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      Emerging Technologies and Platforms for the Immunodetection of Multiple Biochemical Markers in Osteoarthritis Research and Therapy

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          Abstract

          Biomarkers, especially biochemical markers, are important in osteoarthritis (OA) research, clinical trials, and drug development and have potential for more extensive use in therapeutic monitoring. However, they have not yet had any significant impact on disease diagnosis and follow-up in a clinical context. Nevertheless, the development of immunoassays for the detection and measurement of biochemical markers in OA research and therapy is an active area of research and development. The evaluation of biochemical markers representing low-grade inflammation or extracellular matrix turnover may permit OA prognosis and expedite the development of personalized treatment tailored to fit particular disease severities. However, currently detection methods have failed to overcome specific hurdles such as low biochemical marker concentrations, patient-specific variation, and limited utility of single biochemical markers for definitive characterization of disease status. These challenges require new and innovative approaches for development of detection and quantification systems that incorporate clinically relevant biochemical marker panels. Emerging platforms and technologies that are already on the way to implementation in routine diagnostics and monitoring of other diseases could potentially serve as good technological and strategic examples for better assessment of OA. State-of-the-art technologies such as advanced multiplex assays, enhanced immunoassays, and biosensors ensure simultaneous screening of a range of biochemical marker targets, the expansion of detection limits, low costs, and rapid analysis. This paper explores the implementation of such technologies in OA research and therapy. Application of novel immunoassay-based technologies may shed light on poorly understood mechanisms in disease pathogenesis and lead to the development of clinically relevant biochemical marker panels. More sensitive and specific biochemical marker immunodetection will complement imaging biomarkers and ensure evidence-based comparisons of intervention efficacy. We discuss the challenges hindering the development, testing, and implementation of new OA biochemical marker assays utilizing emerging multiplexing technologies and biosensors.

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          Most cited references168

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          Biomarkers and surrogate endpoints: preferred definitions and conceptual framework.

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            Homogenous 96-Plex PEA Immunoassay Exhibiting High Sensitivity, Specificity, and Excellent Scalability

            Medical research is developing an ever greater need for comprehensive high-quality data generation to realize the promises of personalized health care based on molecular biomarkers. The nucleic acid proximity-based methods proximity ligation and proximity extension assays have, with their dual reporters, shown potential to relieve the shortcomings of antibodies and their inherent cross-reactivity in multiplex protein quantification applications. The aim of the present study was to develop a robust 96-plex immunoassay based on the proximity extension assay (PEA) for improved high throughput detection of protein biomarkers. This was enabled by: (1) a modified design leading to a reduced number of pipetting steps compared to the existing PEA protocol, as well as improved intra-assay precision; (2) a new enzymatic system that uses a hyper-thermostabile enzyme, Pwo, for uniting the two probes allowing for room temperature addition of all reagents and improved the sensitivity; (3) introduction of an inter-plate control and a new normalization procedure leading to improved inter-assay precision (reproducibility). The multiplex proximity extension assay was found to perform well in complex samples, such as serum and plasma, and also in xenografted mice and resuspended dried blood spots, consuming only 1 µL sample per test. All-in-all, the development of the current multiplex technique is a step toward robust high throughput protein marker discovery and research.
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              The epidemiology and impact of pain in osteoarthritis.

              T Neogi (2013)
              Osteoarthritis (OA) is the most common form of arthritis and a leading cause of disability worldwide, largely due to pain, the primary symptom of the disease. The pain experience in knee OA in particular is well-recognized as typically transitioning from intermittent weight-bearing pain to a more persistent, chronic pain. Methods to validly assess pain in OA studies have been developed to address the complex nature of the pain experience. The etiology of pain in OA is recognized to be multifactorial, with both intra-articular and extra-articular risk factors. Nonetheless, greater insights are needed into pain mechanisms in OA to enable rational mechanism-based management of pain. Consequences of pain related to OA contribute to a substantial socioeconomic burden. Copyright © 2013 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
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                Author and article information

                Contributors
                Journal
                Front Med (Lausanne)
                Front Med (Lausanne)
                Front. Med.
                Frontiers in Medicine
                Frontiers Media S.A.
                2296-858X
                21 October 2020
                2020
                : 7
                : 572977
                Affiliations
                [1] 1Department of Regenerative Medicine, State Research Institute Centre for Innovative Medicine , Vilnius, Lithuania
                [2] 2Department of Experimental, Preventive and Clinical Medicine, State Research Institute Centre for Innovative Medicine , Vilnius, Lithuania
                [3] 3Immunoscience, Nordic Bioscience A/S , Herlev, Denmark
                [4] 4Microelectronics Research Unit, Faculty of Information Technology and Electrical Engineering, University of Oulu , Oulu, Finland
                [5] 5Laboratory of Cartilage Biology, Institute of Dental Sciences, Hebrew University of Jerusalem , Jerusalem, Israel
                [6] 6Department of Radiology, Veterans Affairs Boston Healthcare System, Boston University School of Medicine , Boston, MA, United States
                [7] 7Research Unit of Medical Imaging, Physics and Technology, Faculty of Medicine, University of Oulu , Oulu, Finland
                [8] 8Departments of Orthopedics, Rheumatology and Clinical Immunology, University Medical Center Utrecht , Utrecht, Netherlands
                [9] 9Centre for Sport, Exercise and Osteoarthritis Versus Arthritis, Queen's Medical Centre , Nottingham, United Kingdom
                Author notes

                Edited by: Peter Mandl, Medical University of Vienna, Austria

                Reviewed by: Cong-Qiu Chu, Oregon Health and Science University, United States; Garifallia Sakellariou, University of Pavia, Italy; Virginia Kraus, Duke University, United States

                This article was submitted to Rheumatology, a section of the journal Frontiers in Medicine

                Article
                10.3389/fmed.2020.572977
                7609858
                d4a73e18-482f-4bc3-9d5d-4669ebe5f62a
                Copyright © 2020 Bernotiene, Bagdonas, Kirdaite, Bernotas, Kalvaityte, Uzieliene, Thudium, Hannula, Lorite, Dvir-Ginzberg, Guermazi and Mobasheri.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 15 June 2020
                : 31 August 2020
                Page count
                Figures: 1, Tables: 4, Equations: 0, References: 169, Pages: 22, Words: 17717
                Funding
                Funded by: European Commission 10.13039/501100000780
                Categories
                Medicine
                Review

                osteoarthritis (oa),biochemical marker,multiplexing technologies,biosensors,nanotechnology,immunodetection,magnetic resonance imaging (mri)

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