Search

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.)

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.)

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 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.)

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.)

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.)

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).)

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).)

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).)

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 detection of biogenic amines released from degraded meats is an effective method for evaluating meat freshness. However, existing traditional methods like titration are deemed tedious, while the use of sophisticated analytical instruments is not amenable to field testing. Herein, a cyanostilbene-based fluorescent array was rapidly fabricated using macroarray synthesis on a cellulose paper surface to detect amines liberated from spoiled beef, fish, and chicken. The fluorescence changes of immobilized molecules from the interaction with gaseous amines were used to monitor changes in freshness levels. Thanks to the high-throughput nature of macroarray synthesis, a set of highly responsive molecules such as pyridinium and dicyanovinyl moieties were quickly revealed. Importantly, this method offers flexibility in sensing applications including (1) sensing by individual sensor molecules, where the fluorescence response correlated well with established titration methods, and (2) collective sensing whereby chemometric analysis was used to provide a cutoff of freshness with 73-100% accuracy depending on meat types. Overall, this study paves the way for a robust and cost-effective tool for monitoring meat freshness., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Synthetic cannabinoids are one of the many substances of abuse widely spreading in modern society. Medical practitioners and law enforcement alike highly seek portable, efficient, and reliable tools for on-site detection and diagnostics. Here, we propose a colorimetric lateral flow assay (LFA) combined with dye-loaded polymersome to detect the synthetic cannabinoid JWH-073 efficiently. Rhodamine B-loaded polymersome was conjugated to antibodies and fully characterized. Two LFA were proposed (sandwich and competitive), showing a high level of sensitivity with a limit of detection (LOD) reaching 0.53 and 0.31 ng/mL, respectively. The competitive assay was further analyzed by fluorescence, where the LOD reached 0.16 ng/mL. The application of the LFA over spiked synthetic saliva or real human saliva demonstrated an overall response of 94% for the sandwich assay and 97% for the competitive LFA. The selectivity of the system was assessed in the presence of various interferents. The analytical performance of the LFA system showed a coefficient of variation below 6%. The current LFA system appears as a plausible system for non-invasive detection of substance abuse and shows promise for synthetic cannabinoid on-site sensing., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

The potential reach of point-of-care (POC) diagnostics into daily routines for exposure to reactive oxygen species (ROS) and Cu in aerosolized particulate matter (PM) demands that microfluidic paper-based analytical devices (μPADs) take into consideration the simple detection of these toxic PM components. Here, we propose μPADs with a dual-detection system for simultaneous ROS and Cu(II) detection. For colorimetric ROS detection, the glutathione (GSH) assay with a folding design to delay the reaction yielded complete ROS and GSH oxidation, and improved homogeneity of color development relative to using the lateral flow pattern. For electrochemical Cu(II) determination, 1,10-phenanthroline/Nafion modified graphene screen-printed electrodes showed ability to detect Cu(II) down to pg level being low enough to be applied to PM analysis. No intra- and inter-interference affecting both systems were found. The proposed μPADs obtained LODs for 1,4-naphthoquinone (1,4-NQ), used as the ROS representative, and Cu(II) of 8.3 ng and 3.6 pg, respectively and linear working ranges of 20 to 500 ng for ROS and 1 × 10 -2 to 2 × 10 2 ng for Cu(II). Recovery of the method was between 81.4 and 108.3% for ROS and 80.5-105.3% for Cu(II). Finally, the sensors were utilized for simultaneous ROS and Cu(II) determination in PM samples and the results statistically agreed with those using the conventional methods at 95% confidence., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Molecularly imprinted polymers are efficient and selective adsorbents which act as artificial receptors for desired compounds with the ability to recognize the size, shape, and functional groups of the compounds simultaneously. A molecularly imprinted polymer is prepared by the polymerization of functional monomers around a template (analyte) molecule. Afterward, the removal of the template from the polymer matrix leaves a selective cavity behind. The fabrication and development of molecularly imprinted polymers grew rapidly, due to their low cost, simple preparation, selectivity, sensitivity, and stable physicochemical properties. Traditionally, molecularly imprinted polymers can be synthesized using two main methods, namely bulk and surface imprinting. For more efficient use of the latter method, researchers have developed molecularly imprinted polymers grafted on the solid-phase matrix (substrate). This grafting technique would be particularly useful for surface imprinting of macromolecules, such as proteins. Cellulose fibers of papers with unique properties such as being abundant, retaining a porous structure, having good adsorption properties, and possessing hydroxyl groups naturally have gained much attention as substrate. The goal of this review is to introduce molecularly imprinted polymer-grafted or molecularly imprinted polymer-coated paper, as an interesting, simple, and efficient method in the detection and separation of small and large molecules. Therefore, in the present paper, several recent preparation techniques and applications of molecularly imprinted polymer-grafted paper are reviewed and discussed in detail. Green, cost-effective, selective, and sensitive paper-based sensor prepared via grafting molecularly imprinted polymer on paper surface with the potential use for online detection trace of analytes in the point-of-care testing., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Paper-based analytical devices (PADs) are powerful platforms for point-of-need testing since they are inexpensive devices fabricated in different shapes and miniaturized sizes, ensuring better portability. Additionally, the readout and detection systems can be accomplished with portable devices, allying with the features of both systems. These devices have been introduced as promising analytical platforms to meet critical demands involving rapid, reliable, and simple testing. They have been applied to monitor species related to environmental, health, and food issues. Herein, an outline of chronological events involving PADs is first reported. This work also introduces insights into fundamental parameters to engineer new analytical platforms, including the paper type and device operation. The discussions involve the main analytical techniques used as detection systems, such as colorimetry, fluorescence, and electrochemistry. It also showed recent advances involving PADs, especially combining optical and electrochemical detection into a single device. Dual/combined detection systems can overcome individual barriers of the analytical techniques, making possible simultaneous determinations, or enhancing the devices' sensitivity and/or selectivity. In addition, this review reports on distance-based detection, which is also considered a trend in analytical chemistry. Distance-based detection offers instrument-free analyses and avoids user interpretation errors, which are outstanding features for analyses at the point of need, especially for resource-limited regions. Finally, this review provides a critical overview of the practical specifications of the recent analytical platforms involving PADs, demonstrating their challenges. Therefore, this work can be a highly useful reference for new research and innovation., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

