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In this study, the potential of ultrafiltered xylano-pectinolytic enzymatic bleaching approach was investigated, for manufacturing wheat straw-based paper. The enzymatic step was found to be most effective, with xylanase-pectinase dose of 4-1.7 IU/g pulp and time period of 180 min. The absorption spectra of the pulp free filtrate samples obtained after treatment of the pulp with ultrafiltered enzymes showed the removal of more impurities, in comparison to the treatment with crude enzymes. Microscopic analysis also showed the removal of lignin impurities in enzymatically bleached pulp samples. This bleaching approach using enzymes resulted in 27% reduction in ClO 2 dose. Ultrafiltered enzymes treated pulp samples also showed improved quality-related parameters, and Gurley porosity, burst index, breaking length, double fold, tear index, and viscosity increased by 19.05, 13.70, 8.18, 29.27, 4.41, and 13.27%, respectively. The lignin content, TDS, TSS, BOD and COD values also decreased in the effluent samples obtained after enzymatic bleaching plus 73% chemical bleaching dose. The BOD and COD values of the effluent samples improved by 23.01 and 23.66%, respectively. Thus, indicating the potential of ultrafiltered xylano-pectinolytic enzymes in reducing pollution during bleaching of wheat straw. This is the first study, mentioning the efficacy of ultrafiltered enzymes in the bleaching of wheat straw-based paper with better optical-strength-related properties and effluent characteristics., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

This paper describes the design and construction of dual microfluidic paper-based analytical devices (dual-μPADs) as a lab-on-paper platform involving a "do-it-yourself" fabrication protocol. The device comprises a colorimetric and electrochemical module to obtain a dual-mode signal readout sensing strategy. A 3D pen polymeric resin was used to prepare graphite carbon-based electrodes and hydrophobic barriers on paper substrates. The proposed carbon-based ink was employed to manufacture electrodes on paper based on a stencil-printing approach, which were further characterized by electrochemical and morphological analyses. The analytical performance of the dual-μPADs was simultaneously evaluated for lactate, pH, nitrite, and salivary amylase (sAA) analysis. To demonstrate the proof-of-concept, saliva samples collected from both healthy individuals and those with periodontitis were successfully tested to demonstrate the feasibility of the proposed devices. Samples collected from individuals previously diagnosed with periodontitis showed high levels of nitrite and sAA (> 94 μmol L -1 and > 610 U mL -1 ) in comparison with healthy individuals (≤ 16 μmol L -1 and 545 U mL -1 ). Moreover, periodontitis saliva resulted in acid solution and almost null lactate levels. Notably, this protocol supplies a simple way to manufacture dual-μPADs, a versatile platform for sensitive detecting of biomarkers in saliva playing a crucial role towards the point-of-care diagnosis of periodontal disease., (© 2023. Springer-Verlag GmbH Germany, part of Springer Nature.)

The global advocacy of resource conservation and waste management emphasizes the significance of sustainable practices, particularly in sectors such as paper manufacturing and recycling. Currently, conventional chemical methods are predominant for paper production, necessitating the use of substantial amount of toxic chemicals. This chemical-intensive approach compromises the recycled fiber quality, generates hazardous effluent causing serious ecological threats which triggers regulatory complexities for the mills. To address these challenges modern research suggests adopting sustainable eco-friendly practices such as employing enzymes. This review aims to explore the applicability of 'laccase' enzyme for paper recycling, investigating its properties and contribution to improved recycling practices. By delving into the potential application of laccase integration into the papermaking process, this article sheds light on the limitations inherent in traditional methods surmounted within both research and translational landscapes. Culture and process optimization studies, supporting the technological improvements and the future prospects have been documented., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The development of distance-based paper analytical devices (dPADs) integrated with molecularly imprinted polymers (MIPs) to monitor Escherichia coli (E. coli) levels in food samples is presented. The fluidic workflow on the device is controlled using a designed hydrophilic bridge valve. Dopamine serves as a monomer for the formation of the E. coli-selective MIP layer on the dPADs. The detection principle relies on the inhibition of the E. coli toward copper (II) (Cu 2+ )-triggered oxidation of o-phenylenediamine (OPD) on the paper substrate. Quantitative detection is simply determined through visual observation of the residual yellow color of the OPD in the detection zone, which is proportional to E. coli concentration. The sensing exhibits a linear range from 25.0 to 1200.0 CFU mL -1 (R 2  = 0.9992) and a detection limit (LOD) of 25.0 CFU mL -1 for E. coli detection. Additionally, the technique is highly selective with no interference even from the molecules that have shown to react with OPD to form oxidized OPD. The developed device demonstrates accuracy and precision for E. coli quantification in food samples with recovery percentages between 98.3 and 104.7% and the highest relative standard deviation (RSD) of 4.55%. T-test validation shows no significant difference in E. coli concentration measured between our method and a commercial assay. The proposed dPAD sensor has the potential for selective and affordable E. coli determination  in food samples without requiring sample preparation. Furthermore, this strategy can be extended to monitor other molecules for which MIP can be developed and integrated into paper-microfluidic platform., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Overwintering insects are facing energetic challenges because of food shortage, low temperature, and desiccation stress. Paper wasps of the genus Polistes overwinter as mated adults (gynes) in hibernacula protecting them from predation, snow, and rain but barely from low environmental temperature. In different climates, they face differing overwintering temperature regimes, and therefore they may differ in their energy use. We investigated how much of energy resources built up until autumn is used during diapause dormancy in natural hibernacula by measuring lipid, glycogen, and free carbohydrate content in autumn and early spring in Polistes dominula from temperate European (Austrian) and warm Mediterranean (Italian) climate and Polistes gallicus from Mediterranean climate. Winter energy consumption amounted to ~ 339 and ~ 310 J per wasp in the Austrian and Italian Polistes dominula populations. The smaller Italian Polistes gallicus consumed ~ 247 J. This amounts to 2.62, 2.35, and 1.79 J per day. Of this, the energy demand was mainly fuelled by lipids (84%, 93%, and 90%, respectively), but glycogen stores contributed also considerably (16%, 6%, and 9%). Free carbohydrates decreased only by 0.7%, 1%, and 0.8%. While fat stores seem still sufficient in spring, the wasps depleted most of their carbohydrates. The energy reserves of 396, 400, and 147 J per wasp remaining in spring in the three populations seem sufficient to fuel rest or simple brood care activities for a whole summer but restrict foraging flights to a few hours (~ 3.5-6 h). Results suggest that energy supply might become challenging in expected future climate scenarios., (© 2024. The Author(s).)

