Search

We report the development of a distance-based paper analytical device combined with a hydrophilic bridge valve (B-dPAD) as a quantitative immunoassay method to monitor human interleukin-6 (IL-6) in human samples. Our device design features (i) a circular sample inlet zone, (ii) a circular capture zone with immobilized anti-IL-6 (anti-Ab

Uric acid (UA) is an important biomarker for many diseases. A sensitive point-of-care (POC) testing platform is designed for the digital quantification of salivary UA based on a colorimetric reaction on an easy-to-build smartphone-assisted microfluidic paper-based analytical device (SμPAD). UA levels are quantified according to the color intensity of Prussian blue on the SμPAD with the aid of a MATLAB code or a smartphone APP. A color correction method is specifically applied to exclude the light effect. Together with the engineering design of SμPADs, the background calibration function with the APP increases the UA sensitivity by 100-fold to reach 0.1 ppm with a linear range of 0.1-200 ppm. The assay time is less than 10 min. SμPADs demonstrate a correlation of 0.97 with a commercial UA kit for the detection of salivary UA in clinical samples. SμPADs provide a sensitive, fast, affordable, and reliable tool for the noninvasive POC quantification of salivary UA for early diagnosis of abnormal UA level-associated health conditions.

Paper-based microfluidic devices are popular for their ability to automate multistep assays for chemical or biological sensing at a low cost, but the design of paper microfluidic networks has largely relied on experimental trial and error. A few mathematical models of flow through paper microfluidic devices have been developed and have succeeded in explaining experimental flow behavior. However, the reverse engineering problem of designing complex paper networks guided by appropriate mathematical models is largely unsolved. In this article, we demonstrate that a two-dimensional paper network (2DPN) designed to sequentially deliver three fluids to a test zone on the device can be computationally designed and experimentally implemented without experimental trial and error. This was accomplished by three new developments in modeling flow through paper networks: (i) coupling of the Richards equation of flow through porous media to the species transport equation, (ii) modeling flow through assemblies of multiple paper materials (test membrane and wicking pad), and (iii) incorporating limited-volume fluid sources. We demonstrate the application of this model in the optimal design of a paper-based signal-enhanced immunoassay for a malaria protein, PfHRP2. This work lays the foundation for the development of a computational design toolbox to aid in the design of paper microfluidic networks. ©

Lithium carbonate is an effective medicine for the treatment of the bipolar disorder, but the concentration of lithium in the patient's blood must be frequently monitored because of its toxicity. To date, no colorimetric methods of lithium ion detection in whole blood without pretreatment have been reported. Here, we report a colorimetric paper-based device that allows point-of-care testing in one step. This device is composed of two paper-based elements linked to each other: a blood cell separation unit and a colorimetric detection unit. After a portion of whole blood has been placed on the end of the separation unit, plasma in the sample is automatically transported to the detection unit, which displays a diagnostic color. The key feature of this device is its simple, user-friendly operation. The limit of detection is 0.054 mM and the coefficient of variance is below 6.1%, which are comparable to those of conventional instruments using the same colorimetric reaction. Furthermore, we achieved high recovery (>90%) and reproducibility (

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 (R2 = 0.993), and a detection limit of 5 pg mL-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 digital fluorescence detector (DFD), a handheld fluorescence detection device, can convert the fluorescence signal of samples into the corresponding fluorescer concentration. Herein, by adopting a DFD as the readout, a novel intelligent platform was developed based on a ratiometric paper-based device (RPD) for multiple aminoglycoside detection. There are five layers and four parallel channels contained in the designed RPD, functioning as reagent storage, fluidic path control and signal processing, respectively. The rationale of this design lies in the fact that aptamer/graphitic carbon nitride nanosheet (Apt/g-C3N4 NS) modified layers can catalyze o-phenylenediamine to fluorescent 2,3-diaminophenazine (DAP) in the presence of H2O2. When Apt was removed from nanosheets via the Apt-target reaction, the peroxidase-like activity would be decreased, thus decreasing the production of DAP. All the changes of the fluorescence DAP signal can be read out using a portable DFD. Based on the DFD signal change related to the concentration of the target, a quantitative reaction platform was established. Furthermore, the sample flow and Apt-target reaction time can be reasonably regulated using the H2O2-cleavable hydrophobic compound modified layer placed between the target recognition region and detection region. Then, the practicality of this platform was verified through realizing sensitive analysis of streptomycin, tobramycin, and kanamycin simultaneously. Overall, with merits including portability and ease of operation, the platform shows great potential in on-site simultaneous detection of multiple targets, especially in resource-limited settings.

