Fabrication of an electrospun polycaprolactone substrate for colorimetric bioassays.

Colorimetric assays rely on detecting colour changes to measure the concentration of target molecules. Paper substrates are commonly used for the detection of biomarkers due to their availability, porous structure, and capillarity. However, the morphological and mechanical properties of paper, such as fibre diameter, pore size, and tensile strength, cannot be easily tuned to meet the specific requirements of colorimetric sensors, including liquid capacity and reagent immobilisation. As an alternative to paper materials, biodegradable polymeric membranes made of electrospun polycaprolactone (PCL) fibres can provide various tunable properties related to fibre diameter and pore size.We aimed to obtain a glucose sensor substrate for colorimetric sensing using electrospinning with PCL. A feeding solution was created by mixing PCL/chloroform and 3,3',5',5'-tetramethylbenzidine (TMB)/ethanol solutions. This solution was electrospun to fabricate a porous membrane composed of microfibres consist of PCL and TMB. The central area of the membrane was made hydrophilic through air plasma treatment, and it was subsequently functionalized with a solution containing glucose oxidase, horseradish peroxidase, and trehalose.The sensing areas were evaluated by measuring colour changes in glucose solutions of varying concentrations. The oxidation reactions of glucose and TMB in sensor substrates were recorded and analysed to establish the correlation between different glucose concentrations and colour changes. For comparison, conventional paper substrates prepared with same parameters were evaluated alongside the electrospun PCL substrates. As a result, better immobilization of reagents and higher sensitivity of glucose were achieved with PCL substrates, indicating their potential usage as a new sensing substrate for bioassays.

Mononuclear Zn(II) Complex Based on N2O Ligand Compartment: First Case to Detect Nitro Explosives.

This paper scrutinises the development of low-cost hypersensitive fluorescent probes manipulated chemically with Schiff base complexes and their prospective applicability for the detection of nitro explosives in light of the rapidly expanding demand for anti-trafficking measures. In this study, a new Zn(II) metal complex has been synthesized in one pot using the Schiff base ligand L= 2-methoxy-5-methyl-N-(2-pyridin-2-ylmethylene) aniline. The complex was also thoroughly characterised using various spectroscopic tools and subjected to single crystal XRD analysis. In the asymmetric unit, square pyramidal zinc (II) centre exist in the inner N2O compartment of the ligand L. The intermolecular Cg···Cg interactions exist between two different asymmetric residual units lead to supramolecular assembly along b axis. By turning off the fluorescence response, the complex serves as a sensor for the detection of nitro aromatics in CH3CN solution. A significant quenching efficiency has been reported with a quenching constant (KSV) 1.8 × 104 M-1 for 4-nitrobenzoic acid during investigation of sensing phenomenon in solution phase. In addition, determining the binding stoichiometry of the chemosensor with NO2 and the binding constant, the mechanism of fluorescence quenching has also been postulated. The detection limit of NO2 is 7.6×10 -7 M, with the binding constant k = 1.1021× 108 M-1. Additionally, the DFT calculation makes it easier to comprehend the appropriate binding process in light of the findings of experiments. We also designed a paper sensor strip for the visual detection of Nitro Explosive Residues in light of the sensor's potential used in forensic investigations.

Simple and cheap preparation of fluorescence paper sensor based in carbon dot for visual detection of chloramphenicol.

Carbon dots (CDs) are nanometer-scale particles produced from carbon sources that exhibit fluorescence emission. The present work presents the synthesis and characterization of CDs, as well as the sensing studies for the determination of chloramphenicol (CAP). CAP is an antibiotic used in human medicine and agriculture, and its indiscriminate use and inappropriate disposal have caused damage to human health and the environment. The carbonaceous precursor used in the synthesis of CDs was 3,4-diaminobenzoic acid (3,4-DABA) through the hydrothermal method via domestic microwave irradiation. The first synthesis procedure was carried out in the presence of water/ethanol (a-CDs) and the second in the presence of 1 mol/L sodium hydroxide/ethanol (b-CDs). The CDs were initially characterized in terms of spectroscopic properties in the ultraviolet and visible region (UV-visible), Fourier-transform infrared (FTIR) spectra, Raman spectroscopy, and fluorescence emission spectroscopy. Sensing studies for the antibiotic C were performed by fluorescence suppression in the presence of a- and b-CDs, as well as the precursor 3,4-DABA. The a- and b-CDs presented similar values of linear range 0.00080-0.0050 mg/ml and limit of detection (LOD) = 0.00030 mg/ml (0.30 ppm) for CAP. Then, a- and b-CDs were embedded in Whatman and Mellita® filter paper, and CAP sensing was evaluated through UV light excitation.