The rapid discrimination of bacteria is currently an emerging trend in the fields of food safety, medical detection, and environmental observation. Traditional methods often require lengthy culturing processes, specialized analytical equipment, and bacterial recognition receptors. In response to this need, we have developed a paper-based fluorescence sensor array platform for identifying different bacteria. The sensor array is based on three unique carbon quantum dots (CQDs) as sensing units, each modified with a different antibiotic (polymyxin B, ampicillin, and gentamicin). These antibiotic-modified CQDs can aggregate on the bacterial surface, triggering aggregation-induced fluorescence quenching. The sensor array exhibits varying fluorescent responses to different bacterial species. To achieve low-cost and portable detection, CQDs were formulated into fluorescent ink and used with an inkjet printer to manufacture paper-based sensor arrays. A smartphone was used to collect the responses generated by the bacteria and platform. Diverse machine learning algorithms were utilized to discriminate bacterial types. Our findings showcase the platform's remarkable capability to differentiate among five bacterial strains, within a detection range spanning from 1.0 × 10 3  CFU/mL to 1.0 × 10 7  CFU/mL. Its practicality is further validated through the accurate identification of blind bacterial samples. With its cost-effectiveness, ease of fabrication, and high degree of integration, this platform holds significant promise for on-site detection of diverse bacteria., (© 2024. The Author(s).)

Uric acid (UA) is an important biomarker, as a high concentration in blood can lead to gout and further renal syndrome. Although several point-of-care testing (POCT) devices have been reported to detect UA, there are some limitations such as the requirement for uricase and the complicated pretreatment of serum/plasma samples, which restricts their use at home or in undeveloped areas. In this work, we developed an approach by applying Zn 2+ to precipitate proteins and cells in whole blood to avoid interference with the chromogenic reaction. We used carboxymethylcellulose (CMC) to immobilize tetramethylbenzidine (TMB) on a nitrocellulose membrane for colorimetric detection. Using the oxidization properties of H 2 O 2 , which turns TMB into oxidized tetramethylbenzidine (TMBox) in the presence of catalyst gold nanoparticles (AuNPs), we successfully constructed an enzyme-free paper-based POCT device using the reduction reaction of UA and TMBox for simple, speedy, and cheap colorimetric detection of UA, achieving a detection time of 8 min, a linear range of 0-150 μg/mL, and an LOD of 25.79 μg/mL. The UA concentration in whole blood samples was further measured and correlated well with the clinical value (R 2  = 0.8212). Thus, the proposed assay has the potential for POCT diagnosis, monitoring, and prognosis of diseases related to UA., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

We report the development of a competitive ELISA-based origami microfluidic paper-based analytical device (μPAD) for the detection of mycotoxins in animal feed material. The μPAD was patterned using the wax printing technique with the design of a testing pad in the middle and two absorption pads at the side. Anti-mycotoxin antibodies were effectively immobilized on chitosan-glutaraldehyde-modified sample reservoirs in the μPAD. The determination of zearalenone, deoxynivalenol, and T-2 toxin in corn flour was successfully achieved by performing competitive ELISA on the μPAD in 20 min. Colorimetric results were easily distinguished by the naked eye with a detection limit of 1 µg/mL for all three mycotoxins. The μPAD integrated with competitive ELISA holds potential for practical applications in the livestock industry for rapid, sensitive, and cost-effective detection of different mycotoxins in animal feed materials., (© 2023. Springer-Verlag GmbH Germany, part of Springer Nature.)

The existence of pesticide residues in the hydrosphere, biosphere, and anthroposphere can cause acute or chronic diseases and deteriorate the environment. Therefore, efficient detection of pesticide residues is of great significance to prevent food poisoning, control food pollution, and protect human lives by recognizing their distribution and concentration. Herein, a novel smartphone-coupled three-layered paper-based microfluidic chip is proposed as a facile platform to detect the pesticides. The stereoscopic capillary-driven fluid transport is enabled by the three-layered microfluidic chip configuration. The detection mechanism is based on the enzyme inhibition reaction and the chromatic reaction. The detection results are obtained by a smartphone and figured out by colorimetric quantitative analysis. Taking advantages of the above merits, we demonstrate the utilization of this smartphone-coupled three-layered paper-based microfluidic chip for the effective analysis of typical pesticides (profenofo and methomyl). The linear ranges of profenofo and methomyl are 0.27-2.1 μmol L -1 and 0.14-1.85 μmol L -1 , respectively. The corresponding limits of detection in the chips are 55 nM and 34 nM, respectively. The paper-based chips are also highly cost-effective with a total cost of 0.082 ¥ per piece. It can be anticipated that this technique will open new avenues for the mass fabrication of paper-based microfluidic chips and provide state-of-the-art methods in the field of analytical chemistry., (© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.)

Iron is an important micronutrient involved in several mechanisms in the human body and can be an important biomarker. In this work, a simple and disposable microfluidic paper-based analytical device (µPAD) was developed for the quantification of iron in urine samples. The detection was based on the colorimetric reaction between iron(II) and bathophenanthroline and the reduction of iron(III) to iron(II) with hydroxylamine. The developed µPAD enabled iron determination in the range 0.07-1.2 mg/L, with a limit of detection of 20 µg/L and a limit of quantification of 65 µg/L, thus suitable for the expected values in human urine. Additionally, targeting urine samples, the potential interference of the samples color was overcome by incorporating a sample blank assessment for absorbance subtraction. Stability studies revealed that the device was stable for 15 days prior to usage and that the formed colored product was stable for scanning up to 3 h. The accuracy of the developed device was established by analyzing urine samples (#26) with the developed µPAD and with the atomic absorption spectrometry method; the relative deviation between the two sets of results was below 9.5%., (© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.)

Urinary tract infections (UTIs) make up a significant proportion of the global burden of disease in vulnerable groups and tend to substantially impair the quality of life of those affected, making timely detection of UTIs a priority for public health. However, economic and societal barriers drastically reduce accessibility of traditional lab-based testing methods for critical patient groups in low-resource areas, negatively affecting their overall healthcare outcomes. As a result, cellulose-based materials such as paper and thread have garnered significant interest among researchers as substrates for so-called frugal analytical devices which leverage the material's portability and adaptability for facile and reproducible diagnoses of UTIs. Although the field may be only in its infancy, strategies aimed at commercial penetration can appreciably increase access to more healthcare options for at-risk people. In this review, we catalogue recent advances in devices that use cellulose-based materials as the primary housing or medium for UTI detection and chart out trends in the field. We also explore different modalities employed for detection, with particular emphasis on their ability to be ported onto discreet casings such as sanitary products., (© 2021. The Author(s).)

