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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 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.)

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.)

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).)

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.)

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.

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.

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).)

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).)

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 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.)

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.)

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.)

Bacillus cereus is one of the most common foodborne pathogens found in various kinds of staple foods such as rice and wheat. A rapid and accurate detection method for this pathogen is highly desirable for the sustainable production of relevant food products. While several classical and molecular-based detection methods are available for the identification of B. cereus, they suffered one or more limitations such as the requirement for a tedious and time-consuming process, less than ideal specificity, and the lack of portability. Herein, we developed the first paper-based sensing device that exhibits high species specificity with sufficiently low limit of detection for the visual detection of specific DNA sequences of B. cereus. The success is attributed to the strategic planning of fabrication in various dimensions including thorough bioinformatics search for highly specific genes, the use of the pyrrolidinyl peptide nucleic acid (PNA) probe whose selectivity advantage is well documented, and an effective PNA immobilization and DNA-binding visualization method with an internal cross-checking system for validating the results. Testing in rice matrices indicates that the sensor is capable of detecting and distinguishing B. cereus from other bacterial species. Hence, this paper-based sensor has potential to be adopted as a practical means to detect B. cereus in food industries., (© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.)

Simple and visual quantitative detection of foodborne pathogens can effectively reduce the outbreaks of foodborne diseases. Herein, we developed a simple and sensitive quantum dot (QD)-based paper device for visual and quantitative detection of Escherichia coli (E. coli) O157:H7 based on immunomagnetic separation and nanoparticle dissolution-triggered signal amplification. In this study, E. coli O157:H7 was magnetically separated and labeled with silver nanoparticles (AgNPs), and the AgNP labels can be converted into millions of Ag ions, which subsequently quench the fluorescence of QDs in the paper strip, which along with the readout can be visualized and quantified by the change in length of fluorescent quenched band. Owing to the high capture efficiency and effective signal amplification, as low as 500 cfu mL -1 of E. coli O157:H7 could be easily detected by naked eyes. Furthermore, this novel platform was successfully applied to detect E. coli O157:H7 in spiked milk samples with good accuracy, indicating its potential in the detection of foodborne pathogens in real samples.

The fast-growing healthcare demand for user-friendly and affordable analytical tools is driving the efforts to develop reliable platforms for the customization of therapy based on individual health conditions. In this overall scenario, we developed a paper-based electrochemical sensor for the quantification of iron ions in serum as a cost-effective sensing tool for the correct supplement administration. In detail, the working electrode of the screen-printed device has been modified with a nanocomposite constituted of carbon black and gold nanoparticles with a drop-casting procedure. Square wave voltammetry has been adopted as an electrochemical technique. This sensor was further modified with Nafion for iron quantification in serum after sample treatment with trifluoroacetic acid. Under optimized conditions, iron ions have been detected with a LOD down to 0.05 mg/L and a linearity up to 10 mg/L in standard solution. The obtained results have been compared with reference methods namely commercial colorimetric assay and atomic absorption spectroscopy, obtaining a good correlation within the experimental errors. These results demonstrated the suitability of the developed paper-based sensor for future applications in precision medicine of iron-deficiency diseases., (© 2023. Springer-Verlag GmbH Germany, part of Springer Nature.)

Mitigation of the peroxide explosive threat, specifically triacetone triperoxide (TATP) and hexamethylene triperoxide diamine (HMTD), is a priority among the law enforcement community, as scientists and canine (K9) units are constantly working to improve detection. We propose the use of paper spray ionization-high-resolution mass spectrometry (PSI-HRMS) for detection of peroxide explosives in biological matrices. Occurrence of peroxide explosives and/or their metabolites in biological samples, obtained from urine or blood tests, give scientific evidence of peroxide explosives exposure. PSI-HRMS promote analysis of samples in situ by eliminating laborious sample preparation steps. However, it increases matrix background issues, which were overcome by the formation of multiple alkali metal adducts with the peroxide explosives. Multiple ion formation increases confidence when identifying these peroxide explosives in direct sample analysis. Our previous work examined aspects of TATP metabolism. Herein, we investigate the excretion of a TATP glucuronide conjugate in the urine of bomb-sniffing dogs and demonstrate its detection using PSI from the in vivo sample.

SARS-CoV-2 has mutated many times since the onset of the COVID-19 pandemic, and the omicron is currently the most dominant variant. Determining the specific strain of the virus is beneficial in providing proper care and containment of the disease. We have previously reported a novel method of counting the number of particle immunoagglutination on a paper microfluidic chip using a smartphone-based fluorescence microscope. A single-copy-level detection was demonstrated from clinical saline gargle samples. In this work, we further evaluated two different SARS-CoV-2 monoclonal antibodies to spike vs. nucleocapsid antigens for detecting omicron vs. delta and spike vs. nucleocapsid proteins. The SARS-CoV-2 monoclonal antibody to nucleocapsid proteins could distinguish omicron from delta variants and nucleocapsid from spike proteins. However, such distinction could not be found with the monoclonal antibody to spike proteins, despite the numerous mutations found in spike proteins among variants. This result may suggest a clue to the role of nucleocapsid proteins in recognizing different variants., (© 2022. Springer-Verlag GmbH Germany, part of Springer Nature.)