In this work, we introduce our recent finding that the carbon fiber paper (CFP) treated by simple air annealing (OCFP) could be used for exceptionally high-performance electrochemical nitrite sensing. The air-annealing process endows the pristine CFP with higher defective edge/plane sites, more oxygen-containing functional groups, higher roughness, and improved wettability. The electrochemical studies show that the OCFP exhibits excellent sensing performance for nitrite, with an ultralow determination limit of 0.1 μM and a detection limit of 0.07 μM, an ultrawide linear determination range of 0.1-3838.5 μM, a fast current response of 1 s, and a high sensitivity of 930.4 μA mM

Salmon fish farmers face remarkable problems in fish rearing and handling due to the spread of disease by infectious pancreatic necrosis virus (IPNV). Therefore, we developed a straightforward and sensitive technique to detect IPNV-based on recombinant human apoferritin heavy chain (hAFN-H) protein nanoparticles. In this study, the 24 subunits of the hAFN-H were genetically modified to express 6×His-tag and protein-G at their C-terminal site using Escherichia coli. We thus achieved a two-step signal amplifying strategy that utilizes a recombinant hAFN-H nanoprobe having a protein-G-binding site that targets the Fc region of monoclonal antibodies and a 6×His-tag that actively interacts with the functionalized Ni-NTA derivatives. In this study, we report a considerable advancement in magnetic bead-based detection systems that use Ni-NTA-Atto 550, reliably exhibiting detection limits of 1.02 TCID50/mL (50% tissue culture infective dose). Additionally, we propose a lateral flow chip-based detection method that uses the hAFN-H surface functionalized with 5 nm of the Ni-NTA-nanogold complex as a nanoprobe; the limit of detection towards IPNV was 0.88 TCID50/mL. The detection of IPNV by this recombinant hAFN-H nanoprobe was linear to virus titers in the range of 101-103 TCID50/mL.

Minimally invasive devices to detect molecules in dermal interstitial fluid (ISF) are desirable for point-of-care diagnostic and monitoring applications. In this study, we developed a microneedle (MN) patch that collects ISF for on-patch biomarker analysis by surface-enhanced Raman scattering (SERS). The micrometer-scale MNs create micropores in the skin surface, through which microliter quantities of ISF are collected onto plasmonic paper on the patch backing. The plasmonic paper was prepared by immobilizing poly(styrenesulfonate) (PSS) coated gold nanorods (AuNRs) on a thin strip of filter paper using plasmonic calligraphy. Negatively charged PSS was used to bind positively charged rhodamine 6G (R6G), which served as a model compound, and thereby localize R6G on AuNR surface. R6G bound on the AuNR surface was detected and quantified by acquiring SERS spectra from the plasmonic paper MN patch. This approach was used to measure pharmacokinetic profiles of R6G in ISF and serum from rats in vivo. This proof-of-concept study indicates that a plasmonic paper MN patch has the potential to enable on-patch measurement of molecules in ISF for research and future medical applications.

Paper-based optoelectronic noses (OENs) are being developed based on printing of organic and organometallic reagents on hydrophilic substrates that can visualize the odor of volatiles. In this work, we report for the first time the use of nanoparticles for fabrication of novel paper-based OENs, which represent much higher sensitivity and produce simple but discriminant colorimetric signature of volatile metabolomes. This nano-optoelectronic nose (NOEN) system, which is fabricated by dropping of gold and silver nanoparticles (each synthesized by 8 chemical species) on the paper, gives obvious colorimetric signatures for chemicals having individual or combined functional groups. Owning to their ultrasensitivity, these simple devices need very small amounts of analytes. These devices could detect and discriminate 45 volatile organic compounds in 9 chemical families including phenols, alchohols, ketones, aldehydes, amines, acids, esters, arenes, and hydrocarbons. In addition to excellent discrimination ability, this NOEN sensor shows ultrahigh sensitivity such that could determine volatile compounds with detection limits around or lower than 10 ppb. Moreover, it can be combined with multivariate calibration methods for quantitative analysis of a metabolite in a complex mixture.