A turn-on fluorescent aptasensor based on a paper-based microfluidic chip was developed to detect arsenite via aptamer competition strategy and smartphone imaging. The chip was prepared by wax-printing hydrophilic channels on filter paper. It is portable, low-cost, and environmentally friendly. Double-stranded DNA consisting of aptamer and fluorescence-labeled complementary strands was immobilized on the reaction zone of the paper chip. Due to the specific strong binding between aptamer and arsenite, the fluorescent complementary strand was squeezed out and driven by capillary force to the detection area of the paper chip, so that the fluorescent signal arose in the detection area under the excitation wavelength of 488 nm. Arsenite can be quantified by using smartphone imaging and RGB image analysis. Under the optimal conditions, the paper-based microfluidic aptasensor exhibited excellent linear response over a wide range of 1 to 1000 nM, with a detection limit as low as 0.96 nM (3σ)., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

A highly stable and luminescent lead-free manganese(II) halide hybrid MnBr 4 (TMN) 2 (C 34 H 42 Br 4 MnN 4 ) was designed and synthesized by introducing a large cationic organic spacer. The MnBr 4 (TMN) 2 displays high luminescence with quantum yields up to 77% and possesses turn-off fluorescence behavior (E x /E m =365/546 nm) for water. These properties make the MnBr 4 (TMN) 2 a promising candidate as an alternative indicator for the detection of water with potential applications for the fabrication of LEDs. Herein, a paper-based sensor based on MnBr 4 (TMN) 2 is described for the determination of water content in organic solvents. The mechanism of water sensing can be tentatively explained by fluorescence quenching originating from the destruction of water due to the Mn-Br bonds of MnBr 4 (TMN) 2 . The MnBr 4 (TMN) 2 -based paper sensor exhibits an excellent discrimination ability of water content in the range 0-25.0% with a detection limit of 0.27%. Satisfactory recoveries (94.91±4.09% to 103.23±2.38%) are obtained in spiked ethanol solvent samples, which demonstrate that the MnBr 4 (TMN) 2 -based paper sensor is capable of detecting water content in real ethanol solvent samples., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

An electrochemical paper-based sensor was developed for the detection of bacterial infection (BI)-specific biomarker procalcitonin (PCT). Reduced graphene oxide-gold nanoparticles (rGO-AuNP) and poly(3,4-ethylene dioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) were synthesized and were fabricated to a disposable, portable, and inexpensive cellulose fiber paper (CFP) substrate. rGO-AuNP-PEDOT:PSS nanocomposite-modified conductive paper-based biosensing platform was efficaciously fabricated by a constant and simple coating procedure. rGO-AuNP-PEDOT:PSS nanocomposite-modified conductive paper electrode was found to provide a sensitive and conductive substrate for PCT detection. The presence of rGO-AuNP-PEDOT:PSS nanocomposite on CFP substate was investigated by Fourier transform infrared spectrometry, field emission scanning electron microscopy, ultraviolet-visible spectroscopy, and X-ray diffraction studies. The electrochemical behavior of rGO-AuNP-PEDOT:PSS @CFP surface was studied with impedance spectroscopy, cyclic voltammetry, and chronoamperometry techniques. This low-cost paper-based biosensor has a linear range for PCT of 1 × 10 3 to 6 × 10 7  fg mL -1 . This developed sensor exhibited good reproducibility with a relative standard deviation (RSD) of about 3.7%. The proposed CFP-based biosensor has been proven as an accelerated simple point-of-care (POC) exploratory approach for early PCT diagnosis in inadequate areas with limited production facilities, computational techniques, and highly skilled experts., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

