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Food safety is an issue that cannot be ignored at any time because of the great impact of food contaminants on people's daily life, social production, and the economy. Because of the extensive demand for high-quality food, it is necessary to develop rapid, reliable, and efficient devices for food contaminant detection. Microfluidic paper-based analytical devices (μPADs) have been applied in a variety of detection fields owing to the advantages of low-cost, ease of handling, and portability. This review systematically discusses the latest progress of μPADs, including the fundamentals of fabrication as well as applications in the detection of chemical and biological hazards in foods, hoping to provide suitable screening strategies for contaminants in foods and accelerating the technology transformation of μPADs from the lab into the field.

Microfluidic paper-based analytical devices (μPADs) are emerging as prominent platform for disease detection, specifically in developing countries. This paper device offers simplicity and affordability not typically seen in centralized laboratory settings. However, detection limits in μPADs are inadequate and often require tests results to be read within a specific time interval to ensure accuracy. To overcome these challenges, we are developing an on-chip mass spectrometry (MS) detection strategy for immunoassays performed on paper substrates. Herein, we present our initial results from a proof-of-concept study toward the development of μPADs capable of storing immunoassay reagents within the confinements of the 3D device, automatic splitting of biofluid into four individual test zones, immuno-capture of disease biomarker, and on-chip MS detection of captured species. The reported study encourages the development of point-of-care and direct-to-customer testing using the disposable μPAD to collect samples, followed by sensitive analysis using portable mass spectrometers. We demonstrate this capability using malaria Plasmodium falciparum histidine-rich protein 2 (PfHRP2) antigen detection.

We present how harmful different wood extractives carried over to paper mill with unbleached softwood Kraft pulp are for the strength of packaging papers and boards. The investigations were done by simulating industrial papermaking conditions in laboratory-scale trials for handsheet production. It was found that fatty acids are the most relevant compounds in the carryover pitch extractives (CPEs), as they readily interfere in fiber–fiber bonding strength, control the properties of CPE micelles, and are furthermore the most abundant compounds. Addition of cationic starch improved strength and evened out the strength differences of handsheets with different CPE compounds. Oleic acid (unsaturated fatty acid) was an exception, as it was above average harmful for paper strength without cationic starch and also heavily impaired the functioning of cationic starch. As a whole, these findings demonstrate that fatty acids, especially unsaturated ones, are the most relevant CPE compounds contributing to the reduced efficiency of cationic starch and decreased strength of unbleached softwood Kraft paper. This makes the cleaning of process waters by precipitating CPEs on the pulp fibers harmful for paper strength.

An innovative consolidation strategy for degraded paper is presented based on the reversible application of cellulose nanocrystals as sustainable fillers to reinforce mechanical properties and resistance to further degradation. The compatibility and efficacy of the proposed consolidation treatment are assessed first on pure cellulose paper, used as a model, by reliable techniques such as field emission scanning electron microscopy, atomic force microscopy, tensile tests, X-ray powder diffraction, and Fourier transform infrared spectroscopy, evidencing the influence of the surface functionalization of nanocellulose on the consolidation and protection effects. Then, the consolidation technique is applied to real aged paper samples from Breviarium romanum ad usum Fratrum Minorum S.P. (1738), demonstrating the promising potential of the suggested approach. Amperometric measurements, carried out with a smart electrochemical tool developed in our laboratory, demonstrate the reversibility of the proposed treatment by removal of the nanocrystalline cellulose from the paper surface with a suitable cleaning hydrogel. This completely new feature of the consolidation treatment proposed here satisfies a pivotal requisite in cultural heritage conservation because the methodological requirement for the ″reversibility″ of any conservation measure is a fundamental goal for restorers. A paper artifact, in fact, is subject to a number of natural and man-made hazards, inducing continuous degradation. With time, monitoring and consolidation actions need to be often performed to ensure conservation, and this tends to modify the status quo and compromise the artifact integrity. Removable treatments can potentially avoid erosion of the artifact integrity.

