title: Thermal Contrast Amplification Reader Yielding 8-Fold Analytical Improvement for Disease Detection with Lateral Flow Assays.
abstract: There is an increasing need for highly sensitive and quantitative diagnostics at the point-of-care. The lateral flow immunoassay (LFA) is one of the most widely used point-of-care diagnostic tests; however, LFAs generally suffer from low sensitivity and lack of quantification. To overcome these limitations, thermal contrast amplification (TCA) is a new method that is based on the laser excitation of gold nanoparticles (GNPs), the most commonly used visual signature, to evoke a thermal signature. To facilitate the clinical translation of the TCA technology, we present the development of a TCA reader, a platform technology that significantly improves the limit of detection and provides quantification of disease antigens in LFAs. This TCA reader provides enhanced sensitivity over visual detection by the human eye or by a colorimetric reader (e.g., BD Veritor System Reader). More specifically, the TCA reader demonstrated up to an 8-fold enhanced analytical sensitivity and quantification among LFAs for influenza, malaria, and Clostridium difficile. Systematic characterization of the laser, infrared camera, and other components of the reader and their integration into a working reader instrument are described. The development of the TCA reader enables simple, highly sensitive quantification of LFAs at the point-of-care.
authors.affiliation: Department of Mechanical Engineering, University of Minnesota - Twin Cities , Minneapolis, Minnesota 55455, United States.
authors.forename: Yiru
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Mechanical Engineering, University of Minnesota - Twin Cities , Minneapolis, Minnesota 55455, United States.
authors.forename: Zhenpeng
authors.initials: Z
authors.lastname: Qin
authors.affiliation: Infectious Diseases and International Medicine, Department of Medicine, University of Minnesota - Twin Cities , Minneapolis, Minnesota 55455, United States.
authors.forename: David R
authors.initials: DR
authors.lastname: Boulware
authors.affiliation: Division of Clinical Microbiology, Mayo Clinic , Rochester, Minnesota 55905, United States.
authors.forename: Bobbi S
authors.initials: BS
authors.lastname: Pritt
authors.affiliation: Division of Clinical Microbiology, Mayo Clinic , Rochester, Minnesota 55905, United States.
authors.forename: Lynne M
authors.initials: LM
authors.lastname: Sloan
authors.affiliation: Foundation of New Innovative Diagnostics , Geneva, 1202, Switzerland.
authors.forename: Iveth J
authors.initials: IJ
authors.lastname: González
authors.affiliation: Independent Consultant, 5 Voie de Gex, Geneva, 1202, Switzerland.
authors.forename: David
authors.initials: D
authors.lastname: Bell
authors.forename: Roxanne R
authors.initials: RR
authors.lastname: Rees-Channer
authors.forename: Peter
authors.initials: P
authors.lastname: Chiodini
authors.affiliation: Department of Chemistry, University of Toronto , Toronto, Ontario M5S 3H6, Canada.
authors.forename: Warren C W
authors.initials: WC
authors.lastname: Chan
authors.affiliation: Department of Mechanical Engineering, University of Minnesota - Twin Cities , Minneapolis, Minnesota 55455, United States.
authors.forename: John C
authors.initials: JC
authors.lastname: Bischof
mesh_terms: D016360:Clostridioides difficile / Q000302:isolation & purification*; D006046:Gold / Q000737:chemistry; D006801:Humans; D007118:Immunoassay / Q000379:methods*; D007251:Influenza, Human / Q000175:diagnosis*; D008288:Malaria / Q000175:diagnosis*; D053768:Metal Nanoparticles / Q000737:chemistry; D000067716:Point-of-Care Testing; D013696:Temperature
chemical_list: D006046:Gold