We developed a paper-based colorimetric sensor for facile and cost-effective detection of Pb 2+ in drinking and environmental water samples. The Pb 2+ ion-selective optodes are fabricated by inkjet printing of ionophore, chromoionophore, and ion exchanger on cellulose paper. Pb 2+ in water samples induces deprotonation of the pH chromoionophore and changes the optode color, which is acquired and analyzed by a smartphone. The paper-based optode without any plasticizer or polymer has a dynamic range and selectivity comparable to those of traditional optodes using PVC polymer and/or plasticizer. Furthermore, the response time of the plasticizer/polymer-free paper-based optode is much shorter than those of plasticized PVC-based optodes on paper and glass (5 min vs. 15 and 50 min). Moreover, the plasticizer/polymer-free optode preserves the water-wicking capability of porous cellulose paper, allowing for the design of pump-free microfluidic devices. Chloramine, a widely used disinfectant in drinking water, was found to be a strong and generic interference species for heavy metal ion detection via ion-selective optodes. A fully inkjet-printed lateral-flow paper-based device consisting of a sodium thiosulfate-based chloramine elimination zone and a plasticizer/polymer-free sensing zone was designed for Pb 2+ detection in tap water disinfected by chloramine. The dynamic range of the Pb 2+ sensor may be shifted from the current 10 -6 to 10 -5  M to lower concentrations by using stronger ionophores, but this work lays a foundation for the design of paper-based heavy metal ion sensors without detrimental interference from disinfectants., (© 2022. Springer-Verlag GmbH Germany, part of Springer Nature.)

Background noise due to nonspecific binding of biomolecules on the assay substrates is one of the most common challenges that limits the sensitivity of microarray-based immunoassays. Background signal intensity usually increases when complex biological fluids are used because they have a combination of molecules and vesicles that can adsorb onto substrate surfaces. Blocking strategies coupled with surface chemistries can reduce such nonspecific binding and improve assay sensitivity. In this paper, we conducted a systematic optimization of blocking strategies on a variety of commonly used substrates for protein measurement in complex biofluids. Four blocking strategies (BSA, non-fat milk, PEG, and a protein-free solution) coupled with four surface chemistries (3-glycidoxypropyltrimethoxysilane (GPS), poly-L-lysine (PLL), aminoalkylsilane (AAS), and nitrocellulose (NC)) were studied for their effect on background, microspot, and net signal intensities. We have also explored the effect that these blocking strategies have when proteins in complex samples (plasma, serum, cell culture media, and EV lysate) are measured. Irregular spot morphology could affect signal extraction using automated software. We found that the microspots with the best morphology were the ones printed on GPS glass surfaces for all immunoassays. On NC membrane, the protein-based blocking strategies yielded the highest net fluorescent intensity with the antigen contained in PBS, plasma, serum, and serum-free cell culture media. Differently, with EV lysate samples, Pierce™ protein-free blocker yielded the best net signal intensity on both GPS and NC surfaces. The choice of blocking strategies highly depends on the substrate. Moreover, the findings discovered in this study are not limited to microarray-based immunoassays but can provide insights for other assay formats., (© 2023. Springer-Verlag GmbH Germany, part of Springer Nature.)

Nowadays, in the clinical, pharmaceutical, and environmental sectors, the development of facile and sensitive analytical methods and/or innovative devices for the follow-up and detection of antibiotics and pharmaceutical formulations, in general, are urgently needed and still challenging. This work declared three vital applications for broad-spectrum nitrofurantoin (macrofuran) antibiotic detection and quantification: A colorimetric method, a coated paper strip-based nano-lanthanum complex prototype and fabrication of smart electronic color sensor device-based coated paper strips. The colorimetric method showed a significant response upon increasing the concentration of the nitrofurantoin in a range between (1.0-100.0 ng/mL) via a visual color change from orange-yellow to red colors degree with detection and quantification limits of 0.175 and 0.53 ng/mL, respectively, whereas the nano-lanthanum complex coated paper strip prototype showed qualitative on-site sensing for nitrofurantoin via naked eye color changes which can be detected anywhere. Moreover, a smart prototype for detecting macrofuran in the means of paper color change in the RGB color component extraction algorithm and the grayscale projection value processing algorithm was fabricated. The change in RGB color on the coated paper strip was detected using an electronic color sensor device. The developed colorimetric method, coated paper strip, and the electronic color sensor device prototype exhibited fast, simple, costless, and selective towards macrofuran over the competing analyzed. As well as, showed good applicability in the different real samples spiked with different concentrations of macrofuran., (© 2022. The Author(s).)

