Abstract
An alternating-current magnetosusceptometer of antibody-functionalized magnetic nanoparticles (MNPs) was developed for immunomagnetic reduction (IMR). A high-sensitivity, high-critical-temperature superconducting quantum interference device was used in the magnetosusceptometer. Minute levels of biomarkers of early-stage neurodegeneration diseases were detectable in serum, but measuring each biomarker required approximately 4 h. Hence, an eight-channel platform was developed in this study to fit minimal screening requirements for Alzheimer’s disease. Two consistent results were measured for three biomarkers, namely Aβ40, Aβ42, and tau protein, per human specimen. This paper presents the instrument configuration as well as critical characteristics, such as the low noise level variations among channels, a high signal-to-noise ratio, and the coefficient of variation for the biomarkers’ IMR values. The instrument’s ultrahigh sensitivity levels for the three biomarkers and the substantially shorter total measurement time in comparison with the previous single- and four-channels platforms were also demonstrated in this study. Thus, the eight-channel instrument may serve as a powerful tool for clinical high-throughput screening of Alzheimer’s disease.
Highlights
To accurately screen for and diagnose diseases at early stages, precise immunoassays such as a single-molecule array [1], mesoscale discovery assay [2], and single-molecule count [3] have been reported to exhibit higher sensitivity than current clinical methods such as enzyme-linked immunosorbent assays (ELISAs) and radioimmunoassay
An intuitive explanation of this phenomenon is that the rotational velocity, the direction of which is influenced by the ac magnetic field, is slower for a large magnetic cluster than for a single, smaller magnetic nanoparticles (MNPs)
All reagents exhibited the same results for the biomarker-free mixture (Figure 4) because the only differences among the three reagents were the bioprobes, which were coated on the same batch of MNPs
Summary
To accurately screen for and diagnose diseases at early stages, precise immunoassays such as a single-molecule array [1], mesoscale discovery assay [2], and single-molecule count [3] have been reported to exhibit higher sensitivity than current clinical methods such as enzyme-linked immunosorbent assays (ELISAs) and radioimmunoassay. An IMR instrument is used to measure the variation of the alternating-current (ac) magnetic susceptibility χac of the mixture under a bioconjugation process. Target molecules connect to bioprobes on MNPs, and a large magnetic cluster forms. With regard to the ac excitation field (i.e., χac ), the magnetic cluster exhibits a substantially lower response than a single MNP. An intuitive explanation of this phenomenon is that the rotational velocity, the direction of which is influenced by the ac magnetic field, is slower for a large magnetic cluster than for a single, smaller MNP. The formation of a large magnetic cluster results in the reduction of χac. Further reduction of χac occurs as the concentration of target molecules increases
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