BMC Springer Open Data

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    Development of an ultra-high sensitive immunoassay with plasma biomarker for differentiating Parkinson disease dementia from Parkinson disease using antibody functionalized magnetic nanoparticles
    (2016-06-08) Yang, Shieh-Yueh; Chiu, Ming-Jang; Lin, Chin-Hsien; Horng, Herng-Er; Yang, Che-Chuan; Chieh, Jen-Jie; Chen, Hsin-Hsien; Liu, Bing-Hsien
    Abstract Background It is difficult to discriminate healthy subjects and patients with Parkinson disease (PD) or Parkinson disease dementia (PDD) by assaying plasma α-synuclein because the concentrations of circulating α-synuclein in the blood are almost the same as the low-detection limit using current immunoassays, such as enzyme-linked immunosorbent assay. In this work, an ultra-sensitive immunoassay utilizing immunomagnetic reduction (IMR) is developed. The reagent for IMR consists of magnetic nanoparticles functionalized with antibodies against α-synuclein and dispersed in pH-7.2 phosphate-buffered saline. A high-Tc superconducting-quantum-interference-device (SQUID) alternative-current magnetosusceptometer is used to measure the IMR signal of the reagent due to the association between magnetic nanoparticles and α-synuclein molecules. Results According to the experimental α-synuclein concentration dependent IMR signal, the low-detection limit is 0.3 fg/ml and the dynamic range is 310 pg/ml. The preliminary results show the plasma α-synuclein for PD patients distributes from 6 to 30 fg/ml. For PDD patients, the concentration of plasma α-synuclein varies from 0.1 to 100 pg/ml. Whereas the concentration of plasma α-synuclein for healthy subjects is significantly lower than that of PD patients. Conclusions The ultra-sensitive IMR by utilizing antibody-functionalized magnetic nanoparticles and high-Tc SQUID magnetometer is promising as a method to assay plasma α-synuclein, which is a potential biomarker for discriminating patients with PD or PDD.
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    Assaying Carcinoembryonic Antigens by Normalized Saturation Magnetization
    (2015-07-03) Huang, Kai-Wen; Chieh, Jen-Jie; Shi, Jin-Cheng; Chiang, Ming-Hsien
    Abstract Biofunctionalized magnetic nanoparticles (BMNs) that provide unique advantages have been extensively used to develop immunoassay methods. However, these developed magnetic methods have been used only for specific immunoassays and not in studies of magnetic characteristics of materials. In this study, a common vibration sample magnetometer (VSM) was used for the measurement of the hysteresis loop for different carcinoembryonic antigens (CEA) concentrations (Φ CEA) based on the synthesized BMNs with anti-CEA coating. Additionally, magnetic parameters such as magnetization (M), remanent magnetization (M R), saturation magnetization (M S), and normalized parameters (ΔM R/M R and ΔM S/M S) were studied. Here, ΔM R and ΔM s were defined as the difference between any ΦCEA and zero Φ CEA. The parameters M, ΔM R, and ΔM S increased with Φ CEA, and ΔM S showed the largest increase. Magnetic clusters produced by the conjugation of the BMNs to CEAs showed a ΔM S greater than that of BMNs. Furthermore, the relationship between ΔM S/M S and Φ CEA could be described by a characteristic logistic function, which was appropriate for assaying the amount of CEAs. This analytic ΔM S/M S and the BMNs used in general magnetic immunoassays can be used for upgrading the functions of the VSM and for studying the magnetic characteristics of materials.
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    Dual-imaging model of SQUID biosusceptometry for locating tumors targeted using magnetic nanoparticles
    (2015-02-12) Chieh, Jen-Jie; Huang, Kai-Wen; Lee, Yi-Yan; Wei, Wen-Chun
    Abstract Background For intraoperative imaging in operating theaters or preoperative imaging in clinics, compact and economic integration rather than large and expensive equipment is required to coregister structural and functional imaging. However, current technologies, such as those integrating optical and gamma cameras or infrared and fluorescence imaging, involve certain drawbacks, including the radioactive biorisks of nuclear medicine indicators and the inconvenience of conducting measurements in dark environments. Methods To specifically and magnetically label liver tumors, an anti-alpha-fetoprotein (AFP) reagent was synthesized from biosafe iron oxide magnetic nanoparticles (MNPs) coated with anti-AFP antibody and solved in a phosphate buffered saline solution. In addition, a novel dual-imaging model system integrating an optical camera and magnetic scanning superconducting-quantum-interference device (SQUID) biosusceptometry (SSB) was proposed. The simultaneous coregistration of low-field magnetic images of MNP distributions and optical images of anatomical regions enabled the tumor distribution to be determined easily and in real time. To simulate targeted MNPs within animals, fewer reagents than the injected dose were contained in a microtube as a sample for the phantom test. The phantom test was conducted to examine the system characteristics and the analysis method of dual images. Furthermore, the animal tests were classified into two types, with liver tumors implanted either on the backs or livers of rats. The tumors on the backs were to visually confirm the imaging results of the phantom test, and the tumors on the livers were to simulate real cases in hepatocellular carcinoma people. Results A phantom test was conducted using the proposed analysis method; favorable contour agreement was shown between the MNP distribution in optical and magnetic images. Consequently, the positioning and discrimination of liver tumors implanted on the backs and livers of rats were verified by conducting in vivo and ex vivo tests. The results of tissue staining verified the feasibility of using this method to determine the distribution of liver tumors. Conclusion The results of this study indicate the clinical potential of using anti-AFP-mediated MNPs and the dual-imaging model SSB for discriminating and locating tumors.
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    Anti-CEA-functionalized superparamagnetic iron oxide nanoparticles for examining colorectal tumors in vivo
    (2013) Huang, Kai-Wen; Chieh, Jen-Jie; Lin, In-Tsang; Horng, Herng-Er; Yang, Hong-Chang; Hong, Chin-Yih