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Surface-enhanced Raman Scattering (SERS) has become a powerful spectroscopic technology for highly sensitive detection. However, SERS is still limited in the lab because it either requires complicated preparation or is limited to specific compounds, causing poor applicability for practical applications. Herein, a micro-macro SERS strategy, synergizing polymer-assisted printed process with paper-tip enrichment process, is proposed to fabricate highly sensitive paper cartridges for sensitive practical applications. The polymer-assisted printed process finely aggregates nanoparticles with a discrete degree of 1.77, and SERS results are matched with theoretical enhancement, indicating small cluster-dominated hotspots at the micro-scale and thus 41-fold SERS increase compared to other aggregation methods. The paper-tip enrichment process moves molecules in a fluid into small tips filled with plasmonic clusters, and molecular localization at hotspots is achieved by the simulation and optimization of fluidic velocity at the macro-scale, generating a 39.5-fold SERS sensibility increase in comparison with other flow methods. A highly sensitive paper cartridge contains a paper-tip and a 3D-printed cartridge, which is simple, easy-to-operate, and costs around 2 US dollars. With a detection limit of 10 -12  M for probe molecules, the application of real samples and multiple analytes achieves single-molecule level sensitivity and reliable repeatability with a 30-min standardized procedure. The micro-macro SERS strategy demonstrates its potential in practical applications that require point-of-care detection., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. We wish to confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome. We confirm that the manuscript has been read and approved by all named authors and that there are no other persons who satisfied the criteria for authorship but are not listed. We further confirm that the order of authors listed in the manuscript has been approved by all of us. We confirm that we have given due consideration to the protection of intellectual property associated with this work and that there are no impediments to publication, including the timing of publication, with respect to intellectual property. In so doing we confirm that we have followed the regulations of our institutions concerning intellectual property. We understand that the Corresponding Author is the sole contact for the Editorial process (including Editorial Manager and direct communications with the office). He/she is responsible for communicating with the other authors about progress, submissions of revisions and final approval of proofs. We confirm that we have provided a current, correct email address which is accessible by the Corresponding Author., (Copyright © 2024 Elsevier B.V. All rights reserved.)

In this article, we present the first demonstration of a distance-based paper analytical device (dPAD) for uric acid quantification in human urine samples with instrument-free readout and user-friendliness for the rapid diagnosis and prognosis of various related diseases. By employing gold nanoparticles (AuNPs) as a peroxidase-like nanozyme, our proposed technique eliminates the utilization of horseradish peroxidase (HRP), making the device cost-effective and stable. In our dPAD, uric acid in the sample is oxidized by the uricase enzyme and subsequently catalysed with AuNPs in the sample zone, generating hydroxyl radicals (˙OH). Then, the produced ˙OH reacts with 3,3'-diaminobenzidine (DAB) to form poly DAB (oxDAB), resulting in a coloured distance signal in the detection zone of the dPAD. The variation of the distance of the observed red-brown colour is directly proportional to the uric acid concentration. Our sensor exhibited a linear range from 0.50 to 6.0 mmol L -1 ( R 2 = 0.9922) with a detection limit (LOD) of 0.25 mmol L -1 , covering the clinical range of uric acid in urine. Hence, there is no need for additional sample preparation or dilution. Additionally, this assay is highly selective, with no interferences. We also found that this approach could accurately and precisely determine uric acid in human control samples with the recovery ranging from 99.37 to 100.35 with the highest RSD of 4.05%. Our method is comparable with the use of a commercially available uric acid sensor at a 95% confidence interval. Consequently, the developed dPAD offers numerous advantages such as cost-effectiveness, simplicity, and ease of operation with unskilled individuals. Furthermore, this concept can be applied for extensive biosensing applications in monitoring other biomarkers as an alternative analytical point-of-care (POC) device.

SERS measurements for monitoring bactericides in dairy products are highly desired for food safety problems. However, the complicated preparation process of SERS substrates greatly impedes the promotion of SERS. Here, we propose acoustofluidic one-step synthesis of Ag nanoparticles on paper substrates for SERS detection. Our method is economical, fast, simple, and eco-friendly. We adopted laser cutting to cut out appropriate paper shapes, and aldehydes were simultaneously produced at the cutting edge in the pyrolysis of cellulose by laser which were leveraged as the reducing reagent. In the synthesis, only 5 μL of Ag precursor was added to complete the reaction, and no reducing agent was used. Our recently developed acoustofluidic device was employed to intensely mix Ag + ions and aldehydes and spread the reduced Ag nanoparticles over the substrate. The SERS substrate was fabricated in 1 step and 3 min. The standard R6G solution measurement demonstrated the excellent signal and prominent uniformity of the fabricated SERS substrates. SERS detection of the safe concentration of three bactericides, including tetracycline hydrochloride, thiabendazole, and malachite green, from food samples can be achieved using fabricated substrates. We take the least cost, time, reagents, and steps to fabricate the SERS substrate with satisfying performance. Our work has an extraodinary meaning for the green preparation and large-scale application of SERS., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Cancer is the second leading cause of death globally, with 9.7 million fatalities in 2022. While routine screenings are vital for early detection, healthcare disparities persist, highlighting the need for equitable solutions. Recent advancements in cancer biomarker identification, particularly microRNAs (miRs), have improved early detection. MiR-21 is notably overexpressed in various cancers and can be a valuable diagnostic tool. Traditional detection methods, though accurate, are costly and complex, limiting their use in resource-limited settings. Paper-based electrochemical biosensors offer a promising alternative, providing cost-effective, sensitive, and rapid diagnostics suitable for point-of-care use. This study introduces an innovative electrochemical paper-based biosensor that leverages gold inkjet printing for the quantitative detection of miR-21. The biosensor, aimed at developing cost-effective point-of-care devices for low-resource settings, uses thiolated self-assembled monolayers to immobilize single-stranded DNA-21 (ssDNA-21) on electrodeposited gold nanoparticles (AuNPs) on the printed gold surface, facilitating specific miR-21 capture. The hybridization of ssDNA-21 with miR-21 increases the anionic barrier density, impeding electron transfer from the redox probe and resulting in a current suppression that correlates with miR-21 concentration. The biosensor exhibited a linear detection range from 1 fM to 1 nM miR-21 with a sensitivity of 7.69 fM µA -1 cm 2 and a rapid response time (15 min). With a low detection limit of 0.35 fM miR-21 in serum, the biosensor also demonstrates excellent selectivity against interferent species. This study introduces an electrochemical paper-based biosensor that uses gold inkjet printing to precisely detect miR-21, a key biomarker overexpressed in various cancers. This innovative device highlights the potential for cost-effective, accessible cancer diagnostics in underserved areas.