Hypochlorous acid (HClO), the core bactericidal substance of the human immune system, plays a vital role in many physiological and pathological processes in the human body. In this work, we designed and synthesized a novel deep-red fluorescent probe TCF-ClO for the determination of hypochlorous acid through theoretical analysis. The results showed that probe TCF-ClO exhibited excellent characteristics of long-wavelength emission (635 nm), fast response (< 1 min), and low detection limit (24 nM). In addition, it had been successfully used for imaging of HClO in living HeLa cells. More importantly, the TCF-ClO composited paper-based sensing material was successfully constructed. The RGB/gray value was obtained from a mobile phone and computer, which could achieve the quantitative detection of HClO, with a linear detection range of 0-50 μM and a detection limit of 1.09 μM (RGB mode)/3.38 μM (gray mode). The function of the paper-based sensor extended from qualitative to quantitative detection of HClO, and it is expected to become a portable device widely used in the environmental area., (© 2022. Springer-Verlag GmbH Germany, part of Springer Nature.)

Traditionally, specific bioreceptors such as antibodies have rapidly identified bacterial species in environmental water samples. However, this method has the disadvantages of requiring an additional process to conjugate or immobilize bioreceptors on the assay platform, which becomes unstable at room temperature. Here, we demonstrate a novel mix-and-match method to identify bacteria species by loading the bacterial samples with simple bacteria interacting components (not bioreceptors), such as lipopolysaccharides, peptidoglycan, and bovine serum albumin, and carboxylated particles, all separately on multiple channels. Neither covalent conjugation nor surface immobilization was necessary. Interactions between bacteria and the above bacteria interacting components resulted in varied surface tension and viscosity, leading to various flow velocities of capillary action through the paper fibers. The smartphone camera and a custom Python code recorded multiple channel flow velocity, each loaded with different bacteria interacting components. A multi-dimensional data set was obtained for a given bacterial species and concentration and used as a machine learning training model. A support vector machine was applied to classify the six bacterial species: Escherichia coli, Salmonella Typhimurium, Pseudomonas aeruginosa, Staphylococcus aureus, Enterococcus faecium, and Bacillus subtilis. Under optimized conditions, the training model predicts the bacterial species with an accuracy of > 85% of the six bacteria species., (© 2022. Springer-Verlag GmbH Germany, part of Springer Nature.)

The modification of an easily available resource like paper to circumvent expensive or intensive sample pretreatment could be the answer to sample analysis in resource-poor regions. Therefore, a novel on-paper device combining sample collection with affinity sample pretreatment is introduced here. Universal smart affinity samplers are produced by a simple KIO 4 -mediated oxidation of cellulose, which functionalizes the paper. This is followed by immobilization of streptavidin. Streptavidin serves as a universal anchor for biotinylated antibodies, enabling simple preparation of tailor-made affinity samplers. The functionality of the device was tested using a model protein (human chorionic gonadotropin, hCG) and biotinylated anti-hCG antibodies for affinity capture. In a laboratory setting, the performance was demonstrated, and a 14-fold increase of target binding compared to binding without bmAb was achieved. The recovery of hCG captured with bmAb-treated samplers was determined to be 33% and comparable to previously described affinity capture approaches. Application of the smart affinity samplers to human serum containing hCG showed an R 2 of 0.98 (200-1000 pg mL -1 ), precision of ≤ 9.1% RSD, and estimated limit of detection of 65 pg mL -1 . Although further optimization and validation are necessary prior to application to real samples in clinical settings, the potential of the device for use in determination of low abundant biomarkers in complex samples has been demonstrated., (© 2022. The Author(s).)

Paper has been widely employed as cheap material for the development of a great number of sensors such as pregnancy tests, strips to measure blood sugar, and COVID-19 rapid tests. The need for new low-cost analytical devices is growing, and consequently the use of these platforms will be extended to different assays, both for the final consumer and within laboratories. This work describes a paper-based electrochemical sensing platform that uses a paper disc conveniently modified with recognition molecules and a screen-printed carbon electrode (SPCE) to achieve the detection of gluten in a deep eutectic solvent (DES). This is the first method coupling a paper biosensor based on aptamers and antibodies with the DES ethaline. Ethaline proved to be an excellent extraction medium allowing the determination of very low gluten concentrations. The biosensor is appropriate for the determination of gluten with a limit of detection (LOD) of 0.2 mg L -1 of sample; it can detect gluten extracted in DES with a dynamic range between 0.2 and 20 mg L -1 and an intra-assay coefficient of 10.69%. This approach can be of great interest for highly gluten-sensitive people, who suffer from ingestion of gluten quantities well below the legal limit, which is 20 parts per million in foods labeled gluten-free and for which highly sensitive devices are essential., (© 2021. The Author(s).)

