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      Cytokine and Cancer Biomarkers Detection: The Dawn of Electrochemical Paper-Based Biosensor

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          Abstract

          Although the established ELISA-based sensing platforms have many benefits, the importance of cytokine and cancer biomarkers detection for point-of-care diagnostics has propelled the search for more specific, sensitive, simple, accessible, yet economical sensor. Paper-based biosensor holds promise for future in-situ applications and can provide rapid analysis and data without the need to conduct in a laboratory. Electrochemical detection plays a vital role in interpreting results obtained from qualitative assessment to quantitative determination. In this review, various factors affecting the design of an electrochemical paper-based biosensor are highlighted and discussed in depth. Different detection methods, along with the latest development in utilizing them in cytokine and cancer biomarkers detection, are reviewed. Lastly, the fabrication of portable electrochemical paper-based biosensor is ideal in deliberating positive societal implications in developing countries with limited resources and accessibility to healthcare services.

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          Most cited references84

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          Historical insights into cytokines.

          Cytokines affect nearly every biological process; these include embryonic development, disease pathogenesis, non-specific response to infection, specific response to antigen, changes in cognitive functions and progression of the degenerative processes of aging. In addition, cytokines are part of stem cell differentiation, vaccine efficacy and allograft rejection. This short insight focuses on the milestones in cytokine biology and how the various and often contradictory activities of these small, non-structural proteins affected the fields of inflammation and immunology. Multiple biological properties or pleiotropism is the hallmark of a cytokine. Today, the term "cytokine" encompasses interferons, the interleukins, the chemokine family, mesenchymal growth factors, the tumor necrosis factor family and adipokines. As of this writing, 33 cytokines are called interleukins, but many are part of families of related but distinct gene products. There are certainly over 100 separate genes coding for cytokine-like activities, many with overlapping functions and many still unexplored. Also discussed in this overview are the failures and successes of cytokines as therapeutic targets. A recent advance in the field has been that of differential cytokine production, which can be used to classify human disease as being "autoimmune" or "autoinflammatory" thus impacting on therapeutic interventions.
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            Hypothalamic-pituitary-gut axis dysregulation in irritable bowel syndrome: plasma cytokines as a potential biomarker?

            Irritable bowel syndrome (IBS) is a functional disorder with an etiology that has been linked to both psychological stress and infection. The primary aim of this study was to examine the hypothalamic-pituitary-adrenal axis in patients with IBS and to relate such response to plasma cytokine profiles. A total of 151 subjects, 76 patients and 75 controls, were recruited. The patients with IBS were diagnosed according to Rome II criteria. Forty-nine patients and 48 matched controls had cytokine levels measured, and a subset of 21 patients and 21 controls also underwent a corticotropin-releasing hormone (CRH) stimulation test with plasma levels of adrenocorticotropic hormone (ACTH) and cortisol measured. The remaining 27 patients and 27 controls underwent a dexamethasone (1 mg) challenge. Cortisol and the proinflammatory cytokines interleukin (IL)-6 (together with its soluble receptor) and IL-8 were elevated in all IBS subgroups (diarrhea predominant, constipated, and alternators), although the elevation was most marked in the constipated subgroup. There was no alteration in the anti-inflammatory cytokine IL-10. Following CRH infusion, an exaggerated release of both ACTH and cortisol was observed in patients with IBS. There was a significant correlation between the ACTH response (deltaACTH) and the IL-6 levels. A similar relationship existed between the deltaACTH/deltacortisol ratio and the IL-6 levels. Dexamethasone suppression of cortisol was similar in patients and controls. IBS is characterized by an overactivation of the hypothalamic-pituitary-adrenal axis and a proinflammatory cytokine increase.
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              A low-cost, simple, and rapid fabrication method for paper-based microfluidics using wax screen-printing.

              Wax screen-printing as a low-cost, simple, and rapid method for fabricating paper-based microfluidic devices (µPADs) is reported here. Solid wax was rubbed through a screen onto paper filters. The printed wax was then melted into the paper to form hydrophobic barriers using only a hot plate. We first studied the relationship between the width of a hydrophobic barrier and the width of the original design line. We also optimized the heating temperature and time and determined the resolution of structures fabricated using this technique. The minimum width of hydrophilic channel and hydrophobic barrier is 650 and 1300 µm, respectively. Next, our fabrication method was compared to a photolithographic method using the reaction between bicinchoninic acid (BCA) and Cu(1+) to demonstrate differences in background reactivity. Photolithographically defined channels exhibited a high background while wax printed channels showed a very low background. Finally, the utility of wax screen-printing was demonstrated for the simultaneous determination of glucose and total iron in control human serum samples using an electrochemical method with glucose oxidase and a colorimetric method with 1,10-phenanthroline. This study demonstrates that wax screen-printing is an easy-to-use and inexpensive alternative fabrication method for µPAD, which will be especially useful in developing countries.
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                Author and article information

                Journal
                Sensors (Basel)
                Sensors (Basel)
                sensors
                Sensors (Basel, Switzerland)
                MDPI
                1424-8220
                27 March 2020
                April 2020
                : 20
                : 7
                : 1854
                Affiliations
                School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore 639798, Singapore; songwei.loo@ 123456ntu.edu.sg
                Author notes
                [* ]Correspondence: tspui@ 123456ntu.edu.sg
                Author information
                https://orcid.org/0000-0001-5669-6578
                Article
                sensors-20-01854
                10.3390/s20071854
                7180619
                32230808
                54363fbb-b0b5-4ee3-a0c9-60c2b2259e13
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 05 March 2020
                : 24 March 2020
                Categories
                Review

                Biomedical engineering
                electrochemical detection,paper-based device,biosensor,cytokine,cancer biomarkers,point-of-care device

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