N, Cl-doped carbon dots (N, Cl-CDs) were prepared by hydrothermal method from rhodamine B (RhB) and ethylenediamine (EDA). The resulting N, Cl-CDs exhibited fascinating solvent dependence and strict excitation independence. As the polarity of the solvent increased (from tetrahydrofuran (THF) to water), the emission spectrum of N, Cl-CDs was redshifted and the fluorescence efficiency decreased, which were attributed to hydrogen bond-induced aggregation. Taking advantage of these attributes, the N, Cl-CDs were used as suitable probes for fluorescence and colorimetric dual-mode detection of water in THF. The linear relationship was 0.5-100% water with the detection limit down to 0.093%. Moreover, the sensing platform was converted into a paper-based sensor for handy, real-time, and visible humidity sensing. N, Cl-CDs/PVA films were fabricated and realized continuously tunable solid-state fluorescence, further expanding their practical application., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

MicroRNAs (miRNAs), found in blood and body fluids, have emerged as potential non-invasive biomarkers for disease and injury. miRNAs are quantitatively evaluated using typical RNA analysis methods such as the quantitative reverse transcription polymerase chain reaction, microarrays, and Northern blot, all of which require complex procedures and expensive reagents. To utilize miRNAs as practical biomarkers, it will be helpful to develop simple and user-friendly sensors. In this study, a paper-based miRNA sensor was developed by combining two methods: (1) target-recycled DNAzyme (Dz) amplification and (2) graphene oxide-assisted Dz blotting on paper. The Dz spots on paper caused a miRNA-dependent color change in presence of colorimetric reagents and facilitated the quantification of absolute amount of the target miRNA, irrespective of the volume, with high reproducibility. This approach is technologically straightforward and enables quantification of as low as 7.75 fmol miRNA using a portable smartphone., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

A paper-based analytical device (PAD) with an integrated composite electrode has been designed and fabricated for non-enzymatic creatinine sensing. Reduced graphene oxide (rGO) was employed to modify the PAD so that it could function as a solid-contact transducer. A new macrocyclic pyrido-hexapeptide derivative was made and used as a special ionophore in the creatinine membrane sensor. The synthesized PAD showed a detection limit of 1.0 µM (S/N = 3) and a potentiometric response towards creatinine throughout a log-linear range of 2.0 µM-10 mM (R 2  = 0.9998). The sensor shows significant selectivity for a few related substances, including ephedrine, codeine, ketamine, caffeine, urea, urate, carbinoxamine, and dextromethorphan. It has been established that the testing method is appropriate for the direct potentiometric detection of creatinine in a variety of human urine sample types. When an indicating electrode and a reference electrode are put on the same flexible disposable, this lets applications with a small sample volume be done. For point-of-care creatinine measurement, the developed paper-based analytical equipment is a good choice because it is affordable, easily accessible, and self-pumping (especially when combined with potentiometric detection)., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Hydroxyl radical (•OH) detection is pivotal in medicine, biochemistry and environmental chemistry. Yet, electrochemical method-specific detection is challenging because of hydroxyl radicals' high reactivity and short half-life. In this study, we aimed to modify the electrode surface with a specific recognition probe for •OH. To achieve this, we conducted a one-step hydrothermal process to fabricate a CoZnMOF bimetallic organic framework directly onto conductive graphite paper (Gp). Subsequently, we introduced salicylic acid (SA) and methylene blue (MB), which easily penetrated the pores of CoZnMOF. By selectively capturing •OH by SA and leveraging the electrochemical signal generated by the reaction product, we successfully developed an electrochemical sensor Gp/CoZnMOF/SA + MB. The prepared sensor exhibited a good linear relationship with •OH concentrations ranging from 1.25 to 1200 nM, with a detection limit of 0.2 nM. Additionally, the sensor demonstrated excellent reproducibility and accuracy due to the incorporation of an internal reference. It exhibited remarkable selectivity for •OH detection, unaffected by other electrochemically active substances. The establishment of this sensor provides a way to construct MOF-modified sensors for the selective detection of other reactive oxygen species (ROS), offering a valuable experimental basis for ROS-related disease research and environmental safety investigations., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

A smartphone-assisted, paper-based ratio fluorescence probe is presented for the rapid, low-cost and on-site quantification of total flavonol glycosides in Ginkgo biloba extracts (GBE). The Al 3+ /Eu-MOF/paper-based probe utilizes lanthanide metal-organic framework (Ln-MOF) nanoparticles immobilized on Whatman filter paper along with Al 3+ for detecting flavonols, which are the hydrolyzed products of flavonol glycosides. The color change of the paper-based fluorescence image from red to orange depends on the concentration of the target analyte in the sample solution. The smartphone equipped with a red, green, blue (RGB) color detector measured the fluorescence signal intensity on the paper substrate after adding flavonol. The analytical variables affecting the performance of the probe, including the addition sequence of the aluminum nitrate solution, its concentration, that of the Ln-MOF solution, the drying time of the paper probe, the reaction time and the sensitivity parameters of the mobile phone camera (ISO), were optimized. Under optimal conditions, the Al 3+ /Eu-MOF/paper-based probe has good linear response in the concentration range 7 ~ 80 µg mL - 1 and a lower detection limit of 2.07 µg mL - 1 . The results obtained with the paper-based ratio fluorescence probe and smartphone combination were validated by comparing them with high-performance liquid chromatography (HPLC) measurements. This study provides a potential strategy for fabricating Al 3+ /Eu-MOF/paper-based probe used for total flavonol glycosides determination., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

