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Journal ArticleDOI: 10.1016/J.SAA.2020.119285

Paper microfluidic device using carbon dots to detect glucose and lactate in saliva samples.

Abstract: Bioanalyses are commonly performed with blood or serum samples. However, these analyses often require invasive and painful blood collection using a needle or finger pricking. Saliva is an alternative and very attractive biological medium for performing clinical analyses, since it contains many types of clinically relevant biomarkers and compounds. Its collection is straightforward and can be achieved in a non-invasive and stress-free way. However, the analytes are frequently present at low concentrations, while the viscosity of whole saliva hinders its analysis using paper devices, especially those with multiple layers (3D-μPADs). This work explores the use of a simple, fast, and low-cost saliva sample pretreatment using a cotton-paper-syringe filtration system, allowing the analysis of saliva samples using multilayer paper devices. The proposed methodology employs the oxidation of glucose and lactate, catalyzed by specific oxidase enzymes, producing hydrogen peroxide. The detection is based on the fluorescence quenching of carbon dots in the presence of hydrogen peroxidase. The concentrations of the analytes showed good linear correlations with the fluorescence quenching, with LODs of 2.60 × 10−6 and 8.14 × 10−7 mol L−1 for glucose and lactate, respectively. The proposed method presented satisfactory intra-day and inter-day repeatabilities, with %RSD values in the range 3.82–6.61%. The enzymatic systems proved to be specific for the analytes and the matrix had no significant influence on the glucose and lactate determinations. The proposed methodology was successfully applied to saliva and serum samples and was validated using certified material.

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Open accessPosted ContentDOI: 10.1101/2021.07.06.21260080
Cecile Frampas1, Katie Longman1, Matt Spick1, Holly M. Lewis1  +11 moreInstitutions (3)
07 Jul 2021-medRxiv
Abstract: Background The COVID-19 pandemic is likely to represent an ongoing global health issue given the potential for vaccine escape and the low likelihood of eliminating all reservoirs of the disease. Whilst diagnostic testing has progressed at pace, there is an unmet clinical need to develop tests that are prognostic, to triage the high volumes of patients arriving in hospital settings. Recent research has shown that serum metabolomics has potential for prognosis of disease progression. 1 In a hospital setting, collection of saliva samples is more convenient for both staff and patients, and therefore offers an alternative sampling matrix to serum. We demonstrate here for the first time that saliva metabolomics can reveal COVID-19 severity. Methods 88 saliva samples were collected from hospitalised patients with clinical suspicion of COVID-19, alongside clinical metadata. COVID-19 diagnosis was confirmed using RT-PCR testing. COVID severity was classified using clinical descriptors first proposed by SR Knight et al. Metabolites were extracted from saliva samples and analysed using liquid chromatography mass spectrometry. Results In this work, positive percent agreement of 1.00 between a PLS-DA metabolomics model and the clinical diagnosis of COVID severity was achieved. The negative percent agreement with the clinical severity diagnosis was also 1.00, for overall percent agreement of 1.00. Conclusions This research demonstrates that liquid chromatography-mass spectrometry can identify salivary biomarkers capable of separating high severity COVID-19 patients from low severity COVID-19 patients in a small cohort study.

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2 Citations


Journal ArticleDOI: 10.1016/J.MICROC.2021.106506
Abstract: Lab-on-a-chip (LOC) devices have revolutionized the metabolic detection field by bringing together the advantages of biosensors and microfluidics in a single chip. Saliva, which contains a variety of biomarkers, has recently been recognized as a non-invasive biofluidic alternative for many diagnostic purposes. Hence, the application of LOCs for saliva analysis can be a promising diagnostic technique for a wide range of medical situations and diseases. Herein we present a review on the LOCs applied so far for diseases detection using saliva and future horizons. In this regard, after a brief introduction of LOC and saliva, a list of novel LOCs designed or used for the detection of different bacteria and viruses, cytokines, metabolites, kidney related diseases, prostate cancer and oral diseases along with their pros and cons is provided. We are also going to report how these advancements could help with the current pandemic.

