Biosensors — Open Access Journal

The detection of adenine molecules at very low concentrations is important for biological and medical research and applications. This paper reports a silver-based surface-enhanced Raman scattering (SERS) sensor with a very low detection limit for adenine molecules. Clusters of closely packed silver nanoparticles on surfaces of discrete ball-like copper bumps partially covered with graphene are deposited by immersion in silver nitrate. These clusters of silver nanoparticles exhibit abundant nanogaps between nanoparticles, where plasmonic coupling induces very high local electromagnetic fields. Silver nanoparticles growing perpendicularly on ball-like copper bumps exhibit surfaces of large curvature, where electromagnetic field enhancement is high. Between discrete ball-like copper bumps, the local electromagnetic field is low. Silver is not deposited on the low-field surface area. Adenine molecules interact with silver by both electrostatic and functional groups and exhibit low surface diffusivity on silver surface. Adenine molecules are less likely to adsorb on low-field sensor surface without silver. Therefore, adenine molecules have a high probability of adsorbing on silver surface of high local electric fields and contribute to the measured Raman scattering signal strength. We demonstrated SERS sensors made of clusters of silver nanoparticles deposited on discrete ball-like copper bumps with very a low detection limit for detecting adenine water solution of a concentration as low as 10⁻¹¹ M. Full article

Paper-based carbon working electrodes were modified with mercury or bismuth films for the determination of trace metals in aqueous solutions. Both modification procedures were optimized in terms of selectivity and sensitivity for the determination of different heavy metals, aiming their simultaneous determination. Cd (II), Pb (II) and In (III) could be quantified with both films. However, Cu (II) could not be determined with bismuth films. The modification with mercury films led to the most sensitive method, with linear ranges between 0.1 and 10 µg/mL and limits of detection of 0.4, 0.1, 0.04 and 0.2 µg/mL for Cd (II), Pb (II), In (III) and Cu (II), respectively. Nevertheless, the bismuth film was a more sustainable alternative to mercury. Tap-water samples were analyzed for the determination of metals by standard addition methodology with good accuracy, by using a low-cost and easily disposable paper-based electrochemical platform. This system demonstrated its usefulness for monitoring heavy metals in water. Full article

Biosensors are regarded as a powerful tool to detect and monitor environmental contaminants, toxins, and, more generally, organic or chemical markers of potential threats to human health. They are basically composed of a sensor part made up of either live cells or biological active molecules coupled to a transducer/reporter technological element. Whole-cells biosensors may be based on animal tissues, bacteria, or eukaryotic microorganisms such as yeasts and microalgae. Although very resistant to adverse environmental conditions, yeasts can sense and respond to a wide variety of stimuli. As eukaryotes, they also constitute excellent cellular models to detect chemicals and organic contaminants that are harmful to animals. For these reasons, combined with their ease of culture and genetic modification, yeasts have been commonly used as biological elements of biosensors since the 1970s. This review aims first at giving a survey on the different types of yeast-based biosensors developed for the environmental and medical domains. We then present the technological developments currently undertaken by academic and corporate scientists to further drive yeasts biosensors into a new era where the biological element is optimized in a tailor-made fashion by in silico design and where the output signals can be recorded or followed on a smartphone. Full article

Fecal volatile organic compounds (VOC) reflect human and gut microbiota metabolic pathways and their interaction. VOC behold potential as non-invasive preclinical diagnostic biomarkers in various diseases, e.g., necrotizing enterocolitis and late onset sepsis. There is a need for standardization and assessment of the influence of clinical and environmental factors on the VOC outcome before this technique can be applied in clinical practice. The aim of this study was to investigate the influence of gestational age (GA) and mode of delivery on the fecal VOC pattern in preterm infants born below 30 weeks of gestation. Longitudinal fecal samples, collected on days 7, 14, and 21 postnatally, were analyzed by an electronic nose device (Cyranose 320^®). In total, 58 preterm infants were included (29 infants born at GA 24–26 weeks vs. 29 at 27–29 completed weeks, 24 vaginally born vs. 34 via C-section). No differences were identified at any predefined time point in terms of GA and delivery mode (p > 0.05). We, therefore, concluded that correction for these factors in this population is not warranted when performing fecal VOC analysis in the first three weeks of life. Full article

