenes. A new framework for the systematic characterisation of the underlying genetic components and for further development of biosensors is presented, and we identify focus areas that should be targeted to enable progression of more biosensor candidates to commercialisation and deployment in industry and in the environment.

Discovery of DNA-Carbon Nanotube Sensors for Serotonin with Machine Learning and Near-infrared Fluorescence Spectroscopy.

DNA-wrapped single walled carbon nanotube (SWNT) conjugates have distinct optical properties leading to their use in biosensing and imaging applications. A critical limitation in the development of DNA-SWNT sensors is the current inability to predict unique DNA sequences that confer a strong analyte-specific optical response to these sensors. Here, near-infrared (nIR) fluorescence response data sets for ∼100 DNA-SWNT conjugates, narrowed down by a selective evolution protocol starting from a pool of ∼1010 unique DNA-SWNT candidates, are used to train machine learning (ML) models to predict DNA sequences with strong optical response to neurotransmitter serotonin. First, classifier models based on convolutional neural networks (CNN) are trained on sequence features to classify DNA ligands as either high response or low response to serotonin. Second, support vector machine (SVM) regression models are trained to predict relative optical response values for DNA sequences. Finally, we demonstrate with validation experiments that integrating the predictions of ensembles of the highest quality neural network classifiers (convolutional or artificial) and SVM regression models leads to the best predictions of both high and low response sequences. With our ML approaches, we discovered five DNA-SWNT sensors with higher fluorescence intensity response to serotonin than obtained previously. Overall, the explored ML approaches, shown to predict useful DNA sequences, can be used for discovery of DNA-based sensors and nanobiotechnologies.

Streamlining cell-free protein synthesis biosensors for use in human fluids: In situ RNase inhibitor production during extract preparation

Cell-free protein synthesis (CFPS) biosensors provide flexible, fast, and on-demand diagnosis of biomarkers in human body fluids. Considering the high concentrations of many different RNases in human body fluids, RNase inhibitor is an important reagent for the human-body-fluid-based biosensors and accounts for more than 90% of the total cost of E. coli-lysate-based CFPS biosensors. Here an E. coli extract with RNase inhibition activity was developed which reduces the total cost of a CFPS biosensor by ~90%. Murine RNase inhibitor (m-RI) was overexpressed in E. coli cells at different growth temperatures, redox buffers, and folding chaperones. Reduced growth temperature accompanied by overexpression of GroEL/ES folding chaperones were found to be necessary to maintain RNase inhibition activity despite reduced m-RI expression capability. Further, to optimize protein synthesis capability of CFPS biosensors, E. coli extract containing m-RI was mixed with regular E. coli extract that did not contain m-RI. The optimized CFPS biosensor reagent mixture was lyophilized and rehydrated with 0–100% (v/v) of three human body fluids of saliva, serum, and urine. Rehydration with saliva showed the least drop in protein expression compared to serum and urine. Finally, the CFPS biosensor reagents were assessed with a saliva-based CFPS biosensor sensitive to glutamine concentrations.

A High-Throughput Method for Identifying Novel Genes That Influence Metabolic Pathways Reveals New Iron and Heme Regulation in Pseudomonas aeruginosa.

