Ultrasensitive quantification of cardiac troponin I by a Single Molecule Counting method: analytical validation and biological features

• Published in: Clinica chimica acta Vol. 486; pp. 224 - 231
• Main Authors: Garcia-Osuna, Alvaro, Gaze, David, Grau-Agramunt, Margarita, Morris, Thomas, Telha, Catarina, Bartolome, Amelita, Bishop, Jeffrey J., Monsalve, Luis, Livingston, Richard, Estis, Joel, Nolan, Niamh, Sandlund, Johanna, Ordonez-Llanos, Jordi
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-11-2018
• Subjects: Analytical performance; Biological features; Cardiac troponin I; Female; Humans; Male; Sensitivity and Specificity; Single Molecule Counting; Software; Troponin I - blood; Cardiac troponin I; Analytical performance; Biological features; Single Molecule Counting
• ISSN: 0009-8981; 1873-3492
• DOI: 10.1016/j.cca.2018.08.015

To evaluate analytical and biological characteristics of the Singulex Clarity® cTnI assay, based upon Single Molecule Counting technology.
Assay's analytical sensitivity, precision, linearity, hook effect, cross-reactivity or interference by endogenous and exogenous substances, stability, 99th reference percentile [p99th] in EDTA plasma were evaluated in single or multi-site studies.
Detection limit was 0.12 ng/L. Sensitivity was 0.14 ng/L at 20% CV (functional sensitivity) and 0.53 ng/L at 10% CV. Imprecision was 3.16%–10.0% in a multi-lot, single-site study, and 5.5%–12.0% in a single-lot, multi-site study; assay was linear from 0.08 to 25,000 ng/L. No hook effect was observed; any cross-reactivity/interference exceeded the 10%. Healthy subjects were recruited using clinical history, normal NT-proBNP and eGFR (n = 560) or plasma creatinine (n = 535) as inclusion criteria. cTnI was detectable in 96.8% of healthy subjects. The p99th were 8.01 (eGFR used) and 8.15 ng/L (plasma creatinine); both were measured with ≤5.7% CV. Median cTnI were significantly higher in older and male than in young and female subjects.
The Singulex Clarity cTnI assay show analytical features and % detection in healthy subjects that improve the corresponding values of most of the existing high-sensitivity cTnI assays.
•A cTnI assay by Single Molecule Counting technology was evaluated.•Limit of detection (0.12 ng/L) was lower than the reported for any other cTnI assay.•The 99th reference percentile was obtained with less than 5.7% imprecision.•The assay detects cTnI in more than 96% of healthy subjects.•The assay largely fulfills the criteria to be designed as of high sensitivity.