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      Feasibility of a point-of-care test based on quantum dots with a mobile phone reader for detection of antibody responses

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          Abstract

          We developed a novel and portable fluorescent sensor that integrates a lateral flow assay with a quantum dot (Qdots) label and a mobile phone reader for detection of specific antibodies in human serum. We evaluated the utility of this assay to test for antibodies to the Taenia solium rT24H antigen. It was a retrospective study by examining 112 positive human sera from patients with neurocysticercosis (NCC) including samples from patients with single viable cyst (n = 18), two or more viable cysts (n = 71), and subarachnoid (racemose) cysts (n = 23). These samples were collected from previous study subjects in Lima, Peru under an approved study protocol in Peru. The sera were made anonymous under a protocol approved by the CDC Institutional Review Board. Definitive diagnosis of the subject was established by computed-tomography and/or magnetic resonance imaging. To test the specificity of the assay, we evaluated a panel of serum samples obtained from patients with other infections (n = 24), and serum samples from persons in the United States and Egypt who had not traveled outside their country, and therefore are presumed negative for cysticercosis (n = 128). The assay specificity in the negative panel was 99% (95–100%) while assay sensitivity was 89% (79–95%) in NCC patients with two or more viable cysts. Our assay has performance characteristics similar to those of traditional platforms for the detection of NCC and shows promise as a mobile phone reader-based point-of-care test for antibody detection.

          Author summary

          Point-of-care (POC) assays are important tools in control and elimination of parasitic diseases such as lymphatic filariasis, malaria, and leishmaniasis. Most POC assays use immunochromatographic and lateral flow assay principles with gold nanoparticles as a reporter. Assays based on gold nanoparticles usually provide qualitative or semi-quantitative results and have relatively low sensitivity. However, other reporter alternatives are available, including quantum dots (Qdots), up-converting phosphor nanoparticles, and superparamagnetic particles. We developed a Qdots-based test in a lateral flow assay format with a mobile phone reader to detect antibody responses, using neurocysticercosis (NCC) as a disease model, and found that the performance is similar to the traditional platform for detecting antibody responses in subjects with NCC. The incorporation of the mobile phone reader offers the advantage of portability and adaptability for use in areas where laboratories are not immediately accessible. This novel POC assay with mobile phone reader is a feasible option for antibody response s detection.

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          Most cited references23

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          Proposed diagnostic criteria for neurocysticercosis.

          Neurocysticercosis is the most common helminthic infection of the CNS but its diagnosis remains difficult. Clinical manifestations are nonspecific, most neuroimaging findings are not pathognomonic, and some serologic tests have low sensitivity and specificity. The authors provide diagnostic criteria for neurocysticercosis based on objective clinical, imaging, immunologic, and epidemiologic data. These include four categories of criteria stratified on the basis of their diagnostic strength, including the following: 1) absolute--histologic demonstration of the parasite from biopsy of a brain or spinal cord lesion, cystic lesions showing the scolex on CT or MRI, and direct visualization of subretinal parasites by funduscopic examination; 2) major--lesions highly suggestive of neurocysticercosis on neuroimaging studies, positive serum enzyme-linked immunoelectrotransfer blot for the detection of anticysticercal antibodies, resolution of intracranial cystic lesions after therapy with albendazole or praziquantel, and spontaneous resolution of small single enhancing lesions; 3) minor--lesions compatible with neurocysticercosis on neuroimaging studies, clinical manifestations suggestive of neurocysticercosis, positive CSF enzyme-linked immunosorbent assay for detection of anticysticercal antibodies or cysticercal antigens, and cysticercosis outside the CNS; and 4) epidemiologic--evidence of a household contact with Taenia solium infection, individuals coming from or living in an area where cysticercosis is endemic, and history of frequent travel to disease-endemic areas. Interpretation of these criteria permits two degrees of diagnostic certainty: 1) definitive diagnosis, in patients who have one absolute criterion or in those who have two major plus one minor and one epidemiologic criterion; and 2) probable diagnosis, in patients who have one major plus two minor criteria, in those who have one major plus one minor and one epidemiologic criterion, and in those who have three minor plus one epidemiologic criterion.
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            Point of Care Testing for Infectious Diseases -- Past, Present and Future.

            Point-of-care (POC) diagnostics provide rapid actionable information for patient care at the time and site of encounter with the health care system. The usual platform has been the lateral flow immunoassay. Recently, emerging molecular diagnostics have met requirements for speed, low cost and ease of use for POC applications. A major driver for POC development is the ability to diagnose infectious diseases at sites with limited infrastructure. Potential use in both wealthy and resource-limited settings has fueled an intense effort to build on existing technologies and to generate new technologies for diagnosis of a broad spectrum of infectious diseases.
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              Membrane-based lateral flow immunochromatographic strip with nanoparticles as reporters for detection: A review.

