title: Clinical Validation of Quantum Dot Barcode Diagnostic Technology.
abstract: There has been a major focus on the clinical translation of emerging technologies for diagnosing patients with infectious diseases, cancer, heart disease, and diabetes. However, most developments still remain at the academic stage where researchers use spiked target molecules to demonstrate the utility of a technology and assess the analytical performance. This approach does not account for the biological complexities and variabilities of human patient samples. As a technology matures and potentially becomes clinically viable, one important intermediate step in the translation process is to conduct a full clinical validation of the technology using a large number of patient samples. Here, we present a full detailed clinical validation of Quantum Dot (QD) barcode technology for diagnosing patients infected with Hepatitis B Virus (HBV). We further demonstrate that the detection of multiple regions of the viral genome using multiplexed QD barcodes improved clinical sensitivity from 54.9-66.7% to 80.4-90.5%, and describe how to use QD barcodes for optimal clinical diagnosis of patients. The use of QDs in biology and medicine was first introduced in 1998 but has not reached clinical care. This study describes our long-term systematic development strategy to advance QD technology to a clinically feasible product for diagnosing patients. Our "blueprint" for translating the QD barcode research concept could be adapted for other nanotechnologies, to efficiently advance diagnostic techniques discovered in the academic laboratory to patient care.
authors.affiliation: Institute of Biomaterials and Biomedical Engineering, University of Toronto , Toronto, Ontario M5S 3G9, Canada.|Terrence Donnelly Centre for Cellular and Bimolecular Research, University of Toronto , Toronto, Ontario M5S 3E1, Canada.
authors.forename: Jisung
authors.initials: J
authors.lastname: Kim
authors.affiliation: Sandra Rotman Centre for Global Health, University Health Network , Toronto, Ontario M5G 1L7, Canada.
authors.forename: Mia J
authors.initials: MJ
authors.lastname: Biondi
authors.affiliation: Sandra Rotman Centre for Global Health, University Health Network , Toronto, Ontario M5G 1L7, Canada.
authors.forename: Jordan J
authors.initials: JJ
authors.lastname: Feld
authors.affiliation: Institute of Biomaterials and Biomedical Engineering, University of Toronto , Toronto, Ontario M5S 3G9, Canada.|Terrence Donnelly Centre for Cellular and Bimolecular Research, University of Toronto , Toronto, Ontario M5S 3E1, Canada.|Department of Chemistry, University of Toronto , Toronto, Ontario M5S 3H6, Canada.|Department of Chemical Engineering, University of Toronto , Toronto, Ontario M5S 3E5, Canada.|Department of Materials Science and Engineering, University of Toronto , Toronto, Ontario M5S 3E4, Canada.
authors.forename: Warren C W
authors.initials: WC
authors.lastname: Chan
mesh_terms: D001681:Biological Assay / Q000379:methods; D004279:DNA, Viral / Q000097:blood*; D005456:Fluorescent Dyes / Q000737:chemistry; D006509:Hepatitis B / Q000175:diagnosis*; D006515:Hepatitis B virus / Q000235:genetics; D006801:Humans; D057230:Limit of Detection; D058185:Magnetite Nanoparticles / Q000737:chemistry; D008856:Microscopy, Fluorescence; D008863:Microspheres; D060885:Multiplex Polymerase Chain Reaction; D045663:Quantum Dots / Q000737:chemistry*; D012680:Sensitivity and Specificity; D017422:Sequence Analysis, DNA; D013499:Surface Properties
chemical_list: D004279:DNA, Viral; D005456:Fluorescent Dyes; D058185:Magnetite Nanoparticles
keywords: clinical; diagnosis; hepatitis B virus; in vitro diagnostic assay; infectious diseases; multiplex; nanotechnology; patient samples; quantum dot; quantum dot barcodes; sensitivity; specificity