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1 Citations


Journal ArticleDOI: 10.1007/S10404-021-02476-1
Zeji Hao1, Hongyu Chen1, Xin Shi1, Wei Tan1  +1 moreInstitutions (1)
Abstract: Paper-based microfluidic analytical devices (μPADs) have shown great potential in the field of analysis due to their advantages of rapid analysis, environmental friendliness and the ability to realize the flow of fluid without external power. Saliva is an emerging biofluid which is used in diseases diagnostic and screening for the easy collection and the reflection of the physiological state. This review focuses on the fabrication methods for two-dimensional (2D) and three-dimensional (3D) μPADs and their applications on the saliva analysis. In the first part, the flow mechanism in μPADs is discussed. The second part mainly introduces the fabrication methods for the μPADs and compares the different methods. The third part presents the application of μPADs in the detection of biomarkers such as nitrite, glucose, and thiocyanate in saliva. Finally, the research directions of saliva analysis are discussed in the conclusion. There have been a lot of researches on μPADs, but the fabrication methods and applications need to be further studied to meet the commercial needs.

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Open accessJournal ArticleDOI: 10.3390/BIOS11120482
27 Nov 2021-Biosensors
Abstract: A point-of-care (POC) can be defined as an in vitro diagnostic test that can provide results within minutes. It has gained enormous attention as a promising tool for biomarkers detection and diagnosis, as well as for screening of chronic noncommunicable diseases such as diabetes mellitus. Diabetes mellitus type 2 is one of the metabolic disorders that has grown exponentially in recent years, becoming one of the greatest challenges to health systems. Early detection and accurate diagnosis of this disorder are essential to provide adequate treatments. However, efforts to reduce incidence should remain not only in these stages but in developing continuous monitoring strategies. Diabetes-monitoring tools must be accessible and affordable; thus, POC platforms are attractive, especially paper-based ones. Paper-based POCs are simple and portable, can use different matrixes, do not require highly trained staff, and are less expensive than other platforms. These advantages enhance the viability of its application in low-income countries and hard-to-reach zones. This review aims to present a critical summary of the main components required to create a sensitive and affordable enzymatic paper-based POC, as well as an oriented analysis to highlight the main limitations and challenges of current POC devices for diabetes type 2 monitoring and future research opportunities in the field.

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Open accessPosted ContentDOI: 10.1101/2021.09.23.461386
24 Sep 2021-bioRxiv
Abstract: Diabetes, a chronic condition, is one of the prevalent afflictions of the 21st century, and if left unchecked, this ailment could lead to severe life-threatening complications. A widely accepted methodology for monitoring diabetes is the estimation of the glucose and ketone contents in the body-fluids, viz. blood, urine, etc. Additionally, certain conditions such as starvation, and following a protein rich diet (e.g., keto-diet) could also lead to significant changes in the ketone content, thereby resulting in false-positive diagnosis. Hence, a precise, portable, and on-demand procedure for the rapid and combined estimation of glucose and ketone in the bodily-fluids is of utmost importance. To that end, paper-based analytical devices (PADs) are promising tools, owing to their multitudinous advantages, and compatibility with biofluids. Although, numerous researchers have contributed substantially in the fundamental investigation, design, and fabrication of PADs for various applications, a combined platform capable of rapid, accurate and on-demand glucose and ketone detection, that is easy to fabricate, is still relatively unexplored. Moreover, the flow dynamics of an analyte, in combination with enzyme-catalysed (for glucose) and uncatalyzed reactions (for ketone), within a porous paper matrix is also vaguely understood. Herein, we present a facile laser-printing based fabrication of colorimetric sensors on a filter paper, for rapid, and non-invasive estimation of glucose and ketone contents in urine. The urine sample, upon being deposited in a particular expanse, is wicked through the paper matrix, and reacts with specific reagents in the designated zone(s), giving rise to a final color, concomitant with the glucose or ketone content in the sample. The device design enables the liquid to be wicked into the porous matrix in a way that would concentrate the colored product in a dedicated detection zone, thereby augmenting the feasibility for accurate colorimetric detection. Furthermore, we present for the first time, a detailed dynamic model of the flow-field in a variable cross-section paper device using the Richards equation, while also considering the species transport and reaction kinetics within the porous media. The results of the numerical simulation agree well with those observed experimentally, thereby validating the present model. Finally, we also developed a web and desktop-based application that would enable the user to upload the images of the colored zones to provide an accurate estimate of the glucose and ketone content in the sample. We believe that our model, in combination with the proposed fabrication methodology, and the in-house developed app., would enable rapid and reliable fabrication of PADs for various fundamental investigations, and applications pertaining to affordable health-care monitoring. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=59 SRC="FIGDIR/small/461386v1_ufig1.gif" ALT="Figure 1"> View larger version (28K): org.highwire.dtl.DTLVardef@2d514forg.highwire.dtl.DTLVardef@13547c9org.highwire.dtl.DTLVardef@fc08d3org.highwire.dtl.DTLVardef@a76382_HPS_FORMAT_FIGEXP M_FIG C_FIG