A Turn-On and Colorimetric Probe Based on Isophorone Skeleton for Detecting Nerve Agent Mimic Diethyl Chlorophosphite.

A new turn-on probe (SWJT-20) based on isophorone fluorophore for the detection of nerve agent mimic diethyl chlorophosphite (DCP) was designed and synthesized. SWJT-20 could rapidly respond to DCP within 2 s using UV-Vis or fluorescent spectra, accompanied by a significant change in the solution color under visible light or UV light, which could be observed by the naked eyes. The detection limit of SWJT-20 to DCP was as low as 8.3 nM, which is lower than those of most reported fluorescent probes for DCP detection. Additionally, SWJT-20 could quantitatively measure DCP using ratio changes in A427/A645 in absorption spectra. Furthermore, facile paper as sensors with the visualization of colorimetric/fluorometric responses based on SWJT-20 has been fabricated. Notably, this probe could detect DCP vapor through gas diffusion experiments.

A Fluorescent Molecularly Imprinted Polymer-Coated Paper Sensor for On-Site and Rapid Detection of Glyphosate.

Due to the massive use and abuse of pesticides, practices which have led to serious threats to human health, the research community must develop on-site and rapid detection technology of pesticide residues to ensure food safety. Here, a paper-based fluorescent sensor, integrated with molecularly imprinted polymer (MIP) targeting glyphosate, was prepared by a surface-imprinting strategy. The MIP was synthesized by a catalyst-free imprinting polymerization technique and exhibited highly selective recognition capability for glyphosate. The MIP-coated paper sensor not only remained selective, but also displayed a limit of detection of 0.29 µmol and a linear detection range from 0.5 to 10 µmol. Moreover, the detection time only took about 5 min, which is beneficial for rapid detection of glyphosate in food samples. The detection accuracy of such paper sensor was good, with a spiked recovery rate of 92-117% in real samples. The fluorescent MIP-coated paper sensor not only has good specificity, which is helpful to reduce the food matrix interference and shorten the sample pretreatment time, but it also has the merits of high stability, low-cost and ease of operation and carrying, displaying great potential for application in the on-site and rapid detection of glyphosate for food safety.

Colorimetric detection of H2O2 with Fe3O4@Chi nanozyme modified µPADs using artificial intelligence.

Peroxidase mimicking Fe3O4@Chitosan (Fe3O4@Chi) nanozyme was synthesized and used for high-sensitive enzyme-free colorimetric detection of H2O2. The nanozyme was characterized in comparison with  Fe3O4 nanoparticles (NPs) using X-ray diffraction, Fourier-transform infrared spectroscopy, dynamic light scattering, and thermogravimetric analysis. The catalytic performance of Fe3O4@Chi nanozyme was first evaluated by UV-Vis spectroscopy using 3,3',5,5'-tetramethylbenzidine. Unlike Fe3O4NPs, Fe3O4@Chi nanozyme exhibited an intrinsic peroxidase activity with a detection limit of 69 nM. Next, the nanozyme was applied to a microfluidic paper-based analytical device (µPAD) and colorimetric analysis was performed at varying concentrations of H2O2 using a machine learning-based smartphone app called "Hi-perox Sens++ ." The app with machine learning classifiers made the system user-friendly as well as more robust and adaptive against variation in illumination and camera optics. In order to train various machine learning classifiers, the images of the µPADs were taken at 30 s and 10 min by four smartphone brands under seven different illuminations. According to the results, linear discriminant analysis exhibited the highest classification accuracy (98.7%) with phone-independent repeatability at t = 30 s and the accuracy was preserved for 10 min. The proposed system also showed excellent selectivity in the presence of various interfering molecules and good detection performance in tap water.