Heme is an essential metabolite for most life on earth. Bacterial pathogens almost universally require iron to infect a host, often acquiring this nutrient in the form of heme. The Gram-negative pathogen Pseudomonas aeruginosa is no exception, where heme acquisition and metabolism are known to be crucial for both chronic and acute infections. To unveil unknown genes and pathways that could play a role with heme metabolic flux in this pathogen, we devised an omic-based approach we dubbed "Met-Seq," for metabolite-coupled transposon sequencing. Met-Seq couples a biosensor with fluorescence-activated cell sorting (FACS) and massively parallel sequencing, allowing for direct identification of genes associated with metabolic changes. In this work, we first construct and validate a heme biosensor for use with P. aeruginosa and exploit Met-Seq to identify 188 genes that potentially influence intracellular heme levels. Identified genes largely consisted of metabolic pathways not previously associated with heme, including many secreted virulence effectors, as well as 11 predicted small RNAs (sRNAs) and riboswitches whose functions are not currently understood. We verify that five Met-Seq hits affect intracellular heme levels; a predicted extracytoplasmic function (ECF) factor, a phospholipid acquisition system, heme biosynthesis regulator Dnr, and two predicted antibiotic monooxygenase (ABM) domains of unknown function (PA0709 and PA3390). Finally, we demonstrate that PA0709 and PA3390 are novel heme-binding proteins. Our data suggest that Met-Seq could be extrapolated to other biological systems and metabolites for which there is an available biosensor, and provides a new template for further exploration of iron/heme regulation and metabolism in P. aeruginosa and other pathogens.IMPORTANCE The ability to simultaneously and more directly correlate genes with metabolite levels on a global level would provide novel information for many biological platforms yet has thus far been challenging. Here, we describe a method to help address this problem, which we dub "Met-Seq" (metabolite-coupled Tn sequencing). Met-Seq uses the powerful combination of fluorescent biosensors, fluorescence-activated cell sorting (FACS), and next-generation sequencing (NGS) to rapidly identify genes that influence the levels of specific intracellular metabolites. For proof of concept, we create and test a heme biosensor and then exploit Met-Seq to identify novel genes involved in the regulation of heme in the pathogen Pseudomonas aeruginosa Met-Seq-generated data were largely comprised of genes which have not previously been reported to influence heme levels in this pathogen, two of which we verify as novel heme-binding proteins. As heme is a required metabolite for host infection in P. aeruginosa and most other pathogens, our studies provide a new list of targets for potential antimicrobial therapies and shed additional light on the balance between infection, heme uptake, and heme biosynthesis.

Reduced Thiol Compounds – Induced Biosensing, Bioimaging Analysis and Targeted Delivery

Reduced thiol compounds (RTCs), such as glutathione (GSH), cysteine (Cys), and homocysteine (Hcy), are important components of many amino acids and proteins. They are also basic building blocks that make up organisms and play an important role in physiology and pathology. Therefore, based on the fundamental characteristics of RTCs in vivo, researchers have reported their use in biosensing and imaging analysis and as carriers in life sciences and health sciences. In this review, we will introduce the principles of RTCs and highlight their applications in biosensing and imaging analysis and as carriers reported from 2015 to 2020.

Plasmonic Modulation of the Upconversion Luminescence Based on Gold Nanorods for Designing a New Strategy of Sensing MicroRNAs.

Upconversion nanoparticles (UCNPs) have potential applications in biosensing and bioimaging. However, the UCNPs-based sensors constructed by luminescence resonance energy transfer (LRET) always suffer from low quenching efficiency, hindering their application. Therefore, exploring a new strategy to resolve this issue is highly desirable. Herein, a strategy based on the surface plasmon resonance (SPR) effect of gold nanorods (AuNRs) is presented. The luminescence of UCNPs was modulated by adjusting the SiO2 thickness of AuNRs@SiO2 and the structure of UCNPs; an enhancement factor of ≈50 times was obtained. Based on the results of the SPR effect of AuNRs, we designed two kinds of potential upconversion microRNA sensors using microRNA-21 as a model to resolve the problem of the lower quenching efficiency resulting from a dye as a quencher. Studies revealed that the proposed strategy could be successfully used to construct upconversion microRNA sensors for avoiding the limitation of the low quenching efficiency. The sensitivity was ≈10 000 times higher than that of the upconversion sensor using dyes as quenchers. Importantly, the assay of microRNA-21 was successfully achieved using this sensor in human serum samples and human breast cancer cell (MCF-7) lysates. It provides a new method for designing upconversion microRNA sensors and may have potential for use in biosensing and bioimaging.

