title: Multiplexed Anti-Toxoplasma IgG, IgM, and IgA Assay on Plasmonic Gold Chips: towards Making Mass Screening Possible with Dye Test Precision.
abstract: Toxoplasmosis is an infection caused by the protozoan parasite Toxoplasma gondii that can lead to severe sequelae in the fetus during pregnancy. Definitive serologic diagnosis of the infection during gestation is made mostly by detecting T. gondii-specific antibodies, including IgG and IgM, individually in a single serum sample by using commercially available kits. The IgA test is used by some laboratories as an additional marker of acute infection. Most of the commercial tests have failed to reach 100% correlation with the reference method, the Sabin-Feldman dye test for the detection of Toxoplasma IgG antibodies. For Toxoplasma IgM and IgA antibodies, there is no reference method and their evaluation is done by comparing the results of one assay to those of another. There is a need for multiplexed assay platforms, as the serological diagnosis of T. gondii infection does not rely on the detection of a single Ig subtype. Here we describe the development of a plasmonic gold chip with vast fluorescence enhancement in the near-infrared region for simultaneous detection of IgG, IgM, and IgA antibodies against T. gondii in an ∼1-μl serum or whole-blood sample. When 168 samples were tested on this platform, IgG antibody detection sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were all 100%. IgM antibody detection achieved 97.6% sensitivity and 96.9% specificity with a 90.9% PPV and a 99.2% NPV. Thus, the nanoscience-based plasmonic gold platform enables a high-performance, low-cost, multiplexed assay requiring ultrasmall blood volumes, paving the way for the implementation of universal screening for toxoplasmosis infection during gestation.
authors.affiliation: Department of Chemistry, Stanford University, Stanford, California, USA.
authors.forename: Xiaoyang
authors.initials: X
authors.lastname: Li
authors.affiliation: Division of Infectious Diseases, Stanford University, Stanford, California, USA.|Palo Alto Medical Foundation Toxoplasma Serology Laboratory, Palo Alto, California, USA.|INSERM, U1065, Centre Méditerranéen de Médecine Moléculaire, C3M, Toxines Microbiennes dans la Relation Hôte Pathogènes-Université de Nice Sophia Antipolis, Faculté de Médecine, Nice, France.|Parasitologie-Mycologie, Centre Hospitalier Universitaire l'Archet, Nice, France.
authors.forename: Christelle
authors.initials: C
authors.lastname: Pomares
authors.affiliation: Virologie, Centre Hospitalier Universitaire l'Archet, Nice, France.|INSERM, U1065, Centre Méditerranéen de Médecine Moléculaire, C3M, Toxines Microbiennes dans la Relation Hôte Pathogènes-Université de Nice Sophia Antipolis, Faculté de Médecine, Nice, France.
authors.forename: Géraldine
authors.initials: G
authors.lastname: Gonfrier
authors.affiliation: Department of Chemistry, Stanford University, Stanford, California, USA.
authors.forename: Byumseok
authors.initials: B
authors.lastname: Koh
authors.affiliation: Department of Chemistry, Stanford University, Stanford, California, USA.
authors.forename: Shoujun
authors.initials: S
authors.lastname: Zhu
authors.affiliation: Department of Chemistry, Stanford University, Stanford, California, USA.
authors.forename: Ming
authors.initials: M
authors.lastname: Gong
authors.affiliation: Division of Infectious Diseases, Stanford University, Stanford, California, USA hdai@stanford.edu gilberto@stanford.edu.|Palo Alto Medical Foundation Toxoplasma Serology Laboratory, Palo Alto, California, USA.
authors.forename: Jose G
authors.initials: JG
authors.lastname: Montoya
authors.affiliation: Department of Chemistry, Stanford University, Stanford, California, USA hdai@stanford.edu gilberto@stanford.edu.
authors.forename: Hongjie
authors.initials: H
authors.lastname: Dai
mesh_terms: D000913:Antibodies, Protozoan / Q000097:blood*; D006801:Humans; D007118:Immunoassay / Q000379:methods*; D007070:Immunoglobulin A / Q000097:blood*; D007074:Immunoglobulin G / Q000097:blood*; D007075:Immunoglobulin M / Q000097:blood*; D008403:Mass Screening / Q000379:methods*; D012680:Sensitivity and Specificity; D014122:Toxoplasma / Q000276:immunology; D014123:Toxoplasmosis / Q000175:diagnosis*
chemical_list: D000913:Antibodies, Protozoan; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007075:Immunoglobulin M