Hollow Microneedles on a Paper Fabricated by Standard Photolithography for the Screening Test of Prediabetes.

Microneedle (MN) is a novel technique of the biomedical engineering field because of its ability to evaluate bioinformation via minimal invasion. One of the urgent requirements for ground-breaking health care monitoring is persistent monitoring. Hollow microneedles are extremely attractive to extract skin interstitial fluid (ISF) for analysis, which makes them perfect for sensing biomarkers and facilitating diagnosis. Nevertheless, its intricate fabrication process has hampered its extensive application. The present research demonstrates an easy one-step preparation approach for hollow MNs on the foundation of the refraction index variations of polyethylene glycol diacrylate (PEGDA) in the process of photopolymerization. The fabricated hollow microneedle exhibited ideal mechanical characteristics to penetrate the skin. Hydrodynamic simulations showed that the liquid was risen in a hollow microneedle by capillary force. Furthermore, a paper-based glucose sensor was integrated with the hollow microneedle. We also observed that the MN array smoothly extracted ISF in vitro and in vivo by capillary action. The outcomes displayed the applicability of the MN patch to persistent blood glucose (GLU) monitoring, diagnosis-related tests for patients and pre-diabetic individuals.

New microfluidic paper-based analytical device for iron determination in urine samples.

Iron is an important micronutrient involved in several mechanisms in the human body and can be an important biomarker. In this work, a simple and disposable microfluidic paper-based analytical device (µPAD) was developed for the quantification of iron in urine samples. The detection was based on the colorimetric reaction between iron(II) and bathophenanthroline and the reduction of iron(III) to iron(II) with hydroxylamine. The developed µPAD enabled iron determination in the range 0.07-1.2 mg/L, with a limit of detection of 20 µg/L and a limit of quantification of 65 µg/L, thus suitable for the expected values in human urine. Additionally, targeting urine samples, the potential interference of the samples color was overcome by incorporating a sample blank assessment for absorbance subtraction. Stability studies revealed that the device was stable for 15 days prior to usage and that the formed colored product was stable for scanning up to 3 h. The accuracy of the developed device was established by analyzing urine samples (#26) with the developed µPAD and with the atomic absorption spectrometry method; the relative deviation between the two sets of results was below 9.5%.

Advanced graphene oxide-based paper sensor for colorimetric detection of miRNA.

MicroRNAs (miRNAs), found in blood and body fluids, have emerged as potential non-invasive biomarkers for disease and injury. miRNAs are quantitatively evaluated using typical RNA analysis methods such as the quantitative reverse transcription polymerase chain reaction, microarrays, and Northern blot, all of which require complex procedures and expensive reagents. To utilize miRNAs as practical biomarkers, it will be helpful to develop simple and user-friendly sensors. In this study, a paper-based miRNA sensor was developed by combining two methods: (1) target-recycled DNAzyme (Dz) amplification and (2) graphene oxide-assisted Dz blotting on paper. The Dz spots on paper caused a miRNA-dependent color change in presence of colorimetric reagents and facilitated the quantification of absolute amount of the target miRNA, irrespective of the volume, with high reproducibility. This approach is technologically straightforward and enables quantification of as low as 7.75 fmol miRNA using a portable smartphone.

Smartphone coupled with paper-based chemical sensor for on-site determination of iron(III) in environmental and biological samples.

We report a smartphone-paper-based sensor impregnated with cetyltrimethylammonium bromide modified silver nanoparticles (AgNPs/CTAB) for determination of Fe3+ in water and blood plasma samples. The methodology for determination of Fe3+ is based on the change in signal intensity of AgNPs/CTAB fabricated on a paper substrate after the deposition of analyte, using a smartphone followed by processing with ImageJ software. The mechanism of sensing for detection and determination of Fe3+ is based on the discoloration of AgNPs which impregnated the paper substrate. The discoloration is attributed to the electron transfer reaction taking place on the surface of NPs in the presence of CTAB. Fe3+ was determined when the paper was impregnated with 1 mM AgNPs for 5 min of reaction time and the substrate was kept under acidic conditions. The linear range for determination of total iron in terms of Fe3+ was 50-900 µg L-1 with a limit of determination (LOD) of 20 µg L-1 and coefficient of variation (CV) of 3.2%. The good relative recovery of 91.3-95.0% and interference studies showed the selectivity of the method for determination of total iron in water and blood plasma samples. Smartphone-paper-based sensors have advantages of simplicity, rapidity, user-friendliness, low cost, and miniaturization of the method for on-site determination of total iron compared to methods that require sophisticated analytical instruments. Graphical abstract Smartphone-paper-based sensor with cetyltrimethylammonium bromide modified silver nanoparticles for determination of Fe3+ in water and blood plasma samples.

