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Iron gall Inks corrosion causes paper degradation (browning, embrittlement) and treatments were developed to tackle this issue. They often include resizing with gelatin to reinforce the paper and its cellulosic fibers (of diameter approx. 10 µm). This work aimed at measuring the distribution of ink components at the scale of individual paper fibers so as to give a better understanding of the impact of gelatin (re-)sizing on iron gall ink corrosion. For this purpose, scanning transmission X-ray microscopy (STXM) was used at the Canadian light source synchrotron (CLS, Saskatoon). This technique combines nano-scale mapping (resolution of 30 nm) and near edge X-ray absorption fine structure (NEXAFS) analysis. Fe L-edge measurements enabled to map iron distribution and to locate iron(II) and iron(III) rich areas. N K-edge measurement made it possible to map gelatin distribution. C K-edge measurements allowed mapping and discrimination of cellulose, gallic acid, iron gall ink precipitate and gelatin. Three fibers were studied: an inked fiber with no size, a sized fiber that was afterwards inked and an inked fiber sprayed with gelatin. Analysis of gelatin and ink ingredients distribution indicated a lower amount of iron inside the treated cellulosic fiber, which may explain the beneficial effect of gelatin on iron gall ink corrosion.

Cellulose nanopaper (CNP) has been considered as a promising material with great application potential in diverse fields. However, the hydrophilic nature of CNP significantly limits its practical application. In order to improve its water resistance, we demonstrate a facile approach to functionalize CNP by impregnating it with chitosan (CS), followed by in situ polymerization of polypyrrole (PPy). The results indicate that the obtained CNP/CS/PPy shows excellent water resistance with the wet tensile strength of up to 80 MPa, which is more than 10 times higher than that of the pure CNP. Intriguingly, new features (e.g., electrical conductivity, antibacterial activity, and so forth) are achieved at the same time. The functionalized CNP/CS/PPy shows a high conductivity of 6.5 S cm-1, which can be used for electromagnetic interference shielding applications with a high shielding performance of around 18 dB. In addition, the CNP/CS/PPy exhibits good antibacterial activity toward Staphylococcus aureus and Escherichia coli, with the bacterial reductions of 99.28 and 95.59%, respectively. Thus, this work provides a simple and versatile approach to functionalize CNP for achieving multifunctional properties.

Isothermal amplification strategies capable of rapid, inexpensive, and accurate nucleic acid detection provide new options for large-scale pathogen detection, disease diagnosis, and genotyping. Here we report a highly sensitive multicomponent XNA-based nucleic acid detection platform that combines analyte preamplification with X10-23-mediated catalysis to detect the viral pathogen responsible for COVID-19. The platform, termed RNA-Encoded Viral Nucleic Acid Analyte Reporter (REVEALR), functions with a detection limit of ≤20 aM (∼10 copies/μL) using conventional fluorescence and paper-based lateral flow readout modalities. With a total assay time of 1 h, REVEALR provides a convenient nucleic acid alternative to equivalent CRISPR-based approaches, which have become popular methods for SARS-CoV-2 detection. The assay shows no cross-reactivity for other in vitro transcribed respiratory viral RNAs and functions with perfect accuracy against COVID-19 patient-derived clinical samples.

In this study, the effects of the lacquer applied to the printing materials which were printed by electrophotographic printing method on printing quality were investigated. In practice, printing materials with the same weight and different optical properties were used and the study was carried out in three stages. The optical and physical properties of the printing materials used in the first part were determined, in the second part, the printing of these materials by electrophotographic printing method and printability tests were performed. In the third chapter, matte and glossy lacquers were applied to these printed materials and printability tests were repeated. As a result of the study, it was observed that the application of gloss and matte lacquer caused a decrease in the printing density values and also the application of matte lacquer caused a decrease in the gloss values.

Graphical abstract Enzyme-linked immunosorbent assay (ELISA) is widely used for the detection of disease biomarkers. However, it utilizes time-consuming procedures and expensive instruments, making it infeasible for point-of-care (POC) analysis especially in resource-limited settings. In this work, a multicolorimetric ELISA biosensor integrated on a paper/polymer hybrid microfluidic device was developed for rapid visual detection of disease biomarkers at point of care, without using costly equipment. This multicolormetric ELISA platform was built on multiple distinct color variants resulted from the catalytic oxidation of 3,3′,5,5′-tetramethylbenzidine (TMB) and the etching of gold nanorods (AuNRs). The vivid color changes could be easily distinguished by the naked eye, and their red mean values allowed quantitative biomarker detection, without using any sophisticated instruments. When this multicolorimetric ELISA was integrated on a paper/polymer hybrid analytical device, it not only provided integrated processing and high portability but also enabled fast assays in about 50 min due to the unique advantages of paper/polymer hybrid devices. The limit of detection of 9.1 ng/μL of the hepatitis C virus core antigen, a biomarker for hepatitis C, was achieved using this multicolorimetric ELISA platform. This multicolor ELISA analytical device provides a new versatile, user-friendly, affordable, and portable immunosensing platform with high potential for on-site detections of various viruses, proteins, and biomarkers for low-resource settings such as at home, public venues, rural areas, and developing nations. Supplementary Information The online version contains supplementary material available at 10.1007/s00216-021-03359-8.

Novel ways to track and verify items of a high value or security is an ever-present need. Taggants made from deoxyribonucleic acid (DNA) have several advantageous properties, such as high information density and robust synthesis; however, existing methods require laboratory techniques to verify, limiting applications. Here, we leverage DNA nanotechnology to create DNA taggants that can be validated in the field in seconds to minutes with a simple equipment. The system is driven by toehold-mediated strand-displacement reactions where matching oligonucleotide sequences drive the generation of a fluorescent signal through the potential energy of base pairing. By pooling different "input" oligonucleotide sequences in a taggant and spatially separating "reporter" oligonucleotide sequences on a paper ticket, unique, sequence-driven patterns emerge for different taggant formulations. Algorithmically generated oligonucleotide sequences show no crosstalk and ink-embedded taggants maintain activity for at least 99 days at 60 °C (equivalent to nearly 2 years at room temperature). The resulting fluorescent signals can be analyzed by the eye or a smartphone when paired with a UV flashlight and filtered glasses.

On-site detection of multiple small-molecule analytes in complex sample matrixes would be highly valuable for diverse biosensing applications. Paper electrochemical devices (PEDs) offer an especially appealing sensing platform for such applications due to their low cost, portability, and ease of use. Using oligonucleotide-based aptamers as biorecognition elements, we here for the first time have developed a simple, inexpensive procedure for the fabrication of aptamer-modified multiplex PEDs (mPEDs), which can robustly and specifically detect multiple small molecules in complex samples. These devices are prepared via an ambient vacuum filtration technique using carbon and metal nanomaterials that yields precisely patterned sensing architecture featuring a silver pseudo-reference electrode, a gold counter electrode, and three gold working electrodes. The devices are user-friendly, and the fabrication procedure is highly reproducible. Each working electrode can be readily modified with different aptamers for sensitive and accurate detection of multiple small-molecule analytes in a single sample within seconds. We further demonstrate that the addition of a PDMS chamber allows us to achieve detection in microliter volumes of biological samples. We believe this approach should be highly generalizable, and given the rapid development of small-molecule aptamers, we envision that facile on-site multi-analyte detection of diverse targets in a drop of sample should be readily achievable in the near future.

