Analytical performance of a single epitope B-type natriuretic peptide sandwich immunoassay on the Minicare platform for point-of-care diagnostics

Abstract

Point-of-care B-type natriuretic peptide (BNP) testing with adequate analytical performance has the potential to improve patient flow and provide primary care givers with easy-to-use advanced diagnostic tools in the management of heart failure. We present the analytical evaluation of the Minicare BNP immunoassay under development on the Minicare I-20 platform for point-of-care testing. Analytical performance was evaluated using EDTA venous whole blood, EDTA plasma and capillary whole blood. Method comparison with a lab-testing system was performed using samples from 187 patients. Normal values were determined based on 160 healthy adults, aging from 19 to 70 years. Limit of blank (LoB), limit of detection (LoD) were determined to be 3.3 ng/L, 5.8 ng/L. Limit of quantitation (LoQ) in whole blood at 20% and 10% coefficient of variation (CV) was found < 9 ng/L and <30 ng/L respectively without significant differences between EDTA whole blood and EDTA plasma. Total CV was found to be from 6.7% to 9.7% for BNP concentrations between 92.6 and 3984 ng/L. The sample type comparison study demonstrated correlation coefficients between 0.97 and 0.99 with slopes between 1.03 and 1.09 between the different samples. Method comparison between Minicare BNP and Siemens ADVIA Centaur BNP demonstrated a correlation coefficient of 0.92 with a slope of 1.06. The 97.5% URL of a healthy population was calculated to be 72.6 ng/L. The Minicare BNP assay is a robust, easy-to-use and sensitive test for rapid determination of BNP concentrations that can be used in a near-patient setting.

Keywords: Analytical performance; B-type natriuretic peptide; BNP, B-type Natriuretic Peptide; CI, confidence interval; CLSI, clinical laboratory standards institute; CV, coefficient of variation; Capillary blood; Diagnosis; EDTA, ethylene-diamine-tetraacetic acid; HAMA, human anti-mouse antibody; HF, heart failure; Heart failure; K2-EDTA, dipotassium ethylene-diamine-tetraacetic acid; Li-heparin, lithium heparin; LoB, limit of blank; LoD, limit of detection; LoQ, limit of quantitation; NP, Natriuretic Peptide; NYHA, New York Heart Association; POC, point-of-care; Point-of-care; RF, rheumatoid factor; RFID, radiofrequency identification; RT, room temperature; SD, standard deviation; URL, upper reference limit; fTIR, frustrated total internal reflection.

Fig. 1

(a) Minicare I-20 platform consisting of the Minicare I-20 analyzer and a disposable plastic cartridge. (b–d) Schematic representation of the Magnotech single-epitope sandwich assay. First (b) the analyte, i.e. BNP, binds to the functionalized optical detection surface. Subsequently (c) magnetic particles are attracted to the surface and bind the complexes. Lastly (d) unbound particles are removed from the surface to enable detection of BNP-bound particle complexes via fTIR.

Fig. 2

CV profile for EDTA whole blood. On the horizontal axis the average Minicare BNP concentration in ng/L is depicted. The line is a guide to the eye.

Fig. 3

Method comparison between Minicare BNP whole blood (WB) and (A) Siemens ADVIA Centaur BNP, (B) Alere Triage BNP, and (C) Abbott I-STAT BNP. Data is shown on a logarithmic scale. Passing-Bablok regression results are shown in the inset. The solid black line corresponds to the regression line.