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Open accessJournal ArticleDOI: 10.1002/ANIE.200603817
12 Feb 2007-Angewandte Chemie
Abstract: This communication describes a simple method for patterning paper to create well-defined, millimeter-sized channels, comprising hydrophilic paper bounded by hydrophobic polymer. We believe that this type of patterned paper will become the basis for low-cost, portable, and technically simple multiplexed bioassays. We demonstrate this capability by the simultaneous detection of glucose and protein in 5 μL of urine. The assay system is small, disposable, easy to use (and carry), and requires no external equipment, reagents, or power sources. We believe this kind of system is attractive for uses in less-industrialized countries, in the field, or as an inexpensive alternative to more advanced technologies already used in clinical settings.[1-4] The analysis of biological fluids is necessary for monitoring the health of populations,[2] but these measurements are difficult to implement in remote regions such as those found in less-industrialized countries, in emergency situations, or in home health-care settings.[3] Conventional laboratory instruments provide quantitative measurements of biological samples, but they are unsuitable for these situations since they are large, expensive, and require trained personnel and considerable volumes of biological samples.[2] Other bioassay platforms provide alternatives to more expensive instruments,[5-7] but the need remains for a platform that uses small volumes of sample and that is sufficiently inexpensive to be used widely for measuring samples from large populations. We believe that paper may serve as a particularly convenient platform for running bioassays in the remote situations locations. As a prototype for a mthod we believe to be particularly promosing, we patterned photoresist onto chromatography paper to form defined areas of hydrophilic paper separated by hydrophobic lines or “walls”; these patterns provide spatial control of biological fluids and enable fluid transport, without pumping, due to capillary action in the millimeter-sized channels produced. This method for patterning paper makes it possible to run multiple diagnostic assays on one strip of paper, while still using only small volumes of a single sample. In a fully developed technology, patterned photoresist would be replaced by an appropriate printing technology, but patterning paper with photoresist is: i) convenient for prototyping these devices, and ii) a useful new micropatterning technology in its own right. We patterned chromatography paper with SU-8 2010 photoresist as shown in Figure 1a and as described below: we soaked a 7.5-cm diameter piece of chromatography paper in 2 mL of SU-8 2010 for 30 s, spun it at 2000 rpm for 30 s, and then baked it at 95 °C for 5 min to remove the cyclopentanone in the SU-8 formula. We then exposed the photoresist and paper to 405 nm UV light (50 mW/cm2) for 10 s through a photo-mask (CAD/Art Services, Inc.) that was aligned using a mask aligner (OL-2 Mask Aligner, AB-M, Inc). After exposure, we baked the paper a second time at 95 °C for 5 min to cross-link the exposed portions of the resist. The unpolymerized photoresist was removed by soaking the paper in propylene glycol monomethyl ether acetate (PGMEA) (5 min), and by washing the pattern with propan-2-ol (3 × 10 mL). The paper was more hydrophobic after it was patterned, presumably due to residual resist bound to the paper, so we exposed the entire surface to an oxygen plasma for 10 s at 600 millitorr (SPI Plasma-Prep II, Structure Probe, Inc) to increase the hydrophilicity of the paper (Figures 2a and 2b). Figure 1 Chromatography paper patterned with photoresist. The darker lines are cured photoresist; the lighter areas are unexposed paper. (a) Patterned paper after absorbing 5 μL of Waterman red ink by capillary action. The central channel absorbs the sample ... Figure 2 Assays contaminated with (a) dirt, (b) plant pollen, and (c) graphite powder. The pictures were taken before and after running an artificial urine solution that contained 550 mM glucose and 75 μM BSA. The particulates do not move up the channels ... The patterned paper can be derivatized for biological assays by adding appropriate reagents to the test areas (Figures 1b and ​and2b).2b). In this communication, we demonstrate the method by detecting glucose and protein,[8] but the surface should be suitable for measuring many other analytes as well.[7] The glucose assay is based on the enzymatic oxidation of iodide to iodine,[9] where a color change from clear to brown is associated with the presence of glucose.[10] The protein assay is based on the color change of tetrabromophenol blue (TBPB) when it ionizes and binds to proteins;[11] a positive result in this case is indicated by a color change from yellow to blue. For the glucose assay, we spotted 0.3 μL of a 0.6 M solution of potassium iodide, followed by 0.3 μL of a 1:5 horseradish peroxidase/glucose oxidase solution (15 units of protein per mL of solution). For the protein assay, we spotted 0.3 μL of a 250-mM citrate buffer (pH 1.8) in a well separate from the glucose assay, and then layered 0.3 μL of a 3.3 mM solution of tetrabromophenol blue (TBPB) in 95% ethanol over the citrate buffer. The spotted reagents were allowed to air dry at room temperature. This pre-loaded paper gave consistent results for the protein assay regardless of storage temperature and time (when stored for 15 d both at 0 °C and at 23 °C, wrapped in aluminum foil). The glucose assay was sensitive to storage conditions, and showed decreased signal for assays run 24 h after spotting the reagents (when stored at 23 °C); when stored at 0 °C, however, the glucose assay was as sensitive after day 15 as it was on day 1. We measured artificial samples of glucose and protein in clinically relevant ranges (2.5-50 mM for glucose and 0.38-7.5 μM for bovine serum albumin (BSA))[12, 13] by dipping the bottom of each test strip in 5 μL of a pre-made test solution (Figure 2d). The fluid filled the entire pattern within ca. one minute, but the assays required 10-11 min for the paper to dry and for the color to fully develop.[14] In all cases, we observed color changes corresponding roughly in intensity to the amount of glucose and protein in the test samples, where the lowest concentrations define the lower limits to which these assays can be used (Figure 2e). For comparison, commercially-available dipsticks detect glucose at concentrations as low as 5 mM[7, 9] and protein as low as 0.75 μM;[6, 15] these limits indicate that these paper-based assays are comparable in sensitivity to commercial dipstick assays. Our assay format also allows for the measurement of multiple analytes. This paper-based assay is suitable for measuring multiple samples in parallel and in a relatively short period of time. For example, in one trial, one researcher was able to run 20 different samples (all with 550 mM glucose and 75 μM BSA) within 7.5 min (followed by another 10.5 min for the color to fully develop). An 18-min assay of this type—one capable of measuring two analytes in 20 different sample—may be efficient enough to use in high-throughput screens of larger sample pools. In the field, samples will not be measured under sterile conditions, and dust and dirt may contaminate the assays. The combination of paper and capillary action provides a mechanism for separating particulates from a biological fluid. As a demonstration, we purposely contaminated the artificial urine samples with quantities of dirt, plant pollen, and graphite powder at levels higher than we might expect to see in the samples in the field. These particulates do not move up the channels under the action of capillary wicking, and do not interfere with the assay (Figure 3). Paper strips have been used in biomedical assays for decades because they offer an inexpensive platform for colorimetric chemical testing.[1] Patterned paper has characteristics that lead to miniaturized assays that run by capillary action (e.g., without external pumping), with small volumes of fluids. These methods suggest a path for the development of simple, inexpensive, and portable diagnostic assays that may be useful in remote settings, and in particular, in less-industrialized countries where simple assays are becoming increasingly important for detecting disease and monitoring health,[16, 17], for environmental monitoring, in veterinary and agricultural practice and for other applications.