Due to their unique properties, paper-based biosensors have attracted attention as inexpensive devices for on-site analysis. To achieve fast and sensitive detection of analytes, immobilization of enzymes with high apparent activities on paper is highly desirable; however, this is challenging. Herein, we report an improved approach to attach a malathion degrading enzyme, PoOPHM9, on paper via an interlocking network of Pluronic F127 (PF127)–poly(acrylic acid)–enzyme conjugates. The addition of PF127 improved retention of enzymatic activity as the apparent kinetic constant Vmax of the immobilized enzyme increased two-fold compared with the paper prepared without PF127. The PF127–poly(acrylic acid)–PoOPHM9 papers provided rapid colorimetric detection of malathion at 0.1–50 mM. The detection was completed within 5 min using a smartphone and image analysis software. As a proof-of-concept, malathion-contaminated water, plant, and apple samples were analyzed with the papers successfully. This material is promising for on-site rapid analysis of malathion-contaminated samples.

A newly developed research topic, fabricated paper-based microfluidic sensors, was discussed in the field of low-cost environmental detection. Distinguished with the traditional dipstick or lateral-flow setups, these paper-based microfluidic sensors can serve as a tool for onsite quantitative and semi-quantitative measurements, without risks to cause environmental pollution. They have attracted increasing interest since the first easy-fabricated paper-based setup reported by Whitesides group in 2007. Most of the publications utilized paper-based sensors in clinical detection. In recent years, some groups started to use these sensors in environmental measurement, leading to precise, easy operation, low-cost, and eco-friendly methods for onsite detection. In this review, paper-based microfluidic sensors were briefly introduced, followed by literatures review and discussion for future perspectives.

Flexible paper-based sensors may be applied in numerous fields, but this requires addressing their limitations related to poor thermal and water resistance, which results in low service life. Herein, we report a paper-based composite sensor composed of carboxylic carbon nanotubes (CCNTs) and poly-m-phenyleneisophthalamide (PMIA), fabricated by a facile papermaking process. The CCNT/PMIA composite sensor exhibits an ability to detect pressures generated by various human movements, attributed to the sensor's conductive network and the characteristic "mud-brick" microstructure. The sensor exhibits the capability to monitor human motions, such as bending of finger joints and elbow joints, speaking, blinking, and smiling, as well as temperature variations in the range of 30-90 °C. Such a capability to sensitively detect pressure can be realized at different applied frequencies, gradient sagittas, and multiple twists with a short response time (104 ms) even after being soaked in water, acid, and alkali solutions. Moreover, the sensor demonstrates excellent mechanical properties and hence can be folded up to 6000 times without failure, can bear 5 kg of load without breaking, and can be cycled 2000 times without energy loss, providing a great possibility for a long sensing life. Additionally, the composite sensor shows exceptional Joule heating performance, which can reach 242 °C in less than 15 s even when powered by a low input voltage (25 V). From the perspective of industrialization, low-cost and large-scale roll-to-roll production of the paper-based sensor can be achieved, with a formed length of thousands of meters, showing great potential for future industrial applications as a wearable smart sensor for detecting pressure and temperature, with the capability of electric heating.

The plasmonic properties of gold nanoparticles (AuNPs) are a promising tool to develop sensing alternatives to traditional, enzyme-catalyzed reactions. The need for sensing alternatives, especially in underdeveloped areas of the world, has given rise to the application of nonenzymatic sensing approaches paired with cellulosic substrates to biochemical analysis. Herein, we present three individual, low-step, wet-chemistry, colorimetric assays for three target biomarkers, namely, glucose, uric acid, and free cholesterol, relevant in diabetes control and their translation into paper-based assays and microfluidic platforms for multiplexed analysis. For glucose determination, an in situ AuNPs synthesis approach was applied into the developed μPAD, giving semiquantitative measures in the physiologically relevant range. For uric acid and cholesterol determination, modified AuNPs were used to functionalize paper with a gold-on-paper approach with the optical properties changing based on different aggregation degrees and hydrophobic properties of particles dependent on analyte concentration. These paper-based assays show sensitivity ranges and limits of detection compatible for target analyte level determination and detection limits comparable to those of similar enzymatic, colorimetric systems, relying only on plasmonic transduction without the need for enzymatic activity or other chromogenic substrates. The resulting paper-based assays were integrated into a single 3D, multiplex paper-based device using paper microfluidics, showing the capability for performing different colorimetric assays with distinct requirements in terms of sample flow and sample uptake in test zones using a combination of both horizontal and vertical flows inside the same device. The presented device allows for multiparametric, colorimetric measures of different metabolite levels from a single complex sample matrix drop using digital color analysis, showing the potential for development of low-cost, low-complexity tools for diagnostics toward the point-of-care.

In the tourism industry, the sales of local specialties is an important part, and the package design and integrity of the specialties are very important. This paper first introduced the support vector machine (SVM) algorithm that was used for detecting defects on the surface of paper packages. Then, the design of red wind packages was briefly described, and the simulation experiment was carried out on SVM algorithm using red wine packages with different degrees of surface defects. Proper parameters were tested using the k-fold cross-validation method. The results demonstrated that the properties of paper improved the value of packages and the SVM algorithm had better accuracy than artificial recognition in recognizing different degrees of defects on the surface of packages. In conclusion, this paper describes the application of paper in packages and provides an effective method for the defection of defects on the surface of packages. This study provides an effective references to the improvement of package values and the enhancement of package integrity.

Lab-on-paper, or microfluidic paper-based analytical devices (μPADs), use paper as a substrate material, and are patterned with a system of microchannels, reaction zones and sensing elements to perform analysis and detection. The sample transfer in such devices is performed by capillary action. As a result, external driving forces are not required, and hence the size and cost of the device are significantly reduced. Lab-on-paper devices have thus attracted significant attention for point-of-care medical diagnostic purposes in recent years, particularly in less-developed regions of the world lacking medical resources and infrastructures. This review discusses the major advances in lab-on-paper technology for blood analysis and diagnosis in the past five years. The review focuses particularly on the many clinical applications of lab-on-paper devices, including diabetes diagnosis, acute myocardial infarction (AMI) detection, kidney function diagnosis, liver function diagnosis, cholesterol and triglyceride (TG) analysis, sickle-cell disease (SCD) and phenylketonuria (PKU) analysis, virus analysis, C-reactive protein (CRP) analysis, blood ion analysis, cancer factor analysis, and drug analysis. The review commences by introducing the basic transmission principles, fabrication methods, structural characteristics, detection techniques, and sample pretreatment process of modern lab-on-paper devices. A comprehensive review of the most recent applications of lab-on-paper devices to the diagnosis of common human diseases using blood samples is then presented. The review concludes with a brief summary of the main challenges and opportunities facing the lab-on-paper technology field in the coming years.

Detecting vascular endothelial growth factor C (VEGF-C), a kind of tumor biomarker, is of significant clinical importance in evaluating the prognosis of patients with cancer. However, laboratory analyses are usually not suitable for point-of-care testing because they are expensive and time consuming. In response to these challenges, we fabricated an origami paper-based microfluidic electrochemical device. To improve the specificity of VEGF-C detection, nanocomposites, synthesized by new methylene blue (NMB), amino-functional single-walled carbon nanotubes (NH2-SWCNTs), and gold nanoparticles (AuNPs), were used to modify the surface of working electrodes. Results of electrochemical detection showed that the immunosensor had excellent linearity, ranging from 0.01 to 100 ng mL−1 (R2 = 0.988), and the limit of detection was 10 pg mL−1. To confirm the high specificity of the device under real-world conditions, we evaluated the device using clinical serum samples from our hospital. The results demonstrated that the device had an excellent performance and could provide a platform for real-time detection of cancers., Sun, Wang et al. report an origami paper-based immunosensor for the electrochemical detection of the VEGF-C biomarker in blood serum. The immunosensor is made by modifying the surface of working electrodes with new methylene blue, amino-functional single-walled carbon nanotubes, and gold nanoparticles and demonstrates excellent performance with a limit of detection in the range of picograms per milliliter.