The traditional qPCR instrument is bulky, expensive, and inconvenient to carry, so we report a portable rotary real-time fluorescent PCR (polymerase chain reaction) that completes the PCR amplification of DNA in the field, and the reaction can be observed in real-time. Through the analysis of a target gene, namely pGEM-3Zf (+), the gradient amplification and melting curves are compared to commercial devices. The results confirm the stability of our device. This is the first use of a mechanical rotary structure to achieve gradient amplification curves and melting curves comparable to commercial instruments. The average power consumption of our system is about 7.6 W, which is the lowest energy consumption for real-time fluorescence quantification in shunting PCR and enables the use of our device in the field thanks to its self-contained power supply based on a lithium battery. In addition, all of the equipment costs only about 710 dollars, which is far lower than the cost of a commercial PCR instrument because the control system through mechanical displacement replaces the traditional TEC (thermoelectric cooler) temperature control. Moreover, the equipment has a low technical barrier, which can suit the needs of non-professional settings, with strong repeatability. Full article

Background: Urinary tract infections (UTI) are among the most common infections in children. The primary tool to detect UTI is dipstick urinalysis; however, this has limited sensitivity and specificity. Therefore, urine culture has to be performed to confirm a UTI. Urinary volatile organic compounds (VOC) may serve as potential biomarker for diagnosing UTI. Previous studies on urinary VOCs focused on detection of UTI in a general population; therefore, this proof-of-principle study was set up in a clinical high-risk pediatric population. Methods: This study was performed at a tertiary nephro-urological clinic. Patients included were 0–18 years, clinically suspected of a UTI, and had abnormal urinalysis. Urine samples were divided into four groups, i.e., urine without bacterial growth, contamination, colonization, and UTI. VOC analysis was performed using an electronic nose (eNose) (Cyranose 320^®) and VOC profiles of subgroups were compared. Results: Urinary VOC analysis discriminated between UTI and non-UTI samples (AUC 0.70; p = 0.048; sensitivity 0.67, specificity 0.70). The diagnostic accuracy of VOCs improved when comparing urine without bacterial growth versus with UTI (AUC 0.80; p = 0.009, sensitivity 0.79, specificity 0.75). Conclusions: In an intention-to-diagnose high-risk pediatric population, UTI could be discriminated from non-UTI by VOC profiling, using an eNose. Since eNose can be used as bed-side test, these results suggest that urinary VOC analysis may serve as an adjuvant in the diagnostic work-up of UTI in children. Full article

Parmigiano Reggiano cheese is one of the most appreciated Italian foods on account of its high nutrient content and taste. Due to its high cost, these characteristics make this product subject to counterfeiting in different forms. In this study, an approach based on an array of gas sensors has been employed to assess if it was possible to distinguish different samples based on their aroma. Samples were characterized in terms of rind percentage, seasoning, and rind working process. From the responses of the sensors, five features were extracted and the capability of these parameters to recognize target classes was tested with statistical analysis. Hence, the performance of the sensors’ array was quantified using artificial neural networks. To simplify the problem, a hierarchical approach has been used: three steps of classification were performed, and in each step one parameter of the grated cheese was identified (firstly, seasoning; secondly, rind working process; finally, rind percentage). The accuracies ranged from 88.24% to 100%. Full article

Affinity characterization is essential to develop reliable aptamers for tumor biomarker detection. For alpha-fetoprotein (AFP), a biomarker of hepatocellular carcinoma (HCC), two DNA aptamers were described with very different affinity. In this work, we estimate the dissociation constant of both of them by means of a direct assay on magnetic beads modified with AFP and electrochemical detection on carbon screen-printed electrodes (SPCE). Unlike previous works, both aptamers showed similar dissociation constant (K_d) values, in the subµM range. In order to improve the performance of these aptamers, we proposed the isothermal amplification of the aptamers by both terminal deoxynucleotidyl transferase (TdT) and rolling circle amplification (RCA). Both DNA amplifications improved the sensitivity and also the apparent binding constants from 713 nM to 189 nM for the short aptamer and from 526 nM to 32 nM for the long aptamer. This improvement depends on the true affinity of the binding pair, which ultimately limits the analytical usefulness. Full article