A user-friendly, cost-effectively, portable, and environmentally friendly colorimetric sensor for the quantitative determination of formaldehyde was developed based on the combining of microfluidic paper-based analytical device (μPAD), headspace microextraction (HSME), and digital image colorimetry. Coupling HSME and μPAD led to enhancements in selectivity and sensitivity of the sensor through sample cleanup and analyte enrichment. To construct the μPAD-HSME device, two pieces of paper as the sample and detection zone were placed facing each other so that a small common and sealed space was created between them. The color change occurred when the analyte in the gaseous form crossed this gap and reached the detection zone. Colorimetric sensing in the detection zone was performed based on the Hantzsch reaction. The color change in the detection zone was recorded by a smartphone and digital images were processed using image analysis software based on the RGB model. The influence of some key variables on the sensitivity of the method including derivatization reagent composition, sample volume, extraction temperature, and extraction time was studied and optimized. The linear dynamic range of the method was obtained in two ranges of 0.10-0.75 and 0.75-5.0 mg L -1 with a limit of detection of 0.03 mg L -1 . The recoveries were in the range 80-126% for the quantification of formaldehyde in textile, milk, and wastewater samples., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Surface-enhanced Raman scattering (SERS) has been recognized as one of the most sensitive analytical methods by adsorbing the target of interest onto a plasmonic surface. Growing attention has been directed towards the fabrication of various substrates to broaden SERS applications. Among these, flexible SERS substrates, particularly paper-based ones, have gained popularity due to their easy-to-use features by full contact with the sample surface. Herein, we reviewed the latest advancements in flexible SERS substrates, with a focus on paper-based substrates. Firstly, it begins by introducing various methods for preparing paper-based substrates and highlights their advantages through several illustrative examples. Subsequently, we demonstrated the booming applications of these paper-based SERS substrates in abiotic and biological matrix detection, with particular emphasis on their potential application in clinical diagnosis. Finally, the prospects and challenges of paper-based SERS substrates in broader applications are discussed., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Rapid and sensitive detection of enteropathogenic Escherichia coli (EPEC) in fluids with complex background is an important task for safety quality control in the field of medicine, environment, and food. In this study, a gold foil paper-based aptasensor was developed for the detection of enteropathogenic EPEC O26:K60 with surface-enhanced Raman spectroscopy (SERS) and magnetic separation technology mediated by Fe 3 O 4 @Au composite. The gold foil paper was firstly modified with thiolated capture probe and SERS tag. The thiolated aptamer probe for EPEC was immobilized onto a Fe 3 O 4 @Au composite. In the presence of EPEC, highly specific recognition between the aptamer probe and EPEC made the Fe 3 O 4 @Au composite partially dissociated from the gold foil paper. This led to a decreased Raman intensity response, which showed an obvious negative linear correlation with increasing concentration of EPEC over a wide concentration range from 10 to 10 7  CFU/mL under an excitation wavelength of 633 nm. The detection limit was about 2.86 CFU/mL in a buffer solution and a licorice extractum and the detection time was only 2.5 h. The results demonstrate that the gold foil paper-based aptasensor can be an excellent biosensing platform that offers a reliable, rapid, and sensitive alternative for EPEC detection., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Herein we report a quantitative, multiplex assay for disease markers in plasma based on an integrated setup of a portable scanner and a disposable paper-based analytical device (PAD). The quantitative analysis relies on the digital colorimetric reading of the three-layer PAD with 30 assay sites for performing respective chromogenic reactions for plasma uric acid, glucose, and triglyceride, which are considered as important risk factors for cardiovascular diseases. A portable scanner with WiFi transmission capability was used to produce high-quality color images of the PADs and wirelessly transfer them to a smartphone or other mobile devices for data processing. The concentrations of biomarkers in both standard solutions and plasma samples can be directly obtained using a custom-designed smartphone app that is also capable of constructing calibration curves. The detection limits of uric acid, glucose, and triglyceride were determined to be 0.50 mg/dL, 0.84 mmol/L, and 14 mg/dL, respectively, which are below the normal limits and adequate for clinical validation. Owing to the distinct advantages-simple, portable, and cost-effective-this mobile assay protocol can be used for point-of-care (POC) settings or resource-limited situations, and potentially for the diagnosis and prevention of infectious diseases.

To evaluate the morphology of the "athlete's heart", left ventricular (LV) wall thickness (WT) and end-diastolic internal diameter (LVIDd) at rest were addressed in publications on skiers, rowers, swimmers, cyclists, runners, weightlifters (n = 927), and untrained controls (n = 173) and related to the acute and maximal cardiovascular response to their respective disciplines. Dimensions of the heart at rest and functional variables established during the various sport disciplines were scaled to body weight for comparison among athletes independent of body mass. The two measures of LV were related (r = 0.8; P = 0.04) across athletic disciplines. With allometric scaling to body weight, LVIDd was similar between weightlifters and controls but 7%-15% larger in the other athletic groups, while WT was 9%-24% enlarged in all athletes. The LVIDd was related to stroke volume, oxygen pulse, maximal oxygen uptake, cardiac output, and blood volume (r =  ~ 0.9, P < 0.05), while there was no relationship between WT and these variables (P > 0.05). In conclusion, while cardiac enlargement is, in part, essential for the generation of the cardiac output and thus stroke volume needed for competitive endurance exercise, an enlarged WT seems important for the development of the wall tension required for establishing normal arterial pressure in the enlarged LVIDd., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

An electroanalytical platform capable to take and dilute the sample has been designed in order to fully integrate the different steps of the analytical process in only one device. The concept is based on the addition of glass-fiber pads for sampling and diluting to an electrochemical cell combining a paper-based working electrode with low-cost connector headers as counter and reference electrodes. In order to demonstrate the feasibility of this all-in-one platform for biosensing applications, an enzymatic sensor for glucose determination (requiring a potential as low as -0.1 V vs. gold-plated wire by using ferrocyanide as mediator) was developed. Real food samples, such as cola beverages and orange juice, have been analyzed with the bioelectroanalytical lab-on-paper platform. As a proof-of-concept, and trying to go further in the integration of steps, sucrose was successfully detected by depositing invertase in the sampling strip. This enzyme hydrolyzes sucrose into fructose and glucose, which was determined using the enzymatic biosensor. This approach opens the pathway for the development of devices applying the lab-on-paper concept, saving costs and time, and making possible to perform decentralized analysis with high accuracy., (© 2021. The Author(s).)

A microcapillary grooved paper-based analytical device capable of dual-mode sensing (colorimetric and electrochemical detection) was demonstrated for analysis of viscous samples (e.g., human saliva). Herein, a hollow capillary channel was constructed via laser engraved micropatterning functions as a micropump to facilitate viscous fluidic transport, which would otherwise impede analysis on paper devices. Using salivary thiocyanate as a model analyte, the proposed device was found to exhibit a promising sensing ability on paper devices without the need for sample pretreatment or bulky instrumentation, as normally required in conventional methods used for saliva analysis. An extensive linear dynamic range covering detection of salivary thiocyanate for both high and trace level regimes (5 orders of magnitude working range) was collectively achieved using the dual-sensing modes. Under optimal conditions, the limit of detection was 6 μmol L -1 with a RSD of less than 5%. An excellent stability for the μpumpPAD was also observed for over 30 days. Real sample analysis using the proposed device was found to be in line with the standard chromatographic method. Benefitting from simple fabrication and operation, portability, disposability, low sample volume (20 μL), and low cost (< 1 USD), the μpumpPAD is an exceptional alternative tool for the detection of various biomarkers in saliva specimens.

This work presents a microfluidic paper-based analytical device (μPAD) for the determination of sucrose using the Benedict's test. An asymmetric dumbbell-shaped hydrophobic barrier was produced by rubber stamping the barrier pattern onto a laboratory filter paper. Hydrochloric acid and solution containing sucrose were successively deposited onto the sample reservoir of the μPAD attached to a glass slide. The device was placed in a plastic bag and dipped into boiling water for accelerating the hydrolysis of sucrose into the reducing sugars. Then the Benedict's reagent was added at the narrow straight channel connecting the two circular zones of the μPAD, which was replaced in the plastic bag and heated again for reduction of Cu(II) by the reducing sugars. Precipitate of brick-red copper(I) oxide was formed. The image of the μPAD was recorded by a smartphone. The ratio of the red to blue intensities gave linear correlation with the concentration of sucrose in the range of 0.5-10% w/v. The relative standard deviation of the measurement was less than 5% for 2 and 4% w/v sucrose (n = 10), with limit of determination, calculated using standard deviation of regression divided by slope of calibration, of 0.26% w/v sucrose. The method was successfully validated using the dinitrosalicylic acid method for sucrose measurement. Percent recoveries of sucrose were evaluated using ten sugarcane samples. The recoveries were in the range of 89 to 101%, demonstrating that there were no significant sample matrix effects on the quantification., (© 2022. Springer-Verlag GmbH Germany, part of Springer Nature.)