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Topics: Fluid transport (55%)

2,261 Citations


Journal ArticleDOI: 10.1021/AC9013989
Abstract: Microfluidic paper-based analytical devices (μPADs) are a new class of point-of-care diagnostic devices that are inexpensive, easy to use, and designed specifically for use in developing countries. (To listen to a podcast about this feature, please go to the Analytical Chemistry multimedia page at pubs.acs.org/page/ancham/audio/index.html.)

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2,171 Citations


Journal ArticleDOI: 10.1021/AC9007573
Abstract: We report the first demonstration of electrochemical detection for paper-based microfluidic devices. Photolithography was used to make microfluidic channels on filter paper, and screen-printing technology was used to fabricate electrodes on the paper-based microfluidic devices. Screen-printed electrodes on paper were characterized using cyclic voltammetry to demonstrate the basic electrochemical performance of the system. The utility of our devices was then demonstrated with the determination of glucose, lactate, and uric acid in biological samples using oxidase enzyme (glucose oxidase, lactate oxidase, and uricase, respectively) reactions. Oxidase enzyme reactions produce H2O2 while decomposing their respective substrates, and therefore a single electrode type is needed for detection of multiple species. Selectivity of the working electrode for H2O2 was improved using Prussian Blue as a redox mediator. The determination of glucose, lactate, and uric acid in control serum samples was performed using chron...

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Topics: Glucose oxidase (58%), Cyclic voltammetry (53%), Working electrode (53%) ... read more

895 Citations



Open accessBook
15 Jan 1996-
Abstract: Tietz fundamentals of clinical chemistry , Tietz fundamentals of clinical chemistry , کتابخانه مرکزی دانشگاه علوم پزشکی تهران

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679 Citations