This paper describes an approach for colorimetric detection of salivary α-amylase, one of the potential biomarkers of autonomic nervous system (ANS) activity, for enabling assessment of fatigue. The ability of α-amylase to cleave α-bonds of polysaccharides is utilized for developing a colorimetric assay. In the proposed approach, 2-chloro-4-nitrophenyl-α-d-maltotrioside as substrate releases a colored byproduct upon cleavage by salivary α-amylase. Introduction of maltose as a noncompetitive inhibitor yields desirable linear responses in the physiologically relevant concentration range (20–500 μg/mL) with a limit of detection (LOD) of 8 μg/mL (in aqueous solution). The concentrations of substrate and noncompetitive inhibitor are subsequently optimized for colorimetric detection of salivary α-amylase. A facile paper-based “strip” assay is proposed for analysis of human saliva samples with marginal interference from saliva components. The proposed assay is rapid, specific, and easy-to-implement for colorimetric detection of salivary α-amylase between 20 and 500 μg/mL. Complementary RGB (red, green, blue components) analysis offers quantitative detection with a LOD of 11 μg/mL. The two assay formats are benchmarked against the Phadebas test, a state of the art method for spectrophotometric detection of α-amylase. The reported paper-based methodology possesses a high potential for estimation of altered ANS responses toward stressors that possibly could find applications in assessment of fatigue and for monitoring onset of fatigue. Nanyang Technological University Accepted version This work is supported by Provost’s office and Institute for Sports Research (ISR), School of Mechanical and Aerospace Engineering, Nanyang Technological University, Singapore.

One of the concerns of parents in the first days of their baby's birth is the baby's risk of jaundice/hyperbilirubinemia. This is because more than 60% of babies are born with jaundice that, if not timely diagnosed and subsequently treated, can lead to serious damage to their health. On the other hand, despite recent progress in sensor technology for clinical applications, the development of easy-to-use, cost-effective, sensitive, specific, and portable diagnostic devices, which use nontoxic and biodegradable materials in their design and fabrication, is still in high demand. Herein we present an easy-to-use, cost-effective, selective, nontoxic, and disposable photoluminescent nanopaper-based assay kit with a smartphone readout for easy diagnosis of neonatal jaundice through visual determination of Bilirubin (BR) in infants' blood samples. The developed BR assay kit comprises highly photoluminescent carbon dot (CD) sensing probes embedded in a bacterial cellulose (BC) nanopaper substrate (CDBN). The photoluminescence (PL) of the developed BR sensor is quenched in the presence of BR as a PL quencher and then selectively recovered upon blue light (λ = 470 nm) exposure, due to conversion of the unconjugated BR to the colorless oxidation products (non-PL quencher) through BR photoisomerization and photooxidation, that subsequently leads to selective PL enhancement of CDBN. The recovered PL intensity of the developed BR assay kit, which was monitored by integrated smartphone camera, was linearly proportional to the concentration of BR in the range of 2-20 mg dL

In this study, a novel photoluminescence material for the detection of tributyltin (TBT) was developed by using a paper-based nanocomposite system. For this purpose, molecularly imprinted polymeric nanoparticles (MIN) were synthesized with mini-emulsion polymerization technique. Graphene quantum dots obtained by the hydrothermal pyrolysis were immobilized to the nanoparticle surface via EDC-NHS coupling. The fabrication of sensing platform for TBT can be divided into two steps that are the preparation of nanocomposite and the applying the nanocomposite onto nitrocellulose membrane. The selectivity constant and association kinetics were calculated to analyze the interaction of TBT with immobilized MINs. The results proved that the developed nanosensor is promising for the determination of TBT with high selectivity and sensitivity reaching a detection limit of 0.23 ppt in seawater. This novel photoluminescent nanosensor has the potential to pave the way for further studies and applications., Recep Üzek thanks to TUBITAK for the given scholarship. We acknowledge the support from European Commission through the Graphene Flagship Core 2 project and from Ministerio de Economıa, Industria y Competitividad (MINECO), Agencia Estatal de Investigacion (AEI) for the project MAT2017-87202-P. The ICN2 is funded by the CERCA Programme/Generalitat de Catalunya. ICN2 is supported by the Severo Ochoa program from Spanish MINECO (Grant No. SEV2017-0706).