The development of reliable biosensing platforms plays a key role in the detection of proteins in clinically and environmentally derived samples for diagnostics, as well as for process monitoring in biotechnological productions. For this purpose, the biosensor has to be stable and reproducible, and highly sensitive to detect potentially extremely low concentrations and prevent the nonspecific binding of interfering compounds. In this review, we present an overview of recently published (2017–2019) immobilization techniques for aptamers on gold electrodes for the electrochemical detection of proteins. These include the direct immobilization of thiolated aptamers and the utilization of short linkers, streptavidin/biotin interaction, as well as DNA nanostructures and reduced graphene oxide as immobilization platforms. Applied strategies for signal amplification and the prevention of biofouling are additionally discussed, as they play a crucial role in the design of biosensors. While a wide variety of amplification strategies are already available, future investigations should aim to establish suitable antifouling strategies that are compatible with electrochemical measurements. The focus of our review lies on the detailed discussion of the underlying principles and the presentation of utilized chemical protocols in order to provide the reader with promising ideas and profound knowledge of the subject, as well as an update on recent discoveries and achievements. Full article

Previous studies report periodontitis and peri-implantitis being able to induce systemic low-grade inflammation, which is known to be associated with increased risk for some systemic medical disease such as cardiovascular disease. In this regard, recent studies have shown that host modulation therapy (HMT) together with traditional mechanical and surgical treatment not only cease the progression of periodontitis but also reduce the systemic collagenolytic biomarkers in both oral fluids and circulation. This suggests that the corresponding adjunctive HMT-medication could be effective in the prevention and treatment of dental peri-implantitis, as well. Furthermore, low-cost, safe, and practical oral fluid active matrix metalloproteinase-8 (aMMP-8) lateral-flow immunotests have been proposed as point-of-care/chair-side diagnostic tools to detect peri-implantitis and periodontitis, and to monitor their effective resolutions, while using various therapeutic strategies, including host modulation. This study reports the potential benefits of HMT-medication in the prevention and treatment of dental peri-implantitis among five patients (four of five were current/ex-smokers). In addition, the aMMP-8 point-of-care test diagnosed 20 peri-implantitis and 20 healthy controls correctly. In conclusion, this study and previous studies support the potential effectiveness of HMT-medication(s) and point-of-care/chair-side technologies in the treatment and diagnostics/monitoring of peri-implantitis. However, more studies are needed to further confirm this. Full article

In this work, we report the development of a highly sensitive biosensor for sulfapyridine detection based on an integrated bio micro-electromechanical system (Bio-MEMS) containing four gold working electrodes (WEs), a platinum counter electrode (CE), and a reference electrode (RE). Firstly, the cleaned WEs were modified with 4-aminophenylacetic acid (CMA). Then, (5-[4-(amino)phenylsulfonamide]-5-oxopentanoic acid (SA2BSA) was immobilized onto the transducers surface by carbodiimide chemistry. The analyte was quantified by competitive detection with SA2BSA immobilized on the WE toward a mixture of Ab155 antibody (with fixed concentration) and sulfapyridine. In order to obtain a highly sensitive biosensor, Ab155 was immobilized onto magnetic latex nanoparticles surface to create a 3D architecture (Ab-MLNp). Using electrochemical impedance spectroscopy (EIS), we investigated the influence of the Ab-MLNp on the sensitivity of our approach. The optimized system was analyzed, as competitive assay, with different concentrations of sulfapyridine (40 µM, 4 µM, and 2 nM) and with phosphate buffer solution. From data fitting calculations and graphs, it was observed that the EIS showed more linearity when Ab-MLNp was used. This result indicates that the magnetic latex nanoparticles increased the sensitivity of the biosensor. Full article