One of the problems in the distance-based microfluidic paper-based analytical device (DB-µPAD) that limits the detection resolution is the mixing of reagents from the detection to the sampling zone or vice versa due to spreading by capillary action. In the present paper, to overcome mixing of the reagents in the zones, a multi-functional connector using a three-dimensional (3D) design has been developed externally to connect the two zones. Using such a novel design, it is acertained that there is no any mixing due to the dispersion of the reagents in the two zones. Interestingly, the simple 3D connector has other functions, such as its potential to be used as a masking zone and/or reaction zone whenever is needed. Based on this proposed 3D connector-based DB-µPAD, three parallel microchannels were built as detection zones with one sampling zone for multiplex analysis for the detection of Fe 2+ , Ni 2+ , and hardness of water. In the Ni 2+ channel, the connector piece worked as both masking part and connection part. In the Fe 2+ line, the connector served as the connector and reducing pad (Fe 3+ to Fe 2+ ions). While in the third channel, the connector has connection function only. Satisfactory limit of detection (LoD), accuracy, and precision were obtained using this design. The LODs obtained with the proposed design were 1.13, 0.62, and 1.87 mg.L -1 for total hardness, Fe 2+ , and Ni 2+ , respectively., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

A paper-based analytical device (PAD) is presented with colorimetric/electrochemical dual readouts for the simultaneous sensing of total chromium (Cr) and hexavalent chromium (Cr(VI)). This device consists of a homemade three-electrode system and a patterned paper chip, integrating multiple functions including electrochemical detection, fluid driving, online oxidation, and colorimetric detection. The fiberglass filter paper with a hydrophilic microchannel was used to achieve self-driving fluidics without external equipment. One end of the microchannel was integrated with a homemade three-electrode system to achieve sample loading and electrochemical detection. The middle region on the microchannel was modified with oxidizing reagents to perform online pretreatment, and the yield of Cr(III) oxidation can reach 97.9%, ensuring reliable colorimetric detection of total Cr at another end of the microchannel modified with chromogenic agents. With this device, the signals of Cr(VI) (the signal peak at 0.29 V vs. Ag/AgCl) and total Cr can be obtained in one single injection. After optimization, the limit of detection (LOD) of Cr(VI) and total Cr were 0.01 mg L -1 and 0.06 mg L -1 and the linear ranges were 0.05-3.0 mg L -1 and 0.2-3.0 mg L -1 , respectively. The relative standard deviations (RSD) of the electrochemical testing of Cr(VI) results were in a range 1.3%-8.7% (n = 3), and the RSD values of the colorimetric testing of total Cr were between 0.7-9.2% (n = 3). The device's reliability was demonstrated by performing the practical speciation of Cr in tap water, river water, and electroplating wastewater while the recoveries obtained using the present method were in the range 93.5-106%. Overall, the proposed device provides high application prospect in the on-site rapid Cr speciation., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

The simultaneous determination is reported of arginine (Arg) and valine (Val) amino acids in plasma using flower-shaped μPADs and PMMA/paper hybrid microfluidic chip based on AuNPs capped with R-thiazolidine-4-carboxylic acid (THP). In this article, the evaluation procedure is based on the smartphone colorimetric detection mechanism that results from the aggregation of the THP-AuNPs with the addition of amino acids and visual color change from red to blue. Arg and Val were selectively determined with good reproducibility and an acceptable linearity range. The flower-shaped (μPADs) provides many advantages, including low cost, reasonable sensitivity, simple and fast performance, simultaneous detection, disposable use, and high sample throughput compared with conventional colorimetric method using cuvette cells. The ratios between the absorbance wavelength at (A 650 /A 525 ) and (A 685 /A 525 ) are linearly proportional to the concentration of Arg and Val. Under the optimum conditions, the calibration range in aqueous solutions is 0.0068-100.0 and 0.0056-75.0 µM with a limit of detection of 2.25 and 1.86 nM for Arg and Val at pH 7.0, respectively. In the case of μPADs, the calibration curves for Arg and Val showed good linearity in the concentration range 0.01-75.0 µM. The detection limits for the analytes were 3.51 nM and 3.44 nM for Arg and Val, respectively. In addition, a PMMA/paper hybrid microfluidic chip was successfully employed to determine Arg and Val in plasma samples with a relative error below 5%., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Taking advantage of the intrinsic photocatalysis of TiO 2 , hydrophilic reactor arrays were lithographically patterned on a hydrophobic paper via a simple UV irradiation. As a proof-of-concept, alkaline phosphatase (ALP) was used as the model analyte for colorimetric analysis. As ALP can induce hydrolysis of pyrophosphate-Zn(II) framework, the released Zn 2+ ions are subsequently coordinated with red-colored zincon to form blue-colored zincon-Zn(II) chelate complex, and these color differences were applied for further colorimetric assay. The sensing platform showed response to ALP ranging from 20 ~ 800 U L -1 with a detection limit of 3 U L -1 , and the recoveries of ALP in serum samples were in the range 95.7 ~ 104.5% with relative standard deviations from 2.10 to 3.84%. Additionally, the distinct wettability features of the proposed sensing platform effectively prevent lateral fluid spread out of hydrophilic reactors, thus allowing not only the use of minimum amount of analyte but it has also a high potential for simultaneous quantification of multiple samples., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

