Sensitive and quantitative detection of cardiac troponin I with upconverting nanoparticle lateral flow test with minimized interference

Kim Pettersson,Carita Rautanen,Pirjo Hedberg,Heidi Hyytiä,Iida Martiskainen,Sherif Bayoumy,Saara Wittfooth,Taina Heikkilä

doi:10.1038/s41598-021-98199-y

Kim Pettersson, Carita Rautanen

Open Access

https://doi.org/10.1038/s41598-021-98199-y

Copy DOI

Journal: Scientific Reports	Publication Date: Sep 21, 2021
Citations: 17	License type: open-access

Affiliation: University of Turku, University of Oulu, NordLab

Abstract

Measurement of cardiac troponin I (cTnI) should be feasible for point-of-care testing (POCT) to diagnose acute myocardial infarction (AMI). Lateral flow immunoassays (LFIAs) have been long implemented in POCT and clinical settings. However, sensitivity, matrix effect and quantitation in lateral flow immunoassays (LFIAs) have been major limiting factors. The performance of LFIAs can be improved with upconverting nanoparticle (UCNP) reporters. Here we report a new methodological approach to quantify cTnI using UCNP-LFIA technology with minimized plasma interference. The performance of the developed UCNP-LFIA was evaluated using clinical plasma samples (n = 262). The developed UCNP-LFIA was compared to two reference assays, the Siemens Advia Centaur assay and an in-house well-based cTnI assay. By introducing an anti-IgM scrub line and dried EDTA in the LFIA strip, the detection of cTnI in plasma samples was fully recovered. The UCNP-LFIA was able to quantify cTnI concentrations in patient samples within the range of 30–10,000 ng/L. The LoB and LoD of the UCNP-LFIA were 8.4 ng/L and 30 ng/L. The method comparisons showed good correlation (Spearman’s correlation 0.956 and 0.949, p < 0.0001). The developed UCNP-LFIA had LoD suitable for ruling in AMI in patients with elevated cTnI levels and was able to quantify cTnI concentrations in patient samples. The technology has potential to provide simple and rapid assay for POCT in ED setting

Highlights

Measurement of cardiac troponin I should be feasible for point-of-care testing (POCT) to diagnose acute myocardial infarction (AMI)
In Lateral flow immunoassays (LFIAs) strips constructed without a scrub line and Ethylenediamine tetra-acetic acid (EDTA) in the sample pad, the addition of cardiac troponin I (cTnI) to lithium heparin (LiH) plasma samples led to significantly lower signal recovery as compared to what was seen with 7.5% BSA-TSA buffer
LFIA strips with a scrub line and EDTA treatment induced around fivefold improvement in signals compared to the untreated LiH plasma and a

Summary

Introduction

Measurement of cardiac troponin I (cTnI) should be feasible for point-of-care testing (POCT) to diagnose acute myocardial infarction (AMI). Lateral flow immunoassays (LFIAs) have been long implemented in POCT and clinical settings. The performance of the developed UCNP-LFIA was evaluated using clinical plasma samples (n = 262). The UCNP-LFIA was able to quantify cTnI concentrations in patient samples within the range of 30–10,000 ng/L. The developed UCNP-LFIA had LoD suitable for ruling in AMI in patients with elevated cTnI levels and was able to quantify cTnI concentrations in patient samples. The technology has potential to provide simple and rapid assay for POCT in ED setting Cardiac troponin I (cTnI) has been used clinically, for years, for diagnosis and risk stratification in patients with suspected acute myocardial infarction (AMI)[1]. Lateral flow immunoassays (LFIAs) can be used in POCT, in settings where the cost of the high-tech instrumentation may be prohibitive. The limitations regarding sensitivity and quantification have hindered its use in many

Methods

Results

Conclusion