Development and Preliminary Clinical Validation of a High Sensitivity Assay for Cardiac Troponin Using a Capillary Flow (Single Molecule) Fluorescence Detector

Value of Cardiac Troponin I Cutoff Concentrations below the 99th Percentile for Clinical Decision-Making

“…Our results are an important addition to the existing literature because the superior analytical performance of the highly sensitive assay used in our analysis allowed for the reliable determination of risk associated with troponin concentrations below the 99th percentile. Our data raise the question of what troponin cutoff should be regarded as the most appropriate biochemical criterion for decision-making in ACS, particularly because recent data suggest that normal values are substantially lower than measured by any of the currently available assays (3 ).…”

“…Current guidelines suggest the use of the 99th percentile of troponin concentrations from a healthy reference population as a cutoff for diagnostic and prognostic assessment (1,2 ). With the implementation of assays with improved analytical sensitivity, however, the reliable determination of troponin even at concentrations well below the previously defined 99th percentile values has become possible (3,4 ). Concentrations below the 99th percentile measured with several different assays have been shown to provide robust prognostic information (4 -7 ).…”

Emerging Technologies to Increase Ligand Binding Assay Sensitivity

“…The size of the laser interrogation space and sampling time through the detection space is precisely set so that only one fluorescent entity is present during the detection phase for lower concentrations (15). Fluorescence events are digitally counted by photon detectors within the instrument and are considered positive if the signal is 5-6 standard deviations above the threshold of background fluorescence.…”

“…Compared with analog signal read-outs used in traditional LBAs where a single data point is used to represent all the molecules present in a sample, this digital technology allows for multiple individual data points to be summed over a specified time interval to create total signal. At higher analyte concentrations, the instrument switches to analog mode, using a unique algorithm to calculate the total number of photons, and hence, a very broad dynamic range is possible using this technology (∼4.5 logs) (15,16).…”

Identification of myocardial injury in the emergency setting

“…There are also research-use or precommercial hs-cTn assays that are more sensitive, with LoD concentrations in the integer ng/L range, compared to present-day assays in clinical use with LoDs expressed in decimal μg/L [33,47,[49][50][51][52][53][54][55]. These hs-cTn assays have 99th percentiles near 10 ng/L and achieve the required 10%CV below the 99th percentile [49,51,53].…”