A flexible, ultrasensitive, and practical SERS chip is presented based on a paper/f-TiO 2 /Ag structure. The chip enhances the self-assembly of Ag nanoparticles on a cellulose fiber matrix, facilitated by smart functionalized TiO 2 nanomaterials (f-TiO 2 ). This design enables superior detection of the hazardous pesticide tricyclazole (TCZ) on crops using an advanced, simple, and efficient analytical method. Despite its straightforward fabrication process via a solvent immersion method, the intrinsic smart surface properties of the TiO 2 bridging material - both hydrophilic and hydrophobic - enable the uniform and dense self-assembly of hydrophilic Ag nanoparticles (NPs) on the cellulose fiber paper substrate. This innovative design provides superior sensing efficiency for TCZ molecules with a detection limit reaching 2.1 × 10 -9  M, a remarkable improvement compared to Paper/Ag substrates lacking f-TiO 2 nanomaterials, which register at 10 -5  M. This flexible SERS substrate also exhibits very high reliability as indicated by its excellent reproducibility and repeatability with relative standard deviations (RSD) of only 5.93% and 4.73%, respectively. Characterized by flexibility and a water-attractive yet non-soluble surface, the flexible Paper/f-TiO 2 /Ag chips offer the convenience of direct immersion into the analytical sample, facilitating seamless target molecule collection while circumventing interference signals. Termed the "dip and dry" technique, its advantages in field analysis are indisputable, boasting in situ deployment, simplicity, and high efficiency, while minimizing interference signals to negligible levels. Through the application of this advanced technique, we have successfully detected TCZ in two high-value crops, ST25 rice and dragon fruit, achieving excellent recovery values ranging from 90 to 128%. This underscores its immense potential in ensuring food quality and safety. As a proof of concept, flexible Paper/f-TiO 2 /Ag SERS chips, with a simple fabrication process, advanced analytical technique, and superior sensing efficiency, bring SERS one step closer to field applications beyond the laboratory., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Mercury ions (Hg 2+ ) are highly toxic heavy metals that are commonly found in natural environments. Owning to their non-biodegradability and accumulation in the food chain, the precise detection of trace amounts of Hg 2+ is essential for preventing chronic accumulation and ensuring food safety. In this study, we present a dual-mode paper sensor for simultaneous colorimetric and Surface-Enhanced Raman Spectroscopy (SERS) detection of Hg 2+ in tea, achieving ultrasensitive, rapid, and on-site screening. 4-Mercaptopyridine (4-MPY) was effectively chemisorbed onto the gold nanoparticles (AuNPs), acting as a signal probe for colorimetric methods. Moreover, it can produce plasmonic hot spots for SERS by interacting with the pyridine ring. To enhance the signal intensity of both colorimetry and SERS, a silver shell is in-situ grown on the surface of AuNPs captured on the paper sensor by reduction of Ag + , achieving signal amplification. The visual limit of detection (LOD) for the colorimetric biosensor is 2.5 pM, while the LOD of SERS is 0.48 pM with this dual-mode paper sensor. The sensitivity of both the colorimetric method and SERS was improved by approximately 200 and 500 times, respectively, with the designed signal amplification strategy. The system allows for multiple parallel screening of the same sample, ensuring accurate results without any false-positive or false-negative. This study provides a valuable platform for the accurate detection of various other heavy metal ions and provides effective strategies for improving the performance of colorimetric methods., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Rapid and accurate detection of tumor markers at extremely low levels is crucial for the early diagnosis of cancers. In this work, we developed a portable label-free sliding electrochemical paper-based analytical device (ePAD) using copper/cuprous sulfide@N-doped C@Au nanoparticles (Cu/Cu 2 S@NC@Au) hollow nanoboxes as the signal amplifier for the ultrasensitive detection of alpha-fetoprotein (AFP). Cu/Cu 2 S@NC nanoboxes were synthesized by sacrificial template and interface reaction methods, on which Au nanoparticles were electrodeposited to construct unique heterostructure for effectively capturing anti-AFP and serving as signal amplifier. The designed ePAD incorporates sliding microfluidic paper chips to form a flexible three-electrode system, enabling highly sensitive detection of AFP with a wide linear range of 0.005-50 ng mL -1 and a low detection limit of 0.62 pg mL -1 . The practicality of the prepared ePAD was validated through AFP detection in clinical human serum, which was consistent with chemiluminescence immunoassay. In addition, the developed immunosensor demonstrates excellent specificity, repeatability and stability. This novel platform exhibits significant potential for rapid on-site analysis and point-of-care diagnosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Homocysteine (Hcy) and C-reactive protein (CRP) are critical biomarkers for numerous chronic diseases, with cardiovascular disease (CVD) being the most prevalent. The ability to simultaneously detect both biomarkers in point-of-care settings is in high demand for CVD early diagnosis and prevention. Herein, we prepared the eutectic gallium indium (EGaIn) nanoparticles decorated with p -phenylenediamine (PPD) on the surface to facilitate the subsequent attachment of gold nanoparticles (AuNPs) to achieve EGaIn-PPD@Au, which was modified on the screen-printed electrochemical paper-based analytical devices (ePADs). Aptamers that are specific to Hcy and CRP were then immobilized on the EGaIn-PPD@Au surface to achieve the sensing interface on ePADs. The presence of EGaIn-PPD@Au significantly enhanced the electrical conductivity, leading to amplified electrochemical signals. This aptasensor demonstrated high specificity, capable of detecting Hcy in a range of 1-50 μM with a detection limit of 0.22 μM, and the detection range for CRP was 1-100 ng/mL with a detection limit of 0.039 ng/mL. The aptasensor also effectively detected Hcy and CRP in clinical saliva samples, yielding an area under the curve (AUC) of about 0.80 when the individual biomarker was considered and 0.93 when both biomarkers were taken into account. The positive correlation observed between salivary and blood concentrations of Hcy and CRP, coupled with their association with cardiovascular disease (CVD), suggested the potential of this methodology as a noninvasive point-of-care strategy for the early diagnosis of CVD.

Nitric oxide (NO) in human tears regulates numerous ocular surface processes, such as tear generation, corneal wound healing, conjunctival vascular tone, and so forth. Any deviation from its normal concentration is linked to various ocular syndromes, including microbial keratitis, conjunctivitis, pterygium, dry eye, retinitis, glaucoma, and so forth. Therefore, precise monitoring of NO in tears can be considered as a potential biomarker for ocular diseases. Here, we report a highly sensitive and selective electrochemical NO sensor using carbon ink-based electrodes. Counter, working (WE), and reference electrodes have been designed and painted on a butter paper by using carbon ink. To improve the sensing performance, the WE has been modified with a gold nanoparticle (Au NP)-deposited carbon cloth (CC). Such a paper-based sensor demonstrated high sensitivity of ∼0.34 μA μM -1 cm -2 , ultralow detection limit of ∼2.35 nM, wide linear range of 10 nM-0.4 mM, and fast response time (0.35 s). The sensor also showed excellent stability and selectivity toward the interfering agents in human body fluids. Such a low-cost, flexible paper-based sensor was employed for the detection of NO in artificial tears.