Target-responsive nanomaterials attract growing interest in the application of drug delivery, bioimaging, and sensing due to the responsive releasing of guest molecules by the smart molecule gate. However, it remains a challenge to develop smart nanomaterials with simple assembly and low nonspecific leakage starting from encapsulation strategies, especially in the sensing field. Herein, Au nanoclusters (Au NCs) were first grown on porous carbon derived from ZIF-8 (PCZIF) to be employed as nanocarriers. By employing the Au NCs as linkers and aptamer (Apta) double-strand hybrids (target Apta and SH-complementary DNA) as capping units, we reported the novel target-responsive nanomaterials of Apta/Au NCs-PCZIF/hemin through Au-S binding encapsulation for sensing assays. The Au-S binding encapsulation strategy simplified the packaging procedure and reduced non-target responsive leakage. As a proof, ochratoxin A (OTA) as a model target participates in the double-strand hybrid competitive displacement reaction and triggered Apta conformation switches from a coil to a G-quadruplex structure accompanied by the dissociation of the gatekeeper. Simultaneously, the released hemin can initiate a self-assembly to form G-quadruplex/hemin DNAzyme. Interestingly, owing to DNAzyme providing electron transfer mediators and peroxidase-like activity, we proposed an electrochemical/colorimetric dual-mode paper-based analytical device (PAD) that provided self-verification to enhance reliability and accuracy, benefiting from independent signal conversion and transmission mechanism. As a consequence, the proposed dual-mode PAD could achieve sensitive electrochemical detection and visual prediction of OTA in the range of 1 pg/mL to 500 ng/mL and 50 pg/mL to 500 ng/mL, respectively. The electrochemical detection limit for OTA was as low as 0.347 pg/mL (

Graphene paper (GP), a macroscopic self-supporting material, has exceptional flexibility and preserves the excellent physical and chemical properties of graphene nanomaterials. But its applications in regenerative medicine remain to be further explored. Here, we biologically functionalized GP with hydroxyapatite (HA) nanorods by the use of GP-binding peptides as an affinity linker. This strategy solved two daunting challenges for regenerative medicine applications of GP: the lack of good hydrophilicity for supporting cell growth and the difficulty in forming composites by binding with nanobiomaterials. Briefly, we first screened a high-affinity GP-binding peptide (TWWNPRLVYFDY) by the phage display technique. Then we chemically conjugated the GP-binding peptide to the synthetic HA nanorods. The GP-binding peptide on the resultant HA nanorods enabled them to be bound and assembled onto the GP substrate with high affinity, forming a GP-peptide-HA composite with significantly improved hydrophilicity of GP. The composite promoted the attachment and proliferation of mesenchymal stem cells (MSCs), demonstrating its outstanding biocompatibility. Due to the unique compositions of the composite, it was also found to induce osteogenic differentiation of MSCs in vitro in the absence of other inducers in the medium, by verifying the expression of the osteogenic markers including collagen-1, bone morphogenetic proteins 2, runx-related transcription factor 2, osteocalcin, and alkaline phosphatase. Our work suggests that the GP-binding peptide can be used to link inorganic nanoparticles onto GP to facilitate the biomedical applications of GP.

Paper-based fluorescence devices, with smartphone aids, bring considerable operation convenience for tetracycline (TC) sensing. Nevertheless, they must meet the challenge in real determination against complicated backgrounds. Considering that, we present a programmable-printing paper-based device and then apply it to TC determination for various natural samples. MoS2 NPs and Gmp/Eu-Cit are synthetized as composite probes. A static quenching process is found with MoS2 NP fluorescence at 430 nm, while significant magnification of Gmp/Eu-Cit emission is obtained at 617 nm, establishing a valuable ratiometric indicator. Remarkably, two-stage programmable printing maximizes the proposed sensing capability. A transitive device, containing a gradually changing amount of a certain probe, is prepared to sense TC. With a homemade smartphone application and 3D-printed measurement chamber, the corresponding signals are examined to explore optimal setups. These setups are automatically processed to prepare the final-version device, not requiring manual operations. Benefitting from this interesting feature, the proposed device gains many rewards in performances. It effectively senses TC in a wide range from 12.7 nM to 80 μM and simultaneously provides naked eye-legible signals and smartphone-based readouts with confident selectivity and stability. This device is consequently applied for various samples of soil, river water, milk, and serum and meets well with HPLC-MS and recovery tests.

