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Whole-cell biosensor with tuneable limit of detection enables low-cost agglutination assays for medical diagnostic applications

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Title: Whole-cell biosensor with tuneable limit of detection enables low-cost agglutination assays for medical diagnostic applications
Authors: Kylilis, N
Riangrungroj, P
Lai, H-E
Salema, V
Fernández, LÁ
Stan, G-B
Freemont, PS
Polizzi, KM
Item Type: Journal Article
Abstract: Whole-cell biosensors can form the basis of affordable, easy-to-use diagnostic tests that can be readily deployed for point-of-care (POC) testing, but to date, the detection of analytes such as proteins that cannot easily diffuse across the cell membrane has been challenging. Here we developed a novel biosensing platform based on cell agglutination using an E. coli whole-cell biosensor surface-displaying nanobodies which bind selectively to a target protein analyte. As a proof-of-concept, we show the feasibility of this design can detect 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 using straight-forward design rules and a mathematical model. Finally, we re-engineer our whole-cell biosensor for the detection of a medically relevant biomarker by the display of two different nanbodies against 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 field-testing in the developing world, emergency or disaster relief sites as well as routine medical testing and personalized medicine.
Issue Date: 9-Jan-2019
Date of Acceptance: 9-Jan-2019
URI: http://hdl.handle.net/10044/1/65633
DOI: https://dx.doi.org/10.1021/acssensors.8b01163
ISSN: 2379-3694
Publisher: American Chemical Society
Journal / Book Title: ACS Sensors
Copyright Statement: © 2019 American Chemical Society. This document is the Accepted Manuscript version of a Published Work that appeared in final form in ACS Sensors, after peer review and technical editing by the publisher. To access the final edited and published work see https://dx.doi.org/10.1021/acssensors.8b01163
Sponsor/Funder: Engineering & Physical Science Research Council (EPSRC)
Engineering & Physical Science Research Council (EPSRC)
Funder's Grant Number: EP/K038648/1
EP/M002187/1
Publication Status: Published online
Conference Place: United States
Embargo Date: 2020-01-09
Online Publication Date: 2019-01-09
Appears in Collections:Faculty of Engineering
Bioengineering
Chemical Engineering



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