Food adulteration presents a significant challenge due to the evasion of legal oversight and the difficulty of identification. Addressing this issue, there is an urgent need for on-site, rapid, visually based small-scale equipment, along with large-scale screening technology, to enable prompt results without providing opportunities for dishonest traders to react. Colorimetric reactions offer advantages in terms of speed, visualization, and miniaturization. However, there is a scarcity of suitable colorimetric reactions for food adulteration detection, and interference from colored food impurities and easily comparable color results affects accuracy. To overcome limitations, this study introduces a novel approach utilizing polydopamine magnetic nanoparticles to enrich DNA in food samples, effectively eliminating interfering components. By employing gold nanoparticles to generate magnetic-gold nanoparticles, a single magnetic bead achieves simultaneous enrichment, impurity removal, and detection. The use of paper-based biosensors and visualization equipment allows for the visualization and digital analysis of results, achieving a low detection limit of 4.59 nmol mL -1 . The method also exhibits high accuracy and repeatability, with a RSD ranging from 1.6 % to 4.0 %. This innovative colorimetric method addresses the need for rapid, miniaturized, and large-scale detection, thus providing a solution for food adulteration challenges., Competing Interests: Declaration of Competing Interest The author declare that there are no conflicts of interest associated with this manuscript. This research was conducted with utmost integrity and impartiality, adhering to the highest ethical standards. We have no financial or personal relationships that could inappropriately influence the content or interpretation of this work., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Hydrogen Peroxide (H 2 O 2 ) is a highly hazardous, toxic, and carcinogenic chemical compound utilised in various industries-based applications. Despite strict restriction, they are deliberately added to food items such as milk as preservatives to increase its shelf life. Herein, we have formulated a green rapid colorimetric nanosensor for detection of H 2 O 2 in milk using cotton leaves as both reducing and functionalizing agent for synthesis of silver nanoparticles (AgNPs). UV-Vis spectra exhibit a strong plasmonic peak at around 434 nm. X-Ray Diffraction (XRD) analysis was performed to determine the crystallinity of the nanoparticles. Field Emission Scanning Electron Microscope (FESEM) and Transmission Electron Microscope (TEM) characterizations revealed spherical morphology with size approximately ∼16 nm. This functionalized nanoparticle could colorimetrically sense presence of H 2 O 2 in milk samples both in liquid media and on paper substrates with Limit of Detection (LOD) of 8.46 ppm even in presence of other interfering substances in milk. This inexpensive route will pave the way for in depth research., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The monitoring of foodborne bacterial contamination requires simple and convenient biosensors. This work describes a novel paper-based colorimetric biosensor for the rapid and sensitive bacteria detection. The biosensor was constructed via the encapsulation of D-alanyl-D-alanine capped gold nanoparticles (DADA-AuNPs) in a modified paper that was fabricated by the freeze-drying of TEMPO-oxidized cellulose nanofibers/cationic guar gum composite hydrogel-modified filter paper. The results indicated that the size of DADA-AuNPs largely determined the color of their aqueous system and they exhibited light red to dark red as their size increased from around 6 to 36 nm. All these different sized DADA-AuNPs turned into colorless when encountered with either S. aureus or E. coli. In particular, the smaller the DADA-AuNPs size, the faster the discoloration. The encapsulation of DADA-AuNPs into modified paper negligibly changed their responsiveness towards bacteria. In comparison to the original filter paper and oven-dried hydrogel-modified filter paper, the freeze-dried hydrogel-modified paper was demonstrated to be a better substrate for the encapsulation of DADA-AuNPs since they could be loaded with a larger amount of DADA-AuNPs in a faster way and showed a better perceivable color. This work demonstrated a promising paper-based colorimetric biosensor for the facile and rapid detection of bacteria., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

This study introduces the development of a photothermal-based microfluidic paper analytical device (PT-µPAD) integrated with near-field communication (NFC) technology and smartphone readout for enzyme-free glucose quantification in human samples. With the properties of gold nanoparticles (AuNPs) both as a nanozyme and as a photothermal substrate, there is no need for costly reagents like enzymes or a readout instrumentation for the selective and sensitive detection of glucose. In PT-µPADs, AuNPs are etched by hydrogen peroxide (H 2 O 2 ) generated from glucose catalysis. Photothermal detection from the plasmonic heating of these AuNPs when illuminated by a 533nm LED light source is achieved by inserting the PT-µPAD sensor into a portable NFC platform suitable for smartphone readout. Temperature variation is directly proportional to the glucose concentration. After optimization, we acquired a linear range between 5.0 and 20.0 µmol L -1 ( R 2 = 0.9967) and a limit of detection (LOD) of 25.0 nmol L -1 for glucose. Additionally, while our sensor does not utilize any enzyme, it is remarkably selective to glucose with no effects from interferences. Recovery studies in various human control samples indicated a range of 99.73-102.66% with the highest RSD of 3.53%, making it highly accurate and precise. Moreover, our method is more sensitive than other methods relying on conventional µPADs for glucose sensing. By integrating the potential benefits of microfluidics, nanomaterials as nanozymes, and NFC technology for wireless readout, our sensor demonstrates great promise as an accessible, affordable, and shelf-stable device for glucose quantification. Moreover, this concept can be extended to detect other molecules of interest as a point-of-care (POC) diagnostics device.

Excessive emissions of heavy metals not only cause environmental pollution but also pose a direct threat to human health. Therefore, rapid and accurate detection of heavy metals in the environment is of great significance. Herein, we propose a method based on laser-induced breakdown spectroscopy (LIBS) combined with filter paper modified with bovine serum albumin-protected gold nanoclusters (LIBS-FP-AuNCs) for the rapid and sensitive detection of Cr 3+ and Mn 2+ . The filter paper modified with AuNCs was used to selectively enrich Cr 3+ and Mn 2+ . Combined with the multi-element detection capability of LIBS, this method achieved the simultaneous rapid detection of Cr 3+ and Mn 2+ . Both elements showed linear ranges for concentrations of 10-1000 μg L -1 , with limits of detection of 7.5 and 9.0 μg L -1 for Cr 3+ and Mn 2+ , respectively. This method was successfully applied to the determination of Cr 3+ and Mn 2+ in real water samples, with satisfactory recoveries ranging from 94.6% to 105.1%. This method has potential application in the analysis of heavy metal pollution.

We present a colorimetric probe based on polyvinylpyrrolidone-capped gold nanoparticles (PVP-AuNPs) that is sensitive and selective for cysteine (Cys). A microfluidic paper-based analytical device (μ-PAD) with embedded dried PVP-AuNPs at the polyethersulfone (PES) paper surface is used for Cys detection. When thiol molecules attach to PVP-AuNPs in the presence of Cys, they clump together, and this causes the solution's color to shift from red to blue within 5 minutes. The device is capable of detecting Cys levels between 1.0 μM and 50.0 μM with a limit of detection (LOD) of 0.2 μM under optimized conditions. The stability of the μ-PAD was tested for 100 days, demonstrating re-dispersibility to detect Cys levels in blood. Dried PVP-AuNP-μPADs were integrated with blood plasma separation modules for point-of-care (POC) Cys detection. Consequently, the device shows potential as a self-sustaining, quantification platform with a recovery percentage ranging from 98.44 to 111.9 in clinical samples.

The exploration into nanomaterial-based nonenzymatic biosensors with superb performance in terms of good sensitivity and anti-interference ability in disease marker monitoring has always attained undoubted priority in sensing systems. In this work, we report the design and synthesis of a highly active nanocatalyst, i.e., palladium and platinum nanoparticles (Pt&Pd-NPs) decorated ultrathin nanoporous gold (NPG) film, which is modified on a homemade graphene paper (GP) to develop a high-performance freestanding and flexible nanohybrid electrode. Owing to the structural characteristics the robust GP electrode substrate, and high electrochemically catalytic activities and durability of the permeable NPG support and ultrafine and high-density Pt&Pd-NPs on it, the resultant Pt&Pd-NPs-NPG/GP electrode exhibits excellent sensing performance of low detection limitation, high sensitivity and anti-interference capability, good reproducibility and long-term stability for the detection of small molecular biomarkers hydrogen peroxide (H 2 O 2 ) and glucose (Glu), and has been applied to the monitoring of H 2 O 2 in different types of live cells and Glu in body fluids such as urine and fingertip blood, which is of great significance for the clinical diagnosis and prognosis in point-of-care testing.

