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Optimization of flow path parameters for enhanced sensitivity lateral flow devices

Optimization of flow path parameters for enhanced sensitivity lateral flow devices
Optimization of flow path parameters for enhanced sensitivity lateral flow devices
Lateral flow devices (LFDs) or lateral flow tests (LFTs) are one of the most widely used biosensor platforms for point-of-care (POC) diagnostics. The basic LFD design has remained largely unchanged since its first appearance, and this has limited LFD use in clinical applications due to a general lack of analytical sensitivity. We report here a comprehensive study of the use of laser-patterned geometric control barriers that influence the flow dynamics within an LFD, with the specific aim of enhancing LFD sensitivity and lowering the limit of detection (LOD). This control of sample flow produces an increase in the time available for optimizing the binding kinetics of the implemented assay. The geometric modification to the flow path is in the form of a constriction that is produced by depositing a photo-sensitive polymer onto the nitrocellulose membrane which when polymerized, creates impermeable barrier walls through the depth of the membrane. Both the position of the constriction within the flow path and the number of constrictions allow for an increase in the sensitivity because of a slower overall flow rate within the test and a larger volume of sample per unit width of the test line. For these high sensitivity LFDs (HS-LFD), through optimization of the constriction position and addition of a second constriction we attained a 62% increase in test line color intensity for the detection of procalcitonin (PCT) and were also able to lower the LOD from 10 ng/mL to 1 ng/mL. In addition, of relevance for future commercial exploitation, this also significantly decreases the antibody consumption per device leading to reduced costs for test production. We have further tested our HS-LFD with contrived human samples, validating its application for future clinical use.
Flow, Flow dynamics, Geometric, High sensitivity, High sensitivity lateral Flow device (HS-LFD), Lateral flow
0039-9140
Iles, Alice
b0e82316-6070-4bda-8731-a1b6163a6d30
He, Peijun
2e303166-6aa5-4a09-b22e-440d96a54a9f
Katis, Ioannis
ee383bba-d183-4d30-a496-d4a28174eee4
Horak, Peter
520489b5-ccc7-4d29-bb30-c1e36436ea03
Eason, R.W.
e38684c3-d18c-41b9-a4aa-def67283b020
Sones, Collin
9de9d8ee-d394-46a5-80b7-e341c0eed0a8
Iles, Alice
b0e82316-6070-4bda-8731-a1b6163a6d30
He, Peijun
2e303166-6aa5-4a09-b22e-440d96a54a9f
Katis, Ioannis
ee383bba-d183-4d30-a496-d4a28174eee4
Horak, Peter
520489b5-ccc7-4d29-bb30-c1e36436ea03
Eason, R.W.
e38684c3-d18c-41b9-a4aa-def67283b020
Sones, Collin
9de9d8ee-d394-46a5-80b7-e341c0eed0a8

Iles, Alice, He, Peijun, Katis, Ioannis, Horak, Peter, Eason, R.W. and Sones, Collin (2022) Optimization of flow path parameters for enhanced sensitivity lateral flow devices. Talanta, 248, [123579]. (doi:10.1016/j.talanta.2022.123579).

Record type: Article

Abstract

Lateral flow devices (LFDs) or lateral flow tests (LFTs) are one of the most widely used biosensor platforms for point-of-care (POC) diagnostics. The basic LFD design has remained largely unchanged since its first appearance, and this has limited LFD use in clinical applications due to a general lack of analytical sensitivity. We report here a comprehensive study of the use of laser-patterned geometric control barriers that influence the flow dynamics within an LFD, with the specific aim of enhancing LFD sensitivity and lowering the limit of detection (LOD). This control of sample flow produces an increase in the time available for optimizing the binding kinetics of the implemented assay. The geometric modification to the flow path is in the form of a constriction that is produced by depositing a photo-sensitive polymer onto the nitrocellulose membrane which when polymerized, creates impermeable barrier walls through the depth of the membrane. Both the position of the constriction within the flow path and the number of constrictions allow for an increase in the sensitivity because of a slower overall flow rate within the test and a larger volume of sample per unit width of the test line. For these high sensitivity LFDs (HS-LFD), through optimization of the constriction position and addition of a second constriction we attained a 62% increase in test line color intensity for the detection of procalcitonin (PCT) and were also able to lower the LOD from 10 ng/mL to 1 ng/mL. In addition, of relevance for future commercial exploitation, this also significantly decreases the antibody consumption per device leading to reduced costs for test production. We have further tested our HS-LFD with contrived human samples, validating its application for future clinical use.

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Optimization of flow path parameters for enhanced sensitivity lateral flow devices
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Submitted date: 10 March 2021
Accepted/In Press date: 20 May 2022
Published date: 1 October 2022
Additional Information: Funding Information: The authors acknowledge the funding received via the Engineering and Physical Sciences Research Council (EPSRC) Grant Nos. EP/N004388/1 , EP/P025757/1 , EP/M027260/1 and EP/S003398/1 . The underpinning data for this paper can be found at https://doi.org/10.5258/SOTON/D2016 .
Keywords: Flow, Flow dynamics, Geometric, High sensitivity, High sensitivity lateral Flow device (HS-LFD), Lateral flow

Identifiers

Local EPrints ID: 480108
URI: http://eprints.soton.ac.uk/id/eprint/480108
ISSN: 0039-9140
PURE UUID: 8b377da7-81e2-449c-bb9e-b0a3f0b20ad5
ORCID for Peter Horak: ORCID iD orcid.org/0000-0002-8710-8764
ORCID for R.W. Eason: ORCID iD orcid.org/0000-0001-9704-2204

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Date deposited: 01 Aug 2023 16:49
Last modified: 31 May 2024 04:01

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Contributors

Author: Alice Iles
Author: Peijun He
Author: Ioannis Katis
Author: Peter Horak ORCID iD
Author: R.W. Eason ORCID iD
Author: Collin Sones

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