Leukocyte esterase (LE) is a useful marker that can be used in establishing a diagnosis of urinary tract infections (UTIs). The development of a UTI diagnostic method with quantitative determinations of biomarkers across all age groups is becoming more important. In this report, microfluidic resistance sensors based on silver ink (Ag ink) and silver ink mixed with ZnO nanoparticles (Ag-ZnO ink) were synthesized and coated on cellulose paper, namely LE-Ag-μPADs and LE-Ag-ZnO-μPADs, respectively, for the sensitive detection of LE. The microfluidic design increases the precision of data and further allows for quantitative determination and early detection of LE in human urine. The quantification of LE relies on the change in the resistance readout coating with Ag ink as well as Ag-ZnO ink in the detection zone. A mixture of 3-(N-tosyl-l-alaninyloxy)-5-phenylpyrrole (PE) and 1-diazo-2-naphthol-4-sulfonic acid (DAS) was deposited in the sample zone to selectively recognize LE, and the resulting nonconductive products, i.e., azo compounds, further reacted with the Ag ink and Ag-ZnO ink to increase resistance. The quantitative detectable LE concentrations between 2 to 32 (×5.2 U mL-1), i.e. ≈12 to 108 μg L-1, cover the commercial dipstick range of trace, +1 and +2. The minimum detectable concentration of LE in urine was 1 (×5.2 U mL-1). The lower concentrations of LE detectable by LE-Ag-μPADs (1-8 × 5.2 U mL-1) are below the value achieved with the ELISA LE kit. Urine samples from inpatients with indwelling urinary catheters were used, and the LE levels measured by the present device were highly correlated with those determined by a commercial urine analyser.

The dating of organic findings is a fundamental task for many scientific fields. Radiocarbon dating is currently the most commonly used method. For wood, dendrochronology is another state‐of‐the‐art method. Both methods suffer from systematic restrictions, leading to samples that have not yet been able to be dated. Molecular changes over time are reported for many materials under different preservation conditions. Many of them are intrinsically monotonous. These monotonous molecular decay (MD) patterns can be understood as clocks that start at the time when a given molecule was formed. Factors that influence these clocks include input material composition and preservation conditions. Different wood species, degrees of pyrolysis, and pretreatments lead to different prediction models. Preservation conditions might change the speed of a given clock and lead to different prediction models. Currently published models for predicting the age of wood, paper, and parchment depend on infrared spectroscopy. In contrast to radiocarbon dating, dating via MD does not comprise a single methodology. Some clocks may deliver less precise results than the others. Ultimately, developing a completely different, new dating strategy‐such as MD dating–will help to bring to light a treasure trove of information hidden in the darkness of organic findings., This review focuses on molecular changes over time. Having been discussed since the 1960s, the variety of molecular clocks includes the change in amino acids in the primary structure of a protein over time. Molecular decay (MD) has a mainly monotonous function, a prerequisite to serving as such a clock. In addition, such clocks need a defined starting point and a defined decay function. In contrast to the decay of alpha and beta emitters, MD is influenced by several environmental factors indicated by preservation conditions. The MD method has the potential to be used for different organic materials and different scientific fields.

Infectious diseases cause millions of deaths annually in the developing world. Recently, microfluidic paper-based analytical devices (μPADs) have been developed to diagnose such diseases, as these tests are low cost, biocompatible, and simple to fabricate. However, current μPADs are difficult to use in resource-limited areas due to their reliance on external instrumentation to measure and analyze the test results. In this work, we propose an electricity and external instrumentation-free μPAD sensor based on the colorimetric enzyme-linked immunosorbent assay (ELISA) for the diagnosis of infectious disease (3D-tPADs). Designed based on the principle of origami, the proposed μPAD enables the sequential steps of the colorimetric ELISA test to be completed in just ∼10 min. In addition, in order to obtain an accurate ELISA result without using any instrument, we have integrated an electricity-free "timer" within the μPAD that can be controlled by the buffer viscosity and fluid path volume to indicate the appropriate times for washing and color development steps, which can avoid false positive or false negative results caused by an extended or shortened amount of washing and development times. Due to the low background noise and high positive signal intensity of the μPAD, positive and negative detection results can be distinguished by just the naked eye. Furthermore, the ELISA result can be semi-quantified by comparing the results shown on the μPAD with a color chart diagram with a detection limit of HIV type 1(HIV-1) p24 antigen as low as 0.03 ng mL-1. These results demonstrate the proposed sensor can perform infectious disease diagnosis without external instrumentation or electricity, extending the application of the μPAD test for on-site detection and use in resource-limited settings.

Paper-based microfluidic devices are popular for their ability to automate multistep assays for chemical or biological sensing at a low cost, but the design of paper microfluidic networks has largely relied on experimental trial and error. A few mathematical models of flow through paper microfluidic devices have been developed and have succeeded in explaining experimental flow behavior. However, the reverse engineering problem of designing complex paper networks guided by appropriate mathematical models is largely unsolved. In this article, we demonstrate that a two-dimensional paper network (2DPN) designed to sequentially deliver three fluids to a test zone on the device can be computationally designed and experimentally implemented without experimental trial and error. This was accomplished by three new developments in modeling flow through paper networks: (i) coupling of the Richards equation of flow through porous media to the species transport equation, (ii) modeling flow through assemblies of multiple paper materials (test membrane and wicking pad), and (iii) incorporating limited-volume fluid sources. We demonstrate the application of this model in the optimal design of a paper-based signal-enhanced immunoassay for a malaria protein, PfHRP2. This work lays the foundation for the development of a computational design toolbox to aid in the design of paper microfluidic networks. ©

This paper introduces a novel potential-resolved paper-based biosensor for simultaneous detection of multiple microRNAs (miRNAs) (taking miRNA-155 and miRNA-126 as examples) based on the bipolar electrode (BPE) electrochemiluminescence (ECL) strategy. The proposed multiple-channel paper-based sensing microfluidic platform was prepared by wax-printing technology, screen-printing method, and in situ Au nanoparticles (AuNPs) growth to form hydrophilic areas, hydrophobic boundaries, waterproof electronic bridge, driving electrode regions, and parallel bipolar electrode regions. CdTe quantum dots (QDs)-H2 and Au@g-C3N4 nanosheets (NSs)-DNA1 were used as dual electrochemiluminescence signal probes, and carboxylated Fe3O4 magnetic nanoparticles existed as carriers. CdTe QDs-H2/S2O82- and Au@g-C3N4 NSs-DNA1/S2O82- could exhibit two strong and stable ECL emissions at a drive voltage of 9 and 12 V, respectively, which can be used as effective potential-resolved signal tags. In addition, the proposed three-dimensional (3D) DNA nanomachine model and the target miRNA cycle strategy were used to achieve double amplification of electrochemiluminescence intensity. More importantly, the combination of the bipolar electrode system and the potential-resolved multitarget electrochemiluminescence method can greatly reduce the spatial interference between substances. The prepared ECL biosensor showed a favorable linear response for the detection of miRNA-155 and miRNA-126 with relatively low detection limits of 5.7 and 4.2 fM, respectively. With excellent sensitivity, the strategy may provide an efficient method for clinical application, especially in detection of trace multiple targets.