Expanding the Toolkit of Fluorescent Biosensors for Studying Mitogen Activated Protein Kinases in Plants

Mitogen-activated protein kinases (MAPKs) are key regulators of numerous biological processes in plants. To better understand the mechanisms by which these kinases function, high resolution measurement of MAPK activation kinetics in different biological contexts would be beneficial. One method to measure MAPK activation in plants is via fluorescence-based genetically-encoded biosensors, which can provide real-time readouts of the temporal and spatial dynamics of kinase activation in living tissue. Although fluorescent biosensors have been widely used to study MAPK dynamics in animal cells, there is currently only one MAPK biosensor that has been described for use in plants. To facilitate creation of additional plant-specific MAPK fluorescent biosensors, we report the development of two new tools: an in vitro assay for efficiently characterizing MAPK docking domains and a translocation-based kinase biosensor for use in plants. The implementation of these two methods has allowed us to expand the available pool of plant MAPK biosensors, while also providing a means to generate more specific and selective MAPK biosensors in the future. Biosensors developed using these methods have the potential to enhance our understanding of the roles MAPKs play in diverse plant signaling networks affecting growth, development, and stress response.

Microneedle-based transdermal electrochemical biosensors based on Prussian blue-gold nanohybrid modified screen-printed electrodes.

We report on the fabrication of a microneedle-based electrochemical biosensor for use in transdermal biosensing, which includes a screen-printed electrode containing a Prussian blue-gold nanohybrid as the working electrode. The Prussian blue gold nanohybrid is made from polyethylenime (PEI)- mediated simultaneous synthesis of Prussian blue (PBNP) and gold nanoparticles (AuNP), which forms a PBNP-AuNP nanohybrid with a remarkable change in the Prussian blue character. PEI-protected polycrystalline PBNPs can be synthesized in acidic media from the single precursor potassium ferricyanide [K3 Fe(CN)6 ] at 60°C. Since PEI also enables the controlled formation of gold nanoparticles (AuNPs) in the presence of formaldehyde, nanohybrids containing PBNPs and AuNPs may be prepared. Two different methods of PEI mediated synthesis of AuNP in the presence of PBNP were considered. In Method 1, AuNP and PBNP were made independently and mixed together in an appropriate ratio. In Method 2, PBNPs were made first, followed by PEI- and formaldehyde-mediated reduction of gold cations in the presence of PBNP. PBNP-AuNPs display a remarkable change in Prussian blue behavior such that the absorption maxima of PBNP-AuNPs made through Method 1 tend to increase at 670 nm as a function of gold concentration as compared with the control; the reverse was observed when PBNP-AuNPs were made through Method 2. As made PBNPs and PBNP-AuNPs made through Method 1 display excellent catalytic activity toward both reduction and oxidation of hydrogen peroxide based on peroxidase mimetic activity. In addition, the as-synthesized PBNPs displayed superparamagnetic behavior that can be manipulated in the presence of AuNPs. The results from peroxidase mimetic activity, chemiluminescence, cyclic voltammetry, and amperometry showed suitable analytical performance of the as-made PBNP-AuNP nanohybrid for biomedical applications.

D-type optical fiber immunoglobulin G sensor based on surface plasmon resonance

In this paper, we report a D-type optical fiber biosensor for human immunoglobulin G (HIgG) detection based on surface plasmon resonance (SPR). The SPR phenomenon was both simulated by COMSOL and observed experimentally. To fabricate the sensor, the cladding of a multimode optical fiber (MMF) was polished using a grinding wheel to obtain a D-type cross-section. Next, a gold film was sputtered on the surface of the MMF. The optimal gold layer thickness and grinding depth were determined through simulations. As per the experimental results, the optimized sensor exhibited high refractive index (RI) sensitivity, which ranged from 1590.9 nm/RIU to 3513.3 nm/RIU for RI values of 1.343 to 1.373. Subsequently, Poly dimethyl diallyl ammonium chloride (PDDA) and Poly(sodium-p-styrenesulfonate) (PSS) were deposited four times in sequence to form polyelectrolyte self-assembled multilayers for the surface functionalization of the fiber. HIgG and goat anti-HIgG (GaHIgG) were chosen as the bioconjugate pair for evaluating the functionality of the fabricated biosensor, and the sensitivity to IgG was determined to be 91 nm/(mg/ml). The specificity of the biosensor was also verified through comparison tests performed using gelatin, horse IgG, and swine IgG. The obtained results confirmed the suitability of the biosensor for use in various biochemical applications.

