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A low-cost biological agglutination assay for medical diagnostic applications

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Title: A low-cost biological agglutination assay for medical diagnostic applications
Authors: Kylilis, N
Riangrungroj, P
Lai, H-E
Salema, V
Fernandez, LA
Stan, G-B
Freemont, P
Polizzi, K
Item Type: Working Paper
Abstract: Affordable, easy-to-use diagnostic tests that can be readily deployed for point-of-care (POC) testing are key in addressing challenges in the diagnosis of medical conditions and for improving global health in general. Ideally, POC diagnostic tests should be highly selective for the biomarker, user-friendly, have a flexible design architecture and a low cost of production. Here we developed a novel agglutination assay based on whole E. coli cells surface-displaying nanobodies which bind selectively to a target protein analyte. As a proof-of-concept, we show the feasibility of this design as a new diagnostic platform by the detection of a model analyte at nanomolar concentrations. Moreover, we show that the design architecture is flexible by building assays optimized to detect a range of model analyte concentrations supported using straight-forward design rules and a mathematical model. Finally, we re-engineer E. coli cells for the detection of a medically relevant biomarker by the display of two different antibodies against the human fibrinogen and demonstrate a detection limit as low as 10 pM in diluted human plasma. Overall, we demonstrate that our agglutination technology fulfills the requirement of POC testing by combining low-cost nanobody production, customizable detection range and low detection limits. This technology has the potential to produce affordable diagnostics for both field-testing in the developing world, emergency or disaster relief sites as well as routine medical testing and personalized medicine.
Issue Date: 8-Sep-2018
URI: http://hdl.handle.net/10044/1/70984
DOI: 10.1101/411637
ISSN: 2379-3694
Publisher: American Chemical Society
Copyright Statement: © 2018 The Author(s). CC-BY 4.0 International licenseIt is made available under a (which was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.T
Sponsor/Funder: Imperial College London
Engineering & Physical Science Research Council (EPSRC)
Engineering & Physical Science Research Council (EPSRC)
Funder's Grant Number: Imperial College PhD Scholarship
Publication Status: Published
Open Access location: https://pubs.acs.org/doi/10.1021/acssensors.8b01163
Appears in Collections:Faculty of Engineering
Chemical Engineering
Department of Medicine (up to 2019)