High per- and polyfluorinated alkyl substance (PFAS) concentrations have been detected in agricultural soils in Southwest Germany. Discharges of PFAS-contaminated paper sludge and compost are suspected to be the cause of the contamination. Perfluorinated carboxylic acids (PFCAs) have been detected also in groundwater, drinking water, and plants in this area. Recently, previously unknown compounds have been identified by high-resolution mass spectrometry (HRMS). Major contaminants were polyfluorinated dialkylated phosphate esters (diPAPs) and N-ethyl perfluorooctane sulfonamide ethanol-based phosphate diester (diSAmPAP). In this study, HRMS screening for PFAS was applied to 14 soil samples from the contaminated area and 14 impregnated paper samples which were from a similar period than the contamination. The paper samples were characterized by diPAPs (from 4:2/6:2 to 12:2/12:2), fluorotelomer mercapto alkyl phosphates (FTMAPs; 6:2/6:2 to 10:2/10:2), and diSAmPAP. In soil samples, diPAPs and their transformation products (TPs) were the major contaminants, but also FTMAPs, diSAmPAP, and their TPs occurred. The distribution patterns of the carbon chain lengths of the precursor PFAS in soil samples were shown to resemble those in paper samples. This supports the hypothesis that paper sludge is a major source of contamination. The presence of major degradation products like PFCAs, FTSAs, or PFOS and their distribution of carbon chain lengths indicate the activity of biotic or abiotic degradation processes and selective leaching processes from the upper soil horizons., (© 2021. The Author(s).)

This manuscript reports on a simple paper-based bienzymatic colorimetric assay for sarcosine as an important urinary biomarker of prostate cancer. All required assay reagents are pre-deposited on hydrophilic filter paper spots surrounded by a hydrophobic barrier. Sarcosine in the sample solution is selectively oxidized in the presence of sarcosine oxidase (SOx), resulting in the formation of hydrogen peroxide, which is subsequently detected through the horseradish peroxidase (HRP)-catalyzed conversion of the colorless indicator 3,3',5,5'-tetramethylbenzidine (TMB) into its blue-colored oxidation product. By the modification of the paper with positively charged poly(allylamine hydrochloride) (PAH), a linear response to sarcosine between 0 and 10 μM and a significant lowering of the limit of detection (LOD) (0.6 μM) compared to the unmodified paper substrate (12.6 μM) has been achieved. The improvement of the LOD was attributed to the fact that the presence of the polymer limits the enzyme-driven colorimetric reaction to the surface of the paper substrate, resulting in stronger color development. In experiments in artificial urine matrix, the bicarbonate anion was identified as an inhibitor of the colorimetric reaction. This inhibition was successfully eliminated through on-device sample pH adjustments with pH-buffer components pre-deposited onto assay devices. The LOD for sarcosine achieved in artificial urine matrix (2.5 μM) is below the 5 μM threshold value for this urinary biomarker required for diagnostic purposes. Finally, good selectivity over all 20 natural amino acids and satisfactory long-term storage stability of reagent-modified paper substrates at - 20 °C for a period of 50 days were confirmed., (© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.)

Chemiluminescence (CL) reagent luminol was loaded into the porous structure of cobalt-imidazole metal-organic framework (MOF) ZIF-67 to obtain luminol-functionalized ZIF-67 (luminol@ZIF-67) with CL property. The morphology, composition, CL property, and CL mechanism of luminol@ZIF-67 were carefully investigated. The obtained luminol@ZIF-67 exhibited strong, stable, and visible CL emission that reacted with H 2 O 2 , attributed to the strong catalytic effect of ZIF-67 combined with the shortened diffusion distance between luminol and the catalytic center. The CL intensity of luminol@ZIF-67 was more than 550 times higher than that of luminol. Catechol can effectively quench the CL emission of luminol@ZIF-67 that reacted with H 2 O 2 . Then, a simple paper-based CL imaging detection method was developed for the detection of catechol by using a smartphone as a portable detector. The linear calibration curve of the developed CL assay for catechol ranged from 5 to 100 mg/L with detection limit of 1.1 mg/L (S/N = 3δ). The strong CL emission of luminol@ZIF-67 combined with the effective quench ability of catechol guaranteed high sensitivity of the detection method. The practical application ability of the developed CL assay was tested by the determination of catechol in tea and tap water samples, resulting in acceptable results. This work provides an effective paper-based CL detection method for catechol and enriches the species of the chemiluminescent MOF material.

