Highly Sensitive Immunoassay for Long Forms of Cardiac Troponin T Using Upconversion Luminescence.

IF 7.1 2区医学 Q1 MEDICAL LABORATORY TECHNOLOGY Clinical chemistry Pub Date : 2024-08-01 DOI:10.1093/clinchem/hvae075

Selma M Salonen, Tuulia J K Tuominen, Kirsti I S Raiko, Tuija Vasankari, Rami Aalto, Tapio A Hellman, Satu E Lahtinen, Tero Soukka, K E Juhani Airaksinen, Saara T Wittfooth

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Abstract

Background: Long cardiac troponin T (cTnT) has been proposed to be a promising and more specific biomarker of acute myocardial infarction (AMI). As it represents a subfraction of circulating cTnT, detection of very low concentrations is a requirement. The aim of this study was to develop a novel, highly sensitive immunoassay for long cTnT.

Methods: A two-step sandwich-type immunoassay for long cTnT was developed, utilizing upconverting nanoparticles (UCNPs) as reporters. The limits of detection and quantitation were determined for the assay. Linearity and matrix effects were evaluated. Performance with clinical samples was assessed with samples from patients with non-ST elevation myocardial infarction (NSTEMI, n = 30) and end-stage renal disease (ESRD, n = 37) and compared to a previously developed time-resolved fluorescence (TRF)-based long cTnT assay and a commercial high-sensitivity cTnT assay.

Results: The novel assay reached a 28-fold lower limit of detection (0.40 ng/L) and 14-fold lower limit of quantitation (1.79 ng/L) than the previously developed TRF long cTnT assay. Li-heparin and EDTA plasma, but not serum, were found to be suitable sample matrixes for the assay. In a receiver operating characteristics curve analysis, the troponin ratio (long/total cTnT) determined with the novel assay showed excellent discrimination between NSTEMI and ESRD with an area under the curve of 0.986 (95% CI, 0.967-1.000).

Conclusions: By utilizing upconversion luminescence technology, we developed a highly sensitive long cTnT assay. This novel assay can be a valuable tool for investigating the full potential of long cTnT as a biomarker for AMI. ClinicalTrials.gov Registration Number: NCT04465591.

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使用上转换发光法检测长型心肌肌钙蛋白 T 的高灵敏度免疫测定。

背景：长心肌肌钙蛋白 T（cTnT）已被认为是急性心肌梗死（AMI）的一种有希望且更具特异性的生物标记物。由于长肌钙蛋白 T 是循环中肌钙蛋白 T 的一部分，因此需要检测极低浓度的肌钙蛋白 T。本研究旨在开发一种新型、高灵敏度的长 cTnT 免疫测定法：方法：利用上转换纳米粒子（UCNPs）作为报告物，开发了一种两步夹心式长 cTnT 免疫测定法。确定了该检测方法的检测限和定量限。评估了线性和基质效应。用非 ST 段抬高型心肌梗死（NSTEMI，n = 30）和终末期肾病（ESRD，n = 37）患者的样本评估了临床样本的性能，并与之前开发的基于时间分辨荧光（TRF）的长 cTnT 检测方法和商用高灵敏度 cTnT 检测方法进行了比较：结果：与之前开发的 TRF 长 cTnT 检测法相比，新型检测法的检测限（0.40 纳克/升）低 28 倍，定量限（1.79 纳克/升）低 14 倍。研究发现，肝素利血平和乙二胺四乙酸（EDTA）血浆（而非血清）是适合该测定的样本基质。在接收器操作特性曲线分析中，用这种新型测定法测定的肌钙蛋白比值（长肌钙蛋白/总肌钙蛋白）显示了对 NSTEMI 和 ESRD 的极佳区分度，曲线下面积为 0.986（95% CI，0.967-1.000）：通过利用上转换发光技术，我们开发出了一种高灵敏度的长 cTnT 检测方法。结论：通过利用上转换发光技术，我们开发出了一种高灵敏度的长 cTnT 检测方法，这种新型检测方法是研究长 cTnT 作为急性心肌梗死生物标记物的全部潜力的重要工具。ClinicalTrials.gov 注册号：NCT04465591：NCT04465591。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinical chemistry 医学-医学实验技术

CiteScore

11.30

自引率

4.30%

发文量

212

审稿时长

1.7 months

期刊介绍： Clinical Chemistry is a peer-reviewed scientific journal that is the premier publication for the science and practice of clinical laboratory medicine. It was established in 1955 and is associated with the Association for Diagnostics & Laboratory Medicine (ADLM). The journal focuses on laboratory diagnosis and management of patients, and has expanded to include other clinical laboratory disciplines such as genomics, hematology, microbiology, and toxicology. It also publishes articles relevant to clinical specialties including cardiology, endocrinology, gastroenterology, genetics, immunology, infectious diseases, maternal-fetal medicine, neurology, nutrition, oncology, and pediatrics. In addition to original research, editorials, and reviews, Clinical Chemistry features recurring sections such as clinical case studies, perspectives, podcasts, and Q&A articles. It has the highest impact factor among journals of clinical chemistry, laboratory medicine, pathology, analytical chemistry, transfusion medicine, and clinical microbiology. The journal is indexed in databases such as MEDLINE and Web of Science.