Heavy metals are highly toxic at trace levels and their pollution has shown great threat to the environment and public health worldwide where current detection methods require expensive instrumentation and laborious operation, which can only be accomplished in centralized laboratories. Herein, we report a low-cost, paper-based microfluidic analytical device (μPAD) for facile, portable, and disposable monitoring of mercury, lead, chromium, nickel, copper, and iron ions. Triple indicators or ligands that contain ions or molecules are preloaded on the μPADs and upon addition of a metal ion, the colorimetric indicators will elicit color changes observed by the naked eyes. The color features were quantitatively analyzed in a three-dimensional space of red, green, and blue or the RGB-space using digital imaging and color calibration techniques. The sensing platform offers higher accuracy for cross references, and is capable of simultaneous detection and discrimination of different metal ions in even real water samples. It demonstrates great potential for semiquantitative and even qualitative analysis with a sensitivity below the safe limit concentrations, and a controlled error range.

A novel strategy for fabricating the paper-based valves on microfluidic paper-based analytical devices (μPADs) was described to control fluid in a user-friendly way. Initial prototypes of 3D μPADs manipulate the spatial distribution of fluid within the device. The movable paper channel in a different layer could be achieved using the channel's connection or disconnection to realize the valve function using plastic comb binding spines (PCBS). The entire valve manipulation process was similar to a desk calendar that can be flipped over and turned back. It is notable that this kind of PCBS valve can control a fluid in a simple and easy way without the timing setting or any trigger, and this advantage makes it user-friendly for untrained users to carry out the complex and high throughput operations. The reusable plastic comb binding spines greatly reduce the cost of fabricating paper-based valves. To evaluate the performance, the actual samples of Fe (II) and nitrite were successfully analyzed. We hope this method will introduce a new approach to fabrication of paper-based valves on μPADs in the future.

This paper presents a whole-cell biosensor that operates in conjunction with a smartphone-based fluorescence diagnostic system on a paper device to monitor the concentration of gold ions in human urine. The heavy metal-tolerant bacteria Cupriavidus metallidurans was genetically engineered for use as a chassis in a red fluorescent protein (RFP)-based microbial sensor. The biosensor is highly sensitive to gold ions, with a detection limit of 110 nM. The proposed smartphone-based analysis system provides a user-friendly approach to design tools of personal health monitoring for reporting the presence of gold ions in human urine.

The health and well-being of cattle is a significant concern for global agricultural output. In dairy production within low and middle income countries (LMICs), there is a significant biosensing challenge in detecting sexually transmitted infection (STI) pathogens during animal husbandry, due in part to difficulties associated with the limited infrastructure for veterinary medicine. Here we demonstrate low-cost, multiplexed and sample-to-answer paper-origami tests for the detection of three bovine infectious reproductive diseases in semen samples, collected at a test site in rural India. Pathogen DNA from one viral pathogen, Bovine Herpes virus-1 (BoHV-1) and two bacteria (Brucella and Leptospira) was extracted, amplified (using loop-mediated isothermal amplification, LAMP) and detected fluorescently, enabling

As a cost-effective approach for detecting trace amounts of pesticides, filter paper-based SERS sensors have been the subject of intensive research. One of the hurdles to overcome is the difficulty of retaining nanoparticles on the surface of the paper because of the hydrophilic nature of the cellulose fibers in paper. This reduces the sensitivity and reproducibility of paper-based SERS sensors due to the low density of nanoparticles and short retention time of analytes on the paper surface. In this study, filter paper was treated with alkyl ketene dimer (AKD) to modify its property from hydrophilic to hydrophobic. AKD treatment increased the contact angle of the aqueous silver nanoparticle (AgNP) dispersion, which consequently increased the density of AgNPs. The retention time of the analyte was also increased by preventing its rapid absorption into the filter paper. The SERS signal was strongly enhanced by the increased number of SERS hot spots owing to the increased density of AgNPs on a small contact area of the filter surface. The reproducibility and sensitivity of the SERS signal were optimized by controlling the distribution of AgNPs on the surface of the filter paper by adjusting the concentration of the AgNP solution. Using this SERS sensor with a hydrophobicity-modified filter paper, the spot-to-spot variation of the SERS intensity of 25 spots of 4-aminothiophenol was 6.19%, and the limits of detection of thiram and ferbam as test pesticides were measured to be 0.46 nM and 0.49 nM, respectively. These proof-of-concept results indicate that this paper-based SERS sensor can serve for highly sensitive pesticide detection with low cost and easy fabrication.