Changing lifestyle and food habits are responsible for health problems, especially those related to bone in an aging population. Poor bone health has now become a serious matter of concern for many of us. In order to avoid serious consequences, the early prediction of symptoms and diagnosis of bone diseases have become the need of the hour. From this inspiration, the evolution of different bone health monitoring techniques and measurement methods practiced by researchers and healthcare companies has been discussed. This paper focuses on various types of bone diseases along with the modeling and remodeling phenomena of bones. The evolution of various diagnosis tests for bone health monitoring has been also discussed. Various types of bone turnover markers, their assessment techniques, and recent developments for the monitoring of biochemical markers to diagnose the bone conditions are highlighted. Then, the paper focuses on the potential assessment of the recent sensing techniques (physical sensors and biosensors) that are currently available for bone health monitoring. Considering the importance of electrochemical biosensors in terms of high sensitivity and reliability, specific attention has been given to the recent development of electrochemical biosensors and significance in real-time monitoring of bone health. Full article

Visible/near-infrared (VIS/NIR) spectroscopy is a powerful tool for rapid, nondestructive fruit quality detection. This technology has been widely applied for quality detection of small, thin-peeled fruit, though less so for large, thick-peeled fruit due to a weak spectral signal resulting in a reduction of accuracy. More modeling work should be focused on solving this problem. “Shatian” pomelo is a traditional Chinese large, thick-peeled fruit, and granulation and water loss are two major internal quality factors that influence its storage quality. However, there is no efficient, nondestructive detection method for measuring these factors. Thus, the VIS/NIR spectral signal detection of 120 pomelo samples during storage was performed. Information mining (singular sample elimination, data processing, feature extraction) and modeling were performed in different ways to construct the optimal method for achieving an accurate detection. Our results showed that the water content of postharvest pomelo was optimally detected using the Savitzky–Golay method (SG) plus the multiplicative scatter correction method (MSC) for data processing, genetic algorithm (GA) for feature extraction, and partial least squares regression (PLSR) for modeling (the coefficient of determination and root mean squared error of the validation set were 0.712 and 0.0488, respectively). Granulation degree was best detected using SG for data processing and PLSR for modeling (the detection accuracy of the validation set was 100%). Additionally, our research showed a weak relationship between the pomelo water content and granulation degree, which provided a reference for the existing debates. Therefore, our results demonstrated that VIS/NIR combined with optimal information mining and modeling methodswas feasible for determining the water content and granulation degree of postharvest pomelo, and for providing references for the nondestructive internal quality detection of other large, thick-peeled fruits. Full article

Skin conductivity (i.e., sweat) forms the basis of many physiology-based emotion and stress detection systems. However, such systems typically do not detect the biomarkers present in sweat, and thus do not take advantage of the biological information in the sweat. Likewise, such systems do not detect the volatile organic components (VOC’s) created under stressful conditions. This work presents a review into the current status of human emotional stress biomarkers and proposes the major potential biomarkers for future wearable sensors in affective systems. Emotional stress has been classified as a major contributor in several social problems, related to crime, health, the economy, and indeed quality of life. While blood cortisol tests, electroencephalography and physiological parameter methods are the gold standards for measuring stress; however, they are typically invasive or inconvenient and not suitable for wearable real-time stress monitoring. Alternatively, cortisol in biofluids and VOCs emitted from the skin appear to be practical and useful markers for sensors to detect emotional stress events. This work has identified antistress hormones and cortisol metabolites as the primary stress biomarkers that can be used in future sensors for wearable affective systems. Full article

Point-of-care (POC) diagnostics enables the diagnosis and monitoring of patients from the clinic or their home. Ideally, POC devices should be compact, portable and operatable without the requirement of expertise or complex fluid mechanical controls. This paper showcases a chip-and-dip device, which works on the principle of capillary-driven flow microfluidics and allows analytes’ detection by multiple microchannels in a single microchip via smartphone imaging. The chip-and-dip device, fabricated with inexpensive materials, works by simply dipping the reagents-coated microchip consisting of microchannels into a fluidic sample. The sample is loaded into the microchannels via capillary action and reacts with the reagents to produce a colourimetric signal. Unlike dipstick tests, this device allows the loading of bacterial/pathogenic samples for antimicrobial testing. A single device can be coated with multiple reagents, and more analytes can be detected in one sample. This platform could be used for a wide variety of assays. Here, we show the design, fabrication and working principle of the chip-and-dip flow device along with a specific application consisting in the determination of β-lactamase activity and cortisol. The simplicity, robustness and multiplexing capability of the chip-and-dip device will allow it to be used for POC diagnostics. Full article

