Sub-picomolar lateral flow antigen detection with two-wavelength imaging of composite nanoparticles

Benjamin S Miller; Michael R Thomas; Matthew Banner; Jeongyun Kim; Yiyun Chen; Qingshan Wei; Derek K Tseng; Zoltán S Göröcs; Aydogan Ozcan; Molly M Stevens; Rachel A McKendry

doi:10.1016/j.bios.2022.114133

Sub-picomolar lateral flow antigen detection with two-wavelength imaging of composite nanoparticles

Biosens Bioelectron. 2022 Jul 1:207:114133. doi: 10.1016/j.bios.2022.114133. Epub 2022 Mar 4.

Authors

Affiliations

¹ London Centre for Nanotechnology, University College London, 17-19 Gordon Street, London, WC1H 0AH, United Kingdom; Division of Medicine, University College London, Gower Street London WC1E 6BT, United Kingdom.
² London Centre for Nanotechnology, University College London, 17-19 Gordon Street, London, WC1H 0AH, United Kingdom; Department of Materials, Department of Bioengineering and Institute of Biomedical Engineering, Imperial College London, London, SW7 2BP, United Kingdom; Department of Biochemical Engineering, University College London, Bernard Katz Building, Gower Street, London, WC1E 6BT, United Kingdom.
³ London Centre for Nanotechnology, University College London, 17-19 Gordon Street, London, WC1H 0AH, United Kingdom; Department of Biochemical Engineering, University College London, Bernard Katz Building, Gower Street, London, WC1E 6BT, United Kingdom.
⁴ Department of Materials, Department of Bioengineering and Institute of Biomedical Engineering, Imperial College London, London, SW7 2BP, United Kingdom.
⁵ Electrical and Computer Engineering Department, University of California, Los Angeles, Los Angeles, CA, USA; Department of Chemical and Biomolecular Engineering, North Caroline State University, Raleigh, NC, USA.
⁶ Electrical and Computer Engineering Department, University of California, Los Angeles, Los Angeles, CA, USA.
⁷ London Centre for Nanotechnology, University College London, 17-19 Gordon Street, London, WC1H 0AH, United Kingdom; Division of Medicine, University College London, Gower Street London WC1E 6BT, United Kingdom. Electronic address: r.a.mckendry@ucl.ac.uk.

PMID: 35316759
DOI: 10.1016/j.bios.2022.114133

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.

Keywords: Biosensors; Imaging; Lateral flow; Nanoparticles.

MeSH terms

Biosensing Techniques* / methods
Biotin
Gold
Limit of Detection
Metal Nanoparticles*

Substances

Biotin
Gold

Grants and funding

MR/P024378/1/MRC_/Medical Research Council/United Kingdom