Perfluorooctanesulfonic Acid Detection Using Molecularly Imprinted Polyaniline on a Paper Substrate.

Perfluorinated compounds like perfluorooctanesulfonic acid (PFOS) are synthetic water pollutants and have accumulated in environments for decades, causing a serious global health issue. Conventional assays rely on liquid chromatography and mass spectroscopy that are very expensive and complicated and thus limit the large-scale monitoring of PFOS in wastewater. To achieve low-cost and accurate detection of PFOS, we designed a paper-based sensor with molecularly imprinted polyaniline electrodes that have recognition sites specific to PFOS. The calibration curve of resistivity ratios as a function of PFOS concentrations has a linear range from 1 to 100 ppt with a coefficient of determination of 0.995. The estimated limit of detection is 1.02 ppt. We also investigated attenuated total reflectance Fourier-transform infrared spectroscopy (ATR-FTIR) and X-ray photoelectron spectroscopy (XPS) spectra of the surface of the polyaniline (PANI) electrodes to propose the potential recognition sites in polyaniline matrix and the detection mechanism. This electrical paper sensor with low cost and excellent sensitivity and selectivity provides the potential for large-scale monitoring of wastewater.

A Flexible and Low-Cost Tactile Sensor Produced by Screen Printing of Carbon Black/PVA Composite on Cellulose Paper.

This study presents the design and fabrication of a flexible tactile sensor printed on a cellulose paper substrate using a carbon black (CB) - filled polyvinyl alcohol (PVA) polymer matrix as ink material. In the design, electrodes are obtained by screen printing of CB/PVA composite on dielectric cellulose paper. The screen-printing method is preferred for fabrication because of its simplicity and low manufacturing cost. The tactile sensor is formed by overlapping two ink-printed sheets. Electrical properties are investigated under compressive and tensile strains. The results indicate that the tactile sensor configuration and materials can be used for piezoresistive, capacitive, and also impedance sensors. The same tactile sensor structure is also examined using a commercial carbon-based ink for performance comparison. The comparative study indicates that CB/PVA ink screen-printed on paper demonstrates superior sensitivity for capacitive sensing with low hysteresis, as well as low response and recovery times. The piezoresistive-sensing properties of CB/PVA on cellulose paper show a gauge factor (GF) of 10.68, which is also very promising when conventional metal strain gauges are considered. CB/PVA screen-printed on cellulose paper features impedance-sensing properties and is also sensitive to the measurement frequency. Therefore, the response type of the sensor can be altered with the frequency.

A Low-Cost Paper Glucose Sensor with Molecularly Imprinted Polyaniline Electrode.

For the hundreds of millions of worldwide diabetic patients, glucose test strips are the most important and commonly used tool for monitoring blood glucose levels. Commercial test strips use glucose oxidases as recognition agents, which increases the cost and reduces the durability of test strips. To lower the cost of glucose sensors, we developed a paper-based electrical sensor with molecularly imprinted glucose recognition sites and demonstrated the determination of various glucose concentrations in bovine blood solutions. The sensing electrode is integrated with molecular recognition sites in the conductive polymer. A calibration graph as a function of glucose concentration in aqueous solution was acquired and matched with a correlation coefficient of 0.989. We also demonstrated the determination of the added glucose concentrations ranging from 2.2 to 11.1 mM in bovine blood samples with a linear correlation coefficient of 0.984. This non-enzymatic glucose sensor has the potential to reduce the health care cost of test strips as well as make glucose sensor test strips more accessible to underserved communities.

A Simple DNAzyme-Based Fluorescent Assay for Klebsiella pneumoniae.

