Development of a 36-Channel Instrument for Assaying Biomarkers of Ultralow Concentrations Utilizing Immunomagnetic Reduction

Chen, Hsin-Hsien; Hsu, Ming-Hung; Lee, Kun-Hung; Yang, Shieh‐Yueh

doi:10.1021/acsmeasuresciau.2c00030

Cited by 4 publications

(5 citation statements)

References 38 publications

(52 reference statements)

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“…For example, the concentration of anti-AFP-coated Fe 3 O 4 MPs influenced the saturation magnetization Ms of the entire AFP reagents ( Figure 3 a), and the Ms increased after the bioconjugation with biomarkers ( Figure 3 b and Figure 4 a). Hence, the unit of magnetization is suitable for the AFP reagents in this work and other similar MP works [ 13 , 19 , 20 ].…”

Section: Discussionmentioning

confidence: 98%

“…However, the single MP with bioconjugated biomarkers did not contribute to the M increase by the acoustic type of VSM but significantly resulted in a reduction in AC susceptibility in IMR. Hence, the IMR technology was more sensitive in the low detection limitation of 3 ppb than 8 ppb in this work by the same AFP reagents and standard solvents [ 19 , 20 ] despite dissimilar operating conditions with different inspection instruments.…”

Section: Discussionmentioning

confidence: 99%

“…The elastic phantom was tissue promoted to vibrate MPs under another acoustic vibration, different from the DC H. Hence, for Co MPs in the same concentration of 50%, the area of a hysteresis loop of the uniform distribution (the upper one in the inset of Figure 6 c) was much larger than the precipitation under a thick water layer. Moreover, the Ms of soft magnetic type of MPs, such as Fe 3 O 4 MPs, was generally much lower than that of the hard ones [ 24 ], and the M detection was always too weak to rely on the aforementioned high-cost, complicated SQUID-based technology [ 15 , 20 ]. For the presented high MP concentrations, it could be explained in two aspects of the wide-enough inspection ranges and the experience of the ex vivo general stain, rather than the target after the injection.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Versatile and Accessible Magnetic Diagnosis Platform with Different Types of Magnetic Particles for Liquid and Solid Biopsies

Liu

Chen

Liao

et al. 2023

IJMS

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The diagnosis of liquid and solid biopsies by different instruments makes the clinic loading difficult in many aspects. Given the compositions of magnetic particles (MPs) with diverse characterizations and the innovative acoustic type of vibration sample magnetometer (VSM), the versatile, accessible magnetic diagnosis platform was proposed to meet clinical demands, such as low loading for multiple biopsies. In liquid biopsies of alpha-fetoprotein (AFP) standard solutions and subject serums, molecular concentration was analyzed from saturation magnetization by the soft type of Fe3O4 MPs with AFP bioprobe coating. In the phantom mixture simulated as bounded MPs in tissue, the bounded MPs was evaluated from the area of the hysteresis loop by hard type of cobalt MPs without bio-probes coating. Not only a calibration curve was founded for many hepatic cell carcinoma stages, but also microscale images verified the Ms increase due to magnetic protein clusters, etc. Hence, its wide populations in clinics could be expected.

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Versatile and Accessible Magnetic Diagnosis Platform with Different Types of Magnetic Particles for Liquid and Solid Biopsies

Liu

Chen

Liao

et al. 2023

IJMS

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“…Across the three instruments, p -values were higher than 0.05 in the measured concentrations of any tested biomarkers. Our results show that the SQUID-IMR instrument has high throughput, high stability, and high consistency [ 17 ]. Currently, a 36-channel, SQUID-based, high-Tc AC magnetometer can detect very low concentrations of amyloid and Tau protein in human plasma.…”

