Sub-picomolar lateral flow antigen detection with two-wavelength imaging of composite nanoparticles
File(s)2022-Miller-Biosensors-accepted.pdf (3.99 MB)
Accepted version
Author(s)
Type
Journal Article
Abstract
Lateral flow tests, commonly based on metal plasmonic nanoparticles, are rapid, robust, and low-cost. However, improvements in analytical sensitivity are required to allow detection of low-abundance biomarkers, for example detection of low antigen concentrations for earlier or asymptomatic diagnosis of infectious diseases. Efforts to improve sensitivity often require changes to the assay. Here, we developed optical methods to improve the sensitivity of absorption-based lateral flow tests, requiring no assay modifications to existing tests. We experimentally compared five different lock-in and subtraction-based methods, exploiting the narrow plasmonic peak of gold nanoparticles for background removal by imaging at different light wavelengths. A statistical framework and three fitting models were used to compare limits of detection, giving a 2.0–5.4-fold improvement. We then demonstrated the broad applicability of the method to an ultrasensitive assay, designing 530 nm composite nanoparticles to increase the particle volume, and therefore light absorption per particle, whilst retaining the plasmonic peak to allow background removal and without adding any assay steps. This multifaceted, modular approach gave a combined 58-fold improvement in the fundamental limit of detection using a biotin-avidin model over 50 nm gold nanoparticles with single-wavelength imaging. Applying to a sandwich assay for the detection of HIV capsid protein gave a limit of detection of 170 fM. Additionally, we developed an open-source software tool for performing the detection limit analysis used in this work.
Date Issued
2022-07-01
Online Publication Date
2023-03-03T00:01:19Z
Date Acceptance
2022-02-22
ISSN
0956-5663
Publisher
Elsevier
Start Page
1
End Page
10
Journal / Book Title
Biosensors and Bioelectronics
Volume
207
Copyright Statement
© 2022 Elsevier Ltd. All rights reserved. This manuscript is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International Licence http://creativecommons.org/licenses/by-nc-nd/4.0/
Sponsor
Engineering & Physical Science Research Council (E
Engineering & Physical Science Research Council (E
Royal Academy Of Engineering
Identifier
https://www.sciencedirect.com/science/article/pii/S0956566322001737?via%3Dihub
Grant Number
WT406114
BH171988
CIET2021\94
Subjects
Science & Technology
Life Sciences & Biomedicine
Physical Sciences
Biophysics
Biotechnology & Applied Microbiology
Chemistry, Analytical
Electrochemistry
Nanoscience & Nanotechnology
Chemistry
Science & Technology - Other Topics
Lateral flow
Imaging
Nanoparticles
Biosensors
PAPER
ASSAY
PERFORMANCE
Biosensors
Imaging
Lateral flow
Nanoparticles
Biosensing Techniques
Biotin
Gold
Limit of Detection
Metal Nanoparticles
Gold
Biotin
Biosensing Techniques
Metal Nanoparticles
Limit of Detection
Science & Technology
Life Sciences & Biomedicine
Physical Sciences
Biophysics
Biotechnology & Applied Microbiology
Chemistry, Analytical
Electrochemistry
Nanoscience & Nanotechnology
Chemistry
Science & Technology - Other Topics
Lateral flow
Imaging
Nanoparticles
Biosensors
PAPER
ASSAY
PERFORMANCE
Bioinformatics
0301 Analytical Chemistry
0903 Biomedical Engineering
1007 Nanotechnology
Publication Status
Published
Article Number
ARTN 114133
Date Publish Online
2022-03-04