α-Amanitin is often considered the most poisonous mushroom toxin produced by various mushroom species, which are hard to identify from edible, non-toxic mushrooms. Conventional detection methods require expensive and bulky equipment or fail to meet high analytical sensitivity. We developed a smartphone-based fluorescence microscope platform to detect α-amanitin from dry mushroom tissues. Antibody-nanoparticle conjugates were captured by immobilized antigen-hapten conjugates while competing with the free analytes in the sample. Captured fluorescent nanoparticles were excited at 460 nm and imaged at 500 nm. The pixel numbers of such nanoparticles in the test zone were counted, showing a decreasing trend with increasing analyte concentration. The detection method exhibited a low detection limit (1 pg/mL), high specificity, and selectivity, allowing us to utilize a simple rinsing for toxin extraction and avoiding the need for high-speed centrifugation. In addition, this assay's short response time and portable features enable field detection of α-amanitin from amanitin-producing mushrooms., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

A microfluidic paper-based device (µPAD) has been combined with metal-organic frameworks (MOFs) for total phenolic compounds (TPC) quantification in fruit samples for the first time. The performance of the µPAD, based upon the vertical flow approach, was enhanced in order to determine the TPC content with high accuracy in fruit samples. The method was based on the traditional Folin-Ciocalteu Index using gallic acid or oenotannin as reference phenolic compounds. This novel design and construction of the device are in agreement with the principles of Green Chemistry avoiding wax technology (lower toxicity). The analytical parameters that affect the colorimetric method (using digital imaging of the colored zone) performance were optimized including design, sample volume, and MOF amount. Then, the analytical features of the developed method were investigated such as dynamic range (1.6-30 mg L -1 ), limit of detection (0.5 mg L -1 ), and precision (RSD < 9%). Besides, the in-field analysis is achievable with a color stability up to 6 h after the loading process of the sample and storage stability for at least 15 days without performance losses (under vacuum at - 20 °C). Furthermore, the MOF ZIF-8@paper was characterized to study its composition and the successful combination. The feasibility of the proposed method was demonstrated by determining the TPC in 5 fruit samples using oenotannin as reference solute. The accuracy was validated by comparison of the data with the results obtained with the recommended protocol proposed by the International Organisation of Vine and Wine (OIV)., (© 2023. The Author(s).)

Laser-induced graphene (LIG) is as a promising material for flexible microsupercapacitors (MSCs) due to its simple and cost-effective processing. However, LIG-MSC research and production has been centered on non-sustainable polymeric substrates, such as polyimide. In this work, it is presented a cost-effective, reproducible, and robust approach for the preparation of LIG structures via a one-step laser direct writing on chromatography paper. The developed strategy relies on soaking the paper in a 0.1 M sodium tetraborate solution (borax) prior to the laser processing. Borax acts as a fire-retardant agent, thus allowing the laser processing of sensitive substrates that other way would be easily destroyed under the high-energy beam. LIG on paper exhibiting low sheet resistance (30 Ω sq -1 ) and improved electrode/electrolyte interface was obtained by the proposed method. When used as microsupercapacitor electrodes, this laser-induced graphene resulted in specific capacitances of 4.6 mF cm -2 (0.015 mA cm -2 ). Furthermore, the devices exhibit excellent cycling stability (> 10,000 cycles at 0.5 mA cm -2 ) and good mechanical properties. By connecting the devices in series and parallel, it was also possible to control the voltage and energy delivered by the system. Thus, paper-based LIG-MSC can be used as energy storage devices for flexible, low-cost, and portable electronics. Additionally, due to their flexible design and architecture, they can be easily adapted to other circuits and applications with different power requirements., (© 2022. The Author(s).)

A novel hydrophilic As(V) ion-imprinted cryogel (IIC) was green prepared by cryogelation in aqueous environment which was coincident with the adsorption condition and can improve the specific recognition performance. The methacrylamido propyl trimethyl ammonium chloride (MPTAC) was selected as the functional monomer and the saturated adsorption capacity of the prepared IIC and NIC were 55.0 mg/g and 29.4 mg/g, and with high imprinting factor of 1.87. Additionally, the prepared IIC showed admirable reusability and high selectivity, and the recovery was in the range 81.2-97.9% with RSD range of 1.9-4.3%, which was similar to the value obtained by hydride generation atomic absorption spectrometry. IIC can be used as solid material for colorimetric detection at the ultraviolet wavelength of 858 nm without color interference of material matrix, in the range 5-200 μg/L (R 2  = 0.990) with a detection limit of 0.970 µg/L. Obviously, this synthetic strategy provides a simple, efficient, and green method for the preparation of water-compatible ion-imprinted polymers providing selective separation and detection of trace As(V) in real complex samples., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

The fabrication of fully ink-drawn fluidic electrochemical paper-based analytical devices (ePADs) is reported for the determination of trace Pb(II) and Cd(II) by differential pulse anodic stripping voltammetry (DPASV). The fluidic pattern was formed on the paper substrate using an inexpensive computer-controlled x-y plotter and a commercial hydrophobic marker pen. Then, electrodes were deposited on the devices using a second x-y plotting step with a commercial technical pen filled with a graphite-based conductive ink prepared in house. The fabrication parameters of the ePADs were studied by cyclic voltammetry using the ferro/ferri couple as a probe and by scanning electron microscopy. The ePADs, featuring a bismuth nanoparticle-modified working electrode, were applied to the determination of Pb(II) and Cd(II) by DPASV. The chemical and instrumental conditions were studied. The limits of detection were 3.1 μg L -1 for Cd(II) and 4.5 μg L -1 for Pb(II) whereas the between-device reproducibility (expressed as the % relative standard deviation of the response at 6 different ePADs) was < 14%. Each ePAD requires 120 s to fabricate and costs less than 0.15 € in terms of consumables. The ePADs are suitable for the on-site determination of Pb(II) and Cd(II) in environmental and food samples., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