We proposed a triple functional SERS substrate by immobilized Ag nanoparticles on the surface of filter paper. The high dense Ag nanoparticles were distributed on the SERS substrate via in-situ growth process. By optimizing the parameter in preparation process, the optimal filter paper SERS substrate was fabricated by using 30 mM of AgNO 3 with 20 S growth time. Due to capillary-effect wicking of cellulose fiber, the paper SERS substrate provide simple, fast and pump-free function for transferring analyte onto sharp tip through development of fluid. The fluid flow also brings target concentrate effect within the tip area. Furthermore, the separation feasibility was obtained during the development process of fluid. The preconcentrated effects not only enhanced the SERS signal of analyte, but also improve the fluorescence visible effect. The filter paper SERS substrate was successfully used for separating, concentrating and detecting Sudan dye from chili product, the detection limit could achieve 10 -6 M. This study developed a portable, cost-effective and eco-friendly SERS substrate for separating and detecting trace chemical in food., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Herein, a cost-effective and portable microfluidic paper-based sensor is proposed for the simultaneous and rapid detection of glucose, free amino acids, and vitamin C in fruit. The device was constructed by embedding a poly(carboxybetaine acrylamide) (pCBAA)-modified cellulose paper chip within a hydrophobic acrylic plate. We successfully showcased the capabilities of a filter paper-based microfluidic sensor for the detection of fruit nutrients using three distinct colorimetric analyses. Within a single paper chip, we simultaneously detected glucose, free amino acids, and vitamin C in the vivid hues of cyan blue, purple, and Turnbull's blue, respectively, in three distinctive detection zones. Notably, we employed more stable silver nanoparticles for glucose detection, replacing the traditional peroxidase approach. The detection limits for glucose reached a low level of 0.049 mmol/L. Meanwhile, the detection limits for free amino acids and vitamin C were found to be 0.236 mmol/L and 0.125 mmol/L, respectively. The feasibility of the proposed sensor was validated in 13 different practical fruit samples using spectrophotometry. Cellulose paper utilizes capillary action to process trace fluids in tiny channels, and combined with pCBAA, which has superior hydrophilicity and anti-pollution properties, it greatly improves the sensitivity and practicality of paper-based sensors. Therefore, the paper-based colorimetric device is expected to provide technical support for the nutritional value assessment of fruits in the field of rapid detection.

In this study, nanomaterials capable of enzyme-free glucose quantification and colorimetric readout are integrated into a microfluidic paper-based analytical devices (μPADs). Gold nanoparticles (AuNPs) and silver nanoparticles (AgNPs) were utilized as a peroxidase-like nanozyme and a colorimetric probe to achieve glucose monitoring. In this developed device, glucose is oxidized by AuNPs to generate hydrogen peroxide (H 2 O 2 ), which flows in the paper microchannels toward detection zones. H 2 O 2 then etches the immobilized AgNPs to induce a color change. The intensity of color change is easily monitored using a smartphone application. Following method optimization, we obtained a linear range from 0.50 to 10.0 mmol L -1  (R 2  = 0.9921) and a detection limit (LOD) of 340.0 μmol L -1 . This falls in the clinically relevant range for glucose monitoring and diabetes diagnosis in humans. In addition, the total analysis time is just 20 min, which is significantly less than the same experiment performed in the solution phase. Also, our method is markedly selective; other substrates do not interfere. The recovery test in human control samples was in the range of 98.47-102.34% and the highest relative standard deviation (RSD) was 3.58%. The enzyme-free approach for glucose sensing is highly desirable for diabetes diagnosis as it replaces the more expensive enzyme with cheaper nanomaterials. Furthermore, since nanomaterials are more environmentally stable compared to enzymes, it has the potential for widespread deployment as point-of-care diagnostics (POC) in resource-limited settings., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Herein is presented a novel and efficient portable paper-based sensing platform using paper-incorporated histidine stabilized gold nanoclusters (His-AuNCs), for the sensitive and selective detection of Fe ions from low-volume real water samples based on photoluminescence (PL) quenching. Highly photoluminescent colloidal His-AuNCs are obtained via a novel microwave-assisted method. The His-AuNCs-based sensor reveals a limit of detection (LOD) as low as 0.2 μM and a good selectivity towards Fe ions, in solution. Further, the fabricated portable sensing device based on paper impregnated with His-AuNCs proves to be suitable for the easy detection of hazardous Fe levels from real water samples, under UV light exposure, through evaluating the level of PL quenching on paper. Photographic images are thereafter captured with a smartphone camera and the average blue intensity ratio (I/I 0 ) of the His-AuNCs-paper spots is plotted against [Fe 2+ ] revealing a LOD of 3.2 μM. Moreover, selectivity and competitivity assays performed on paper-based sensor prove that the proposed platform presents high selectivity and accuracy for the detection of Fe ions from water samples. To validate the platform, sensing assays are performed on real water samples from local sources, spiked with 35 μM Fe ions (i.e., Fe 2+ ). The obtained recoveries prove the high sensitivity and accuracy of the proposed His-AuNCs-paper-based sensor pointing towards its applicability as an easy-to-use, fast, quantitative and qualitative sensor suitable for on-site detection of toxic levels of Fe ions in low-volume real water samples.

Herein, a simple microfluidic paper-based analytical device (μPAD) by using platinum nanoparticles (Pt NPs) as highly active peroxidase mimic for simultaneous determination of glucose and uric acid was fabricated. The μPAD consisted of one sample transportation layer, four paper-based detection chips, and two layers of hydrophobic polyethylene terephthalate (PET) films. The four detection chips were immobilized with various chromogenic reagents, Pt NPs, and specific oxidase (glucose oxidase or uricase). H 2 O 2 generated by specific enzymatic reactions could oxidize co-immobilized chromogenic reagents to produce colored products by using Pt NPs as efficient catalyst. The multi-layered structure of μPAD could effectively improve the color uniformity and color intensity. Total color intensity from each two detection chips modified with distinct chromogenic reagents were used for quantitative analysis of glucose and uric acid, respectively, resulting in significantly improved sensitivity. The linear range for glucose and uric acid detection was 0.01-5.0 mM and 0.01-2.5 mM, respectively. Satisfied results were obtained for glucose and uric acid detection in real serum samples. An easy-to-use smartphone APP was developed for convenient and intelligent detection. The developed μPAD integrated with smartphone as detector holds great applicability for simple and portable on-site analysis., (Copyright © 2021 Elsevier B.V. All rights reserved.)

In this study, we describe a monolithic and fully integrated paper-based device for the simultaneous detection of three prognostic biomarkers in saliva. The pattern of the proposed multiplexed device is designed with a central sample deposition zone and three identical arms, each containing a pre-treatment and test zone. Its one-step fabrication is realized by CO 2 laser cutting, providing remarkable parallelization and rapidity (ca. 5 s/device). The colorimetric detection is based on the sensitive and selective target-induced reshaping of plasmonic multibranched gold nanoparticles, which exhibit a clear spectral shift (and blue-to-pink color change) in case of non-physiological concentrations of the three salivary biomarkers. A rapid and multiplexed naked-eye or smartphone-based readout of the colorimetric response is achieved within 10 min. A prototype kit for POCT testing is also reported, providing robustness and easy handling of the device.