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.

Caffeine naturally occurs in tea and cocoa, which is also used as an additive in beverages and has pharmacological effects such as refreshing, antidepressant, and digestion promotion, but excessive caffeine can cause harm to the human body. In this work, based on the specific response between nano zinc 5, 10, 15, 20-tetra(4-pyridyl)-21H-23H-porphine (nano ZnTPyP)-CdTe quantum dots (QDs) and caffeine, combined with chemometrics, a visual paper-based sensor was constructed for rapid and on-site detection of caffeine. The fluorescence of QDs can be quenched by nano ZnTPyP. When caffeine is added to the system, it can pull nano ZnTPyP off the surface of the QDs to achieve fluorescence recovery through electrostatic attraction and nitrogen/zinc coordination. The detection range is 5 × 10 -11 ~3 × 10 -9  mol L -1 , and the detection limit is 1.53 × 10 -11  mol L -1 (R 2  = 0.9990) (S/N = 3). The paper-based sensor constructed exhibits good results in real samples, such as tea water, cell culture fluid, newborn bovine serum, and human plasma. Therefore, the sensor is expected to be applied to the rapid instrument-free detection of caffeine in food and biological samples.Graphical abstract.

In this work, a low-cost and eco-friendly paper-based analytical device (PAD) method is described for the determination of phyto-cannabinoids in cannabis and oral fluids based on a simple colorimetric reaction. The PAD was able to distinguish tetrahydrocannabinol (THC)- and cannabidiol (CBD)-rich plant samples by using 4-aminophenol (4-AP) and later on to quantify total phyto-cannabinoid content (THC + CBD + CBN) in plant and oral fluids by using the Fast Corinth V reagent. The chemical and physical properties regarding paper type and reagent concentration in the PAD were optimized to achieve the best analytical performance. After that, analytical features were obtained, including a linear range of 0.01-0.1 mg mL -1 , a limit of detection (LOD) of 0.003 mg mL -1 , and a suitable precision, expressed as relative standard deviation (RSD) lower than 10%. Furthermore, no significant interferences were observed in colorimetric reactions when tea, herbs, and drug samples were analyzed. Additionally, the PAD proved color stability up to 1 month after the sampling at 25 °C. The developed PAD was suitable for determining total phyto-cannabinoid content in plants and oral fluids, obtaining good results compared to GC-MS. Overall, this method showed good reliability resulting in an operational on-site device for drug monitoring., (© 2023. The Author(s).)

The development of fluorometric paper-based analytical devices (fPADs) integrated with smartphone for fluorometric quantification of ethanol in an instrument-free and portable setup is described. The NAD + -dependent alcohol dehydrogenase immobilized within chitosan modified paper substate was utilized as a bio-recognition element and enzymatically generated NADH was used as a fluorescent probe. 3D-printed imaging setup which houses a paper chip holder and UV-light emitting device (LED) was developed for rapid, accurate capture of the fluorescent images. The biocompatible chitosan layer covering the paper provides a feasible environment for enzyme immobilization and enhances the fluorescence signal. The developed fPADs exhibited high sensitivity for ethanol detection and has a linear range for ethanol detection from 17 µM to 8.75 mM (R 2 =0.99). Additionally, the fPADs were applied to quantify ethanol in four different wine samples including red, white, rose, and sparkling wines successfully. Moreover, the fPADs produce reproducible signals without loss of enzyme activity for at least 14 days and ~80% activity remained till 28 days. Thus, the proposed approach can provide a facile, affordable, portable, and instrument-free tool for the onsite quantification of ethanol in real samples and is applicable for food quality controls., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Dual-emissive fluorescent carbon dots (CDs) were prepared through the solvothermal method with citric acid and urea as raw materials and dimethylformamide as the solvent. Two emission peaks were observed at 465 nm and 630 nm. Hg 2+ could selectively quench the fluorescence at 630 nm, but the fluorescence intensity at 465 nm was less affected. Accordingly, a ratiometric fluorescence sensor for Hg 2+ detection was developed, with a linear detection range of 0.5-40 μM and a limit of detection (LOD) of 37 nM. The dual-emissive CDs were loaded on the surface of the filter paper to fabricate Hg 2+ detection test paper. The color of the test paper could be changed from pink purple to blue by the addition of Hg 2+ , and thus the qualitative and quantitative detection of Hg 2+ could be realized. The concentration distinguishable by the naked eye reached 50 μM, and the quantitative detection range was 5-10,000 μM. This method shows excellent selectivity for Hg 2+ and can be used to detect Hg 2+ in real water samples, providing a highly potential sensing platform for rapid on-site detection of mercury ions., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

A method named imprint paper spray ionization mass spectrometry (imprint-PSI-MS) has been developed and employed for the determination of pungency of peppers. A pepper fruit was cut into a triangular shape, deposited onto a triangular paper, and compressed by a homemade press tool aiming to imprint and transfer the pepper constituents onto the paper surface. Subsequently, the triangular paper was submitted to conventional PSI-MS analysis. Twelve peppers were analyzed, ranging from highly pungent to lowly pungent taste. Pepper pungency values from the Scoville scale (in Scoville heat units, SHU) were compared with the ion intensities of the capsaicin and dihydrocapsaicin compounds obtained from the imprint-PSI-MS analysis, and a correlation coefficient of 0.97 was achieved. In addition, the ion intensities of a sugar compound were monitored in all peppers, and the results were compared with the Scoville scale. Low sugar ion intensities were detected in pungent peppers, while high ion intensities were achieved in low-pungent peppers, suggesting that the pepper pungency may be determined by inversely relating pungency to sugar contents. This work demonstrates the utility of the imprint-PSI-MS method to perform rapid qualitative analyses of peppers and estimate the pungency by monitoring the pepper metabolites. Graphical abstract.