The immunoglobulin E (IgE) level in serum is an important factor in the examination of allergy. Ferrocene (Fc)-modified self-assembled monolayers (SAMs) were placed on an indium tin oxide (ITO) electrode as a sensing layer for the detection of human IgE. The Fc moiety in the SAMs facilitated the electron transfer through the organic SAMs layer and electrocatalytic signal amplification. The electrochemical measurement was accomplished after the sandwich type immobilization of the receptor antibody, target human IgE, and enzyme conjugated secondary antibody. The enzyme product, p-aminophenol, was quantitatively analyzed by redox cycling via Fc. In addition, the electrochemical impedance spectroscopy (EIS) was investigated for the detection of IgE. The limit of detection (LOD), limit of quantification (LOQ), and dynamic range of the electrochemical sensor were 3 IU/mL, 10 IU/mL, and from 10 IU/mL to 100 IU/mL, respectively. Full article

More than 783 million people worldwide are currently without access to clean and safe water. Approximately 1 in 5 cases of mortality due to waterborne diseases involve children, and over 1.5 million cases of waterborne disease occur every year. In the developing world, this makes waterborne diseases the second highest cause of mortality. Such cases of waterborne disease are thought to be caused by poor sanitation, water infrastructure, public knowledge, and lack of suitable water monitoring systems. Conventional laboratory-based techniques are inadequate for effective on-site water quality monitoring purposes. This is due to their need for excessive equipment, operational complexity, lack of affordability, and long sample collection to data analysis times. In this review, we discuss the conventional techniques used in modern-day water quality testing. We discuss the future challenges of water quality testing in the developing world and how conventional techniques fall short of these challenges. Finally, we discuss the development of electrochemical biosensors and current research on the integration of these devices with microfluidic components to develop truly integrated, portable, simple to use and cost-effective devices for use by local environmental agencies, NGOs, and local communities in low-resource settings. Full article

The prominent rostrum of the North American Paddlefish, supported by a lattice-like endoskeleton, is highly durable, making it an important candidate for bio-inspiration studies. Energy dissipation and load-bearing capacity of the structure from extreme physical force has been demonstrated superior to that of man-made systems, but response to continuous hydraulic forces is unknown and requires special instrumentation for in vivo testing on a live fish. A single supply strain gage amplifier circuit has been combined with a digital three-axis accelerometer, implemented in a printed circuit board (PCB), and integrated with the commercial-off-the-shelf Adafruit Feather M0 datalogger with a microSD card. The device is battery powered and enclosed in silicon before attachment around the rostrum with a silicon strap "watch band." As proof-of-concept, we tested the instrumentation on an amputated Paddlefish rostrum in a water-filled swim tunnel and successfully obtained interpretable data. Results indicate that this design could work on live swimming fish in future in vivo experiments. Full article

Heterocyclic amine histamine is a well-known foodborne toxicant (mostly linked to “scombroid poisoning”) synthesized from the microbial decarboxylation of amino acid histidine. In this work, we report the fabrication of a flexible screen-printed immunosensor based on a silver electrode coated with single-walled carbon nanotubes (SWCNTs) for the detection of histamine directly in fish samples. Biosensors were realized by first spray depositing SWCNTs on the working electrodes and by subsequently treating them with oxygen plasma to reduce the unwanted effects related to their hydrophobicity. Next, anti-histamine antibodies were directly immobilized on the treated SWCNTs. Histamine was detected using the typical reaction of histamine and histamine-labeled with horseradish peroxidase (HRP) competing to bind with anti-histamine antibodies. The developed immunosensor shows a wide linear detection range from 0.005 to 50 ng/mL for histamine samples, with a coefficient of determination as high as 98.05%. Average recoveries in fish samples were observed from 96.00% to 104.7%. The biosensor also shows good selectivity (less than 3% relative response for cadaverine, putrescine, and tyramine), reproducibility, mechanical and time stability, being a promising analytical tool for the analysis of histamine, as well as of other food hazards. Full article