In this work, we fabricated a novel origami paper-based analytical device (oPAD) assisted by the nanostructuring effect of in situ Pd decoration of Cu/Co-doped CeO 2 (CuCo-CeO 2 -Pd) nanospheres, functionalized with their strongly enhanced electrocatalytic properties to realize an electrochemical and visual signal readout system in oPAD, for highly sensitive detection of amyloid-β (Aβ). The CuCo-CeO 2 -Pd nanospheres were introduced as an enhanced "signal transducer layer" on account of the electron transfer acceleration caused by catalyzing glucose to produce H 2 O 2 for differential pulse voltammetry signal readout and further 3,3'5,5'-tetramethylbenzidine (TMB) oxidation for colorimetric analysis. Meanwhile, for achieving superior performance of the proposed oPAD, in situ growth of urchin-like gold nanoparticles (Au NPs) onto cellulose fibers was adopted to improve "the recognition layer" in favor of immobilizing antibodies for targeting Aβ through specific antigen-antibody interactions. Combined with the delicate design of oPAD, exhibiting actuation of the conversion procedure between hydrophobicity and hydrophilicity on paper tabs in the assay process, the oPAD successfully enabled sensitive diagnosis of Aβ in a linear range from 1.0 pM to 100 nM with a limit of detection of 0.05 pM (S/N = 3) for electrochemical detection, providing a reliable strategy for quantifying the Aβ protein in clinical applications.

Packaging is as important as the product itself because it is a crucial marketing and communication tool for business. Oxidized nanocellulose (ONC), extracted from agriculture residues of bagasse raw material using ecofriendly ammonium persulfate hydrolysis method, is used as support/reducing agent for the generation of silver nanoparticles (AgNPs) via photochemical procedure and reinforcing element in paper functionalization. The natural polymer, sodium alginate (SA) is exploited to enhance the binding of the ONC-AgNPs over cellulose fibers. The SA/ONC-AgNPs bio-nanocomposite is incorporated on paper matrix, which represents a more suitable choice respect to other substrates for its renewable, biocompatible, biodegradable, and cost-effective properties. Structural and antimicrobial evaluations show that the papers embedded with the SA/ONC-AgNPs possess good mechanical, thermal, barrier and antibacterial properties., Competing Interests: Declaration of competing interest There is no conflict of interest in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

A fast and sensitive colorimetric paper sensor has been developed using silver nanoprisms (Ag NPRs) with an edge length of ~50 nm for the detection of free H 2 S gas. We prepared two types of Ag NPRs-coated H 2 S sensing papers: a multi-zone patterned paper for passive (diffusion mode), and a single-zone patterned paper for pumped mode of H 2 S gas. The change in color intensity was quantitatively analyzed of Ag NPRs-coated paper after KCl treatment depending on the concentration of H 2 S gas, from yellow to purplish brown. As a result, Ag NPRs-coated H 2 S sensing paper showed good sensitivity with a linear range of 1.03 to 32.9 μM H 2 S, high selectivity, and good reproducibility and stability, together with a fast response time of 1 min. The developed H 2 S sensing paper was applied to detect the free H 2 S gas released from three types of garlic including crushed, peeled, and fresh garlic. Therefore, it can be utilized as a simple, fast, and reliable tool for on-site colorimetric detection of free H 2 S gas for quality control of dietary supplements and exhaled breath analysis.Graphical abstract.

Silver nanoparticles (AgNPs) are in situ synthesized for the first time on microfibrillated silk (MFS) exfoliated from domesticated Philosamia cynthia ricini (eri) and Bombyx mori (mulberry) silkworm silk fibers. The process is rapid (hours time), does not rely on harmful chemicals, and produces robust and flexible AgNPs coated MFS (MFS-AgNPs) protein papers with excellent handling properties. None of these can be achieved by approaches used in the past to fabricate AgNPs silk systems. MFS bonds the AgNPs strongly, providing good support and stabilization for the NPs, leading to strong wash fastness. The mechanical properties of the MFS-AgNPs papers largely do not change compared to the MFS papers without nanoparticles, except for some higher concentration of AgNPs in the case of mulberry silk. The improved tensile properties of eri silk papers with or without AgNPs compared to mulberry silk papers can be attributed to the higher degree of fibrillation achieved in eri silk and its inherent higher ductility. MFS-AgNPs from eri silk also exhibit strong antibacterial activity. This study provides the basis for the development of smart protein papers based on silk fiber and functional nanomaterials., (© 2020 Wiley-VCH GmbH.)

Here, we aimed to boost antibacterial performance of cellulose fibers for paper sheet application. Therefore, TiO 2 nanoparticles have been used with controlled loading onto the surface of the fibers. A simple and facile composite preparation route based on ultrasound and mechanical assisted stirring has been developed. We tested cellulose paper enriched by TiO 2 from 1.0 wt% to 8.0 wt%, respectively. Antibacterial performance has been studied against Staphylococcus aureus and Escherichia coli bacteria. Studies showed that all composites exhibit significant capability to reduce living cells of S. aureus and E. coli bacteria at least 60%. The simplicity, low cost, and reproducibility of the prepared method indicates the potential to be scaled up for industrial applications.

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

In the present work, a facile and green synthesis approach for the production of monodispersed, small-sized (2.9 ± 0.7 nm) and stable silver nanoparticles (AgNPs) using soluble soybean polysaccharide (SSPS) was reported. SSPS was used as the reducing and stabilizing agent. The obtained SSPS-stabilized AgNPs (SA) were characterized by UV-vis absorption spectroscopy, X-ray diffraction, Fourier transform infrared spectroscopy, energy dispersive X-ray spectroscopy and transmission electron microscopy. The antimicrobial activity of the SA colloidal dispersion (SACD) was evaluated based on the growth kinetics of bacteria E. coli and S. aureus. Afterwards, the colloidal dispersion was applied as a coating material to Kraft paper. The SACD-coated Kraft paper exhibited excellent antimicrobial activity against above bacteria strains and P. aeruginosa. The effects of SACD coating on surface wettability, barrier property and microstructure of the Kraft paper were also studied. The results suggested that the SSPS-stabilized AgNPs have great potential in antibacterial applications., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

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

Antibiotics abuse now poses a global threat to public health. Monitoring their residual levels as well as metabolites are of great importance, still challenges remain in in situ tracing during the circulation. Herein, taking the typical antibacterial Enrofloxacin (ENR) as a subject, a paper-based aptasensor was tailored by manipulating a duo of aptameric moieties to "sandwich" the target in a lateral-flow regime. To visualize the tight-binding sandwich motif more vividly, an irregular yet robust DNA-bridged gold nanoparticles (AuNPs) proximity strategy was developed with recourse to terminal deoxynucleotidyl transferase, of which the nonaggregate constraining feature was unveiled via optical absorption and scanning probe topography. This complex performed exceptionally better in the test strip context than single-particle tags, leading to an enhanced on-chip focusing. Rather than qualitative color developing, further efforts were taken to visualize the readouts in a quantitative manner by exploiting the smartphone camera for pattern recognition along with data processing in a professional App. Overall, this prototyped contraption realized a rapid and ultrasensitive quantification of ENR down to 0.1 μg/L along with a broad linear range over 5 orders of magnitude, plus excellent selectivity and precision even for real samples. Such innovative fusion across DNA-structured nanomanufacturing and intelligent perception provides a prospective and invigorating solution to point-of-care inspection., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Nowadays, thanks to nanotechnological progress, which itself guides us more and more closely toward not only the efficient design of innovative nanomaterials or nanostructures, but to the improvement of their functionality, we benefit from an important asset in the battle against pathogenic illnesses. Herein, we report a versatile biocompatible plasmonic nanoplatform based on a Whatman paper incorporating positively-charged gold nanospherical particles via the immersion approach. The morphological characterization of the as-engineered-plasmonic paper was examined by SEM (scanning electron microscopy) and HRTEM (high-resolution transmission electron microscopy) investigations, while its surface chemical modification with a synthetic polypeptide, specifically RRWHRWWRR-NH2 (P2), was proved by monitoring the plasmonic response of loaded gold nanospheres and the emission signal of P2 via fluorescence spectroscopy. The as-functionalized plasmonic paper is non-cytotoxic towards BJ fibroblast human cells at bactericidal concentrations. Finally, the antimicrobial activity of the P2-functionalized plasmonic paper on both planktonic bacteria and biofilms was tested against two reference strains: Gram-positive Bacteria, i.e., Staphylococcus aureus and the Gram-negative Bacteria, i.e., Escherichia coli , determining microbial inhibition of up to 100% for planktonic bacteria. In line with the above presented nanoplatform's proper design, followed by their functionalization with active antimicrobial peptides, new roads can be open for determining antibiotic-free treatments against different relevant pathogens.