Peroxidase-Like Behavior of Ni Thin Films Deposited by Glancing Angle Deposition for Enzyme-Free Uric Acid Sensing.

We present a nanozyme-based biosensor fabricated from nanostructured Ni films deposited onto a silicon wafer by glancing angle deposition (GLAD) for enzyme-free colorimetric monitoring of uric acid (UA), a biomarker for gout, high blood pressure, heart disease, and kidney disease. The helically structured Ni GLAD nanozymes exhibit excellent peroxidase-like activity to accelerate the oxidation reaction of colorless 3,3′,5,5′-tetramethylbenzidine (TMB) to a blue product, oxidized TMB (oxTMB), mediated by H2O2. In the presence of UA, oxTMB is reduced, decreasing the optical absorbance by an amount determined by the concentration of UA in the solution. The nanozyme not only mimics peroxidase but also possesses the notable qualities of reusability, simple operation, and reliability, making it environment-friendly and suitable for on-demand analysis. We optimized essential working parameters (pH, TMB concentration, and H2O2 concentration) to maximize the initial color change of the TMB solution. The catalytic activity of this nanozyme was compared with conventional nanofilms using the Michaelis–Menten theory. Based on this, enzyme-free biosensors were developed for colorimetric detection of UA, providing a wide detection range and a limit of detection (3.3 μM) suitable for measurements of UA concentration in sweat. Furthermore, interference from glucose and urea was studied so as to explore the potential of the biosensor for use in the clinical diagnosis of UA biomarkers.

Stimuli-responsive polymer-based systems for diagnostic applications.

Stimuli-responsive polymers exhibit properties that make them ideal candidates for biosensing and molecular diagnostics. Through rational design of polymer composition combined with new polymer functionalization and synthetic strategies, polymers with myriad responsivities, e.g., responses to temperature, pH, biomolecules, CO2, light, and electricity can be achieved. When these polymers are specifically designed to respond to biomarkers, stimuli-responsive devices/probes, capable of recognizing and transducing analyte signals, can be used to diagnose and treat disease. In this review, we highlight recent state-of-the-art examples of stimuli-responsive polymer-based systems for biosensing and bioimaging.

3D‐Printed Sugar Scaffold for High‐Precision and Highly Sensitive Active and Passive Wearable Sensors

In this study, a pairing of a previously unidentified 3D printing technique and soft materials is introduced in order to achieve not only high‐resolution printed features and flexibility of the 3D‐printed materials, but also its light‐weight and electrical conductivity. Using the developed technique and materials, high‐precision and highly sensitive patient‐specific wearable active or passive devices are fabricated for personalized health monitoring. The fabricated biosensors show low density and substantial flexibility because of 3D microcellular network‐type interconnected conductive materials that are readily printed using an inkjet head. Using high‐resolution 3D scanned body‐shape data, on‐demand personalized wearable sensors made of the 3D‐printed soft and conductive materials are fabricated. These sensors successfully detect both actively changing body strain signals and passively changing signals such as electromyography (EMG), electrodermal activity (EDA), and electroencephalogram EEG. The accurately tailored subject‐specific shape of the developed sensors exhibits higher sensitivity and faster real‐time sensing performances in the monitoring of rapidly changing human body signals. The newly developed 3D printing technique and materials can be widely applied to various types of wearable, flexible, and light‐weight biosensors for use in a variety of inexpensive on‐demand and personalized point‐of‐care diagnostics.

Silver-Based Plasmonic Nanoparticles for and Their Use in Biosensing.