Pathogenic bacteria pose a serious threat to public health, and the rapid and cost-effective detection of such bacteria remains a major challenge. Herein, we present a DNAzyme-based fluorescent paper sensor for Klebsiella pneumoniae. The DNAzyme was generated by an in vitro selection technique to cleave a fluorogenic DNA-RNA chimeric substrate in the presence of K. pneumoniae. The DNAzyme was printed on a paper substrate in a 96-well format to serve as mix-and-read fluorescent assay that exhibits a limit of detection (LOD) 105  CFUs mL-1 . Evaluated with 20 strains of clinical bacterial isolates, the DNAzyme produced the desired fluorescence signal with the samples of K. pneumoniae, regardless of their source or drug resistance. The assay is simple to use, rapid, inexpensive, and avoids the complex procedures of sample preparation and equipment. We believe that this DNAzyme-based fluorescent assay has potential for practical applications to identify K. pneumoniae.

A nitrocellulose paper strip for fluorometric determination of bisphenol A using molecularly imprinted nanoparticles.

The authors describe a test stripe for fluorometric determination of the endocrine disruptor bisphenol A (BPA). Graphene quantum dots (GQDs) were immobilized on molecularly imprinted nanoparticles which then were placed on nitrocellulose paper. The GQDs display blue fluorescence (with excitation/emission peaks at 350/440 nm) which is reduced in the presence of BPA. The test stripe has a 43.9 ± 0.8 µg·L-1 limit of detection in case of water samples. The stripe was applied to the determination of BPA in (spiked) tap water and sea water, and the LODs were found to be 1.8 ± 0.2 µg·L-1 and 4.2 ± 0.5 µg·L-1, respectively. Structural analogs of BPA, such as aminophenol, phenol, hydroquinone and naphthol were found not to interfere. Graphical abstract Schematic presentation of graphene quantum dots immobilized on molecularly imprinted nanoparticles placed on nitrocellulose paper for the determination of Bisphenol A in tap water and seawater. The method is based on the fluorescence quenching due to binding of targets in specific recognition sites.

Screen-Printed Sensors for Colorimetric Detection of Hydrogen Sulfide in Ambient Air.

A fast and sensitive method to monitor hydrogen sulfide (H2S) in ambient air based on a visible color change of a printed disposable sensor has been developed. As gas-sensitive material, an immobilized copper(II) complex of the azo dye 1-(2-pyridylazo)-2-naphtol (H-PAN) was synthesized and prepared in an ethyl cellulose matrix for screen printing. If H2S is present in ambient air, the gas sensitive layer changes its color from purple to yellow. A pre-primed polyethylene (PE) foil and a coated offset paper served as the printing substrate. The colorimetric response to the target gas was measured by UV/Vis spectroscopy in reflection at H2S concentrations between 1 to 20 ppm. Possible cross-sensitivities of the printed sensors towards methane (CH4), formaldehyde (CH2O), carbon monoxide (CO), ammonia (NH3), and nitrogen dioxide (NO2), as well as the long-term stability was investigated. Furthermore, reflection measurements of the Cu-PAN complex on an amorphous silica powder under gas admission served as preliminary test for the subsequent paste development.

Cost-Effective and Handmade Paper-Based Immunosensing Device for Electrochemical Detection of Influenza Virus.

Although many studies concerning the detection of influenza virus have been published, a paper-based, label-free electrochemical immunosensor has never been reported. Here, we present a cost-effective, handmade paper-based immunosensor for label-free electrochemical detection of influenza virus H1N1. This immunosensor was prepared by modifying paper with a spray of hydrophobic silica nanoparticles, and using stencil-printed electrodes. We used a glass vaporizer to spray the hydrophobic silica nanoparticles onto the paper, rendering it super-hydrophobic. The super-hydrophobicity, which is essential for this paper-based biosensor, was achieved via 30-40 spray coatings, corresponding to a 0.39-0.41 mg cm-2 coating of nanoparticles on the paper and yielding a water contact angle of 150° ± 1°. Stencil-printed carbon electrodes modified with single-walled carbon nanotubes and chitosan were employed to increase the sensitivity of the sensor, and the antibodies were immobilized via glutaraldehyde cross-linking. Differential pulse voltammetry was used to assess the sensitivity of the sensors at various virus concentrations, ranging from 10 to 104 PFU mL-1, and the selectivity was assessed against MS2 bacteriophages and the influenza B viruses. These immunosensors showed good linear behaviors, improved detection times (30 min), and selectivity for the H1N1 virus with a limit of detection of 113 PFU mL-1, which is sufficiently sensitive for rapid on-site diagnosis. The simple and inexpensive methodologies developed in this study have great potential to be used for the development of a low-cost and disposable immunosensor for detection of pathogenic microorganisms, especially in developing countries.

