Biology subjects

Viereck, T.

Publications and source records attributed to Viereck, T..

4 recordsLinked to original sources

bioRxiv2026

Mind the gap between functional groups and surface of magnetic nanoparticles for highly specific magnetic-based protein assays in biological medium

Magnetic readout-based assays are compatible with unprocessed biological samples as unbound background molecules do not interfere with magnetic signal. Yet, a true challenge is their poor specificity and susceptibility of magnetic nanoparticles (MNPs) to clusters in complex biological media, hampering their true advancement. Here, we demonstrate that the spatial organization of functional groups at the external periphery of custom magnetic nanoparticles by harnessing ultra-dense double-stranded DNA results in an efficient antibody conjugation with good accessibility toward antigen. By labeling our MNPs with anti-S protein neutralizing IgG antibody, we showcase the detection of S1 subunit of SARS-CoV-2 Spike protein in a wash-free fashion in less than five minutes in nM regime using magnetic particle spectrometer. By mixing our IgG-labelled MNPs with DMEM cell culture (10-20% FBS serum), we sense the S1 proteins in a one-pot fashion with high specificity. Our results show that by having the ultra-dense dsDNA shell on MNPs, the entropic cost of an irreversible protein binding to particle surface is high, thus allowing the formation of dynamic protein corona on the DNA shell that can be replaced with S1 protein with high affinity. When the azide moieties are placed at the close proximity of MNPs by using non-functional dsDNA, antibody conjugation becomes inefficient, to a level not sufficient for S1 protein detection. Our study highlights the importance of spatial organization of functional moieties on the nanoscale on magnetic nanoparticles for highly specific assays in biologically complex media.

biochemistry↗

bioRxiv2025

Mismatch-Assisted Toehold Exchange Cascades for Magnetic Nanoparticle-Based Nucleic Acid Diagnostics

Sensitive, simple, and rapid detection of nucleic acid sequences at point-of-care (POC) settings is still an unmet quest. Magnetic readout assays combined with toehold-mediated strand displacement (TMSD)-based circuits are amplification- and wash-free, essential features for contributing to this demand. Nevertheless, nonenzymatic TMSD circuits are slow with low sensitivity for early disease diagnostics. Here, we propose novel mismatch-assisted toehold exchange (MATE) magnetic cascades, wherein magnetic susceptibility increases by dissociation of magnetic nanoparticles (MNPs) from engineered magnetic clusters upon detecting nucleic acid target in solution. The MATE relies on the generation of an allosteric toehold (TH) by spontaneous dissociation to efficiently recycle the target, amplify magnetic signal output, and enhance the assays kinetics. We show that introducing a mismatch in the allosteric TH domain enhances the overall declustering kinetics 7-fold, as also confirmed with oxDNA simulations, with the largest effect gained for the mismatch closest to where the branch migration by the target ends. By integrating MATE into magnetic diagnostics cascades, we demonstrate 3.6-fold better limit-of-detection (LoD) and 12-fold shorter assay time compared to our previous circuit design. Our work makes a major leap towards bringing MNP-based diagnostics much closer to the clinical POC settings by offering a simple, rapid, isothermal, and nonenzymatic assay workflow.

biochemistry↗

bioRxiv2023

Cooperative dynamics of DNA grafted magnetic nanoparticles optimize magnetic biosensing and coupling to DNA origami

Magnetic nanoparticles (MNPs) enable unique capabilities for biosensing and actuation via coupling to DNA origami, yet how DNA grafting density affects their dynamics and accessibility remains poorly understood. Here, we demonstrate functionalization of MNPs with single-stranded DNA (ssDNA) via click chemistry conjugation with tunable grafting density. Several complementary methods show that particle translational and rotational dynamics exhibit a sigmoidal dependence on ssDNA grafting density. At low densities ssDNA strands are coiled and cause small changes to particle dynamics, while at high densities they form polymer brushes that cooperatively change particle dynamics. Intermediate ssDNA densities show the highest magnetic biosensing sensitivity for detection of target nucleic acids. Finally, we demonstrate that MNPs with high grafting densities are required to efficiently couple them to DNA origami. These results together establish ssDNA grafting density as a critical parameter for functionalization of MNPs for use in a broad range of applications.

biochemistry↗

bioRxiv2022

Amplification and extraction free quantitative detection of viral nucleic acids and single-base mismatches using magnetic signal amplification circuit

Established nucleic acid detection assays require extraction and purification before sequence amplification and/or enzymatic reactions, hampering their widespread applications in point-of-care (POC) formats. Magnetic immunoassays based on magnetic particle spectroscopy and magnetic nanoparticles (MNPs) are isothermal, extraction- and purification-free, and can be quantitative and benchtop, making them suitable for POC settings. Here, we demonstrate a Magnetic signal Amplification Circuit (MAC) that combines specificity of toehold-mediated DNA strand displacement with magnetic response of MNPs to a clustering/declustering process. Our MAC assays require neither amplification nor extraction of target nucleic acids, and reveal four times better sensitivity than that of a magnetic circuit without signal amplification. Using MAC, we detect a highly specific 43 nucleotides sequence of SARS-CoV-2 virus. The MAC enables sensing both DNA and RNA targets with varying lengths and resolving single-base mismatches. Our MAC can be a powerful tool for translating research of nucleic acids detection to the clinic.

biochemistry↗