Speciation of chromium (Cr) was demonstrated using microfluidic paper-based analytical devices (μ-PADs) that permit the colorimetric determination of hexavalent chromium (Cr(VI)) and trivalent chromium (Cr(III)) via online oxidation. The μ-PADs consist of left and right channels that allow the simultaneous measurements of Cr(VI) and total Cr based on the colorimetric reaction of Cr(VI) with 1,5-diphenylcarbazide (DPC). For the determination of Cr(VI), a sample solution was directly reacted with DPC in the left channels whereas total Cr was determined in the right channels, which permitted online oxidation in the pretreatment zone containing cerium (IV) (Ce(IV)) followed by a colorimetric reaction with DPC. We found that the online oxidation of Cr(III) proceeded 100% whereas Ce(IV) inhibited the reaction of Cr(VI) with DPC. Therefore, speciation can be achieved by measuring the Cr(VI) and total Cr in the left and right channels followed by the subtraction of Cr(VI) from total Cr. The limits of detection and quantification were 0.008 and 0.02 mg L -1 for Cr(VI) and 0.07 and 0.1 mg L -1 for Cr(III) or total Cr, respectively. The linear dynamic ranges were 0.02-100 mg L -1 and 0.1-60 mg L -1 for Cr(VI) and Cr(III), respectively. The RSDs were less than 7.5%. The results obtained using μ-PADs were in good agreement with those obtained via ICP-OES with recoveries of 92-108% for Cr(III) and 108-110% for Cr (VI) using μ-PADs, and 106-110% for total Cr using ICP-OES. Thus, the μ-PADs could potentially be utilized for the speciation of chromium in developing countries where environmental pollution and the availability of sophisticated instruments are significant problems.

Here, we present the rational design of a pinwheel-shaped three-dimensional microfluidic paper-based analytical device (3D-μPAD) for specific, sensitive and multiplexed detection of heavy metals in coastal waters. A more homogeneous permeation of fluids along the chip than common design, even under unskilled performance, has been achieved by the elaborate chip design of the hydrostatic balancing inlet port and uniformly stressed reversible sealing. With the combination of ion imprinted polymer grafted CdTe quantum-dots and fluid accumulation pad, 4 metals (Cu 2+ , Cd 2+ , Pb 2+ , and Hg 2+ ) in 1 analysis and 25-fold enrichment for each metal can be simultaneously performed within 20 min, with detection limits of 0.007-0.015 μg/L. It has the ability to selectively recognize these 4 metals in mixtures and immunizing to interferences from components found in coastal waters, which provided results that were in agreement with values gained from atomic absorption. The inexpensive and portable nature as well as the highly sensitive and flexible performance of the new developed 3D-μPAD could make it attractive as an on-site testing approach for marine environmental monitoring.

Microfluidic paper-based analytical devices (μPADs) have developed rapidly in recent years, because of their advantages, such as small sample volume, rapid detection rates, low cost, and portability. Due to these characteristics, they can be used for in vitro diagnostics in the laboratory, or in the field, for a variety of applications, including food evaluation, disease screening, environmental monitoring, and drug testing. This review will present various detection methods employed by μPADs and their respective applications for the detection of target analytes. These include colorimetry, electrochemistry, chemiluminescence (CL), electrochemiluminescence (ECL), and fluorescence-based methodologies. At the same time, the choice of labeling material and the design of microfluidic channels are also important for detection results. The construction of novel nanocomponents and different smart structures of paper-based devices have improved the performance of μPADs and we will also highlight some of these in this manuscript. Additionally, some key challenges and future prospects for the use of μPADs are briefly discussed.

During epidemics, such as the frequent and devastating Ebola virus outbreaks that have historically plagued regions of Africa, serological surveillance efforts are critical for viral containment and the development of effective antiviral therapeutics. Antibody serology can also be used retrospectively for population-level surveillance to provide a more complete estimate of total infections. Ebola surveillance efforts rely on enzyme-linked immunosorbent assays (ELISAs), which restrict testing to laboratories and are not adaptable for use in resource-limited settings. In this manuscript, we describe a paper-based immunoassay capable of detecting anti-Ebola IgG using Ebola virus envelope glycoprotein ectodomain (GP) as the affinity reagent. We evaluated seven monoclonal antibodies (mAbs) against GP-KZ52, 13C6, 4G7, 2G4, c6D8, 13F6, and 4F3-to elucidate the impact of binding affinity and binding epitope on assay performance and, ultimately, result interpretation. We used biolayer interferometry to characterize the binding of each antibody to GP before assessing their performance in our paper-based device. Binding affinity (K D ) and on rate (k on ) were major factors influencing the sensitivity of the paper-based immunoassay. mAbs with the best K D (3-25 nM) exhibited the lowest limits of detection (ca. μg mL -1 ), while mAbs with K D  > 25 nM were undetectable in our device. Additionally, and most surprisingly, we determined that observed signals in paper devices were directly proportional to k on . These results highlight the importance of ensuring that the quality of recognition reagents is sufficient to support desired assay performance and suggest that the strength of an individual's immune response can impact the interpretation of assay results.

