Sensitive mix-and-measure magnetic immunoassay for SARS-CoV-2 virus detection: towards benchtop point-of-need diagnostics

• Applicants: Dr. Aidin Lak; Dr. Maren Schubert; Dr.-Ing. Thilo Viereck
• Subject Area: Medical Physics, Biomedical Technology ; Synthesis and Properties of Functional Materials
• Term: since 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 503667663

Sensitive, economical, and easy-to-operate virus and antibody detection assays have never been highlighted to this extend before the breakout of the ongoing COVID19 pandemic. The need for simple and quantitative detection assays is immense when the emergence of a new viral outbreak is most likely inevitable. While being fairly easy to perform and evaluate, the available colorimetric rapid antigen tests are not sensitive enough for screening patients with even medium (106-107 virions/swab) viral loads and they provide qualitative readout only. The latter is a highly relevant missing information for corona containment.In this proposal, we will explore quantitative magnetic immunoassays based on magnetic particle spectroscopy (MPS) that provide fast and sensitive diagnostics at the point-of-need. Our detection approach, using antibody-conjugated magnetic nanoparticles (MNP) as biomarkers, can be performed directly on patient biofluid (e.g. saliva) with a small benchtop device using a simple mix-and-measure procedure for easy use by untrained personnel.We will address fundamental questions for establishing homogenous magnetic immunoassays for generic virus detection (beyond SARS-CoV-2) by combining expertise from materials science (magnetic nanoparticles), biology (antibodies) and engineering (MPS device). We will customize our magnetic nanoparticles in terms of dynamic magnetic properties for high magnetic signal, and we will engineer the surface chemistry by tailoring charge and hydrophilicity to offer highly specific binding to viruses and antigens and excellent stability in biofluids. We will establish monoclonal antibody-MNP conjugates with optimized binding properties, controlled binding directionality, and low off-rate to enable both sensitive and quantitative assays. We will also build a tailored small benchtop MPS device, which enables users to easily conduct magnetic immunoassays at low cost and without specific training directly at the point-of-need.In addition to answering basic research questions on antibody-MNP markers, measurement technology, and assay protocol, we will establish and validate all steps in relevant biological environments (biofluids). Finally, we will test our assays on virions directly from cell culture samples.Combining our three unique expertise, we will – for the first time – build an all-optimized highly sensitive and compact MPS-based detection system to realize a competitive magnetic immunoassay for sensitive, low-cost, fast, and quantitative diagnostics of SARS-CoV-2 and beyond, that will achieve the limit of detection relevant for large scale screening of patient samples.

• DFG Programme: Research Grants