Analyzer-to-Analyzer Variations in Assaying Ultralow Concentrated Biomarkers Associated with Neurodegenerative Diseases Using Immunomagnetic Reduction

Abstract

By utilizing a high-temperature superconducting quantum interference device (high-T_c SQUID) magnetometer, an alternating current (AC) magnetosusceptometer, referred to as an analyzer, was developed for ultrasensitive immunoassays. The analyzer has been applied to assay biomarkers in human plasma associated with Alzheimer’s disease (AD) and Parkinson’s disease (PD). The involved assay methodology is the so-called immunomagnetic reduction (IMR). Such an analyzer has been approved for clinical use in Taiwan and Europe. The mass production of the analyzer is needed for clinical utilities. The issue of exploring analyzer-to-analyzer variations in the performances becomes critical. Unfortunately, there is no standard characterization to determine the variations in performances among analyzers. In this study, key characterizations, such as output signal stability, signal-to-noise ratio, measured concentrations of a control sample, etc., are proposed. In total, three analyzers are characterized in this work. The detected biomarkers include amyloid peptides, total tau protein, phosphorylated tau protein, and α-synuclein protein for AD and PD. Through one-way ANOVA for any of the characterizations among the three analyzers, it was found that there was no significant difference in any of these characterizations among the analyzers (p > 0.05). Furthermore, the three analyzers are applied to assay biomolecules for AD and PD in reference samples. High correlations (r > 0.8) in measured concentrations of any of these biomarkers in reference samples were obtained among the three analyzers. The results demonstrate that the proposed characterizations are feasible for achieving consistent performance among high-T_c SQUID-based AC magnetosusceptometers for assaying biomolecules.