A rapid in situ analytical method was developed for the detection of generated carcinogenic aromatic amines from banned azo dyes utilizing a photocatalytic reduction-based liquid microjunction surface sampling (LMJSS)-mass spectrometry (MS) system. We utilized photocatalytic reduction under UV irradiation with TiO 2 as catalyst to have rapid and mild reduction of azo dyes. The reaction conditions were optimized to have complete photocatalytic reduction within 2-5 min in pure methanol at room temperature. TiO 2 was immobilized in the inner wall of the capillaries in the LMJSS system to achieve in situ sampling-online rapid reduction-MS detection for aromatic amines originating from azo dyes in packaging surface. The yields of in-tube photocatalytic reduction were near 100% by delivering the azo dye extracts through the capillary at 1 μL/min under UV irradiation. With this design, in situ analysis was completed within 2 min via direct MS detection and 7 min via liquid chromatography (LC)-MS detection. The detection limits for five aromatic amines originating from four different azo dyes were in the range of 1-17 mg/kg with relative standard deviations (RSDs) < 8.5%. In the application of the new method, four carcinogenic aromatic amines were detected and identified in three commercial packaging materials, and the quantitation results were comparable with those obtained by the conventional chemical reduction-LC-MS method (relative recovery, 81-121%). Moreover, due to the spatial resolution of the present method with a flow probe, MS imaging was achieved demonstrating clear azo dye patterns of a lab-made sample., (© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.)

The growing interest in the development of cost-effective, straightforward, and rapid analytical systems has found cellulose-based materials, including cellulose derivatives, cellulose-based gels, nanocellulosic materials, and the corresponding (nano)cellulose-based composites, to be valuable platforms for sensor development. The present work presents recent advances in the development of cellulose-based sensors for the determination of volatile analytes and derivatives of analytical relevance. In particular, strategies described in the literature for the fabrication and modification of cellulose-based substrates with responsive materials are summarized. In addition, selected contributions reported in the field of paper-based volatile sensors are discussed, with a particular emphasis on quick response (QR) code paper-based platforms, intelligent films for food freshness monitoring, and sensor arrays for volatile discrimination purposes. Furthermore, analytical strategies devised for the determination of ionic species by in situ generation of volatile derivatives in both paper-based analytical devices (PADs) and microfluidic PADs will also be described., (© 2023. The Author(s).)

Prototyping analytical devices with three-dimensional (3D) printing techniques is becoming common in research laboratories. The attractiveness is associated with printers' price reduction and the possibility of creating customized objects that could form complete analytical systems. Even though 3D printing enables the rapid fabrication of electrochemical sensors, its wider adoption by research laboratories is hindered by the lack of reference material and the high "entry barrier" to the field, manifested by the need to learn how to use 3D design software and operate the printers. This review article provides insights into fused deposition modeling 3D printing, discussing key challenges in producing electrochemical sensors using currently available extrusion tools, which include desktop 3D printers and 3D printing pens. Further, we discuss the electrode processing steps, including designing, printing conditions, and post-treatment steps. Finally, this work shed some light on the current applications of such electrochemical devices that can be a reference material for new research involving 3D printing., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

Environmental pollution by plastics is a global issue of increasing concern. However, microplastic analysis in complex environmental matrices, such as soil samples, remains an analytical challenge. Destructive mass-based methods for microplastic analysis do not determine plastics' shape and size, which are essential parameters for reliable ecological risk assessment. By contrast, nondestructive particle-based methods produce such data but require elaborate, time-consuming sample preparation. Thus, time-efficient and reliable methods for microplastic analysis are needed. The present study explored the potential of frequency-domain fluorescence lifetime imaging microscopy (FD-FLIM) for rapidly and reliably identifying as well as differentiating plastics and natural materials from terrestrial environments. We investigated the fluorescence spectra of ten natural materials from terrestrial environments, tire wear particles, and eleven different transparent plastic granulates <5 mm to determine the optimal excitation wavelength for identification and differentiation via FD-FLIM under laboratory conditions. Our comparison of different excitation wavelengths showed that 445 nm excitation exhibited the highest fluorescence intensities. 445 nm excitation was also superior for identifying plastic types and distinguishing them from natural materials from terrestrial environments with a high probability using FD-FLIM. We could demonstrate that FD-FLIM analysis has the potential to contribute to a streamlined and time-efficient direct analysis of microplastic contamination. However, further investigations on size-, shape-, color-, and material-type detection limitations are necessary to evaluate if the direct identification of terrestrial environmental samples of relatively low complexity, such as a surface inspection soil, is possible., (© 2024. The Author(s).)