An enhanced ratiometric fluorescence sensor was built for on-site visual detection of doxycycline (DOX) through the interaction with bovine serum albumin on the surface of red emissive copper nanoclusters. Upon the addition of weakly fluorescent DOX, the red fluorescence from copper nanoclusters gradually decreased through the inner-filter effect (IFE), while a green fluorescence appears and significantly increases, forming an interesting fluorescent isosbestic point, which was assigned to DOX due to sensitization effect of bovine serum albumin. On the basis of this ratiometric fluorescence, the system possessed good limit of detection (LOD) of 45 nM and excellent selectivity for DOX over other tetracyclines. Based on these findings, a paper-based sensor has been fabricated for distinct visual detection of trace DOX and combined with smartphone color recognizer for quantitative detection of DOX (LOD = 83 nM). This method shows broad application prospects in environmental monitoring and food safety., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Chlorpyrifos is one of the most widely used organophosphate insecticides in agricultural production. Nevertheless, the residues of chlorpyrifos in agricultural by-product seriously threaten human health. Thus, the ultrasensitive detection of chlorpyrifos residues in agri-food products is of great demand. Herein, an AuNP/HNT-assembled disposable paper SERS substrate was prepared by an electrostatic self-assembly method to detect chlorpyrifos residues. The AuNP/HNT paper substrate exhibited high SERS activity, good reproducibility, and long-term stability, which was successfully used for quantitative detection of chlorpyrifos; the detection limit reached 7.9 × 10 -9  M. For spiked apple samples the calculated recovery was 87.9% with a RSD value of 6.1%. The excellent detection ability of AuNP/HNT paper-based SERS substrate indicated that it will play an important role in pesticide detection in the future. AuNP/HNT assembled disposable paper SERS substrate was prepared by an electrostatic self-assembly method to detect chlorpyrifos residues in fruits., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

The development of cost-effective, portable, and ease-of-use sensing system for on-site genetic diagnostics is highly desirable for pathogen screening and infectious disease diagnosis. This study develops (1) a paper-based biochip which is able to integrate the loop-mediated isothermal amplification (LAMP) protocols for simultaneous detection of Escherichia coli O157:H7, Salmonella spp., and Staphylococcus aureus, and (2) a stand-alone smartphone-based portable device which can control exactly 65 °C for isothermal amplification as well as collect and analyze the thus generated fluorescence signals. The reported sensing system has been successfully demonstrated for foodborne pathogen detection with a limit of detection of 2.8 × 10 -5  ng μL -1 . Spiked milk samples with concentration as low as 10 CFU mL -1 were successfully determined within 4 h, demonstrating the practicality of the reported sensing system in the fields. The reported sensing system featuring simplicity and reliability is ideally suited for genetic diagnostics in low resource settings., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

The development of the first microfluidic paper-based analytical device (µPAD) for the speciation of inorganic arsenic in environmental aqueous samples as arsenite (As(III)) and arsenate (As(V)) which implements hydride generation on a paper platform is described. The newly developed µPAD has a 3D configuration and uses Au(III) chloride as the detection reagent. Sodium borohydride is used to generate arsine in the device's sample zone by reducing As(III) in the presence of hydrochloric acid or both As(III) and As(V) (total inorganic As) in the presence of sulfuric acid. Arsine then diffuses across a hydrophobic porous polytetrafluoroethylene membrane into the device's detection zone where it reduces Au(III) to Au nanoparticles. This results in a color change which can be related to the concentration of As(III) or total inorganic As (i.e., As(III) and As(V)) concentration. Under optimal conditions, the µPAD is characterized by a limit of detection of 0.43 mg L -1 for total inorganic As (As(III) + As(V)) and 0.41 mg L -1 for As(III) and a linear calibration range in both cases of 1.2-8.0 mg As L -1 . The newly developed µPAD-based method was validated by applying it to groundwater and freshwater samples and comparing the results with those obtained by conventional atomic spectrometric techniques., (© 2022. The Author(s).)

