Thayer School of Engineering, Dartmouth College, Hanover, NH 03755, USA.
Fred Hutchinson Cancer Center, Seattle, WA 98109, USA.
Sensors (Basel). 2022 Sep 4;22(17):6690. doi: 10.3390/s22176690.
Magnetic particle spectroscopy (MPS) in the Brownian relaxation regime, also termed magnetic spectroscopy of Brownian motion (MSB), can detect and quantitate very low, sub-nanomolar concentrations of molecular biomarkers. MPS/MSB uses the harmonics of the magnetization induced by a small, low-frequency oscillating magnetic field to provide quantitative information about the magnetic nanoparticles' (mNPs') microenvironment. A key application uses antibody-coated mNPs to produce biomarker-mediated aggregation that can be detected using MPS/MSB. However, relaxation changes can also be caused by viscosity changes. To address this challenge, we propose a metric that can distinguish between aggregation and viscosity. Viscosity changes scale the MPS/MSB harmonic ratios with a constant multiplier across all applied field frequencies. The change in viscosity is exactly equal to the multiplier with generality, avoiding the need to understand the signal explicitly. This simple scaling relationship is violated when particles aggregate. Instead, a separate multiplier must be used for each frequency. The standard deviation of the multipliers over frequency defines a metric isolating viscosity (zero standard deviation) from aggregation (non-zero standard deviation). It increases monotonically with biomarker concentration. We modeled aggregation and simulated the MPS/MSB signal changes resulting from aggregation and viscosity changes. MPS/MSB signal changes were also measured experimentally using 100 nm iron-oxide mNPs in solutions with different viscosities (modulated by glycerol concentration) and with different levels of aggregation (modulated by concanavalin A linker concentrations). Experimental and simulation results confirmed that viscosity changes produced small changes in the standard deviation and aggregation produced larger values of standard deviation. This work overcomes a key barrier to using MPS/MSB to detect biomarkers in vivo with variable tissue viscosity.
在布朗松弛（Brownian relaxation）区的磁性粒子光谱学（Magnetic Particle Spectroscopy，MPS），也被称为布朗运动的磁性光谱学（Magnetic Spectroscopy of Brownian Motion，MSB），可以检测和定量非常低的、亚纳摩尔浓度的分子生物标志物。MPS/MSB 使用小的低频振荡磁场引起的磁化的谐波，提供关于磁性纳米粒子（Magnetic nanoparticles，mNPs）微环境的定量信息。一个关键的应用是使用抗体包覆的 mNPs 产生生物标志物介导的聚集，这些聚集可以使用 MPS/MSB 检测。然而，弛豫变化也可能由粘度变化引起。为了解决这个挑战，我们提出了一个可以区分聚集和粘度的度量。粘度变化以常数乘数缩放 MPS/MSB 谐波比，跨越所有施加的磁场频率。粘度的变化与通用性完全相等，避免了明确理解信号的需要。当粒子聚集时，这种简单的缩放关系会被破坏。相反，必须为每个频率使用单独的乘数。在频率上，乘数的标准偏差定义了一个度量，将粘度（标准偏差为零）与聚集（非零标准偏差）隔离。它随着生物标志物浓度的增加单调增加。我们对聚集进行了建模，并模拟了由聚集和粘度变化引起的 MPS/MSB 信号变化。还使用不同粘度（通过甘油浓度调制）和不同聚集程度（通过伴刀豆球蛋白 A 连接子浓度调制）的溶液中的 100nm 氧化铁 mNPs 进行了实验测量 MPS/MSB 信号变化。实验和模拟结果证实，粘度变化在标准偏差上产生较小的变化，而聚集在标准偏差上产生较大的值。这项工作克服了使用 MPS/MSB 在体内检测具有可变组织粘度的生物标志物的一个关键障碍。
