Development of an experimental method to overcome the hook effect in sandwich-type lateral flow immunoassays guided by computational modelling

Sathishkumar, N and Toley, BJ (2020) Development of an experimental method to overcome the hook effect in sandwich-type lateral flow immunoassays guided by computational modelling. In: Sensors and Actuators, B: Chemical, 324 .

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Abstract

This study presents experimental demonstrations and theoretical underpinnings of how the high-analyte-concentration �hook effect� in sandwich-type lateral flow immunoassays (LFIAs) may be overcome by real-time imaging of test and control lines. The dynamic range of a sandwich LFIA is limited by the �hook effect�, according to which, test line signal intensities reduce with increasing analyte concentration beyond a threshold analyte concentration. In order to understand the effect of analyte concentration on the kinetics of signal generation at the test and control lines, we developed a mathematical model of transport (convection and diffusion)-reaction phenomena occurring in these zones. Guided by the model, we developed a method for the expansion of the dynamic range of commercial unmodified LFIAs. The method involves time-lapse imaging of LFIA strips using a smartphone app and fitting the ratio of intensities at the test and control line (T/C ratio) to empirical equations. The fitting parameters thus obtained are calibrated against the analyte concentration. Using this method, the dynamic range for the detection of human chorionic gonadotropin (hCG) of an unmodified commercially available pregnancy strip was expanded to 3 orders of magnitude (0.5�500 IU/mL), compared to �2 orders of magnitude (0.5�40 IU/mL) achieved by end-point detection. Given the ubiquity of smartphones, this new quantitative method promises to significantly enhance the utility of LFIAs in point-of-care diagnostics. © 2020 Elsevier B.V.

Item Type:	Journal Article
Publication:	Sensors and Actuators, B: Chemical
Publisher:	Elsevier B.V.
Additional Information:	The copyright of this article belongs to Elsevier B.V.
Department/Centre:	Division of Mechanical Sciences > Chemical Engineering
Date Deposited:	04 Sep 2020 10:33
Last Modified:	04 Sep 2020 10:33
URI:	http://eprints.iisc.ac.in/id/eprint/66470

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