Metformin (MET) and sitagliptin (STG) are widely used as the first-line and long-term oral hypoglycemic agents for managing type 2 diabetes mellitus (T2DM). However, the current lack of convenient and rapid measurement methods poses a challenge for individualized management. This study developed a point-of-care (POC) assay method utilizing a miniature mass spectrometer, enabling rapid and accurate quantification of MET and STG concentrations in human blood and urine. By combining the miniature mass spectrometer with paper spray ionization, this method simplifies the process into three to four steps, requires minimal amounts of bodily fluids (50 μL of blood and 2 μL of urine), and is able to obtain quantification results within approximately 2 min. Stable isotope-labeled internal standards were employed to enhance the accuracy and stability of measurement. The MS/MS responses exhibited good linear relationship with concentration, with relative standard deviations (RSDs) below 25%. It has the potential to provide immediate treatment feedback and decision support for patients and healthcare professionals in clinical practice., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

The development of cost-effective and highly efficient electrocatalysts is critical to help electrochemical non-enzymatic sensors achieve high performance. Here, a new class of catalyst, Ru single atoms confined on Cu nanotubes as a single-atom alloy (Ru 1 Cu NTs), with a unique electronic structure and property, was developed to construct a novel electrochemical non-enzymatic glucose sensor for the first time. The Ru 1 Cu NTs with a diameter of about 24.0 nm showed a much lower oxidation potential (0.38 V) and 9.0-fold higher response (66.5 μA) current than Cu nanowires (Cu NWs, oxidation potential 0.47 V and current 7.4 μA) for glucose electrocatalysis. Moreover, as an electrochemical non-enzymatic glucose sensor, Ru 1 Cu NTs not only exhibited twofold higher sensitivity (54.9 μA mM -1  cm -2 ) and wider linear range (0.5-8 mM) than Cu NWs, but also showed a low detection limit (5.0 μM), excellent selectivity, and great stability. According to theoretical calculation results, the outstanding catalytic and sensing performance of Ru 1 Cu NTs could be ascribed to the upshift of the d-band center that helped promote glucose adsorption. This work presents a new avenue for developing highly active catalysts for electrochemical non-enzymatic sensors., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

Drug screening tests are mandatory in the search for drugs in forensic biological samples, and immunological methods and mass spectrometry (e.g., gas chromatography-mass spectrometry and liquid chromatography-tandem mass spectrometry) are commonly used for that purpose. However, these methods have some drawbacks, and developing new screening methods is required. In this study, we develop a rapid-fire drug screening method by probe electrospray ionization tandem mass spectrometry (PESI-MS/MS), which is an ambient ionization mass spectrometry method, for human urine, named RaDPi-U. RaDPi-U is carried out in three steps: (1) mixing urine with internal standard (IS) solution and ethanol, followed by vortexing; (2) pipetting the mixture onto a sample plate for PESI; and (3) rapid-fire analysis by PESI-MS/MS. RaDPi-U targets 40 forensically important drugs, which include illegal drugs, hypnotics, and psychoactive substances. The analytical results were obtained within 3 min because of the above-mentioned simple workflow of RaDPi-U. The calibration curves of each analyte were constructed using the IS method, and they were quantitatively valid, resulting in good linearity (0.972-0.999) with a satisfactory lower limit of detection and lower limit of quantitation (0.01-7.1 ng/mL and 0.02-21 ng/mL, respectively). Further, both trueness and precisions were 28% or less, demonstrating the high reliability and repeatability of the method. Finally, we applied RaDPi-U to three postmortem urine specimens and successfully detected different drugs in each urine sample. The practicality of the method is proven, and RaDPi-U will be a strong tool as a rapid-fire drug screening method not only in forensic toxicology but also in clinical toxicology., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

The ultrasensitive detection of hepatitis C virus (HCV) nucleic acid is crucial for the early diagnosis of hepatitis C. In this study, by combining Ag@Au core/shell nanoparticle (Ag@AuNP)-based surface-enhanced Raman scattering (SERS) tag with hybridization chain reaction (HCR), a novel SERS-sensing method was developed for the ultrasensitive detection of HCV nucleic acid. This SERS-sensing system comprised two different SERS tags, which were constructed by modifying Ag@AuNP with a Raman reporter molecule of 4-ethynylbezaldehyde, two different hairpin-structured HCR sequences (H1 or H2), and a detection plate prepared by immobilizing a capture DNA sequence onto the Ag@AuNP layer surface of the detection wells. When the target nucleic acid was present, the two SERS tags were captured on the surface of the Ag@AuNP-coated detection well to generate many "hot spots" through HCR, forming a strong SERS signal and realizing the ultrasensitive detection of the target HCV nucleic acid. The limit of detection of the SERS-sensing method for HCV nucleic acid was 0.47 fM, and the linear range was from 1 to 10 5 fM., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

