Magnetic Particle Spectroscopy with One-Stage Lock-In Implementation for Magnetic Bioassays with Improved Sensitivities

Chugh, Vinit Kumar; Wu, Kai; Krishna, Venkatramana D.; Girolamo, Arturo Di; Bloom, Robert P.; Wang, Yongqiang Andrew; Saha, Renata; Liang, Shuang; Cheeran, Maxim C.-J.; Wang, Jian Ping

doi:10.1021/acs.jpcc.1c05126

Cited by 13 publications

(13 citation statements)

References 33 publications

(42 reference statements)

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“…However, upon the addition of target analytes, the MNPs undergo clustering events, thus restricting Brownian relaxation, which leads to a drop in the harmonic amplitude. Two important factors help improve the sensitivity of a volumetric bioassay MPS system: (1) Brownian dominant behavior of MNPs, what it means to our context is that a larger % drop (Δ) from the unbound state (simultaneous Brownian and Néel relaxation possible) to the bound state (only Néel relaxation possible) benefits sensitivity; and (2) higher harmonic amplitude from unbound MNPs, this has an indirect effect on sensitivity as it allows for the use of smaller quantities of MNPs for bioassay testing, which has proven to improve the sensitivity significantly. , Because of this unique dependence, instead of giving general guidelines, we will limit ourselves to only a few categorical reviews that can help improve sensitivity.…”

Section: Resultsmentioning

confidence: 99%

“…On one hand, single-core MNPs present with a larger harmonic drop, meaning that the Brownian relaxation mechanism is more dominant for these nanoparticles; on the other hand, they also offer a smaller harmonic amplitude. This means that a smaller number of multicore MNPs can be utilized instead for the generation of a suitable harmonic amplitude for bioassay applications, which has been shown to provide significant sensitivity improvements. , Due to this dichotomy between the harmonic amplitude strength and corresponding Δ, the choice between single- or multicore MNPs for better sensitivity has been left for further in-depth investigation.…”

Section: Conclusion and Future Prospectsmentioning

confidence: 99%

“…This means that a smaller number of multicore MNPs can be utilized instead for the generation of a suitable harmonic amplitude for bioassay applications, which has been shown to provide significant sensitivity improvements. 37,38 Due to this dichotomy between the harmonic amplitude strength and corresponding Δ, the choice between single-or multicore MNPs for better sensitivity has been left for further in-depth investigation.…”

Section: Conclusion and Future Prospectsmentioning

confidence: 99%

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Frequency and Amplitude Optimizations for Magnetic Particle Spectroscopy Applications

et al. 2022

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Nowadays, there is a growing interest in the field of magnetic particle spectroscopy (MPS)-based bioassays. MPS monitors the dynamic magnetic response of surface-functionalized magnetic nanoparticles (MNPs) upon excitation by an alternating magnetic field (AMF) to detect various target analytes. This technology has flourished in the past decade due to its low cost, low background magnetic noise interference from the biomatrix, and fast response time. A large number of MPS variants have been reported by different groups around the world, with applications ranging from disease diagnosis to foodborne pathogen detection and virus detection. However, there is an urgent need for guidance on how to optimize the sensitivity of MPS detection by choosing different types of MNPs, AMF modalities, and MPS assay strategies (i.e., volume-and surface-based assays). In this work, we systematically study the effect of AMF frequencies and amplitudes on the responses of single-and multicore MNPs under two extreme conditions, namely, the bound and unbound states. Our results show that some modalities such as dual-frequency MPS utilizing multicore MNPs are more suitable for surface-based bioassay applications, whereas single-frequency MPS systems using single-or multicore MNPs are better suited for volumetric bioassay applications. Furthermore, the bioassay sensitivities for these modalities can be further improved by a careful selection of AMF frequencies and amplitudes.

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Section: Resultsmentioning

confidence: 99%

Section: Conclusion and Future Prospectsmentioning

confidence: 99%

Section: Conclusion and Future Prospectsmentioning

confidence: 99%

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Frequency and Amplitude Optimizations for Magnetic Particle Spectroscopy Applications

et al. 2022

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“…This feasibility attempt allows us to explore inexpensive bioassays on our MPS platform for future high-volume tests at the users’ ends and in regions with scarce medical resources. Furthermore, it is reported that for MPS-based homogeneous bioassays, lower MNP concentrations could improve the detection sensitivities of biomolecules. , …”

Section: Materials and Methodsmentioning

confidence: 99%

One-Step, Wash-free, Nanoparticle Clustering-Based Magnetic Particle Spectroscopy Bioassay Method for Detection of SARS-CoV-2 Spike and Nucleocapsid Proteins in the Liquid Phase