The localized surface plasmon resonance (LSPR) property of metallic nanoparticles is widely exploited for chemical and biological sensing. Selective biosensing of molecules using functionalized nanoparticles has become a major research interdisciplinary area between chemistry, biology and material science. Noble metals, especially gold (Au) and silver (Ag) nanoparticles, exhibit unique and tunable plasmonic properties; the control over these metal nanostructures size and shape allows manipulating their LSPR and their response to the local environment. In this review, we will focus on Ag-based nanoparticles, a metal that has probably played the most important role in the development of the latest plasmonic applications, owing to its unique properties. We will first browse the methods for AgNPs synthesis allowing for controlled size, uniformity and shape. Ag-based biosensing is often performed with coated particles; therefore, in a second part, we will explore various coating strategies (organics, polymers, and inorganics) and their influence on coated-AgNPs properties. The third part will be devoted to the combination of gold and silver for plasmonic biosensing, in particular the use of mixed Ag and AuNPs, i.e., AgAu alloys or Ag-Au core@shell nanoparticles will be outlined. In the last part, selected examples of Ag and AgAu-based plasmonic biosensors will be presented.

Multimodal Wrist Biosensor for Wearable Cuff-less Blood Pressure Monitoring System

We propose a multimodal biosensor for use in continuous blood pressure (BP) monitoring system. Our proposed novel configuration measures photo-plethysmography (PPG) and impedance plethysmography (IPG) signals simultaneously from the subject wrist. The proposed biosensor system enables a fully non-intrusive system that is cuff-less, also utilize a single measurement site for maximum wearability and convenience of the patients. The efficacy of the proposed technique was evaluated on 10 young healthy subjects. Experimental results indicate that the pulse transit time (PTT)-based features calculated from an IPG peak and PPG maximum second derivative (f14) had a relatively high correlation coefficient (r) to the reference BP, with −0.81 ± 0.08 and −0.78 ± 0.09 for systolic BP (SBP) and diastolic BP (DBP), respectively. Moreover, here we proposed two BP estimation models that utilize six- and one-point calibration models. The six-point model is based on the PTT, whereas the one-point model is based on the combined PTT and radial impedance (Z). Thus, in both models, we observed an adequate root-mean-square-error estimation performance, with 4.20 ± 1.66 and 2.90 ± 0.90 for SBP and DBP, respectively, with the PTT BP model; and 6.86 ± 1.65 and 6.67 ± 1.75 for SBP and DBP, respectively, with the PTT-Z BP model. This study suggests the possibility of estimating a subject’s BP from only wrist bio-signals. Thus, the six- and one-point PTT-Z calibration models offer adequate performance for practical applications.

A Brief Overview of Medical Fiber Optic Biosensors and Techniques in the Modification for Enhanced Sensing Ability.

In this paper, we provide a brief overview of fiber optic biosensors for use in MedTech, specifically to aid in the diagnoses and treatment of those with chronic medical conditions. Fiber optic cables as components of biological sensors make them especially effective in biological systems that may require ultra-sensitive detection of low-frequency signals in hard to reach areas. This systematic review focuses on the differentiating factors of fiber-optic biosensors, which are tailored to apply the sensor to specific health needs. The main components of FOBS (fiber optic biosensors) such as biosensing elements, fiber optic cables, optical element enhancements, transducers, sensing strategies, photodetectors, and signal processing are covered in detail by showcasing the recent developments in modifications to these components. This paper pays particular attention to the alterations made in biosensing elements including pH elements, enzymatic elements, as well as those sensors utilizing antibodies and whole-cell bacteria. This paper reviews and discusses several published examples in the research stage of development to give the reader an overall scope of the field. The need for research on biosensing equipment is increasing, as the number of individuals with chronic diseases and the geriatric population require more effective, accurate, and mobile sensing ability and reduced invasiveness. FOBS offer a sensing solution that is accurate, tailorable to almost any clinical need, has abundant and relatively cheap material requirements, and a well-established technological base in fiber optic technology. This small price tag and large market potential make FOBS a desirable research area.

Graphene and Carbon Quantum Dots-based Biosensors for Use with Biomaterials

Graphene and Carbon Quantum Dots-based Biosensors for Use with Biomaterials