All-paper sensors that are capable of free cutting and folding maximize the merits of papers, which fully utilize the unique potential of papers in cost effectiveness, flexibility, disposability, biodegradability, and a flexible design. However, most of the paper sensors have applied metals as the electrodes and polyimide/polydimethylsiloxane as the encapsulation/sensitive layers, limiting the advantages of the paper sensor. In this work, an all-paper, shape-designable, and reconfigurable capacitive pressure/proximity sensor is fabricated with multilayered tissue paper as the dielectric and polypyrrole printer paper as the electrode/encapsulation. Without the restriction of heterogeneous materials, the all-paper components enable the sensors' flexible shape design for freely cuttable and foldable 2D and 3D sensors including a 2D braille keyboard and even allow reconfiguration from a 3D box sensor to a 3D candy sensor. The all-paper sensor presents superior pressure-sensing performance (0.96 kPa-1 at

Illicit drug use causes over half a million deaths worldwide every year. Drugs of abuse are commonly smuggled through customs and border checkpoints and, increasingly, through parcel delivery services. Improved methods for detection of trace drug residues from surfaces are needed. Such methods should be robust, fieldable, sensitive, and capable of detecting a wide range of drugs. In this work, commercially produced paper with a pressure-sensitive adhesive coating was utilized for the collection and analysis of trace drug residues by paper spray mass spectrometry (MS). This modified substrate was used to combine sample collection of drug residues from surfaces with rapid detection using a single paper spray ticket. The all-in-one ticket was used to probe different surfaces commonly encountered in forensic work including clothing, cardboard, glass, concrete, asphalt, and aluminum. A total of 10 drugs (acetyl fentanyl, fentanyl, clonazolam, cocaine, heroin, ketamine, methamphetamine, methylone, U-47700, and XLR-11) were evaluated and found to be detectable in the picogram range using a benchtop mass spectrometer and in the low nanogram range using a portable ion trap MS. The novel approach demonstrates a simple yet effective sampling strategy, allowing for rapid identification from difficult surfaces via paper spray mass spectrometry.

Timely and rapid detection of biomarkers is extremely important for the diagnosis and treatment of diseases. However, going to the hospital to test biomarkers is the most common way. People need to spend a lot of money and time on various tests for potential disease detection. To make the detection more convenient and affordable, we propose a paper-based aptasensor platform in this work. This device is based on a cellulose paper, on which a three-electrode system and microfluidic channels are fabricated. Meanwhile, novel nanomaterials consisting of amino redox graphene/thionine/streptavidin-modified gold nanoparticles/chitosan are synthesized and modified on the working electrode of the device. Through the biotin-streptavidin system, the aptamer whose 5'end is modified with biotin can be firmly immobilized on the electrode. The detection principle is that the current generated by the nanomaterials decreases proportionally to the concentration of targets owing to the combination of the biomarker and its aptamer. 17β-Estradiol (17β-E2), as one of the widely used diagnostic biomarkers of various clinical conditions, is adopted for verifying the performance of the platform. The experimental results demonstrated that this device enables the determination of 17β-E2 in a wide linear range of concentrations of 10 pg mL-1 to 100 ng mL-1 and the limit of detection is 10 pg mL-1 (S/N = 3). Moreover, it enables the detection of targets in clinical serum samples, demonstrating its potential to be a disposable and convenient integrated platform for detecting various biomarkers.

