COMPASS – rapid and highly sensitive medical point-of-care diagnostic

Abstract

In the last decade Magnetic nanoparticles (MNPs) have gained an enormous interest in specialized areas such as medicine, cancer theranostics, biosensing, catalysis, agriculture, and the environmental protection. By controlled engineering of specific surface properties, named functionalization, MNPs are gaining special features for desired applications, e.g., bioassays for the detection of biomolecules or biomarkers such as antibodies. The characterization as well as a highly specific measurement of such binding states is of high interest and limited to highly sensitive techniques such as ELISA (Enzyme-linked Immunosorbent Assay) or flow cytometry, which are relatively inflexible, difficult to handle, expensive and time-consuming. Novel upcoming methods, such as ACS (AC susceptometry) or MPS (Magnetic Particle Spectroscopy), exploit the magnetization response of functionalized MNP ensembles to assess specific information about the MNP mobility within their environment as well as the conjugations of chemical or biological compounds on their surface. Both methods have shown promising results reaching similar sensitivities within short measurement times but showing difficulties in data interpretation. Here, we report a novel method, COMPASS (Critical Offset Magnetic PArticle SpectroScopy), which is based on a critical offset magnetic field of MNPs, which enables sensitive detection to minimal changes in mobility of MNP ensembles, e.g., resulting from SARS-CoV-2 antibodies binding to the S antigen on the surface of functionalized MNPs. With a validated sensitivity of 0.85 fmole/50 µl sample volume ( ≙ 33 pM) SARS-CoV-2-S1 antibodies, measured with a low-cost portable COMPASS device, the proposed technique is not only competitive with the sensitivity of commonly used ELISA or flow cytometry methods but provides more flexibility, robustness and rapid measurement withinwell below a minute per sample, including sample conjugation, mixing and incubation times. The underlying physical effect is based on an offset magnetic field induced suppression of a higher harmonic in the nonlinear magnetization response of the MNP to a time varying magnetic field resulting in a highly sensitive response of the signal phase to minimal changes in particle mobility. Since this effect is independent of MNP concentration, the sample handling is much simpler and robust. Our method thus may pave the way for deeper insights into complex and rapid binding dynamics of functionalization chemistry and can lead to a huge step forwards in point-of-care diagnostics as well as impacts other fields in research and industries.