              Membrane-based lateral flow immunochromatographic strip (LFICS) is widely used in various fields because of its simplicity, rapidity (detection within 10min), and low cost. However, early designs of membrane-based LFICS for preliminary screening only provide qualitative ("yes/no" signal) or semi-quantitative results without quantitative information. These designs often suffer from low-signal intensity and poor sensitivity and are only capable of single analyte detection, not simultaneous multiple detections. The performance of existing techniques used for detection using LFICS has been considerably improved by incorporating different kinds of nanoparticles (NPs) as reporters. NPs can serve as alternative labels and improve analytical sensitivity or limit of detection of LFICS because of their unique properties, such as optical absorption, fluorescence spectra, and magnetic properties. The controlled manipulation of NPs allows simultaneous or multiple detections by using membrane-based LFICS. In this review, we discuss how colored (e.g., colloidal gold, carbon, and colloidal selenium NPs), luminescent (e.g., quantum dots, up-converting phosphor NPs, and dye-doped NPs), and magnetic NPs are integrated into membrane-based LFICS for the detection of target analytes. Gold NPs are also featured because of their wide applications. Different types and unique properties of NPs are briefly explained. This review focuses on examples of NP-based LFICS to illustrate novel concepts in various devices with potential applications as screening tools. This review also highlights the superiority of NP-based approaches over existing conventional strategies for clinical analysis, food safety, and environmental monitoring. This paper is concluded by a short section on future research trends regarding NP-based LFICS.
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                Author and article information

                Contributors
                Role: Data curationRole: Formal analysisRole: InvestigationRole: ValidationRole: Writing – original draft
                Role: Writing – review & editing
                Role: ConceptualizationRole: MethodologyRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: MethodologyRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Formal analysisRole: MethodologyRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: ResourcesRole: SupervisionRole: ValidationRole: Writing – original draftRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS Negl Trop Dis
                PLoS Negl Trop Dis
                plos
                plosntds
                PLoS Neglected Tropical Diseases
                Public Library of Science (San Francisco, CA USA )
                1935-2727
                1935-2735
                7 October 2019
                October 2019
                : 13
                : 10
                : e0007746
                Affiliations
                [1 ] Medical College of Georgia, AU/UGA Medical Partnership, Athens, Georgia, United States of America
                [2 ] Division of Parasitic Diseases and Malaria, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America
                [3 ] School of Public Health, Oregon Health & Science University and Portland State University, Portland, Oregon, United States of America
                [4 ] School of Veterinary Medicine, Universidad Nacional Mayor de San Marcos, Salamanca de Monterrico, Lima, Peru
                [5 ] Department of Microbiology and Center for Global Health, Universidad Peruana Cayetano Heredia, Lima, Peru
                [6 ] Cysticercosis Unit, Instituto Nacional de Ciencias Neurologicas, Lima, Peru
                Consejo Nacional de Investigaciones Cientificas y Tecnicas, Fundación Mundo Sano, ARGENTINA
                Author notes

                The authors have declared that no competing interests exist.

                ¶ Membership of the Cysticercosis Working Group in Peru is listed in the Disclaimer section.

                Author information
                https://orcid.org/http://orcid.org/0000-0003-4930-7604
                https://orcid.org/http://orcid.org/0000-0001-7375-5875
                Article
                PNTD-D-19-00524
                10.1371/journal.pntd.0007746
                6797214
                31589612
                8cbe847d-615c-4ae5-ac64-024e6e0e0bcf

                This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

                History
                : 11 July 2019
                : 3 September 2019
                Page count
                Figures: 2, Tables: 2, Pages: 11
                Product
                Funding
                The author(s) received no specific funding for this work.
                Categories
                Research Article
                Engineering and Technology
                Equipment
                Communication Equipment
                Cell Phones
                Research and Analysis Methods
                Imaging Techniques
                Neuroimaging
                Biology and Life Sciences
                Neuroscience
                Neuroimaging
                Biology and Life Sciences
                Immunology
                Immune Response
                Antibody Response
                Medicine and Health Sciences
                Immunology
                Immune Response
                Antibody Response
                Engineering and Technology
                Nanotechnology
                Nanoparticles
                Research and Analysis Methods
                Immunologic Techniques
                Immunoassays
                Enzyme-Linked Immunoassays
                Medicine and Health Sciences
                Diagnostic Medicine
                Physical Sciences
                Chemistry
                Chemical Compounds
                Esters
                Nitrocellulose
                Medicine and Health Sciences
                Parasitic Diseases
                Helminth Infections
                Neurocysticercosis
                Medicine and Health Sciences
                Tropical Diseases
                Neglected Tropical Diseases
                Neurocysticercosis
                Custom metadata
                vor-update-to-uncorrected-proof
                2019-10-17
                All relevant data are within the manuscript and its Supporting Information files.

                Infectious disease & Microbiology
                Infectious disease & Microbiology

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