This work describes the development of a system that combines a derivatization protocol based on the Katritzky reaction with paper spray ionization mass spectrometry (PSI-MS) for the analysis of amino acid neurotransmitters in mouse brain tissues. The system is relatively simple, consisting of spraying the derivatization solution onto a mouse brain section mounted on a glass slide, applying a small volume of solvent to moisten the sample, pressing a triangular paper onto the sample surface to transfer the sample constituents to the paper surface, and using the paper as a substrate for PSI-MS analysis. The Katritzky reaction facilitated the ionization of the amino acids by reacting a pyrylium salt with the amino group of the analytes, forming very stable pyridinium cations, which greatly increased the sensitivity of the PSI-MS analysis. Most of the intensities of the amino acids modified by the Katritzky reaction were more than 10 times greater than the nonderivatized ones. The system was applied for the analysis of brain sections obtained from mice with Parkinson's disease, and the amino acids gamma-aminobutyric acid (GABA) and glycine (Gly), two compounds very well-known in studies of Parkinson's disease, were readily detected. The results suggest that the Katritzky reaction combined with PSI-MS might offer a significant advance in the knowledge on protocols that improve the sensitivity of detection of crucial biological compounds.

The spread of Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), resulting in a global pandemic with around four million deaths. Although there are a variety of nucleic acid-based tests for detecting SARS-CoV-2, these methods have a relatively high cost and require expensive supporting equipment. To overcome these limitations and improve the efficiency of SARS-CoV-2 diagnosis, we developed a microfluidic platform that collected serum by a pulling-force spinning top and paper-based microfluidic enzyme-linked immunosorbent assay (ELISA) for quantitative IgA/IgM/IgG measurements in an instrument-free way. We further validated the paper-based microfluidic ELISA analysis of SARS-CoV-2 receptor-binding domain (RBD)-specific IgA/IgM/IgG antibodies from human blood samples as a good measurement with higher sensitivity compared with traditional IgM/IgG detection (99.7% vs 95.6%) for early illness onset patients. In conclusion, we provide an alternative solution for the diagnosis of SARS-CoV-2 in a portable manner by this smart integration of pulling-force spinning top and paper-based microfluidic immunoassay.

Hydrophobic substrates for surface-enhanced Raman scattering (SERS) of adsorbate species are of great interest in chemical analysis because they can concentrate the analyte molecules in a small area of the surface, thereby improving the SERS sensitivity. Here, we propose a general strategy to fabricate hydrophobic paper-based substrates for SERS applications. The paper substrates have been manufactured by inkjet printing of aqueous emulsions containing Ag and polystyrene (PS) colloidal nanoparticles. In a first stage, the SERS performance of the substrates was optimized by varying the relative amounts of polymer/metal colloidal nanoparticles, the number of printing layers, and the degree of hydrophobicity of the substrates, using crystal violet as a molecular probe, which is well known for its strong SERS activity. In these conditions, the strongest surface Raman enhancement was observed for the highest water contact angle (146°) achieved. The selected Ag/PS-coated paper substrates showed wide applicability for several analytes, but in this study, a detailed analysis is provided for the pesticide thiram as a proof of concept. Several samples spiked with thiram have been analyzed by SERS, giving a detection limit of 0.024 ppm thiram in mineral water and apple juice, while in apple peel, the detection limit achieved for the same pesticide was 600 ng/cm2. We suggest that this one-step fabrication method produces a hydrophobic coating whose nanoscale features improve the SERS performance of the paper substrates. published

The majority of chemical experiments conducted during educational programs are carried out in laboratories because they require instructors with special skills, in addition to large, expensive instruments. Recently, there has been an increasing demand for chemical experiments that can be carried out anywhere. Herein, we propose a novel type of paper-based analytical device (PAD) for enabling quantitative analysis without the requirement for a micropipette, since the PAD features a large sample loading zone and a waste zone, enabling accurate volume control of a liquid sample. We initially employed a micropipette to evaluate the PAD and demonstrate the quantitative analysis of ascorbic acid (AA) and pH using different loading volumes. Finally, we determined the AA concentrations and pH values of commercially available beverages using disposable plastic droppers, and the obtained results were in good agreement with those obtained through conventional methods. This PAD format can therefore be used as a novel educational tool for conducting certain chemical analyses in remote learning environments.