Chugh

Krishna

et al. 2021

ACS Appl. Mater. Interfaces

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With the ongoing global pandemic of coronavirus disease 2019 (COVID-19), there is an increasing quest for more accessible, easy-to-use, rapid, inexpensive, and high-accuracy diagnostic tools. Traditional disease diagnostic methods such as qRT-PCR (quantitative reverse transcription-PCR) and ELISA (enzyme-linked immunosorbent assay) require multiple steps, trained technicians, and long turnaround time that may worsen the disease surveillance and pandemic control. In sight of this situation, a rapid, one-step, easy-to-use, and high-accuracy diagnostic platform will be valuable for future epidemic control, especially for regions with scarce medical resources. Herein, we report a magnetic particle spectroscopy (MPS) platform for the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) biomarkers: spike and nucleocapsid proteins. This technique monitors the dynamic magnetic responses of magnetic nanoparticles (MNPs) and uses their higher harmonics as a measure of the nanoparticles’ binding states. By anchoring polyclonal antibodies (pAbs) onto MNP surfaces, these nanoparticles function as nanoprobes to specifically bind to target analytes (SARS-CoV-2 spike and nucleocapsid proteins in this work) and form nanoparticle clusters. This binding event causes detectable changes in higher harmonics and allows for quantitative and qualitative detection of target analytes in the liquid phase. We have achieved detection limits of 1.56 nM (equivalent to 125 fmole) and 12.5 nM (equivalent to 1 pmole) for detecting SARS-CoV-2 spike and nucleocapsid proteins, respectively. This MPS platform combined with the one-step, wash-free, nanoparticle clustering-based assay method is intrinsically versatile and allows for the detection of a variety of other disease biomarkers by simply changing the surface functional groups on MNPs.

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“…In this work, we immobilized MNP chains of varying concentrations and alignments of easy axes relative to the probing magnetic field directions. The static and dynamic magnetization responses of these MNP chain samples are characterized by a standard VSM and a home-built magnetic particle spectroscopy (MPS) system, , respectively. MPS is a 1D magnetic particle imaging (MPI) platform, and it has been reported for magnetic biosensing applications that utilize the dynamic magnetization responses of MNPs as well as for examining the suitability of MNP tracers for MPI imaging.…”

Section: Introductionmentioning

confidence: 99%

Static and Dynamic Magnetization Responses of Self-Assembled Magnetic Nanoparticle Chains

Chugh,

Liang,

Tonini

et al. 2023

J. Phys. Chem. C

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The dynamic magnetization responses of magnetic nanoparticles (MNPs) subjected to alternating magnetic fields have been exploited for many biomedical applications, such as hyperthermia therapy, magnetic biosensing, and imaging. This dynamic process is governed by the combined Brownian and Néel relaxations via various energy terms. Both extrinsic factors, such as external alternating fields, dipolar fields, and the properties of the MNP medium, and intrinsic factors, such as the shape, size, and the magnetic properties of the MNPs, can affect their dynamic magnetization responses. However, due to the complex energy terms and interparticle interactions involved, it can be challenging to characterize how each factor influences the dynamic magnetization responses. In this study, we systematically examined the static and dynamic magnetization responses of an ensemble of MNPs. By solidifying the MNP suspension under a fixation field, the immobilized MNPs form long chains, and their easy axes are artificially tuned. In this simplified model, factors such as relative orientations of MNPs’ easy axes to the external field and the dipolar interactions of MNPs are studied. Using a magnetic particle spectroscopy (MPS) platform, the time domain dynamic magnetization responses, dynamic hysteresis loops, high harmonics (which are of interest for MPS and magnetic particle imaging applications), and phase lag of MNPs’ magnetizations to external fields were recorded. A strong correlation between the phase lag of MNPs and the nonlinearity in AC magnetization loops was established.

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Magnetic Particle Spectroscopy with One-Stage Lock-In Implementation for Magnetic Bioassays with Improved Sensitivities

Cited by 13 publications

References 33 publications

Frequency and Amplitude Optimizations for Magnetic Particle Spectroscopy Applications

Frequency and Amplitude Optimizations for Magnetic Particle Spectroscopy Applications

One-Step, Wash-free, Nanoparticle Clustering-Based Magnetic Particle Spectroscopy Bioassay Method for Detection of SARS-CoV-2 Spike and Nucleocapsid Proteins in the Liquid Phase

Static and Dynamic Magnetization Responses of Self-Assembled Magnetic Nanoparticle Chains

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