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

A novel fluorescence strategy based on the outstanding catalytic capability of CuS nanoparticles (CuS NPs ) has been developed for highly sensitive and specific determination of o,o-dimethyl-o-2,2-dichlorovinyl phosphate (DDVP) under enzyme-free and hydrogen peroxide (H 2 O 2 )-free conditions. In the presence of DDVP, CuS NPs can catalyze non-fluorescence substratum of Amplex red (AR) into resorufin, which exhibits fluorescence emission at 584 nm under excitation at 540 nm. The sensing system exhibits outstanding specificity and only responds to DDVP and no other organophosphorus pesticides (OPs). A wide linear range is obtained from 0.0001 to 0.1 μg/mL, and the limit of detection (LOD) is 0.1 ng/mL. Furthermore, paper-based test strips have been constructed for visual detection of DDVP under ultraviolet light irradiation. By integrating a smartphone installed with Color Picker APP, point-of-care detection with quantitative determination is realized, demonstrating substantial potential applications of the as-developed assay for in situ detection. Graphical abstract.

Estazolam (EST) is a common sedative-hypnotic drug with a risk of abuse. Therefore, rapid on-site detection of EST is necessary to control the abuse of EST. In this paper, a fast, simple, and sensitive method is demonstrated for the detection of EST in both water and beverages, using surface-enhanced Raman spectroscopy (SERS) techniques. Au@Ag core-shell nanoparticles (NPs) assembled on the filter paper as a SERS substrate exhibit good applicability and practicality. At the same time, density functional theory (DFT) is used to assign the vibration mode of the EST molecules, which can be used as a guide for subsequent experiments. The lowest detectable concentration of EST in aqueous solution can be as low as 5 mg/L, and signal uniformity is excellent (RSD 687 = 5.56%, RSD 1000 = 4.35%). In addition, EST components artificially added to orange juice and pomegranate juice can be effectively detected by simple pretreatment with a minimum detection concentration as low as 10 mg/L. Therefore, this study found that the use of Au@Ag core-shell nanoparticles paper-based SERS substrate provides a quick and easy method for the detection of illegally added drugs in beverages.

A method is described for cysteine (Cys) determination on paper-based analytical devices using aspartic acid modified gold nanoparticles (Asp-AuNPs). The Asp-AuNPs were characterized by their size, zeta potential, and UV-visible absorption spectrum. After the addition of Cys, it will interact with Asp-AuNPs selectively and leads to the aggregation of Asp-AuNPs. A color change from red to blue can be observed on the paper-based analytical devices. The results were recorded using a cell phone and subsequently analyzed using the Photoshop software. The ratiometric color intensity at red channel and blue channel (Red/Blue) increased linearly in the range 99.9-998.7 μM for Cys (R = 0.9984), and the limit of detection was 1.0 μM. The effects of assay conditions have been investigated and are discussed. The Cys concentration was determined as (0.27 ± 0.02 mM) in human plasma, and the recovery was from 99.2 to 101.1%. Graphical abstract Schematic representation of the paper-based assay system using aspartic acid modified gold nanoparticles (Asp-AuNPs). The ratiometric color intensity method was used for the cysteine (Cys) determination.

Radiation dosimeters are critical for accurately assessing the levels of radiation exposure of tumor sites and surrounding tissues and for optimizing therapeutic interventions as well as for monitoring environmental exposure. To fill the need for a simple, user-friendly, and inexpensive dosimeter, we designed an innovative colorimetric nanosensor-based assay for detecting ionizing radiation. We show that hydroxyl radicals generated by ionizing radiation can be used to etch gold nanorods (AuNRs) and silver nanoprisms (AgNPRs), yielding reproducible color changes for radiation dose detection in the range of 50-2000 rad, broad enough to cover doses used in hyperfractionated, conventional, and hypofractionated radiotherapy. This range of doses detected by this assay correlates with radiation-induced DNA damage response in mammalian cells. Furthermore, this AuNR- and AgNPR-based sensing platform has been established in a paper format that can be readily adopted for a wide range of applications and translation.

In the present article we report a new hybrid microfluidic device (hyFlow) comprising a disposable paper electrode and a three-dimensional (3D) printed plastic chip for the electrochemical detection of a magnetic bead-silver nanoparticle (MB-AgNP) bioconjugate. This hybrid device evolved due to the difficulty of incorporating micron-scale MBs into paper-only fluidic devices. Specifically, paper fluidic devices can entrap MB-containing conjugates within their cellulose or nitrocellulose fiber matrix. The hyFlow system was designed to minimize such issues and transport MB conjugates more efficiently to the electrochemical detection zone of the device. The hyFlow system retains the benefit of fluid transport by pressure-driven flow, however, no pump is required for its operation. The hyFlow device is capable of detecting either pre-formed MB-AgNP conjugates or conjugates formed in situ. The detection limit of AgNPs using this device is 12 pM, which represents just 22 AgNPs per MB.

In this work, a lab-on-paper cathode photoelectrochemical (PEC) sensing platform was constructed for ultrasensitive microRNA-141 (miRNA-141) assay using cascaded multiple photo-active structures as signal generators and hemin/Pt nanoparticle (Pt NP) trunk-branching-decorated DNA dendrimers as signal reinforcers. Specifically, pyramid-like Cu 2 O was first in situ grown on the Au nanoparticle-functionalized tangled cellulose fibers network, followed by the sensitization of trepang-like BiVO 4 -Bi 2 S 3 heterostructures, forming the cascaded sensitization structures. Then, the DNA dendrimer was introduced into the photocathode sensing interface by coupling the duplex-specific-nuclease (DSN)-induced target recycling reaction with multiple-branched hybridization chain reaction (MHCR). The programmed target recycling procedures propelled using DSN guaranteed the highly amplified transduction of miRNA-141 to the exposed initiator strand, which triggered the cascaded MHCR accompanied by the formation of the DNA dendrimer with unique trunk-branching structures. Finally, the hemin/Pt NP trunk-branching-decorated DNA dendrimer (HPTD) was acquired by the assembly of Pt NPs and hemin on the trunk and branch, respectively. The resulting HPTD with the synergy catalysis of Pt NPs and hemin could efficiently catalyze the decomposition of H 2 O 2 for in situ generation of O 2 as the electron acceptor, leading to an enhanced photocurrent response. Based on the target-dependent photocurrent enhancement, ultrasensitive determination of miRNA-141 was realized with persuasive selectivity, high stability, and excellent reproducibility. Thus, the proposed paper-based cathode PEC sensing platform possessed promising application prospect in clinical miRNA diagnosis.