The rapid detection of insecticides such as parathion-methyl (PM) requires methods with high sensitivities and selectivities. Herein, a dual catalytic amplification strategy was developed using Fe 3 O 4 nanozyme-supported carbon quantum dots and silver terephthalate metal-organic frameworks (Fe 3 O 4 /C-dots@Ag-MOFs) as current amplification elements. Based on this strategy, a novel electrochemical microfluidic paper-based chip was designed to detect PM. Fe 3 O 4 /C-dots@Ag-MOFs were synthesised by a hydrothermal method, and a molecularly imprinted polymer (MIP) was then synthesised on the surface of Fe 3 O 4 /C-dots@Ag-MOFs using PM as a template molecule. Finally, the reaction zone of a chip was modified with MIP/Fe 3 O 4 /C-dots@Ag-MOFs. PM from a sample introduced into the reaction zone was captured by the MIP, which generated a reduction current response at - 0.53 V in a three-electrode system embedded in the chip. Simultaneous catalysis by Fe 3 O 4 /C-dots and Ag-MOFs significantly enhanced the signal. The chip had a detection limit of 1.16 × 10 -11  mol L -1 and was successfully applied to the determination of PM in agricultural products and environmental samples with recovery rates ranging from 82.7 to 109%, with a relative standard deviation (RSD) of less than 5.0%. This approach of combining a dual catalytic amplification strategy with an MIP significantly increased the sensitivity as well as selectivity of chips and can potentially be used to detect a wide variety of target analytes using microfluidic paper-based chips., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Mercury ions (Hg 2+ ) mediating in situ heterojunction formation strategy based on spatially separated dual working areas was developed to achieve sensitive detection of human immunoglobulin G. To be specific, the complex of antibody, the silicon dioxide, and thymine-rich hairpin DNA were immobilized onto the antigen and antibody-modified electrodes, forming a special sandwich type where T-Hg 2+ -T structure could accommodate Hg 2+ . The zinc ions from zinc sulfide (ZnS) photoelectric materials were captured by Hg 2+ to convert ZnS to zinc sulfide-mercuric sulfide nanocomposite. Such ion exchange approach with spatially separated working electrodes endowed the sensing platform with lower background interference and high selectivity, which also avoided damage of illumination on biomolecules. In addition, by regulating the ion recognition probe, the protocol could be extended to numerous other fields like clinical diagnosis, environmental monitoring, and public safety., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

A new contact stamping method for fabrication of paper-based analytical devices (PADs) is reported. It uses an all-purpose acrylic varnish and 3D-printed stamps to pattern hydrophobic structures on paper substrates. The use of 3D printing allows quickly prototyping the desired stamp shape without resorting to third-party services, which are often expensive and time consuming. To the best of our knowledge, this is the first report regarding the use of this material for creation of hydrophobic barriers in paper substrates, as well as this 3D printing-based stamping method. The acrylic varnish was characterized and the features of the stamping method were studied. The PADs developed here presented better compatibility with organic solvents and surfactants compared with similar protocols. Furthermore, the use of this contact stamping method for fabrication of paper electrochemical devices was also possible, as well as multiplexed microfluidic devices for lateral flow testing. The analytical applicability of the varnish-based PADs was demonstrated through the image-based colorimetric quantification of iron in pharmaceutical samples. A limit of detection of 0.61 mg L -1 was achieved. The results were compared with spectrophotometry for validation and presented great concordance (relative error was < 5% and recoveries were between 104 and 108%). Thus, taking into account the performance of the devices explored here, we believe this novel contact stamping method is a very interesting alternative for production of PADs, exhibiting great potentiality. In addition, this work brings a new application of 3D printing in analytical sciences., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Glycated hemoglobin (HbA1c) is one of the most popular biomarkers which can be utilized for the diagnosis and control of diabetes in clinical practice. In this study, a sandwich paper-based electrochemiluminescence (ECL) biosensor has been developed using the zirconium metal-organic framework/Fe 3 O 4 (trimethyl chitosan)/gold nanocluster (Zr-MOF/Fe 3 O 4 (TMC)/AuNCs) nanocomposite as tracing tag to label anti-HbA1c monoclonal antibody and reduced graphene oxide (rGO) as immobilization platform of sensing element. The screen-printed electrodes (SPEs) were constructed and modified by sputtering a thick layer of gold on the paper substrate, followed by electrochemical reduction of aminophenylboronic acid (APBA)-functionalized GO to rGO/APBA, respectively. Different types of surface analysis methods were applied to characterize the Zr-MOF/Fe 3 O 4 (TMC)/AuNCs nanomaterials fabricated. Finally, antibody-labeled Zr-MOF/Fe 3 O 4 (TMC)/AuNCs nanocomposites were subjected to HbA1c in the sample and on the paper-based SPE. Quantitative measurement of HbA1c was performed using ECL and cyclic voltammetry (CV) over a potential range of - 0.2 to 1.7 V vs gold reference electrode with a sweep rate of 0.2 V.s -1 in the presence of triethylamine as a co-reactant after sandwiching the HbA1c target between antibody and APBA on the sensing area. This immunosensor demonstrated the desirable assay performance for HbA1c with a wide response range from 2 to 18% and a low detection limit (0.072%). This new strategy provides an effective method for high-performance bioanalysis and opens avenues for the development of high-sensitive and user-friendly device. Graphical abstract., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

A new mix-mode cellulose-based sorptive phase is described that combines two different polymeric domains (i.e., nylon and polystyrene), thus providing simultaneous hydrophilic and hydrophobic features as a result. By analogy with Janus materials, the new paper-based sorptive phase has been named paper-based polystyrene/nylon Janus-platform (P-Ps/Ny-JP). The main advantages of the proposed P-Ps/Ny-JP are the sustainability, simplicity in synthesis, and low cost of this extraction device. The main parameters affecting the synthesis (i.e., coating procedure and polymers proportion) have been studied, and the resulting material has been characterized via scanning electron microscopy and infrared spectroscopy. As a proof-of-concept, the simultaneous extraction of fourteen UV filters of a wide range of polarity, with log P values ranging from - 0.234 to 16.129, from water samples and their determination by liquid chromatography-tandem mass spectrometry (LC-MS/MS) has been performed. The proposed methodology enables the determination of these chemicals with limits of detection from 12 to 71 ng L -1 , and the precision, expressed as a relative standard deviation, was below 15%. The extraction device was applied to the analysis of real water samples likely to contain UV filters (i.e., two private swimming pool water and one seawater) and the recovery values were in the range 73-121%., (© 2021. The Author(s).)