Microfluidic-based biosensors have been developed for their precise automatic reaction control. However, these biosensors require external devices that are difficult to transport and use. To overcome this disadvantage, our group made an easy-to-use, cheap, and light pumpless three-dimensional photo paper-based microfluidic analytical device (3D-μPAD; weight: 1.5 g). Unlike conventional paper-based microfluidic analytical devices, the 3D-μPAD can be used to control fluid flow in a 3D manner, thus allowing sophisticated multi-step reaction control. This device can control fluid flow speed and direction accurately using only the capillary-driven flow without an external device like a pump. The flow speed is controlled by the width of the microfluidic channel and its surface property. In addition, fluid speed control and 3D-bridge structure enable the control of fluid flow direction. Using these methods, multi-step enzyme-linked immunosorbent assay (ELISA) can be done automatically in sequence by injecting solutions (sample, washing, and enzyme's substrate) at the same time in the 3D-μPAD. All the steps can be performed in 14 min, and data can be analyzed immediately. To test this device, thioredoxin-1 (Trx-1), a biomarker of breast cancer, is used as the target. In the 3D-μPAD, it can detect 0-200 ng/mL of Trx-1, and the prepared 3D-μPAD Trx-1 sensor displays excellent selectivity. Moreover, by analyzing the concentration of Trx-1 in real patients and healthy individuals' blood serum samples using the 3D-μPAD, and comparing results to ELISA, it can be confirmed that the 3D-μPAD is a good tool for cancer diagnosis., (© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.)

β-cyclodextrin-functionalized porous Pd@Au nanostructures (β-CD-Pd@Au) with intrinsic and enhanced peroxidase-like activity were successfully synthesized by a two-step method. The synthesized β-CD-Pd@Au can efficiently catalyze the oxidation of various substrates, such as 3,3',5,5'-tetramethylbenzidine (TMB), mixture of 4-amino antipyrine (4-AAP) and 3,5-dichloro-2-hydroxy acid sodium (DHBS) (4-AAP/DHBS), and mixture of 4-AAP and N-Ethyl-N-(3-sulfopropyl)-3-methyl-aniline sodium salt (TOPS) (4-AAP/TOPS), by H 2 O 2 to generate visual blue, purple, and pink color, respectively. The UV-vis absorbance peak of the three β-CD-Pd@Au catalyzed the chromogenic reaction system located at 650 nm, 510 nm, and 550 nm, respectively. The β-CD-Pd@Au-catalyzed TMB-H 2 O 2 chromogenic reaction exhibited higher absorbance intensity, catalytic efficiency, and color stability in comparison to 4-AAP/DHBS-H 2 O 2 and 4-AAP/TOPS-H 2 O 2 chromogenic reactions. The catalytic activity of β-CD-Pd@Au was enhanced about 4-fold compared to that of Pd@Au in terms of K cat for H 2 O 2 . Using TMB as chromogenic substrate, a colorimetric assay was fabricated for the determination of H 2 O 2 with a detection limit of 2.78 μM (absorbance at 650 nm). The colorimetric determination of glucose with a detection limit of 9.28 μM was further achieved by coupling with glucose oxidase enzymatic reaction, indicating the versatility of the β-CD-Pd@Au-based detection strategy. A paper-based detection method coupled with smartphone for fast visual and instrument-free detection of glucose was further developed. Finally, the developed colorimetric assay and paper-based detection method were successfully applied to the determination of glucose in human serum sample. Graphical abstract.

Microfluidic paper-based analytical devices (μPADs) have been widely used in point-of-care testing owing to their simple operation, low volume of the sample required, and the lack of the need for an external force. To obtain accurate semi-quantitative or quantitative results, μPADs need to respond to the challenges posed by differences in reaction conditions. In this paper, multi-layer μPADs are fabricated by the imprinting method for the colorimetric detection of C-reactive protein (CRP). Different lighting conditions and shooting angles of scenes are simulated in image acquisition, and the detection-related performance of μPADs is improved by using a machine learning algorithm. The You Only Look Once (YOLO) model is used to identify the areas of reaction in μPADs. This model can observe an image only once to predict the objects present in it and their locations. The YOLO model trained in this study was able to identify all the reaction areas quickly without incurring any error. These reaction areas were categorized by classification algorithms to determine the risk level of CRP concentration. Multi-layer perceptron, convolutional neural network, and residual network algorithms were used for the classification tasks, where the latter yielded the highest accuracy of 96%. It has a promising application prospect in fast recognition and analysis of μPADs., (© 2022. Springer-Verlag GmbH Germany, part of Springer Nature.)

Ultrasensitive detection of specific biomarkers in clinical serum is helpful for early diagnosis of cervical cancer. In this paper, a surface-enhanced Raman scattering (SERS)-based immunoassay was developed for the simultaneous determination of squamous cell carcinoma antigen (SCCA) and osteopontin (OPN) in cervical cancer serum. Au-Ag nanoshuttles (Au-AgNSs) as SERS tags and hydrophobic filter paper-based Au nanoflowers (AuNFs) as capture substrate were constructed into a sandwich structure which served as an ultrasensitive SERS-based immunoassay platform. Finite difference time domain simulation confirmed that the electromagnetic field coupled between the AuNFs had a prominent SERS signal enhancement effect, which improved the detection sensitivity. SERS mapping showed that hexadecenyl succinic anhydride hydrophobic treatment could prevent the analyte from being quickly absorbed by the filter paper and increase the retention time to be more evenly distributed on the filter paper substrate. The immunoassay platform was verified to have good selectivity and reproducibility. With this method, the detection limits of SCCA and OPN in human serum were as low as 8.628 pg/mL and 4.388 pg/mL, respectively. Finally, in order to verify the feasibility of its clinical application, the serum samples of healthy subjects; cervical intraepithelial neoplasia I (CINI), CINII, and CINIII; and cervical cancer patients were analyzed, and the reliability of the results was confirmed by enzyme-linked immunosorbent assay experiments. The constructed SERS-based immunoassay platform could be used as a clinical tool for early screening of cancers in the future.

This study investigated the colorimetric response of standard glucose, serum glucose, and nucleic acid assays on various paper surfaces with different wettability, including hydrophilic, hydrophobic, and nearly superhydrophobic surfaces. Water contact angles (WCA) formed by water droplets on each surface were measured using ImageJ software. The hydrophilic surface showed no contact angle, while the hydrophobic and nearly superhydrophobic surfaces exhibited contact angles of 115.667° and 133.933°, respectively. The colorimetric sensitivity of the standard glucose assay was analyzed on these surfaces, revealing enhanced sensitivity on the nearly superhydrophobic surface due to the high molecular crowding effect owing to its non-wetting behavior and eventually confined reaction product at the sample loading zone. The hydrophobic nature of the surface restricts the spreading and diffusion of the reaction product, leading to a controlled and localized concentration of the assay product leading to moderate colorimetric intensity. On the other hand, the hydrophilic surface showed the least enhancement in colorimetric sensitivity; this is attributed to the high wettability of the hydrophilic surface causing the reaction product to spread extensively, resulting in a larger area of dispersion and consequently a lower colorimetric intensity. The measured limit of detection (LOD) for nucleic acid on nearly superhydrophobic surfaces was found to be 16.15 ng/µL, which was almost four-fold lower than on hydrophilic surfaces (60.08 ng/µL). Additionally, the LODs of standard glucose and clinical serum samples were two-fold lower on nearly superhydrophobic surfaces compared to hydrophilic surfaces. Our findings clearly highlight the promising potential of utilizing superhydrophobic surfaces to significantly enhance colorimetric sensitivity in paper-based diagnostic applications. This innovative approach holds promise for advancing point-of-care diagnostics and improving disease detection in resource-limited settings., (© 2023. The Author(s).)

