Author ORCID Identifier

https://orcid.org/0000-0002-0495-5280

Date of Award

Winter 2026

Document Type

Thesis (Ph.D.)

Department or Program

Engineering Sciences

First Advisor

Solomon G. Diamond

Abstract

Magnetic particle spectroscopy (MPS) based aggregation assays rely on target induced changes in functionalized magnetic nanoparticle (fMNP) hydrodynamic diameter and/or changes in fMNP aggregation level to enable target detection. fMNP target binding can be modeled via Brownian and Néel relaxation. We are engineering an MPS-based aggregation assay to sense tumor necrosis factor (TNF)-⍺ in a 3D melanoma tissue culture to aid in the development of immunotherapies for cancer treatment. TNF-⍺ is an inflammatory cytokine, whose production can be linked to cell death.

The first part of this thesis investigates the effects of ligand density, off-target proteins, and salts on fMNP targeting efficacy. fMNP aggregation assays can suffer from inaccuracies due to interactions with salts and off-target proteins. Our results suggest that (1) Derjaguin, Landau, Verwey, and Overbeek simulations can accurately predict the impact of salts on target induced fMNP aggregation, (2) off-target serum proteins refined assay resolution by >10x, and (3) the aggregation assay’s measurable concentration range can be tuned with surface ligand density.

In the second part of this thesis, we physically and magnetically characterized the fMNP-target binding complex to determine which relaxation mechanism was the dominant contributor to target induced changes in assay readout. The mechanism with the shortest relaxation time is dominant. Nèel dominant MPS-based aggregation assays are less susceptible to false readouts due to changes in environmental conditions. Interestingly, the dominant relaxation mechanism contributing to changes in assay readout was dependent on the level of target induced MNP aggregation. Dispersed MNPs were Brownian dominant, while aggregated MNPs were Nèel dominant.

In the final part of this thesis, we outline several methods to use our assay for TNF-⍺ sensing in a 3D tissue culture. We have developed an approach to localize the fMNPs within the 3D tissue culture to monitor target concentration profiles over time and can calibrate fMNP MPS signals to TNF-⍺ concentrations using a Fickian diffusion model. We also built another Fickian diffusion model to predict protein diffusion and consumption throughout the 3D tissue culture. Lastly, we are developing a site-directed method for MNP anti-TNF-⍺ antibody functionalization to promote optimal targeting efficiency.

Original Citation

Moss, G., Knopke, C., & Diamond, S. G. (2024). Effects of Salt Concentration on a Magnetic Nanoparticle-Based Aggregation Assay with a Tunable Dynamic Range. Sensors, 24(19), 6241.

Moss, G., Knopke, C., & Diamond, S. G. (2026). Impact of protein corona on magnetic particle spectroscopy-based bioassays. Nanoscale Advances.

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