A fluorescent paper strip immunoassay in conjunction with carbon nanodots@silica (CND@SiO 2 ) as a label was developed for the quantitative measurements of human serum amyloid A1 (hSAA1) in serum at clinically significant concentrations for lung cancer diagnosis. Monodispersed CND@SiO 2 was prepared by cohydrolysis between silane-crosslinked carbon nanodots and silica precursors via the Ströber method and further attached covalently to anti-hSAA1 (14F8) monoclonal antibody [anti-hSAA1(14F8)] specific to the hSAA1 target. The hSAA1 concentrations were then determined by quantifying the blue fluorescence intensity upon 365 nm excitation of the captured hSAA1 with anti-hSAA1(14F8)-CND@SiO 2 conjugates in the test line on a paper strip where anti-hSAA1 (10G1) monoclonal antibody was physisorbed. The developed fluorescent paper strip with CND@SiO 2 can detect hSAA1 at concentrations ranging from 0.1 to 5 nM (R 2  = 0.995), with a limit of detection of  0.258 nM in 10 mM phosphate buffer pH 7.4 containing human serum albumin. The performance of  recovery (90.98-109.17%) and repeatability (coefficients of variation < 8.46%) obtained was also acceptable for quantitative determinations. The platform was employed for direct determination of hSAA1 concentrations in undiluted serum samples from lung cancer patients (relative standard deviation (RSD) < 7.46%) and healthy humans (RSD < 3.96%). The results were compared with those obtained using a commercially available enzyme-linked immunosorbent assay alongside liquid chromatography with tandem mass spectrometry measurements., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

The Ti 3 C 2 MXene quantum dots (Ti 3 C 2 MQDs) derived from Ti 3 C 2 MXene have received much attention because of their remarkable advantages in biosensing. Nevertheless, the functionalization of Ti 3 C 2 MQDs to improve their properties is just in its infant stage. Herein, we firstly synthesized nitrogen and boron co-doped Ti 3 C 2 MQDs (N, B-Ti 3 C 2 MQDs) with good water solubility, strong stability, and high optical characteristics. The N, B-Ti 3 C 2 MQDs exhibit excitation wavelength-dependent blue photoluminescence with optimal excitation/emission peaks at 335/439 nm. Nowadays, the development of fast and real-time detection of tetracycline (TC) in animal derived food is very essential. In this work, a novel point-of-care testing (POCT) platform was established based on ratiometric fluorescence method using N, B-Ti 3 C 2 MQDs coupled with Eu 3+ . Upon addition of TC in the Eu 3+ /N, B-MQDs system, blue fluorescence emission of N, B-Ti 3 C 2 MQDs was quenched and red fluorescence emission of Eu 3+ was enhanced gradually, which was ascribed to the synergistic inner filter effect and antenna effect. Moreover, we prepared test papers with N, B-Ti 3 C 2 MQDs and Eu 3+ for TC detection based on the change of fluorescence color, which could be recognized by color recognizer app installed in the smartphone. Therefore, great promise for POCT of TC is given with the merits of simplicity and visible detection possibility. The proposed method demonstrated a low detection limit of 20 nM. Application of the platform for TC quantification in milk samples opened a novel means for the potential use of N, B-Ti 3 C 2 MQDs in food safety., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Flunitrazepam is one of the frequently used hypnotic drugs to incapacitate victims for sexual assault. Appropriate diagnostic tools should be available to victims regarding the growing concern about "date-rape drugs" and their adverse impact on society. Miniaturized screen-printed potentiometric sensors offer crucial point-of-care devices that alleviate this serious problem. In this study, all solid-state screen-printed potentiometric flunitrazepam sensors have been designed. The paper device was printed with silver and carbon ink. Formation of an aqueous layer in the interface between carbon-conducting material and ion-sensing membrane nevertheless poses low reproducibility in the solid-contact electrodes. Accordingly, poly(3,4-ethylenedioxythiophene) (PEDT) nano-dispersion was applied as a conducting hydrophobic polymer on the electrode surface to curb water accumulation. Conditioning of ion-sensing membrane in the vicinity of reference membrane has been considered carefully using special protocol. Electrochemical characteristics of the proposed PEDT-based sensor were calculated and compared favorably to PEDT-free one. The miniaturized device was successfully used for the determination of flunitrazepam in carbonated soft drinks, energy drink, and malt beverage. Statistical comparison between the proposed sensor and official method revealed no significant difference. Nevertheless, the proposed sensor provides simple and user-friendly diagnostic tool with less equipment for on-site determination of flunitrazepam.