Children living with achondroplasia are at an increased risk of developing neurological complications, which may be associated with acute and life-altering events. To remediate this risk, the timely acquisition of effective neuroimaging that can help to guide clinical management is essential. We propose imaging protocols and follow-up strategies for evaluating the neuroanatomy of these children and to effectively identify potential neurological complications, including compression at the cervicomedullary junction secondary to foramen magnum stenosis, spinal deformity and spinal canal stenosis. When compiling these recommendations, emphasis has been placed on reducing scan times and avoiding unnecessary radiation exposure. Standardized imaging protocols are important to ensure that clinically useful neuroimaging is performed in children living with achondroplasia and to ensure reproducibility in future clinical trials. The members of the European Society of Pediatric Radiology (ESPR) Neuroradiology Taskforce and European Society of Neuroradiology pediatric subcommittee, together with clinicians and surgeons with specific expertise in achondroplasia, wrote this opinion paper. The research committee of the ESPR also endorsed the final draft. The rationale for these recommendations is based on currently available literature, supplemented by best practice opinion from radiologists and clinicians with subject-specific expertise., (© 2023. Crown.)

Detecting sputum pyocyanin (PYO) with a competitive immunoassay is a promising approach for diagnosing Pseudomonas aeruginosa respiratory infections. However, it is not possible to perform a negative control to evaluate matrix-effects in competitive immunoassays, and the highly complex sputum matrix often interferes with target detection. Here, we show that these issues are alleviated by performing competitive immunoassays with a paper biosensor. The biosensing platform consists of a paper reservoir, which contains antibody-coated gold nanoparticles, and a substrate containing a competing recognition element, which is a piece of paper modified with an albumin-antigen conjugate. Detection of PYO with a limit of detection of 4.7·10 -3  µM and a dynamic range between 4.7·10 -1  µM and 47.6 µM is accomplished by adding the sample to the substrate with the competing element and pressing the reservoir against it for 5 min. When tested with patient samples, the biosensor was able to qualitatively differentiate spiked from non-spiked samples, whereas ELISA did not show a clear cut-off between them. Furthermore, the relative standard deviation was lower when determining sputum with the paper-based biosensor. These features, along with a mild liquefaction step that circumvents the use of harsh chemicals or instruments, make our biosensor a good candidate for diagnosing Pseudomonas infections at the bedside through the detection of sputum PYO., (© 2023. The Author(s).)

Purpose: To evaluate the information that patients undergoing spine surgery truly receive and assimilate when they sign their informed consent documents., Methods: This was a retrospective study on patients who underwent spine arthrodesis or spine discectomy. Patients were given a full explanation of the surgical technique to be employed and its potential risks before they were included on the surgical waiting list. Before surgery, they were asked to sign an informed consent form. The studied variables included whether patients read the informed consent form, whether they recalled the surgical technique used or the spinal segment operated, whether they were aware of the surgical risks involved, and if they had looked for information about their procedure elsewhere. Answers were analyzed by age and educational level., Results: Of a total of 458 total patients, only 51.9% answered all the questions. Sixty-three percent of patients said they had read the informed consent document before surgery. Although 91.6% of patients were aware of the spine segment operated, only 73.5% remembered the surgical technique employed. A total of 63.9% of patients could recall the vertebral levels operated. 39.1% were not aware of the surgical risks involved, and only 16.0% of patients admitted having looked for additional information. A statistically significant correlation was found between the search for additional information and young age (p < 0.001) on the one hand, and high educational level on the other (p = 0.023)., Conclusion: Even though obtaining informed consent is an important procedure before spinal surgery, almost 40% of the patients in this study underwent surgery without reading the informed consent document or being aware of the risks posed by the procedure., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

A new rhodamine B derivative (RDB) was synthesized and utilized for the colorimetric detection of copper ions (Cu 2+ ). This chemosensor utilized a paper strip as a support and a smartphone as a detector for on-site quantitative detection of Cu 2+ in water samples. Silica nanoparticles (SiNPs) were investigated as the modifier nanoparticles to achieve uniform color on the paper strip and showed a color response 1.9-fold higher than the one without SiNPs. The RDB chemosensor-based paper strip provided high selectivity toward Cu 2+ with a detection limit of 0.7 mg/L, and the working concentrations for Cu 2+ ranged from 1 to 17 mg/L. Parallel analyses of eight drinking water samples were conducted by inductively coupled plasma optical emission spectroscopy. The results were in good agreement, indicating the practical reliability of the established method with a short assay time and high selectivity. These indicate its great potential for on-site detection of Cu 2+ ., (© 2023. Springer-Verlag GmbH Germany, part of Springer Nature.)

Pencil drawing is one of the simplest and most cost-effective ways of fabricating miniaturized electrodes on a paper substrate. However, it is limited by the lack of reproducibility regarding the electrode drawing process. A 3D-printed pencil holder (3DPH) is proposed here for simple, reproducible, and low-cost hand-drawn fabrication of paper-based electrochemical devices. 3DPH was designed to keep pressure and angulation of the graphite mine constant on the paper substrate using a micromechanical pencil regardless of the user/operator. This approach significantly improved the reproducibility and cost of making reliable pencil-drawn electrodes. The results showed high reproducibility and accuracy of the 3DPH-assisted electrodes prepared by 4 different operators in terms of sheet resistance and electrochemical behavior. Cyclic voltammetric (CV) curves in the presence of [Fe(CN) 6 ] 3-/4- redox probe showed only 3.9% variation for the anodic peak currents of different electrodes prepared by different operators when compared with electrodes prepared without the 3D-printed support. SEM analyses revealed a more uniform graphite deposition/design of the electrodes prepared with 3DPH, which corroborates the results obtained by CV. As a proof of concept, 3DPH-assisted pencil-drawn graphite electrodes were employed for dopamine detection in synthetic saliva, showing a proportional increase in anodic peak current at 0.12 V vs. carbon pRE with increasing dopamine (DA) concentration, with a detection limit of 0.39μmol L -1 . Moreover recovery was in the range 93-104% of DA (4-7% RSD) in synthetic saliva for three different concentrations, demonstrating the reliability of the approach. Finally, we believe this approach can make pencil-drawn technology more robust, accessible, reliable, and inexpensive for real on-site applications, especially in hard-to-reach locations or research centers with little investment., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Paper-based electrochemical analytical devices (ePADs) have gained significant interest as promising analytical units in recent years because they can be fabricated in simple ways, are low-cost, portable, and disposable platforms that can be applied in various fields. In this sense, paper-based electrochemical biosensors are attractive analytical devices since they can promote diagnose several diseases and potentially allow decentralized analysis. Electrochemical biosensors are versatile, as the measured signal can be improved by using mainly molecular technologies and nanomaterials to attach biomolecules, resulting in an increase in their sensitivity and selectivity. Additionally, they can be implemented in microfluidic devices that drive and control the flow without external pumping and store reagents, and improve the mass transport of analytes, increasing sensor sensitivity. In this review, we focus on the recent developments in electrochemical paper-based devices for viruses' detection, including COVID-19, Dengue, Zika, Hepatitis, Ebola, AIDS, and Influenza, among others, which have caused impacts on people's health, especially in places with scarce resources. Also, we discuss the advantages and disadvantages of the main electrode's fabrication methods, device designs, and biomolecule immobilization strategies. Finally, the perspectives and challenges that need to be overcome to further advance paper-based electrochemical biosensors' applications are critically presented., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

