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      Non-invasive detection of COVID-19 using a microfluidic-based colorimetric sensor array sensitive to urinary metabolites

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          Abstract

          A colorimetric sensor array designed on a paper substrate with a microfluidic structure has been developed. This array is capable of detecting COVID-19 disease by tracking metabolites of urine samples. In order to determine minor metabolic changes, various colorimetric receptors consisting of gold and silver nanoparticles, metalloporphyrins, metal ion complexes, and pH-sensitive indicators are used in the array structure. By injecting a small volume of the urine sample, the color pattern of the sensor changes after 7 min, which can be observed visually. The color changes of the receptors (recorded by a scanner) are subsequently calculated by image analysis software and displayed as a color difference map. This study has been performed on 130 volunteers, including 60 patients infected by COVID-19, 55 healthy controls, and 15 cured individuals. The resulting array provides a fingerprint response for each category due to the differences in the metabolic profile of the urine sample. The principal component analysis-discriminant analysis confirms that the assay sensitivity to the correctly detected patient, healthy, and cured participants is equal to 73.3%, 74.5%, and 66.6%, respectively. Apart from COVID-19, other diseases such as chronic kidney disease, liver disorder, and diabetes may be detectable by the proposed sensor. However, this performance of the sensor must be tested in the studies with a larger sample size. These results show the possible feasibility of the sensor as a suitable alternative to costly and time-consuming standard methods for rapid detection and control of viral and bacterial infectious diseases and metabolic disorders.

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          The online version contains supplementary material available at 10.1007/s00604-022-05423-1.

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          Most cited references25

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          Proteomic and Metabolomic Characterization of COVID-19 Patient Sera

          Summary Early detection and effective treatment of severe COVID-19 patients remain major challenges. Here, we performed proteomic and metabolomic profiling of sera from 46 COVID-19 and 53 control individuals. We then trained a machine learning model using proteomic and metabolomic measurements from a training cohort of 18 non-severe and 13 severe patients. The model was validated using ten independent patients, seven of which were correctly classified. Targeted proteomics and metabolomics assays were employed to further validate this molecular classifier in a second test cohort of 19 new COVID-19 patients, leading to 16 correct assignments. We identified molecular changes in the sera of COVID-19 patients compared to other groups implicating dysregulation of macrophage, platelet degranulation and complement system pathways, and massive metabolic suppression. This study revealed characteristic protein and metabolite changes in the sera of severe COVID-19 patients, which might be used in selection of potential blood biomarkers for severity evaluation.
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            The Human Urine Metabolome

            Urine has long been a “favored” biofluid among metabolomics researchers. It is sterile, easy-to-obtain in large volumes, largely free from interfering proteins or lipids and chemically complex. However, this chemical complexity has also made urine a particularly difficult substrate to fully understand. As a biological waste material, urine typically contains metabolic breakdown products from a wide range of foods, drinks, drugs, environmental contaminants, endogenous waste metabolites and bacterial by-products. Many of these compounds are poorly characterized and poorly understood. In an effort to improve our understanding of this biofluid we have undertaken a comprehensive, quantitative, metabolome-wide characterization of human urine. This involved both computer-aided literature mining and comprehensive, quantitative experimental assessment/validation. The experimental portion employed NMR spectroscopy, gas chromatography mass spectrometry (GC-MS), direct flow injection mass spectrometry (DFI/LC-MS/MS), inductively coupled plasma mass spectrometry (ICP-MS) and high performance liquid chromatography (HPLC) experiments performed on multiple human urine samples. This multi-platform metabolomic analysis allowed us to identify 445 and quantify 378 unique urine metabolites or metabolite species. The different analytical platforms were able to identify (quantify) a total of: 209 (209) by NMR, 179 (85) by GC-MS, 127 (127) by DFI/LC-MS/MS, 40 (40) by ICP-MS and 10 (10) by HPLC. Our use of multiple metabolomics platforms and technologies allowed us to identify several previously unknown urine metabolites and to substantially enhance the level of metabolome coverage. It also allowed us to critically assess the relative strengths and weaknesses of different platforms or technologies. The literature review led to the identification and annotation of another 2206 urinary compounds and was used to help guide the subsequent experimental studies. An online database containing the complete set of 2651 confirmed human urine metabolite species, their structures (3079 in total), concentrations, related literature references and links to their known disease associations are freely available at http://www.urinemetabolome.ca.
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              Optical sensor arrays for chemical sensing: the optoelectronic nose.

              A comprehensive review is presented on the development and state of the art of colorimetric and fluorometric sensor arrays. Optical arrays based on chemoresponsive colorants (dyes and nanoporous pigments) probe the chemical reactivity of analytes, rather than their physical properties. This provides a high dimensionality to chemical sensing that permits high sensitivity (often down to ppb levels), impressive discrimination among very similar analytes and exquisite fingerprinting of extremely similar mixtures over a wide range of analyte types, both in the gas and liquid phases.
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                Author and article information

                Contributors
                h.bagheri@bmsu.ac.ir
                Journal
                Mikrochim Acta
                Mikrochim Acta
                Mikrochimica Acta
                Springer Vienna (Vienna )
                0026-3672
                1436-5073
                5 August 2022
                2022
                : 189
                : 9
                : 316
                Affiliations
                [1 ]GRID grid.411521.2, ISNI 0000 0000 9975 294X, Chemical Injuries Research Center, Systems Biology and Poisonings Institute, , Baqiyatallah University of Medical Sciences, ; Tehran, Iran
                [2 ]GRID grid.412504.6, ISNI 0000 0004 0612 5699, Department of Mechanical Engineering, , Shohadaye Hoveizeh Campus of Technology, Shahid Chamran University of Ahvaz, ; Dashte Azadegan, Khuzestan, Iran
                [3 ]GRID grid.412573.6, ISNI 0000 0001 0745 1259, Department of Chemistry, College of Sciences, , Shiraz University, ; Shiraz, Iran
                Author information
                http://orcid.org/0000-0003-2895-6189
                Article
                5423
                10.1007/s00604-022-05423-1
                9361914
                35927498
                0b0616dc-133a-4432-bcc8-cab1e1ef359b
                © The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature 2022, Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

                This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

                History
                : 24 March 2022
                : 15 July 2022
                Categories
                Original Paper
                Custom metadata
                © Springer-Verlag GmbH Austria, part of Springer Nature 2022

                Analytical chemistry
                colorimetric detection,digital color imaging,paper-based device,nanoparticle receptors,pattern recognition analysis,sensor array,viral infection

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