Prostate and lung cancers are the most common types of cancer and affect a large part of the population around the world, causing deaths. Therefore, the rapid identification of cancer can profoundly impact reducing cancer-related death rates and protecting human lives. Significant resources have been dedicated to investigating new methods for early disease detection. Cancer biomarkers encompass various biochemical entities, including nucleic acids, proteins, sugars, small metabolites, cytogenetic and cytokinetic parameters, and whole tumor cells in bodily fluids. These tools can be utilized for various purposes, such as risk assessment, diagnosis, prognosis, treatment efficacy, toxicity evaluation, and predicting a return. Due to these versatile and critical purposes, there are widespread studies on the development of new, sensitive, and selective approaches for the determination of cancer biomarkers. This review illustrates the significant lung and prostate cancer biomarkers and their determination utilizing electrochemical sensors, which have the advantage of improved sensitivity, low cost, and simple analysis. Additionally, approaches such as improving sensitivity with nanomaterials and ensuring selectivity with MIPs are used to increase the performance of the sensor. This review aims to overview the most recent electrochemical biosensor applications for determining vital biomarkers of prostate and lung cancers in terms of nanobiosensors and molecularly imprinted polymer (MIP)-based biosensors., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

Analytical chemistry is a broad area of science comprised of many sub-disciplines. Although each sub-discipline has its own dominant trends, one trend is common to all of them: greenness and sustainability. Efforts to develop more ecological and environmentally friendly methods have been ongoing for over a decade with initial attempts largely focusing on limiting the necessary volume of solvents required and eliminating the use of toxic solvents. Over time, the miniaturization of analytical devices gained popularity as a way of not only reducing chemical usage, but also enabling analyses using smaller sample volumes and more "remote" applications (e.g., on-site sampling and analysis). Of course, miniaturization poses numerous challenges for researchers, for instance, in relation to the method's sensitivity and reproducibility. Developments in the design of detection systems have largely helped to mitigate these issues, but they also often restrict the potential for on-site analysis. Therefore, attempts have been made to improve analysis throughout the entire analytical process, from sampling through sample preparation and instrumental analysis to data handling. Furthermore, clinical chemistry labs must adhere to certain regulations and use certified protocols and materials, which precludes the rapid implementation of solutions developed in research labs. What are the obstacles in translating such innovations to practical applications, and what inventions can make a difference in the future? The answers to these two questions define the trends in analytical chemistry in the field of medical analysis., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

Molecularly imprinted polymers (MIPs) rely on synthetic engineered materials able to selectively bind and intimately recognise a target molecule through its size and functionalities. The way in which MIPs interact with their targets, and the magnitude of this interaction, is closely linked to the chemical properties derived during the polymerisation stages, which tailor them to their specific target. Hence, MIPs are in-deep studied in terms of their sensitivity and cross-reactivity, further being used for monitoring purposes of analytes in complex analytical samples. As MIPs are involved in sensor development within different approaches, a systematic optimisation and rational data-driven sensing is fundamental to obtaining a best-performant MIP sensor. In addition, the closer integration of MIPs in sensor development requires that the inner properties of the materials in terms of sensitivity and selectivity are maintained in the presence of competitive molecules, which focus is currently opened. Identifying computational models capable of predicting and reporting the best-performant configuration of electrochemical sensors based on MIPs is of immense importance. The application of chemometrics using design of experiments (DoE) is nowadays increasingly adopted during optimisation problems, which largely reduce the number of experimental trials. These approaches, together with the emergent machine learning (ML) tool in sensor data processing, represent the future trend in design and management of point-of-care configurations based on MIP sensing. This review provides an overview on the recent application of chemometrics tools in optimisation problems during development and analytical assessment of electrochemical sensors based on MIP receptors. A comprehensive discussion is first presented to cover the recent advancements on response surface methodologies (RSM) in optimisation studies of MIPs design. Therefore, the recent advent of machine learning in sensor data processing will be focused on MIPs development and analytical detection in sensors., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

Ambient ionization mass spectrometry (AIMS) has been developing explosively since its first debut. The ionization process was hence able to be achieved under atmospheric pressure, facilitating on-site field analysis in a variety of areas, such as clinical diagnosis, metabolic phenotyping, and surface analysis. As part of the ambitious goal of making MS a general device that can be used in everyday life, lots of efforts have been paid to miniaturize the ionization source. This review discusses avant-garde sources that could be entirely hand-held without any accessories. The structure and applications of the devices are described in detail as well. They could be expediently used in real-time and on-site analysis, presenting a great future potential for the routinizing of MS., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

Sample preparation is a constantly evolving step in the measurement process with a positive effect on its performance. Its evolution has been marked by an underlying environmental commitment, with simplification, miniaturization, and automation being three of its driving forces. This trends article deepens how the sample preparation can go sustainable through the efficient design of new sorptive materials, either liquid or solid. This objective can be achieved by using natural and/or biodegradable materials as precursors of the functional sorptive phases and by designing materials that simplify the procedures (thus reducing the energy or resources required). Although environmental performance is a crucial aspect of a new material, its applicability is what really defines its incorporation into the sample preparation toolbox. For this reason, their characteristics and more relevant applications will be briefly presented to conclude with the tendency of their use in the very near future., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)