A new concept of paper-based device has been developed combining the advantages of cellulose supports and the rich surface chemistry of metal-organic frameworks (MOFs). The composite, named as NH 2 -UiO-66@paper, has been developed for the isolation of synthetic cannabinoid receptor agonists (SCRAs) in oral fluids, trying to mimic the interactions of those compounds with the human CB1R and CB2R receptors, mainly governed by hydrogen bonding and π-interactions with serine and histidine residues. MOF selection (UiO-66) and functionalization of the ligand (2-aminoterephthalic acid) has been done according to the following criteria: (i) water stability of the selected MOF, and (ii) promoting appropriate interactions with SCRAs due to the MOF nature. NH 2 -UiO-66@paper composite has been characterized in depth and the results confirmed that the material is stable at the temperature selected for thermal desorption (230 °C). Furthermore, the developed method provided appropriate precision values (RSD < 12%) and a limit of detection as low as 10 ng using ion mobility spectrometry as analytical technique. Lastly, the method has been successfully applied to the isolation of several synthetic cannabinoids from oral fluids. This method claims to be an interesting approach for expanding the combination of MOFs with sustainable support and represents a promising alternative to sophisticated and non-portable systems due to the negligible sample treatment required and the simplicity of the operation, which can be applied with screening purposes., (© 2023. The Author(s).)

The increasing demand for food and the need for a sustainability vision in the agri-food sector have boosted novel approaches for food management, enhancing the valorization of wastes and by-products belonging to the food industry. Herein, we present a novel paper-based origami device to assess the amount of both glucosinolate and glucose in a food waste product belonging to Brassicaceae plants, to evaluate the quality value and the correct management of waste samples. The device has been designed as an origami paper-based platform constituted of two paper-based biosensors to work synergistically in a multiplexed detection. In detail, a monoenzymatic biosensor and a bienzymatic biosensor were configured for the detection of glucose and glucosinolates, respectively, using filter paper pads preloaded with glucose oxidase and/or myrosinase. To complete the paper-based platform, the enzyme-preloaded pads were combined with office paper-based electrodes modified with Carbon black/Prussian Blue nanoparticles for the measurement of enzymatic by-product at a low applied potential (i.e., 0 V versus Ag/AgCl). Overall, this paper-based platform measured glucose and glucosinolate (i.e., sinigrin) with a linear range up to 2.5 and 1.5 mM, and detection limits of 0.05 and 0.07 mM, respectively. The repeatability corresponded to an RSD% equal to 5% by testing 10 mM of glucose, and 10% by testing 1 mM of sinigrin. The accuracy of the developed multiplex device was evaluated by recovery studies at two different levels of sinigrin, i.e., 0.25 and 0.5 mM, obtaining recoveries values equal to (111 ± 3) % and (86 ± 1) %, respectively. The multiplex detection of both glucose and glucosinolate in Brassicaceae samples evaluates the quality values of the waste sample, ensuring the quality of the re-used food product waste by using an eco-designed analytical tool. The combination of paper-based devices for quality control of food waste with the re-use of these food products represents a sustainable approach that perfectly matches sustainable agrifood practices as well as the overall approach of the circular economy., (© 2022. The Author(s).)

A paper-based electrochemiluminescence (ECL) biosensor characterized by the signal amplification of reticular DNA-functionalized PtCu nanoframes (DNA-PtCuTNFs) and analyte-triggered DNA walker was developed for sensitive streptavidin assay. Silver microflower functionalized paper-based sensing platform was prepared to fix the hairpin strand (S1). With addition of the streptavidin, plenty of DNA walkers consisting of the walking strands (S2) labeled with biotin and streptavidin were established, which protected S2 from digestion via the terminal protection mechanism. The sequential introduction of the DNA walker and capture probe initiated the hairpin structure opening of S1 and strand displacement reaction (SDR) happening, causing the S2 release. Subsequently, S1 hybridized with S3. The free S2 further hybridized with adjacent S1 to trigger the next cycle. After multiple cycles, the DNA-PtCuTNFs, the fire-new signal enhancer, with remarkable peroxidase activity, were successfully attached onto the paper electrode via metal-catalyst-free click chemistry. Based on the SDR of the DNA walker and the catalysis of DNA-PtCuTNFs, a significantly boosted ECL signal of luminol was obtained. Under the optimal conditions, the developed sensor for streptavidin assay exhibited a low detection limit of 33.4 fM with a linear range from 0.1 pM to 0.1 μM. Graphical abstract.

Enabled by the coffee-ring effect, a paper-based signal transduce method is employed for catalytic hairpin assembly (CHA) amplification and hybridization chain reaction (HCR) to achieve miRNA quantification. Once the target miRNAs appeared, it was circularly used by CHA to initiate HCR amplification to produce a large number of G-quadruplex, which is combined with hemin to form a hemin/G-quadruplex DNAzyme. The DNAzyme catalyzes a colorimetric reaction to produce colored nanoparticles, which were converted to the end edge of the paper by evaporation-driven flow, forming a visible colored band. Higher concentration of miRNA led to more colored nanoparticles and thus a longer colored band that can simply be measured by a ruler. The results of determination of miRNA in samples demonstrate that the relative standard deviation of the proposed approach is 5.2%, highly sensitive and repeatable, with a working range 1.0 to 1000 pM and a LOD of 0.2 pM. The paper-based analytical device as a novel platform offers a new signal transduce pathway toward the detection of low-abundance biomarkers for diagnosis.Graphical abstract Schematic representation of the principle for quantification of miRNA on paper based on the coffee-ring effect.