Weighing paper-assisted magnetic ionic liquid headspace single-drop microextraction using microwave distillation followed by gas chromatography-mass spectrometry was successfully developed to determine the essential oil components in lavender. The magnetic ionic liquid 1-octyl-3-methylimidazolium tetrachloroferrate was successfully synthesized and used as the optimal extraction solvent. An aliquot of 9 μL of magnetic ionic liquid could be stably suspended on the weighing paper for long time extraction. The increase of the extractant volume resulted in a significantly enhanced in extracting efficiency of the weighing paper-assisted magnetic ionic liquid headspace single-drop microextraction than traditional headspace single-drop microextraction method. In this experiment, the optimal conditions were 1-octyl-3-methylimidazolium tetrachloroferrate as the extraction solvent, extraction time of 12 min, microwave power of 600 W, cyclohexane as back-extractant and sample amount of 30 mg. The developed method was successfully applied to analyze 16 lavender samples from three different harvest years. A total of 39 compounds in lavender were identified and the principal component analysis provided a clear separation between those lavender samples harvested in different years. The results indicated that the proposed weighing paper-assisted magnetic ionic liquid headspace single-drop microextraction is a novel, fast, simple and sensitive microextration technique for the determination of the essential oil components in lavender.

Background: JWH-018 was the first synthetic cannabinoid introduced as a legal high and the first of the new generation of novel psychoactive substances that flooded worldwide drug markets. JWH-018 was marketed as “spice,” “herbal incense,” or “herbal blend,” as a popular and legal (at the time) alternative to cannabis (marijuana). JWH-018 is a potent synthetic cannabinoid with considerable toxicity associated with its use. JWH-018 has qualitatively similar but quantitatively greater pharmacological effects than cannabis, leading to intoxications and even deaths. The mechanisms of action of the drug’s toxicity require research, and thus, the aim of the present study was to investigate the toxicological profile of JWH-018 in human SH-SY5Y neuronal cells. Methods: SH-SY5Y neuronal cells were exposed to increasing concentrations from 5 to 150 μM JWH-018 over 24 h. Cytotoxicity, DNA damage, the apoptotic/necrotic rate, and oxidative stress were assessed following SH-SY5Y exposure. Results: JWH-018 did not produce a significant decrease in SH-SY5Y cell viability, did not alter apoptotic/necrotic rate, and did not cause genotoxicity in SH-SY5Y cells with 24-h exposure. Glutathione reductase and catalase activities were significantly reduced; however, there was no significant change in glutathione peroxidase activity. Also, JWH-018 treatment significantly decreased glutathione concentrations, significantly increased protein carbonylation, and significantly increased malondialdehyde (MDA) concentrations. For significance, all P

There is growing demand for simple to operate, sensitive, on-site quantitative assays to investigate concentrations of drug molecules in pharmaceutical preparations for quality assurance. Here, we report on the development of two colorimetric analysis methods for the study the antibiotic doxycycline hyclate (DOX) and the nasal decongestant oxymetazoline hydrochloride (OXY), in solution as well as in their respective formulations. We compare a UV/vis spectrophotometry method with a color change recorded on a microfluidic paper-based analytical device (μPAD). Detection is based on the pharmaceutical compounds coupling with diazotized 4-aminoacetophenone (DAAP) under alkaline conditions to produce colored azo-dye products. These azo-compounds were monitored by absorbance at 425 nm for DOX and 521 nm for OXY, with linear calibration graphs in the concentration range of 0.5–35 mg L−1 (DOX) and 1.0–40 mg L−1 (OXY) and limits of detection of 0.24 mg L−1 (DOX) and 0.32 mg L−1 (OXY). For the μPAD method, color intensity was measured from photographs and a linear increase was observed at concentrations from above approximately 15 mg L−1 for both compounds and up to 35 mg L−1 for DOX and 40 mg L−1 for OXY. The developed methods were also applied to the formulated pharmaceuticals and no interference was found from the excipient. Thus, the paper-based device provides an inexpensive, simple alternative approach for use outside centralized laboratories with semi-quantitative capability.

Lysergic acid diethylamide (LSD) is a hallucinogen, synthesized from ergot alkaloid, and controlled as a narcotic in Japan. Recently, LSD derivatives have appeared as designer drugs, all over the world. In previous study, we reported identification and analysis of four LSD derivatives in four paper sheet products. In this study, we detected three additional LSD derivatives from three paper sheet products, which were obtained from September 2019 to March 2020 in Japan. We extracted the compounds from paper sheet products with methanol for LC-MS, high-resolution MS and GC-MS analyses. The compounds were identified as 4-cyclopropionyl-N,N-diethyl-7-methyl-4,6,6a,7,8,9-hexahydroindolo[4,3-fg]quinoline-9-carboxamide (1cP-LSD), N-methyl-N-isopropyl-7-methyl-4,6,6a,7,8,9-hexahydroindolo-[4,3-fg]quinoline-9-carboxamide (MIPLA), 4-butyryl-N,N-diethyl-7-methyl-4,6,6a,7,8,9-hexahydroindolo[4,3-fg]quinoline-9-carboxamide (1B-LSD), by GC-MS, LC-MS, LC-Q-TOF-MS and NMR analyses. As well as other N1-acylated LSD derivatives, 1cP-LSD and 1B-LSD were easily deacylated to LSD during GC-MS analysis, we have to be careful to analyze these compounds.

Propofol is a widely used intravenous anesthetic agent in sedation and general anesthesia. To improve the safety and maintain the depth of anesthesia, it is important to develop a rapid, sensitive, and reliable method to monitor the concentration of propofol in blood during anesthesia continuously. Here, we present a novel strategy based on paper spray ionization-mass spectrometry (PSI-MS) to detect propofol. Samples (in 10 μL) were mixed with methanol as protein precipitation solvent and 2,6-dimethylphenol as internal standard. Protein micro-precipitation was achieved with methanol by vortexing and centrifuging for 5 s each, and propofol was extracted to the supernatant. PSI-MS was performed in negative ionization mode, and MS signal lasted for 1 min. The analysis of a single sample was completed within 2 min. The area ratios of propofol to internal standard were calculated for quantification. Limit of detection of 5.5 ng mL−1 and limit of quantification of 18.2 ng mL−1 were achieved for propofol in whole blood. Calibration curve was linear in the range of 0.02–10 μg mL−1. The developed method was used successfully in monitoring the propofol concentration in 3 patients’ whole blood during anesthesia, showing its further application in controlling and feeding-back target concentration infusion.

Application of barrier dispersion coatings on paperboards, which must have proper moisture and grease resistance for food applications, has always been an interesting subject for the packaging industry. In this study, paperboards were coated with a novel dispersion barrier coating prepared through mixing soy protein isolate (SPI) and polyethylene wax (PE-wax). Different characterization methods were used to study the effects of coating and its composition on the physical, mechanical, and barrier characteristics of paperboards. The results indicated that the incorporation of PE-wax into the coating formulation caused significant reduction of the viscosity of coating slurries. It had no effect on the coating weight of the samples but increased the thickness of the coated paperboards as compared with those coated with SPI only. The increase of the wax content led to a reduction of 5-16% in the tensile strength values in comparison with the uncoated paperboards. Barrier characteristics, i.e., water vapor permeability (WVP), surface wettability, and water resistance, improved by adding PE-wax. In addition, it was found that there was a critical level for the addition of PE-wax, 50% of SPI, as no oil migration was detected when the paperboards coated with SPI coatings contained less than 50% PE-wax.

