title: Printed Flexible Plastic Microchip for Viral Load Measurement through Quantitative Detection of Viruses in Plasma and Saliva.
abstract: We report a biosensing platform for viral load measurement through electrical sensing of viruses on a flexible plastic microchip with printed electrodes. Point-of-care (POC) viral load measurement is of paramount importance with significant impact on a broad range of applications, including infectious disease diagnostics and treatment monitoring specifically in resource-constrained settings. Here, we present a broadly applicable and inexpensive biosensing technology for accurate quantification of bioagents, including viruses in biological samples, such as plasma and artificial saliva, at clinically relevant concentrations. Our microchip fabrication is simple and mass-producible as we print microelectrodes on flexible plastic substrates using conductive inks. We evaluated the microchip technology by detecting and quantifying multiple Human Immunodeficiency Virus (HIV) subtypes (A, B, C, D, E, G, and panel), Epstein-Barr Virus (EBV), and Kaposi's Sarcoma-associated Herpes Virus (KSHV) in a fingerprick volume (50 µL) of PBS, plasma, and artificial saliva samples for a broad range of virus concentrations between 10(2) copies/mL and 10(7) copies/mL. We have also evaluated the microchip platform with discarded, de-identified HIV-infected patient samples by comparing our microchip viral load measurement results with reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) as the gold standard method using Bland-Altman Analysis.
authors.affiliation: 1] Division of Biomedical Engineering, Division of Renal Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA [2] Harvard-MIT Division of Health Sciences and Technology, Cambridge, MA, USA.
authors.forename: Hadi
authors.initials: H
authors.lastname: Shafiee
authors.affiliation: 1] Division of Biomedical Engineering, Division of Renal Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA [2] Harvard-MIT Division of Health Sciences and Technology, Cambridge, MA, USA.
authors.forename: Manoj Kumar
authors.initials: MK
authors.lastname: Kanakasabapathy
authors.affiliation: Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Franceline
authors.initials: F
authors.lastname: Juillard
authors.affiliation: 1] Division of Biomedical Engineering, Division of Renal Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA [2] Harvard-MIT Division of Health Sciences and Technology, Cambridge, MA, USA.
authors.forename: Mert
authors.initials: M
authors.lastname: Keser
authors.affiliation: 1] Division of Biomedical Engineering, Division of Renal Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA [2] Harvard-MIT Division of Health Sciences and Technology, Cambridge, MA, USA.
authors.forename: Magesh
authors.initials: M
authors.lastname: Sadasivam
authors.affiliation: 1] Division of Biomedical Engineering, Division of Renal Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA [2] Harvard-MIT Division of Health Sciences and Technology, Cambridge, MA, USA.
authors.forename: Mehmet
authors.initials: M
authors.lastname: Yuksekkaya
authors.affiliation: Division of Infectious Diseases, Brigham and Women's Hospital, Harvard Medical School, MA, USA.
authors.forename: Emily
authors.initials: E
authors.lastname: Hanhauser
authors.affiliation: Division of Infectious Diseases, Brigham and Women's Hospital, Harvard Medical School, MA, USA.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Henrich
authors.affiliation: Division of Infectious Diseases, Brigham and Women's Hospital, Harvard Medical School, MA, USA.
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Kuritzkes
authors.affiliation: Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Kaye
authors.affiliation: 1] Division of Biomedical Engineering, Division of Renal Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA [2] Department of Radiology, Canary Center at Stanford for Cancer Early Detection, Stanford University School of Medicine, Palo Alto, CA, USA.
authors.forename: Utkan
authors.initials: U
authors.lastname: Demirci
mesh_terms: D020031:Epstein-Barr Virus Infections / Q000097:blood / Q000175:diagnosis / Q000821:virology; D015658:HIV Infections / Q000097:blood / Q000175:diagnosis* / Q000821:virology; D015497:HIV-1 / Q000302:isolation & purification* / Q000502:physiology; D006566:Herpesviridae Infections / Q000097:blood / Q000175:diagnosis / Q000821:virology; D004854:Herpesvirus 4, Human / Q000302:isolation & purification* / Q000502:physiology; D019288:Herpesvirus 8, Human / Q000302:isolation & purification* / Q000502:physiology; D006801:Humans; D056656:Lab-On-A-Chip Devices / Q000592:standards*; D019095:Point-of-Care Systems; D012015:Reference Standards; D019562:Viral Load