Herein, we reported a simple, flexible and sensitive surface-enhanced Raman scattering (SERS) substrate to detect methyl parathion residues in real life. The substrate was fabricated by filter paper and gold nanoparticles (Au NPs) with excellent reproducibility and stability. First, Au NPs were synthesized by the seed mediated growth method and assembled to the filter paper through immersion. The Raman probe molecule 4-MBA was used to evaluate performance of the substrate for an optimized signal using a portable Raman spectrometer coupled with 785 nm laser. Then, the paper-based substrate was applied to detect methyl parathion standard solution whose detection limit was down to 0.011 μg/cm 2 , and the linear range was between 0.018 μg/cm 2 and 0.354 μg/cm 2 . Afterwards, actual sample (apple) spiked with methyl parathion was taken to verify the practicality of the substrate by a simple way of "press-peel off". The recovery rate was ranged from 94.09% to 98.72%, indicating that this method is reliable in actual sample detection without complicated pretreatment steps. This work demonstrates that the flexible paper-based substrate combined with portable Raman instruments can be potentially applied to on-site detection of hazardous substances in the field of food safety., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Real-time monitoring of neonicotinoid pesticide residues is of great significance for food security and sustainable development of the ecological environment. Herein, a paper-based surface-enhanced Raman scattering (SERS) amplified approach was proposed by virtue of multilayered plasmonic coupling amplification. The unique plasmonic SERS multilayer was constructed using three-dimensional (3D) silver dendrite (SD)/electropolymerized molecular identifier (EMI)/silver nanoparticle (AgNP) sandwich hybrids with multiple hotspots and a strong electromagnetic field in nanogaps. Dendritelike 3D silver materials with remarkably high accessible surface areas and the lightning rod effect constituted the first-order enhancement of paper-based sensors. Molecular identifiers coated upon an SD layer as the interlayer were used for target capture and enrichment. Subsequently, AgNPs featuring rough surface and local plasma resonance decorated as the top layer formed the secondary enhancement of the amplification strategy. As the most brilliant part, dendritelike 3D silver coupled with AgNPs has established double Ag layers to accomplish a multistage enhancement of SERS signals based on the superposition of their electromagnetic fields. Owning to the distinctive design of the multiple coupling amplification strategy, the fabricated SERS paper chips demonstrated impressive specificity and ultrahigh sensitivity in the detection of imidacloprid (IMI), with a detection limit as low as 0.02811 ng mL -1 . More importantly, the multiple SERS enhancement paper chip holds great potential for automated screening of a variety of contaminants.

An optical colorimetric and smartphone-integrated paper device (SIPD) is demonstrated for determination of As (III) in water and soil samples using sucrose modified gold nanoparticles (AuNPs/Suc) as a nanoprobe. The mechanism for determination of As(III) is experimentally validated by performing UV-Vis, transmission electron microscope (TEM), Fourier transforms infra-red spectroscopy (FTIR) and dynamic light scattering (DLS) measurements. The density function theory (DFT) calculations using B3LYP with 6-311G (2d,2p) and LANL2DZ basis sets is used to theoretically prove the mechanism for determination of As(III). In addition, the paper fabricated with AuNPs/SuC was used as a nanoprobe for quantitative determination of As(III) using smartphone and ImageJ software. Calibration plot was linear over 10-800 μgL -1 for colorimetric determination of As(III) with limit of detection (LOD) of 4 μgL -1 acquired when the absorbance ratio obtained at 594 nm/515 nm. The linearity range of 50-3000 μgL -1 with LOD of 20 μgL -1 was determined using smartphone-integrated paper device. AuNPs/Suc is successfully employed for determination of As (III) from contaminated water and soil samples in colorimetry and SIPD. Graphical abstractColorimetric and Smartphone-integrated paper device used for selective detection of arsenic from contaminated water samples using sucrose modified gold nanoparticles (AuNPs/Suc) as a sensing probe.

Abnormal expression of MicroRNA-21 (miRNA-21) is considered to be a reliable biomarker for the early diagnosis of cancer. In this work, a novel paper based biosensor was fabricated to detect sub-micro molar concentrations of miRNA-21 based on peroxidase mimetic activity of DNA-templated Ag/Pt nanoclusters (DNA-Ag/Pt NCs), which could catalyze the reaction of hydrogen peroxide and 3,3',5,5' tetramethylbenzidine (TMB), to produce a blue color. The Mechanism of reaction was based on the inhibition effect of miRNA-21 on peroxidase-like activity of nanosensor which resulted to quantitative determination of miRNA-21 concentration. It was found that miRNA-21 could be linearly detected in the range from 1-700 pM (A 652  = 0.16x-0.96, R 2  = 0.99; x = -log [miRNA-21]) with a detection limit of 0.6 pM. Moreover, a paper assay was carried out on a Y-shaped paper-based microfluidic device in order to use the distinctive features of micro-channels such as short response time, very low reagent volume, low fabrication cost, etc. After performing paper based assay, a good linear range was observed between 10-1000 pM (y = 0.06x+147.48, R 2  = 0.99; x = [miRNA-21]) with detection limit of 4.1 pM. The practical application of proposed method for detection of miRNA-21 in real sample was assayed in the human urine sample and indicated the colorimetric method had acceptable accuracy., (Copyright © 2019 Elsevier B.V. All rights reserved.)

A paper based sensor array is presented to discriminate and determine five mycotoxins classified into three categories, namely aflatoxins, ochratoxins and zearalenone. The gold and silver nanoparticles, synthesized by three different reducing or capping agents, were employed as sensing elements of the fabricated device. These nanoparticles were poured onto hydrophilic circular zones embedded on the hydrophobic substrate. The response of the assay is dependent on the aggregation of nanoparticles for interaction with mycotoxins. Due to aggregation, the gold and silver nanoparticles changed to purple and brown, respectively. Color changes provide unique colorimetric signatures conducive to recognizing the type of mycotoxin, identifying its chemical structure, and finding the fungi that produce it. The discrimination ability of the assay was investigated by both supervised (linear discriminate analysis) and unsupervised (principle component analysis and hierarchical cluster analysis) pattern recognition methods. The assay was applied to the point of need determination of aflatoxin B1, aflatoxin G1, aflatoxin M1, ochratoxin A and zearalenone with a detection limit of 2.7, 7.3, 2.1, 3.3 and 7.0 ng.mL -1 , respectively. The fabricated device has high potential of simultaneously determining the mycotoxins in pistachio, wheat, coffee and milk with the help of partial least square method. The root mean square errors for prediction of PLS model were 5.7, 5.2, 1.5, 7.2 and 2.9 for aflatoxin B1, aflatoxin G1, aflatoxin M1, ochratoxin A and zearalenone, respectively. Graphical abstractSchematic representation of paper based colorimetric sensor array based on gold and silver nanoparticles for both qualitative and quantitative analysis of aflatoxins, ochratoxin and zearalenone.

Many studies have shown that urokinase plasminogen activator (uPA) is causally involved in promoting cancer invasion and metastasis. Thus, monitoring uPA levels could be very useful in cancer diagnosis, identification of initial metastasis, and guiding cancer treatment. Here, the authors developed a novel and scalable uPA sensor based on a graphene-gold nanoparticle platform that uses fluorescence of quantum dots to rapidly (<1 h) detect uPA up to 100 pM. Indeed, the authors' sensor is highly selective and showed an ability to sense up to 100 pM uPA even in the presence of complex biological milieu such as the fetal bovine serum.