Tuberculosis (TB), one of the deadliest infectious diseases, is caused by Mycobacterium tuberculosis (MTB) and remains a public health problem nowadays. Conventional MTB DNA detection methods require sophisticated infrastructure and well-trained personnel, which leads to increasing complexity and high cost for diagnostics and limits their wide accessibility in low-resource settings. To address these issues, we have developed a low-cost photothermal biosensing method for the quantitative genetic detection of pathogens such as MTB DNA on a paper hybrid device using a thermometer. First, DNA capture probes were simply immobilized on paper through a one-step surface modification process. After DNA sandwich hybridization, oligonucleotide-functionalized gold nanoparticles (AuNPs) were introduced on paper and then catalyzed the oxidation reaction of 3,3',5,5'-tetramethylbenzidine (TMB). The produced oxidized TMB, acting as a strong photothermal agent, was used for the photothermal biosensing of MTB DNA under 808 nm laser irradiation. Under optimal conditions, the on-chip quantitative detection of the target DNA was readily achieved using an inexpensive thermometer as a signal recorder. This method does not require any expensive analytical instrumentation but can achieve higher sensitivity and there are no color interference issues, compared to conventional colorimetric methods. The method was further validated by detecting genomic DNA with high specificity. To the best of our knowledge, this is the first photothermal biosensing strategy for quantitative nucleic acid analysis on microfluidics using a thermometer, which brings fresh inspirations on the development of simple, low-cost, and miniaturized photothermal diagnostic platforms for quantitative detection of a variety of diseases at the point of care.

In this study, a microfluidic paper-based analytical device (mu PAD) was integrated with a smartphone app capable of offline (without internet access) image processing and analysis for the rapid colorimetric detection of glucose. A self-inking stamp was used to form hydrophobic channels on a piece of paper-towel due to its superior water absorption efficiency. As demonstrated, the developed sensor was employed for the colorimetric detection of glucose in artificial saliva in the linear scope of 0 - 1 mM with a calculated detection limit of 29.65 mu M. The experimental results show that the quantitative analysis of glucose with the proposed smartphone platform could be completed in less than one minute. The app developed for the smartphone platform is capable of extracting the color-changing area with an embedded image processing tool which could address the problem of color uniformity in the detection zones of mu PAD. The integrated platform has great potential to be used for non-invasive measurements of glucose in body fluids, like tears, sweat and saliva.

Direct ambient ionization techniques have been developed with the aim to reduce the complexity of mass spectrometry analysis by minimizing sample preparation and chromatographic separation. In this context, paper spray-MS (PS-MS) is an innovative approach that provides faster and cheaper analysis of biofluids by the addition of the sample directly to a paper. In forensic toxicology, the analytical workflow for the detection and quantification of drugs of abuse is onerous, including sample treatment, extraction and clean up, especially regarding complex biological matrices. PS-MS allows the detection of analytes of toxicological interest in blood, plasma and urine using low sample volume. This review aims to discuss the potential use, advances and challenges of PS-MS in forensic toxicology.

As a global shift continues to occur in high burden diseases toward developing countries, the importance of medical diagnostics based on point-of-care testing (POCT) is rapidly increasing. However, most diagnostic tests that meet clinical standards rely on high-end analyzers in central hospitals. Here, we report the development of a simple, low-cost, mass-producible, highly sensitive/quantitative, automated, and robust paper/soluble polymer hybrid-based lateral flow biosensing platform, paired with a smartphone-based reader, for high-performance POCT. The testing architecture incorporates a polymeric barrier that programs/automates sequential reactions via a polymer dissolving mechanism. The smartphone-based reader with simple opto-mechanical parts offers a stable framework for accurate quantification. Analytical performance of this platform was evaluated by testing human cardiac troponin I (cTnI), a preferred biomarker for the diagnosis of myocardial infarction, in serum/plasma samples. Coupled with catalytic/colorimetric gold-ion amplification, this platform produced results within 20 min with a detection limit of 0.92 pg mL

In this study, we aim to compare the performance of systems and forensic facial comparison experts in terms of likelihood ratio computation to assess the potential of the machine to support the human expert in the courtroom. In forensics, transparency in the methods is essential. Consequently, state‐of‐the‐art free software was preferred over commercial software. Three different open‐source automated systems chosen for their availability and clarity were as follows: OpenFace, SeetaFace, and FaceNet; all three based on convolutional neural networks that return a distance (OpenFace, FaceNet) or similarity (SeetaFace). The returned distance or similarity is converted to a likelihood ratio using three different distribution fits: parametric fit Weibull distribution, nonparametric fit kernel density estimation, and isotonic regression with pool adjacent violators algorithm. The results show that with low‐quality frontal images, automated systems have better performance to detect nonmatches than investigators: 100% of precision and specificity in confusion matrix against 89% and 86% obtained by investigators, but with good quality images forensic experts have better results. The rank correlation between investigators and software is around 80%. We conclude that the software can assist in reporting officers as it can do faster and more reliable comparisons with full‐frontal images, which can help the forensic expert in casework.

The need for agile and proper identification of drugs of abuse has encouraged the scientific community to improve and todevelop new methodologies. The drug lysergic acid diethylamide (LSD) is still widely used due to its hallucinogenic effects. The use ofvoltammetric methods to analyze narcotics has increased in recent years, and the possibility of miniaturizing the electrochemical equipmentallows these methods to be applied outside the laboratory; for example, in crime scenes. In addition to portability, the search for affordable andsustainable materials for use in electroanalytical research has grown in recent decades. In this context, employing paper substrate, graphite pen-cil, and silver paint to construct paper-based electrodes is a great alternative. Here, a paper-based device comprising three electrodes was drawnon 300 g/m2watercolor paper with 8B pencils, and its efficiency was compared to the efficiency of a commercially available screen-printedcarbon electrode. Square wave voltammetry was used for LSD analysis in aqueous medium containing 0.05 mol/L LiClO4. The limits of detec-tion and quantification were 0.38 and 1.27 mol/L, respectively. Both electrodes exhibited a similar voltammetric response, which was alsoconfirmed during analysis of a seized LSD sample, with recovery of less than 10%. The seized samples were previously analyzed by GCMStechnique, employing the full scan spectra against the software spectral library. The electrode selectivity was also tested against 3,4-methylene-dioxymethamphetamine (MDMA) and methamphetamine. It was possible to differentiate these compounds from LSD, indicating that the devel-oped paper-based device has potential application in forensic chemistry analyses., Financial support provided by the Polícia Científica do Estado de São Paulo for the partnership, and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP - Process 2016/23825-3), Fundação para a Ciência e Tecnologia, FCT, Portugal, (UID/QUI/00686/2016 and UID/QUI/00686/2019), and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (Process Capes Pro Forenses 25/2014).

