Development of an ultra-high sensitive immunoassay with plasma biomarker for differentiating Parkinson disease dementia from Parkinson disease using antibody functionalized magnetic nanoparticles

Shieh Yueh Yang; Ming Jang Chiu; Chin Hsien Lin; Herng Er Horng; Che Chuan Yang; Jen Jie Chieh; Hsin Hsien Chen; Bing Hsien Liu

doi:10.1186/s12951-016-0198-5

Development of an ultra-high sensitive immunoassay with plasma biomarker for differentiating Parkinson disease dementia from Parkinson disease using antibody functionalized magnetic nanoparticles

Shieh Yueh Yang^*, Ming Jang Chiu, Chin Hsien Lin, Herng Er Horng, Che Chuan Yang, Jen Jie Chieh, Hsin Hsien Chen, Bing Hsien Liu

^*Corresponding author for this work

Undergraduate Program of Electro-Optical Engineering

Research output: Contribution to journal › Article › peer-review

46 Citations (Scopus)

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-T_c 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 0.3fg/ml and the dynamic range is 310pg/ml. The preliminary results show the plasma α-synuclein for PD patients distributes from 6 to 30fg/ml. For PDD patients, the concentration of plasma α-synuclein varies from 0.1 to 100pg/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-T_c SQUID magnetometer is promising as a method to assay plasma α-synuclein, which is a potential biomarker for discriminating patients with PD or PDD.

Original language	English
Article number	41
Journal	Journal of Nanobiotechnology
Volume	14
Issue number	1
DOIs	https://doi.org/10.1186/s12951-016-0198-5
Publication status	Published - 2016 Jun 8

Keywords

Immunomagnetic reduction
Parkinson disease
α-synuclein

ASJC Scopus subject areas

Bioengineering
Medicine (miscellaneous)
Molecular Medicine
Biomedical Engineering
Applied Microbiology and Biotechnology
Pharmaceutical Science

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10.1186/s12951-016-0198-5

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Yang, S. Y., Chiu, M. J., Lin, C. H., Horng, H. E., Yang, C. C., Chieh, J. J., Chen, H. H., & Liu, B. H. (2016). Development of an ultra-high sensitive immunoassay with plasma biomarker for differentiating Parkinson disease dementia from Parkinson disease using antibody functionalized magnetic nanoparticles. Journal of Nanobiotechnology, 14(1), Article 41. https://doi.org/10.1186/s12951-016-0198-5

Development of an ultra-high sensitive immunoassay with plasma biomarker for differentiating Parkinson disease dementia from Parkinson disease using antibody functionalized magnetic nanoparticles. / Yang, Shieh Yueh; Chiu, Ming Jang; Lin, Chin Hsien et al.
In: Journal of Nanobiotechnology, Vol. 14, No. 1, 41, 08.06.2016.

Research output: Contribution to journal › Article › peer-review

Yang, SY, Chiu, MJ, Lin, CH, Horng, HE, Yang, CC, Chieh, JJ, Chen, HH & Liu, BH 2016, 'Development of an ultra-high sensitive immunoassay with plasma biomarker for differentiating Parkinson disease dementia from Parkinson disease using antibody functionalized magnetic nanoparticles', Journal of Nanobiotechnology, vol. 14, no. 1, 41. https://doi.org/10.1186/s12951-016-0198-5

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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 0.3fg/ml and the dynamic range is 310pg/ml. The preliminary results show the plasma α-synuclein for PD patients distributes from 6 to 30fg/ml. For PDD patients, the concentration of plasma α-synuclein varies from 0.1 to 100pg/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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author = "Yang, {Shieh Yueh} and Chiu, {Ming Jang} and Lin, {Chin Hsien} and Horng, {Herng Er} and Yang, {Che Chuan} and Chieh, {Jen Jie} and Chen, {Hsin Hsien} and Liu, {Bing Hsien}",

note = "Funding Information: This work is supported by Ministry of Economic Affairs of Taiwan under grant numbers 101‑EC‑17‑A‑17‑I1‑0074 and by New Taipei City government under the grant number 103049 (SBIR) and by the Ministry of Science and Technol‑ ogy, Taiwan under grant number 104‑2745‑B‑003 ‑002. Publisher Copyright: {\textcopyright} 2016 The Author(s).",

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AU - Yang, Shieh Yueh

AU - Chiu, Ming Jang

AU - Lin, Chin Hsien

AU - Horng, Herng Er

AU - Yang, Che Chuan

AU - Chieh, Jen Jie

AU - Chen, Hsin Hsien

AU - Liu, Bing Hsien

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PY - 2016/6/8

Y1 - 2016/6/8

N2 - 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 0.3fg/ml and the dynamic range is 310pg/ml. The preliminary results show the plasma α-synuclein for PD patients distributes from 6 to 30fg/ml. For PDD patients, the concentration of plasma α-synuclein varies from 0.1 to 100pg/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.

AB - 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 0.3fg/ml and the dynamic range is 310pg/ml. The preliminary results show the plasma α-synuclein for PD patients distributes from 6 to 30fg/ml. For PDD patients, the concentration of plasma α-synuclein varies from 0.1 to 100pg/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.

KW - Immunomagnetic reduction

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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

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