A paper-based electrochemical dual-function biosensor capable of determining pH and TCO 2 was synthesized for the first time using an iridium oxide pH electrode and an all-solid-state ion electrode (ASIE). In the study, to obtain highly reliable results, the biosensor was equipped with a real-time pH correction function before TCO 2 measurements. Compared to traditional liquid-filling carbon dioxide detection sensors, the utilization of ferrocene endows our novel sensor with abundant positive sites, and thus greatly improves its performance. Conversely, the introduction of MXene with conductivity close to that of metals reduces electrode resistance, which is beneficial for accelerating the electrochemical reaction of the sensor and reducing LOD. After optimization, the detection range of TCO 2 is 0.095 nM-0.66 M, with a detection limit of as low as 0.023 nM. In addition, the sensor was used in real serum sample-spiked recovery experiments and comparison experiments with existing clinical blood gas analyzers, which confirmed the effectiveness of its clinical application. This study provides a method for the rational design of paper-based electrochemical biosensors and a new approach for the clinical detection of blood carbon dioxide., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

The development of a disposable electrochemical paper-based analytical device (ePAD) is described using a novel formulation of conductive ink that combines graphite powder, polyester resin, and acetone. As a proof of concept, the proposed sensor was utilized for paracetamol (PAR) sensing. The introduced ink was characterized via morphological, structural, and electrochemical analysis, and the results demonstrated appreciable analytical performance. The proposed ePAD provided linear behavior (R 2  = 0.99) in the concentration range between 1 and 60 µmol L -1 , a limit of detection of 0.2 µmol L -1 , and satisfactory reproducibility (RSD ~ 7.7%, n = 5) applying a potential of + 0.81 V vs Ag at the working electrode. The quantification of PAR was demonstrated in different pharmaceutical formulations. The achieved concentrations revealed good agreement with the labeled values, acceptable accuracy (101% and 106%), and no statistical difference from the data obtained by HPLC at the 95% confidence level. The environmental impact of the new device was assessed using AGREE software, which determined a score of 0.85, indicating that it is eco-friendly. During the pharmacokinetic study of PAR, it was found that the drug has a maximum concentration of 23.58 ± 0.01 µmol L -1 , a maximum time of 30 min, and a half-life of 2.15 h. These results are comparable to other studies that utilized HPLC. This suggests that the combination of graphite powder and polyester resin can transform conductive ink into an effective ePAD that can potentially be used in various pharmaceutical applications., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

To overcome the limitations of current methods for diagnosing paracoccidioidomycosis (PCM), it is critical to develop novel diagnostic strategies that can be implemented in low-resource settings and dramatically improve turnaround times. This study focused on the development of a portable molecular test to screen for Paracoccidioides spp. The proposed approach integrated double-tagging polymerase chain reaction (PCR) and a paper-based lateral flow assay (LFA) for readout, using carbon nanoparticles as a signal generation system. Primers tagged with biotin and digoxigenin were employed to conduct the double-tagging PCR, which can be conveniently carried out on portable thermocyclers. This method can generate billions of tagged DNA copies from a single target molecule, which can be rapidly detected by the LFA platform, providing results within minutes. Avidin-modified carbon nanoparticles served as a signal generation system, enabling detection in the immunochromatographic assay. The LFA demonstrated the capability to detect double-tagged amplicons as low as 0.21 ng or 0.10 ng, depending on whether the results were assessed visually or with a smartphone equipped with an image processor. These findings suggest that the proposed approach holds great promise as a point-of-care diagnostic tool for the early and accurate detection of PCM in low-resource settings. The diagnostic test is rapid and inexpensive, requires minimal handling and can be easily introduced into the general practitioner's armoury for ambulatory screening of infection. This innovative approach has the potential to make a substantial contribution to PCM diagnosis, ultimately reducing morbidity and mortality associated with this disease., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

A ternary hierarchical hybrid Ni@Co x S y /poly(3,4-ethylenedioxythiophene)-reduced graphene oxide (Ni@Co x S y /PEDOT-rGO) is rationally designed and in situ facilely synthesized as electrocatalyst to construct a binder-free sensing platform for non-enzymatic glucose monitoring through traditional electrodeposition procedure. The as-prepared Ni@Co x S y /PEDOT-rGO presents unique hierarchical structure and multiple valence states as well as strong and robust adhesion between Ni@Co x S y /PEDOT-rGO and GCE. Profiting from the aforementioned merits, the sensing platform constructed under optimal conditions achieved a wide detection range (0.2 μM ~ 2.0 mM) with high sensitivity (1546.32 μA cm -2  mM -1 ), a rapid response time (5 s), an ultralow detection limit (0.094 μM), superior anti-interference performance, excellent reproducibility and considerable stability. Furthermore, the sensor demonstrates an acceptable accuracy and appreciable recoveries ranging from 90.0 to 102.0% with less than 3.98% RSD in human blood serum samples, indicating the prospect of the sensor for the real samples analysis. It will provide a strategy to rationally design and fabricate ternary hierarchical hybrid as nanozyme for glucose assay., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)