A laminated paper-based analytical device (LPAD) for histidine detection was fabricated from a chromatography filtration paper and laminate films. Histidine recognition was effected by histidyl-tRNA synthetase (HisRS), and its detection was signaled colorimetrically based on the molybdenum blue reaction. The analytical conditions and detectable concentration range of histidine were examined. The method provided selective quantification from 1 to 100 μM histidine. LPAD fabrication is considerably simple, involving only the craft-cutting of the chromatography filtration paper and laminate film, and is cost-effective.

Bladder cancer is the fourth most common cancer in men, and it is becoming a prevalent malignancy. Most of the regular clinical examinations are prompt evaluations with cystoscopy, renal function testing, which require high-precision instrument, well-trained operators, and high cost. In this study, a microfluidic paper-based analytical device (μPAD) was fabricated to detect nuclear matrix protein 22 (NMP22) and bladder cancer antigen (BTA) from the urine samples. Urine samples were collected from 11 bladder cancer patients and 10 well-beings as experiment and control groups, respectively, to verify the working efficiency of μPAD. A remarkable checkout efficiency of up to 90.91% was found from the results. Meanwhile, this method is feasible for home-based self-detection from urine samples within 10 min for the total process, which provides a new way for quick, economical, and convenient tumor diagnosis, prognosis evaluation, and drug response.

From a circular economy perspective, feeding livestock with food leftovers or former foodstuff products (FFPs) could be an effective option aimed at exploiting food leftover resources and reducing food losses. FFPs are valuable energy sources, characterised by a beneficial starch/sugar content, and also fats. However, besides these nutritional aspects, safety is a key concern given that FFPs are generally derived from packaged food. Packaging materials, such as plastics and paper, are not accepted as a feed ingredient which means that residues should be rigorously avoided. A sensitive and objective detection method is thus essential for an accurate risk evaluation throughout the former food production chain. To this end, former food samples were collected in processing plants of two different European countries and subjected to multivariate analysis of red, green, and blue (RGB) microscopic images, in order to evaluate the possible application of this non-destructive technique for the rapid detection of residual particles from packaging materials. Multivariate Image Analysis (MIA) was performed on single images at the pixel level, which essentially consisted in an exploratory analysis of the image data by means of Principal Component Analysis, which highlighted the differences between packaging and foodstuff particles, based on their colour. The whole dataset of images was then analysed by means of a multivariate data dimensionality reduction method known as the colourgrams approach, which identified clusters of images sharing similar features and also highlighted outlier images due to the presence of packaging particles. The results obtained in this feasibility study demonstrated that MIA is a promising tool for a rapid automated method for detecting particles of packaging materials in FFPs.

Paper is emerging as a versatile platform for automated fluid handling with a broad range of applications in medical diagnostics and analytical chemistry. However, selectively controlling analyte transport in paper to achieve concentration or selection has been a challenge for functional analysis. Here, by combining paper-based microfluidics with acoustics, we present a rapid and powerful method to size dependently control movement of microparticles and cells in paper using surface acoustic waves (SAW). We demonstrate the unique capability of the paper-based SAW approach to trap and concentrate microparticles in paper and release them when required, achieving collection efficiency of over 98%. Given the correlation between collection efficiency, size, and applied power, the paper-based SAW approach is applied to isolate a mixture of microparticles (1.1, 3.2, and 5 μm in diameter) into different regions and also to trap and concentrate human prostate cancer PC3 cells at a predetermined site. This paper-based SAW approach provides opportunities to develop powerful and low-cost selection and analysis tools, capable of processing complex multicomponent samples, with potential applications in medical diagnostics.

The use of nanocelluloses is being conducted for the most diverse applications. Their performance as coating agent has been mainly explored to improve barrier properties, as they emerge as perfect candidate for plastic substitution, but it is also important to explore their potential to improve printing quality. In the present work, the influence of different nanocelluloses, obtained through mechanical, enzymatic, TEMPO-mediated oxidation and carboxymethylation treatments, in the coating process and inkjet printability of office papers was assessed. The results revealed that the cellulose nanofibrils are better for printability than the microfibrils. But the size and charge of the former must be taken into account, since fibrils of very small size penetrate the paper structure, dragging the pigments from the surface, and very anionic nanofibrils can also have negative influence on the optical density. Besides, an interesting synergy between surface-sizing starch and the cellulose nanofibrils was found to occur as the latter closed the paper structure, which prevented starch from penetrating, while potentiating both of their positive effects on ink pigment entrapment. An additional study of characterization of inkjet pigments was also performed.

Postmortem computed tomography (PMCT) is integrated into the evaluation of decedents in several American medical examiner offices and medicolegal death investigative centers in many other countries. We retrospectively investigated the value of PMCT in a series of firearm homicide cases from a statewide centralized medical examiner’s office that occurred during 2016. Autopsies were performed or supervised by board‐certified forensic pathologists who reviewed the PMCT scans prior to autopsy. PMCT scans were re‐evaluated by a forensic radiologist blinded to the autopsy findings and scored by body region (head–neck, thoracoabdominal, and extremities). Injury discrepancies were scored using a modified Goldman classification and analyzed with McNemar’s test. We included 60 males and 20 females (median age 31 years, range 3–73). Based on PMCT, 56 (79.1%) cases had injuries relevant to the cause of death in a single body region (24 head–neck region, 32 thoracoabdominal region). Out of these 56 cases, 9 had a missed major diagnosis by PMCT outside that region, including 6 extremity injuries visible during standard external examination. Yet all had evident lethal firearm injury. We showed that PMCT identifies major firearm injuries in homicide victims and excludes injuries related to the cause of death in other regions when a single body region is injured. Although PMCT has a known limited sensitivity for soft tissue and vascular pathology, it can be combined with external examination to potentially reduce or focus dissections in some of these cases depending on the circumstances and medicolegal needs.

Polygalacturonase (PG) activity in plants can serve as an important index for plant disease. However, the conventional method to detect PG activity is a complex process and requires a skilled technician and expensive analytical equipment. In this study, a paper-based colorimetric sensor was developed based on the principle of the ruthenium red (RR) dye method for easy and simple measurement of PG activity. The proposed paper-based sensor has a three-layer structure for detection of PG activity in samples. The sensor sensitivity was enhanced by optimizing the pH of the sodium acetate buffer used in polygalacturonic acid (PGA)-RR complex formation and the reaction temperature for PG and the PGA-RR complex. Further, for quantitative analysis of PG activity, Delta RGB analysis was conducted to detect color changes in the sensing window of the sensor. Results presented that the linear measurement range of the paper sensor was 0.02-0.1 unit with the limit of detection of 0.02 unit, which showed a similar detection range, but a lower detection limit, compared to the spectrophotometry. Furthermore, PG activity based on culture condition was measured using samples from Sclerotium cepivorum to verify the potential application of the developed paper-based sensor in the field. The measured activity showed no statistically significant difference from the values obtained from the spectrophotometry at 95% confidence level. Therefore, the paper-based colorimetric sensor can be used to predict plant diseases in Allium crops during the stage of pathogen invasion, potentially contributing to the improvement of crop production.

Nanolayer and nanolayer by nanolayer deposition of nanofilms of Ag and C using cold plasma in sequences (Ag, Ag-C, Ag-Ag-C), on porous paper, were used to design three disposable stochastic sensors for the assay of amyloid polypeptide from whole blood. The nanofilms were modified with α-cyclodextrin. The test developed using the nanofilm-based disposable stochastic sensors is used for early detection of diabetes. The wider linear concentration range (1.00 × 10−6–1.00 ng mL−1) and the lower limit of quantification (1.00 × 10−6ng mL−1) were obtained using the disposable stochastic sensors based on Ag-C and Ag-Ag-C, while the highest sensitivity (3.19 × 104 s−1/μg mL−1) was recorded using the disposable stochastic sensor based on Ag-Ag-C. The screening methods were fully validated using whole blood samples from confirmed patients, when the recovery of the islet amyloid polypeptide was higher than 98.00%.