Development of a cobinamide-based end-of-service-life indicator for detection of hydrogen cyanide gas.

We describe an inexpensive paper-based sensor for rapid detection of low concentrations (ppm) of hydrogen cyanide gas. A piece of filter paper pre-spotted with a dilute monocyanocobinamide [CN(H2O)Cbi] solution was placed on the end of a bifurcated optical fiber and the reflectance spectrum of the CN(H2O)Cbi was monitored during exposure to 1.0-10.0 ppm hydrogen cyanide gas. Formation of dicyanocobinamide yielded a peak at 583 nm with a simultaneous decrease in reflectance from 450-500 nm. Spectral changes were monitored as a function of time at several relative humidity values: 25, 50, and 85% relative humidity. With either cellulose or glass fiber papers, spectral changes occurred within 10 s of exposure to 5.0 ppm hydrogen cyanide gas (NIOSH recommended short-term exposure limit). We conclude that this sensor could provide a real-time end-of-service-life alert to a respirator user.

A facile and intelligent detection method for diclazuril based on a stable dual emissive Eu3+-dopped metal-organic framework.

Diclazuril (DIC) is a broad-spectrum anti-coccidiosis drug of the triazine class, widely used in poultry farming. The overuse of DIC may lead to its accumulation in animal bodies, which may enter the food chain and threaten human health. In this work, we fabricated a stable Eu3+-doped UiO-66 fluorescence sensor (EuUHIPA-30) for the sensitive detection of DIC. Among 20 veterinary drugs, the fluorescence of EuUHIPA-30 selectively responds to DIC, with a low detection limit (0.19 µM) and fast response (10 s). EuUHIPA-30 is recyclable and can detect DIC in chicken and eggs with good recoveries. Moreover, a smartphone-integrated paper-based sensor enables the instrument-free, rapid, visual, and intelligent detection of DIC in chickens and eggs. This work provides a promising candidate for practical fluorescent DIC sensing in animal-derived food to promote food safety.

Development of fluorescent GO-AgNPs-Eu3+ nanoparticles based paper visual sensor for foodborne spores detection.

Foodborne spores are ubiquitous with extremely strong resistance, and pose a serious threat to food safety and human health. Therefore, rapid, sensitive, and selective detection of spores are crucial. In this study, a fluorescent probe was developed based on lanthanide ion (Eu3+)-labeled nano-silver-modified graphene oxide (GO-AgNPs-Eu3+) for the detection of 2,6-dipicolinic acid (DPA), a biomarker unique to spores, to allow quantitative spores detection. The GO-AgNPs-Eu3+ nano-fluorescent probe was loaded onto a polyvinylidene fluoride microfiltration membrane, and a smartphone-assisted portable GO-AgNPs-Eu3+ nanoparticles-based paper visual sensor was designed for rapid on-site quantitative and real-time online detection of spores. The results indicated that the developed probe achieved equilibrium binding with DPA within 5 min, and enhanced fluorescence emission through antenna effect. The fluorescence detection presented a good linear relationship in the DPA concentration range of 0-45 µM, with a DPA detection limit of 4.62 nM and spore detection limit of 104 cfu/mL. The developed sensor showed a change in fluorescence from blue to red with increasing DPA concentration, and this color change was quantitatively detected through smartphone RGB variations, with a detection limit of 13.1 µM for DPA and 6.3 cfu/mL for Bacillus subtilis spores. Subsequently, the sensitivity and selectivity of the developed sensor were verified using actual milk and water samples spiked with B. subtilis spores. The results of this study provided objective technological support for rapid detection of spores, which is important for reducing the occurrence of foodborne diseases and improving food safety.