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Employing an effective viscosity model within stochastic coupled N\u00e9el\u2013Brownian simulations, we quantify how viscosity (0.8\u201350\u00a0000\u00a0mPa\u00b7s) affects signal intensity of single\u2010frequency magnetic particle spectroscopy (MPS, 25\u00a0kHz) and frequency\u2010mixing MPS (FM\u2010MPS; f\n                    <jats:sub>H<\/jats:sub>\n                    \u00a0=\u00a040.5\u00a0kHz, f\n                    <jats:sub>L<\/jats:sub>\n                    \u00a0=\u00a00.063\u00a0kHz). We investigate single\u2010core, non\u2010interacting MNP with various core sizes (12\u201328\u00a0nm), hydrodynamic shell thicknesses (5\u2013100\u00a0nm), and anisotropy (4\u2013200\u00a0kJ\u00a0m\n                    <jats:sup>\u2212<\/jats:sup>\n                    <jats:sup>3<\/jats:sup>\n                    ), using dominant readouts (MPS: third\u2010harmonic; FM\u2010MPS:\n                    <jats:italic>\n                      f\n                      <jats:sub>H<\/jats:sub>\n                    <\/jats:italic>\n                    + 2\n                    <jats:italic>\n                      f\n                      <jats:sub>L<\/jats:sub>\n                    <\/jats:italic>\n                    mixing\u2010term). Increasing viscosity progressively suppresses Brownian rotation, with thicker shells affected at lower viscosities, and drives signals toward an immobilization plateau. Under the simulated conditions, MNP appear distinguishable in blood\u2010associated viscosities using MPS, whereas distinguishability is pronounced in cellular\/tissue\u2010like viscosities with FM\u2010MPS. Moderate anisotropy (\u223c20\u201340\u00a0kJ\u00a0m\n                    <jats:sup>\u2212<\/jats:sup>\n                    <jats:sup>3<\/jats:sup>\n                    ) enhances signals by \u223c10%, whereas higher anisotropies suppress relaxation, finally collapsing the signal. While large cores maximize the signal at fixed particle number, dosage\u2010normalized conditions suggest favorable performance for intermediate cores (\u223c15\u201318\u00a0nm). These results propose a cohesive framework linking particle properties, excitation scheme, and physiological environment, thereby providing insight into MNP tracer optimization for biosensing, cell tracking, imaging, and in vivo diagnostics.\n                  <\/jats:p>","DOI":"10.1002\/smll.76201","type":"journal-article","created":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T16:04:45Z","timestamp":1791734685000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Simulation\u2010Guided Tracer Optimization for Magnetic Particle Spectroscopy: Interplay of Core, Shell and Anisotropy Across Physiological\u2010Range Viscosities for Single\u2010 and Dual\u2010Frequency Excitation"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-7043-8606","authenticated-orcid":false,"given":"Mohamad Bilal","family":"Abbas","sequence":"first","affiliation":[{"name":"Department of Medical Engineering and Applied Mathematics FH Aachen University of Applied Sciences  J\u00fclich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-5708-6102","authenticated-orcid":false,"given":"Mohamad Alaa","family":"Abbas","sequence":"additional","affiliation":[{"name":"Department of Medical Engineering and Applied Mathematics FH Aachen University of Applied Sciences  J\u00fclich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4098-4521","authenticated-orcid":false,"given":"Timur","family":"Bikulov","sequence":"additional","affiliation":[{"name":"Institute of Biological Information Processing\u2014Bioelectronics (IBI\u20103) Forschungszentrum J\u00fclich  J\u00fclich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6904-1447","authenticated-orcid":false,"given":"Ali Mohammad","family":"Pourshahidi","sequence":"additional","affiliation":[{"name":"Institute of Biological Information Processing\u2014Bioelectronics (IBI\u20103) Forschungszentrum J\u00fclich  J\u00fclich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7526-9894","authenticated-orcid":false,"given":"Hans\u2010Joachim","family":"Krause","sequence":"additional","affiliation":[{"name":"Institute of Biological Information Processing\u2014Bioelectronics (IBI\u20103) Forschungszentrum J\u00fclich  J\u00fclich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9250-1686","authenticated-orcid":false,"given":"Ulrich M.","family":"Engelmann","sequence":"additional","affiliation":[{"name":"Department of Medical Engineering and Applied Mathematics FH Aachen University of Applied Sciences  J\u00fclich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,11]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"crossref","first-page":"1285","DOI":"10.1002\/jbm.a.35654","article-title":"Current Investigations Into Magnetic Nanoparticles for Biomedical Applications","volume":"104","author":"Li X.","year":"2016","journal-title":"Journal of Biomedical Materials Research Part A"},{"key":"e_1_2_11_3_1","doi-asserted-by":"crossref","first-page":"1146","DOI":"10.1002\/nano.202000162","article-title":"Recent Progress of Magnetic Nanoparticles in Biomedical Applications: A Review","volume":"2","author":"Anik M. 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