title: An Assay System for Point-of-Care Diagnosis of Tuberculosis using Commercially Manufactured PCB Technology.
abstract: Rapid advances in clinical technologies, detection sensitivity and analytical throughput have delivered a significant expansion in our knowledge of prognostic and diagnostic biomarkers in many common infectious diseases, such as Tuberculosis (TB). During the last decade, a significant number of approaches to TB diagnosis have been attempted at Point-of-Care (PoC), exploiting a large variation of techniques and materials. In this work, we describe an electronics-based Enzyme-Linked ImmunoSorbent Assay (eELISA), using a Lab-on-a-Printed Circuit Board (LoPCB) approach, for TB diagnosis based on cytokine detection. The test relies upon an electrochemical (amperometric) assay, comprising a high-precision bioinstrumentation board and amperometric sensors, produced exclusively using standard PCB manufacturing processes. Electrochemical detection uses standard Au and Ag electrodes together with a bespoke, low-power, multichannel, portable data-acquisition system. We demonstrate high-performance assay chemistry performed at microfluidic volumes on Au pads directly at the PCB surface with improved limit of detection (~10 pg/mL) over standard colorimetric ELISA methods. The assay has also been implemented in plasma, showing the utility of the system for medical applications. This work is a significant step towards the development of a low-cost, portable, high-precision diagnostic and monitoring technology, which once combined with appropriate PCB-based microfluidic networks will provide complete LoPCB platforms.
authors.affiliation: Nanoelectronics & Nanotechnology Research Group, School of Electronics and Computer Science, University of Southampton, Southampton, SO17 1BJ, UK. dan_evans@outlook.com.
authors.forename: Daniel
authors.initials: D
authors.lastname: Evans
authors.affiliation: Nanoelectronics & Nanotechnology Research Group, School of Electronics and Computer Science, University of Southampton, Southampton, SO17 1BJ, UK.
authors.forename: Konstantinos I
authors.initials: KI
authors.lastname: Papadimitriou
authors.affiliation: Centre for Immunology and Vaccinology, Division of Infectious Diseases, Department of Medicine, Imperial College London, London, UK.|Infection and Immunity, Imperial College NHS Trust, Charing Cross Hospital, London, UK.
authors.forename: Louise
authors.initials: L
authors.lastname: Greathead
authors.affiliation: Nanoelectronics & Nanotechnology Research Group, School of Electronics and Computer Science, University of Southampton, Southampton, SO17 1BJ, UK.
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Vasilakis
authors.affiliation: Centre for Immunology and Vaccinology, Division of Infectious Diseases, Department of Medicine, Imperial College London, London, UK.|Infection and Immunity, Imperial College NHS Trust, Charing Cross Hospital, London, UK.
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Pantelidis
authors.affiliation: Centre for Immunology and Vaccinology, Division of Infectious Diseases, Department of Medicine, Imperial College London, London, UK.|Infection and Immunity, Imperial College NHS Trust, Charing Cross Hospital, London, UK.
authors.forename: Peter
authors.initials: P
authors.lastname: Kelleher
authors.affiliation: Nanoelectronics & Nanotechnology Research Group, School of Electronics and Computer Science, University of Southampton, Southampton, SO17 1BJ, UK.
authors.forename: Hywel
authors.initials: H
authors.lastname: Morgan
authors.affiliation: Nanoelectronics & Nanotechnology Research Group, School of Electronics and Computer Science, University of Southampton, Southampton, SO17 1BJ, UK.
authors.forename: Themistoklis
authors.initials: T
authors.lastname: Prodromakis
mesh_terms: D015374:Biosensing Techniques; D055664:Electrochemical Techniques; D004581:Electronics / Q000295:instrumentation / Q000379:methods; D006801:Humans; D056656:Lab-On-A-Chip Devices; D000067716:Point-of-Care Testing; D011933:Reagent Kits, Diagnostic; D012680:Sensitivity and Specificity; D014376:Tuberculosis / Q000175:diagnosis*
chemical_list: D011933:Reagent Kits, Diagnostic