Section: Discussionmentioning

confidence: 99%

Applications of Immunomagnetic Reduction Technology as a Biosensor in Therapeutic Evaluation of Chinese Herbal Medicine in Tauopathy Alleviation of an AD Drosophila Model

et al. 2022

Biosensors

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Alzheimer’s disease (AD) is the most common form of dementia. The most convincing biomarkers in the blood for AD are currently β-amyloid (Aβ) and Tau protein because amyloid plaques and neurofibrillary tangles are pathological hallmarks in the brains of patients with AD. The development of assay technologies in diagnosing early-stage AD is very important. The study of human AD subjects is hindered by ethical and technical limitations. Thus, many studies have therefore turned to AD animal models, such as Drosophila melanogaster, to explore AD pathology. However, AD biomarkers such as Aβ and p-Tau protein in Drosophilamelanogaster occur at extremely low levels and are difficult to detect precisely. In this study, we applied the immunomagnetic reduction (IMR) technology of nanoparticles for the detection of p-Tau expressions in hTauR406W flies, an AD Drosophila model. Furthermore, we used IMR technology as a biosensor in the therapeutic evaluation of Chinese herbal medicines in hTauR406W flies with Tau-induced toxicity. To uncover the pathogenic pathway and identify therapeutic interventions of Chinese herbal medicines in Tau-induced toxicity, we modeled tauopathy in the notum of hTauR406W flies. Our IMR data showed that the selected Chinese herbal medicines can significantly reduce p-Tau expressions in hTauR406W flies. Using evidence of notal bristle quantification and Western blotting analysis, we confirmed the validity of the IMR data. Thus, we suggest that IMR can serve as a new tool for measuring tauopathy and therapeutic evaluation of Chinese herbal medicine in an AD Drosophila model.

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“…Intuitionally, the IMR analyzer is a high-temperature superconducting quantum interference device (high- T c SQUID) magnetosusceptometer. Because of the demands of high throughput for clinical use, second-, third-, and fourth-generation IMR analyzers were developed in 2010, 2018, and 2022, respectively. − The evolution from the first-generation to the fourth-generation high- T c SQUID magnetosusceptometer was discussed in ref . Currently, the IMR analyzer is a 36-channel high- T c SQUID magnetosusceptometer.…”

Section: Introductionmentioning

confidence: 99%

Analyzer-to-Analyzer Variations in Assaying Ultralow Concentrated Biomarkers Associated with Neurodegenerative Diseases Using Immunomagnetic Reduction

Lee,

Hsu,

Chen

et al. 2023

ACS Meas. Sci. Au

Self Cite

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By utilizing a high-temperature superconducting quantum interference device (high-T c SQUID) magnetometer, an alternating current (AC) magnetosusceptometer, referred to as an analyzer, was developed for ultrasensitive immunoassays. The analyzer has been applied to assay biomarkers in human plasma associated with Alzheimer’s disease (AD) and Parkinson’s disease (PD). The involved assay methodology is the so-called immunomagnetic reduction (IMR). Such an analyzer has been approved for clinical use in Taiwan and Europe. The mass production of the analyzer is needed for clinical utilities. The issue of exploring analyzer-to-analyzer variations in the performances becomes critical. Unfortunately, there is no standard characterization to determine the variations in performances among analyzers. In this study, key characterizations, such as output signal stability, signal-to-noise ratio, measured concentrations of a control sample, etc., are proposed. In total, three analyzers are characterized in this work. The detected biomarkers include amyloid peptides, total tau protein, phosphorylated tau protein, and α-synuclein protein for AD and PD. Through one-way ANOVA for any of the characterizations among the three analyzers, it was found that there was no significant difference in any of these characterizations among the analyzers (p > 0.05). Furthermore, the three analyzers are applied to assay biomolecules for AD and PD in reference samples. High correlations (r > 0.8) in measured concentrations of any of these biomarkers in reference samples were obtained among the three analyzers. The results demonstrate that the proposed characterizations are feasible for achieving consistent performance among high-T c SQUID-based AC magnetosusceptometers for assaying biomolecules.

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Development of a 36-Channel Instrument for Assaying Biomarkers of Ultralow Concentrations Utilizing Immunomagnetic Reduction

Cited by 4 publications

References 38 publications

Versatile and Accessible Magnetic Diagnosis Platform with Different Types of Magnetic Particles for Liquid and Solid Biopsies

Versatile and Accessible Magnetic Diagnosis Platform with Different Types of Magnetic Particles for Liquid and Solid Biopsies

Applications of Immunomagnetic Reduction Technology as a Biosensor in Therapeutic Evaluation of Chinese Herbal Medicine in Tauopathy Alleviation of an AD Drosophila Model

Analyzer-to-Analyzer Variations in Assaying Ultralow Concentrated Biomarkers Associated with Neurodegenerative Diseases Using Immunomagnetic Reduction

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