Acute myocardial infarction (AMI) causes significant mortality and morbidity. The determination of multiple AMI biomarkers is very important for the timely diagnosis of AMI. In this work, simultaneous determination of three AMI biomarkers were achieved by virtue of a three-dimensional (3D) microfluidic paper-analytical device (μPAD) with temporally resolved chemiluminescence (CL) emissions for the first time. A dual-signal amplification strategy was introduced including by employing primary antibody functionalized gold nanoparticles (Ab 1 -GNPs) immobilized on the detection zone as amplified capture probes, and Co(II) catalyst, secondary antibody, luminol multifunctionalized gold nanoparticles (Co(II)-Ab 2 -luminol-GNPs) with excellent CL activity as amplified signal probes. CL immunoreactions were performed at three detection zone of the fabricated 3D μPAD by assembling Ab 1 -GNPs, antigen, and Co(II)-Ab 2 -luminol-GNPs to form sandwich-type immunocomplexes. Auto separated CL signals with temporal resolution were obtained by time delayed transport of H 2 O 2 to different detection zones for multiplexed analysis. The CL signal obtained by using Co(II)-Ab 2 -luminol-GNPs as signal probe (10576 a.u.) were about 20-fold higher than that by using conventional horseradish peroxidase labeled antibody modified luminol-GNPs as signal probe (531 a.u.). Finally, three AMI biomarkers including heart-type fatty acid-binding protein (H-FABP), cardiac troponin I (cTnI) and copeptin were quantitatively analyzed in one CL detection run by reading the CL intensity of the obtained three CL emission peaks. The detection range were ultra-wide ranged from 0.1 pg/mL to 1 μg/mL, 0.5 pg/mL to 1 μg/mL and 1 pg/mL to 1 mg/mL with the detection limits down to 0.06 pg/mL, 0.3 pg/mL and 0.4 pg/mL for H-FABP, cTnI and copeptin detection, respectively. The developed μPAD based immunoassay performing multiplexed analysis ability, high sensitivity, ultra-wide dynamic range, favorable selectivity, accessible accuracy and reproducibility, have great application potential for the early diagnosis of AMI., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Smart and green construction of noble metal nanostructures on two-dimensional nanomaterials-based flexible paper-like materials have gained extensive attention due to the formed hybrid papers have shown great promise in the applications of energy devices, sensing electronics, actuators, and chemical filters. Herein, a cost-effective and environment-friendly strategy to realize the spontaneous growth of noble metal nanoparticles (Au, Pd, and Pt) on flexible biomimetic MXene paper was proposed. The self-defined regulation of formed noble metal nanoparticles could be easily achieved, and the bimetallic (AuPt, PdPt) nanoparticles decorated MXene paper could be obtained at the mean time. These findings bring a simple, efficient and green way for constructing various hybrid MXene paper with outperforming electrocatalytic activities, which was demonstrated by the sensitive detection of superoxide (O 2 ) and the good stability and reproducibility after a long-term usage. The outstanding analytical performance of the obtained AuPtNPs/MXene paper in O •- monitoring leads to a satisfactory application in real-time extracellular biosensing. The investigation for spontaneous growth and regulation of noble metal nanoparticles on flexible biomimetic MXene paper exhibits a huge application potential for constructing high-performance flexible bioelectronics and energy-related devices.2 •- monitoring leads to a satisfactory application in real-time extracellular biosensing. The investigation for spontaneous growth and regulation of noble metal nanoparticles on flexible biomimetic MXene paper exhibits a huge application potential for constructing high-performance flexible bioelectronics and energy-related devices., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Owing to its critical role in the development of female reproductive tissues and as a clinical biomarker, there is an urgent need to develop a rapid and cost-effective method to sensitively detect 17β-estradiol (E2). In this work, a folding aptasensor platform with microfluidic channels for the label-free electrochemical detection of E2 is described. The platform, designed with a delicate folding structure, integrating filter holes, microfluidic channels, reaction chambers, and a three-electrode system, is extremely easy to use. To increase the detection sensitivity and immobilize the aptamer, we synthesized a novel nanoassembly consisting of amine-functionalized single-walled carbon nanotube/new methylene blue/gold nanoparticles (AuNPs) and modified the working electrode with this nanoassembly. The calibration curve obtained from the experimental results exhibited a linear range between 10 pg mL -1 and 500 ng mL -1 ( R 2 was achieved (S/N = 3). Furthermore, experiments to detect E2 in clinical serum were conducted, and the results were highly similar to those obtained using a large electrochemical luminescence apparatus. By integrating multiple functional components, adopting novel nanoassemblies, and using a folding structure, this paper-based platform not only has great potential as a simple and convenient integrated device for point-of-care testing of E2, but also as a portable, low-cost, and highly sensitive aptasensor platform capable of detecting many diagnostic biomarkers with the appropriate aptamers.-1 was achieved (S/N = 3). Furthermore, experiments to detect E2 in clinical serum were conducted, and the results were highly similar to those obtained using a large electrochemical luminescence apparatus. By integrating multiple functional components, adopting novel nanoassemblies, and using a folding structure, this paper-based platform not only has great potential as a simple and convenient integrated device for point-of-care testing of E2, but also as a portable, low-cost, and highly sensitive aptasensor platform capable of detecting many diagnostic biomarkers with the appropriate aptamers.

A paper-based colorimetric assay for the determination of bilirubin has been developed. The method is based on the in-situ reduction of chloroauric acid to form gold nanoparticles. A chromatographic paper was patterned using a wax printer. Chloroauric acid was drop-cast onto the reagent zone. In the presence of bilirubin, gold(III) ions are reduced and form gold nanoparticles. This leads to a color change from yellow to purple. The intensity of the purple color (peak at 530 nm) increases with bilirubin concentration in the 5.0 to 1000 mg L -1 range. The detection limit is 1.0 mg L -1 . For the quantification of bilirubin, images were captured using a digital camera, and data were processed with the help of machine learning-based supervised prediction using Random Forest classification. The method was applied to the determination of bilirubin in urine samples. The spiked urine samples exhibit more than 95% recovery. Graphical abstractSchematic representation of the paper-based colorimetric assay for the detection of bilirubin based on the in-situ formation of gold nanoparticles. A color band is generated for visual interpretation and used for the testing of bilirubin in urine.

Functional laser scribing carbon paper (LSCP) decorated with highly uniform Ni nanoparticles were constructed through a facile electroless plating. The nanocomposites were characterized by high resolution scanning electron microscope, X-ray photoelectron spectroscopy, electrochemical impedance spectroscopy, cyclic voltammetry and chronoamperometry. The results showed high electron transferring kinetics of this sensor, which can be ascribed to their excellent properties such as rich pore channels, excellent structural durability, and large surface area. These properties facilitated mass transfer and electron conductions. Notably, a systematical response surface methodology simulating-modeling-predicting-optimizing design was employed to simulate, model and optimize processing parameters to gain the optimal conductivity of 8.52 × 10 6  S m -1 . The obtained sensor owned high electrochemical activity and wide linear responses (0.80 μM-2.50 mM and 4.50 mM-15.20 mM), low detection limit of 20 nM (S/N = 3) to the glucose detection. The glucose determination in human serum and perspiration samples are also successful. Therefore, LSCP/NN provides an excellent sensing platform towards flexible biosensors in monitoring physical conditions., (Copyright © 2019 Elsevier B.V. All rights reserved.)