Lithium carbonate is an effective medicine for the treatment of the bipolar disorder, but the concentration of lithium in the patient's blood must be frequently monitored because of its toxicity. To date, no colorimetric methods of lithium ion detection in whole blood without pretreatment have been reported. Here, we report a colorimetric paper-based device that allows point-of-care testing in one step. This device is composed of two paper-based elements linked to each other: a blood cell separation unit and a colorimetric detection unit. After a portion of whole blood has been placed on the end of the separation unit, plasma in the sample is automatically transported to the detection unit, which displays a diagnostic color. The key feature of this device is its simple, user-friendly operation. The limit of detection is 0.054 mM and the coefficient of variance is below 6.1%, which are comparable to those of conventional instruments using the same colorimetric reaction. Furthermore, we achieved high recovery (>90%) and reproducibility (

A complete mathematical model for electromigration in paper-based analytical devices is derived, based on differential equations describing the motion of fluids by pressure sources and EOF, the transport of charged chemical species, and the electric potential distribution. The porous medium created by the cellulose fibers is considered like a network of tortuous capillaries and represented by macroscopic parameters following an effective medium approach. The equations are obtained starting from their open-channel counterparts, applying scaling laws and, where necessary, including additional terms. With this approach, effective parameters are derived, describing diffusion, mobility, and conductivity for porous media. While the foundations of these phenomena can be found in previous reports, here, all the contributions are analyzed systematically and provided in a comprehensive way. Moreover, a novel electrophoretically driven dispersive transport mechanism in porous materials is proposed. Results of the numerical implementation of the mathematical model are compared with experimental data, showing good agreement and supporting the validity of the proposed model. Finally, the model succeeds in simulating a challenging case of free-flow electrophoresis in paper, involving capillary flow and electrophoretic transport developed in a 2D geometry. Fil: Schaumburg, Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentina Fil: Kler, Pablo Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Centro de Investigaciones en Métodos Computacionales. Universidad Nacional del Litoral. Centro de Investigaciones en Métodos Computacionales; Argentina Fil: Berli, Claudio Luis Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentina

Microfluidic paper-based analytical devices (μPADs) allow user-friendly and portable chemical determinations, although they provide limited applicability due to insufficient sensitivity. Several approaches have been proposed to address poor sensitivity in μPADs, but they frequently require bulky equipment for power and/or read-outs. Universal serial buses (USB) are an attractive alternative to less portable power sources and are currently available in many common electronic devices. Here, USB-powered μPADs (USB μPADs) are proposed as a fusion of both technologies to improve performance without adding instrumental complexity. Two ITP USB μPADs were developed, both powered by a 5 V potential provided through standard USB ports. The first device was fabricated using the origami approach. Its operation was analyzed experimentally and numerically, yielding a two-order-of-magnitude sample focusing in 15 min. The second ITP USB μPAD is a novel design, which was numerically prototyped with the aim of handling larger sample volumes. The reservoirs were moved away from the ITP channel and capillary action was used to drive the sample and electrolytes to the separation zone, predicting 25-fold sample focusing in 10 min. USB μPADs are expected to be adopted by minimally-trained personnel in sensitive areas like resource-limited settings, the point-of-care and in emergencies. Fil: Schaumburg, Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentina Fil: Kler, Pablo Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Centro de Investigaciones en Métodos Computacionales. Universidad Nacional del Litoral. Centro de Investigaciones en Métodos Computacionales; Argentina Fil: Carrell, Cody S.. State University of Colorado - Fort Collins; Estados Unidos Fil: Berli, Claudio Luis Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentina Fil: Henry, Charles S.. State University of Colorado - Fort Collins; Estados Unidos

Paper-based microfluidic device was designed with wax-printing to combine potentiometric, fluorimetric and colorimetric detection zones. This newly developed trimodal paper chip has been used for on-site determination of ketamine hydrochloride (KET) as a date rape drug in beverages. The device employed polyaniline nano-dispersion as conducting polymer in ion sensing paper electrodes designed to fit USB plug connector. Carbon dots-gold nanoparticles and cobalt thiocyanate were used in fluorescence and color detection zones, respectively. Cellular phone's camera facilitated the on-site fluorimetric and color detection. The implemented trimodal detection system exhibited specificity for KET detection in the presence of several other beverage interferences i.e., biogenic amines. This innovative sensor brings together analytical figures of merit for effective KET detection in single aliquot of spiked beverages. The proposed paper-based chip also fulfils WHO criteria for point-of-care devices posing the proposed trimodal paper device as an active part for rapid, on-site drug diagnostics and to be applied further for other similar drugs.

Free proline, termed proline, is a biomarker used for diagnosing drought stress in plants. A previously developed proline–ninhydrin reaction-based paper sensor could quickly and easily detect proline, but it was limited by low sensitivity. In this study, we developed an enclosed multilayer paper-based microfluidic sensor with high sensitivity for the quantitative detection of proline in plants. The multilayer paper-based sensor was manufactured using simple wax printing and origami methods, and contained an internal mixing channel to allow good mixing of the proline with ninhydrin, increasing the proline–ninhydrin reactivity and providing accurate and sensitive proline detection. By preloading ninhydrin onto the sample loading area, uniform coloration of the sensing window was achieved, allowing quantitative analysis of various proline concentrations using a constant reaction time. Only the sensing window and sample loading area were exposed to limit sample evaporation and contamination from the external environment. The LOD of the fabricated sensor was 23 μM, which is approximately 29-fold lower than that of the previously proposed paper sensor (657 μM). Samples were extracted from A. thaliana plants subjected to drought stress for proline detection. The proline concentrations measured using the developed paper sensor and a spectrophotometric method were not statistically significant at a confidence level of 95%. Therefore, the developed sensor can be applied to measure proline concentrations precisely in the field with a low detection limit. The developed paper-based sensor can be used to detect the early stages of drought in plants and thus improve crop productivity.

Protein biomarkers often exist as degradation fragments in biological samples, and affinity agents derived using a purified protein may not recognize them, limiting their value for clinical diagnosis. Herein, we present a method to overcome this issue, by selecting aptamers against a degraded form of the toxin B protein, which is a marker for diagnosing toxigenic Clostridium difficile infections. This approach has led to isolation of a DNA aptamer that recognizes degraded toxin B, fresh toxin B, and toxin B spiked into human stool samples. DNA aptamers selected using intact recombinant toxin B failed to recognize degraded toxin B, which is the form present in stored stool samples. Using this new aptamer, we produced a simple paper-based analytical device for colorimetric detection of toxin B in stool samples, or in the NAP1 strain of Clostridium difficile. The combined aptamer-selection and paper-sensing strategy can expand the practical utility of DNA aptamers in clinical diagnosis.

