Digital Magnetic Detection of Biomolecular Interactions with Single Nanoparticles

Abstract

Biomolecular interactions compose a fundamental element of all life forms and are the biological basis of many biomedical assays. However, current methods for detecting biomolecular interactions have limitations in sensitivity and specificity. Here, using nitrogen-vacancy centers in diamond as quantum sensors, we demonstrate digital magnetic detection of biomolecular interactions with single magnetic nanoparticles (MNPs). We first developed a single-particle magnetic imaging (SiPMI) method on 100 nm-sized MNPs with negligible magnetic background, high signal stability, and accurate quantification. The single-particle method was performed on biotin−streptavidin interactions and DNA−DNA interactions in which a single-base mismatch was specifically differentiated. Subsequently, SARS-CoV-2-related antibodies and nucleic acids were examined by a digital immunomagnetic assay derived from SiPMI. In addition, a magnetic separation process improved the detection sensitivity and dynamic range by more than 3 orders of magnitude and also the specificity. This digital magnetic platform is applicable to extensive biomolecular interaction studies and ultrasensitive biomedical assays.

Nitrogen-vacancy center magnetic imaging of Fe3O4 nanoparticles inside the gastrointestinal tract of Drosophila melanogaster

“…Sub-areas of interest could be inspected by NV center magnetometry in order to obtain more detailed information about the MNP distribution within the tissue. In combination with MNP surface functionalization, 42 the magnetic imaging could be used to further explore physiological processes. High spatial resolution imaging of MNPs could also be useful for the further exploration and optimization of various other MNP applications.…”