Pathogen detection is crucial for human, animal, and environmental health; crop protection; and biosafety. Current culture-based methods have long turnaround times and lack sensitivity. Nucleic acid amplification tests offer high specificity and sensitivity. However, their cost and complexity remain a significant hurdle to their applications in resource-limited settings. Thus, point-of-need molecular diagnostic platforms that can be used by minimally trained personnel are needed. The nuclease protection assay (NPA) is a nucleic acid hybridization-based technique that does not rely on amplification, can be paired with other methods to improve specificity, and has the potential to be developed into a point-of-need device. In traditional NPAs, hybridization of an anti-sense probe to the target sequence is followed by single-strand nuclease digestion. The double-stranded target-probe hybrids are protected from nuclease digestion, precipitated, and visualized using autoradiography or other methods. We have developed a paper-based nuclease protection assay (PB-NPA) that can be implemented in field settings as the detection approach requires limited equipment and technical expertise. The PB-NPA uses a lateral flow format to capture the labeled target-probe hybrids onto a nitrocellulose membrane modified with an anti-label antibody. A colorimetric enzyme-substrate pair is used for signal visualization, producing a test line. The nuclease digestion of non-target and mismatched DNA provides high specificity while signal amplification with the reporter enzyme-substrate provides high sensitivity. We have also developed an on-chip sample pretreatment step utilizing chitosan-modified paper to eliminate possible interferents from the reaction and preconcentrate nucleic acids, thereby significantly reducing the need for auxiliary equipment. Graphical abstract.

Mineral oil hydrocarbons (MOH) are widely used in the food industry for applications such as printing inks, additives, adhesives, and processing aids for food additives. Recently, the migration of MOH from food contact paper and board into foods has raised public health concerns. In this study, a total of 110 food contact paper and board samples, including baking and cooking paper (23), baking cups (28), food packaging bags (22), lunch boxes (8), party plates (26), and straws (3) were evaluated to quantify the content and short-term migration levels of MOH. The MOH were separated into mineral oil saturated hydrocarbons (MOSH)/polyolefin oligomeric saturated hydrocarbons (POSH) and mineral oil aromatic hydrocarbons (MOAH) via a validated on-line liquid chromatography-gas chromatography-flame ionisation detection (LC-GC-FID) technique. The coating materials of the sample products comprised polyethylene, polypropylene, polyethylene terephthalate, and silicone. The effects of the coating materials on the content and migration of MOH/POSH were evaluated. Quantitative analysis of the MOH in the samples showed that the MOSH/POSH and MOAH content varied widely, ranging from 16 to 5626 mg kg

Because of numerous inherent and unrivaled features of nanofibers made of chitin, the second most plentiful natural-based polymer (after cellulose), including affordability, abundant nature, biodegradability, biocompatibility, commercial availability, flexibility, transparency, and extraordinary mechanical and physicochemical properties, chitin nanofibers (ChNFs) are being applied as one of the most appealing bionanomaterials in a myriad of fields. Herein, we exploited the beneficial properties offered by the ChNF paper to fabricate transparent, efficient, biocompatible, flexible, and miniaturized optical sensing bioplatforms via embedding/immobilizing various plasmonic nanoparticles (silver and gold nanoparticles), photoluminescent nanoparticles (CdTe quantum dots, carbon dots, and NaYF4:Yb3+@Er3+&SiO2 upconversion nanoparticles) along with colorimetric reagents (curcumin, dithizone, etc.) in the 3D nanonetwork scaffold of the ChNF paper. Several configurations, including 2D multi-wall and 2D cuvette patterns with hydrophobic barriers/walls and hydrophilic test zones/channels, were easily printed using laser printing technology or punched as spot patterns on the dried ChNF paper-based nanocomposites to fabricate the (bio)sensing platforms. A variety of (bio)chemicals as model analytes were used to confirm the efficiency and applicability of the fabricated ChNF paper-based sensing bioplatforms. The developed (bio)sensors were also coupled with smartphone technology to take the advantages of smartphone-based monitoring/sensing devices along with the Internet of Nano Things (IoNT)/the Internet of Medical Things (IoMT) concepts for easy-to-use sensing applications. Building upon the unrivaled and inherent features of ChNF as a very promising bionanomaterial, we foresee that the ChNF paper-based sensing bioplatforms will emerge new opportunities for the development of innovative strategies to fabricate cost-effective, simple, smart, transparent, biodegradable, miniaturized, flexible, portable, and easy-to-use (bio)sensing/monitoring devices., Financial support from the Chemistry & Chemical Engineering Research Centre of Iran (Tehran, Iran), Iran’s National Elites Foundation (INEF), Nano Novin Polymer Co. (Iran), and the Nano Match program of Iran Nanotechnology Initiative Council (INIC) are gratefully acknowledged. The ICN2 is funded by the CERCA Programme/Generalitat de Catalunya. The ICN2 is supported by the Severo Ochoa program of the Spanish Ministry of Economy, Industry and Competitiveness (MINECO; grant nos. SEV-2017-0706 and MAT2017-87202-P). The financial support of “the Czech Science Foundation (No. 19-00676S)” is also greatly appreciated.

In November 2018, Butte County, California, was decimated by the Camp Fire, the deadliest wildfire in state history. Over 150,000 acres were destroyed, and at its peak, the fire consumed eighty acres per minute. The speed and intensity of the oncoming flames killed scores of people, and weeks before the fire was contained, first responders began searching through the rubble of 18,804 residences and commercial buildings. As with most mass disasters, conventional identification modalities (e.g., fingerprints, odontology, hardware) were utilized to identify victims. The intensity and duration of the fire severely degraded most of the remains, and these approaches were useful in only 22 of 84 cases. In the past, the remaining cases would have been subjected to conventional DNA analysis, which may have required months to years. Instead, Rapid DNA technology was utilized (in a rented recreational vehicle outside the Sacramento morgue) in the victim identification effort. Sixty‐nine sets of remains were subjected to Rapid DNA Identification and, of these, 62 (89.9%) generated short tandem repeat profiles that were subjected to familial searching; essentially all these profiles were produced within hours of sample receipt. Samples successfully utilized for DNA identification included blood, bone, liver, muscle, soft tissue of unknown origin, and brain. In tandem with processing of 255 family reference samples, 58 victims were identified. This work represents the first use of Rapid DNA Identification in a mass casualty event, and the results support the use of Rapid DNA as an integrated tool with conventional disaster victim identification modalities.

The incompatibility of most organic solvents with acetylcholinesterase (AChE) inhibition assay normally limits pesticide extraction efficiency in sample pretreatment, which might cause false negatives in real world sample assessment. Herein, a novel method has been developed for an improved AChE inhibition assay via organic solvent extraction combined spontaneous in situ solvent evaporation on microfluidic paper-based analytical devices. Enzyme pre-immobilization procedure was spared and AChE was added to the system after sampling step until a complete in-situ solvent evaporation process was performed on chip. IC50 levels of the six investigated organophosphate and carbamate pesticides indicated a completely eliminated influence of solvents on AChE behavior with the new method. Most importantly, analytical performances were significantly improved in food sample measurements. Reduction in matrix effect was observed when acetonitrile was adopted for lettuce sample pretreatment instead of water. Studies on different pesticides suggested a remarkably decreased discrimination effect on recoveries from sample pretreatment with the new developed method. The recovery level for phoxim spiked head lettuce samples reached (107.5 ± 14.2) %, in comparison with that of (18.6 ± 1.4) % from water-based extraction. Spiked water and apple juice samples with carbaryl concentration of as low as 0.02 mg L−1 were also successfully recognized with the present method by visual detection. This is the first report on direct sampling of organic extracts for AChE inhibition assay on-chip and it might provide a new perspective for real world sample assessments involving bio-reagents.