Highly sensitive/selective 3D nanostructured immunoparticle-based interface on a multichannel sensor array for detecting amyloid-beta in Alzheimer's disease

Ta Chung Liu, Yi Chao Lee, Chiung Yuan Ko, Ren Shyan Liu, Chien Chih Ke, Yu Chun Lo, Pei Sung Hong, Chao Yi Chu, Ching Wen Chang, Pu Wei Wu, You Yin Chen, San Yuan Chen

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Accumulation of β-amyloid (Aβ) peptides is highly associated with Alzheimer's disease (AD) progression in prevailing studies. The successful development of an ultrasensitive detection assay for Aβ is a challenging task, especially from blood-based samples. Methods: We have developed a one-step electrophoresis/electropolymerization strategy for preparing a CSIP hierarchical immunoelectrochemical interface that is easily integrated into a PoCT device. The interface includes conductive silk fibroin-based immunoparticles (CSIPs) via electropolymerized Poly(3,4-ethylenedioxythiophene) (PEDOT) bridging to enable on-site electrochemical detection of serum amyloid-β42 (Aβ42) and -β40 (Aβ40) peptides from an AD blood test. In addition, micro-positron emission tomography (microPET) neuroimaging and behavioral tests were simultaneously performed. Results: This nanostructured conductive interface favors penetration of water-soluble biomolecules and catalyzes a redox reaction, providing limits of detection (LOD) of 6.63 pg/mL for Aβ40 and 3.74 pg/mL for Aβ42. Our proof-of-concept study confirms that the multi-sensing electrochemical immunosensor array (MEIA) platform enables simultaneous measurement of serum Aβ42 and Aβ40 peptide levels and is more informative in early stage AD animals than amyloid-labeling Aβ plaque PET imaging and behavioral tests. Conclusion: We believe this study greatly expands the applications of silk fibroin-based materials, is an important contribution to the advancement of biomaterials, and would also be valuable in the design of new types of multichannel electrochemical immunosensor arrays for the detection of other diseases.

Original languageEnglish
Pages (from-to)4210-4225
Number of pages16
JournalTheranostics
Volume8
Issue number15
DOIs
Publication statusPublished - Jan 1 2018

Fingerprint

Amyloid
Fibroins
Alzheimer Disease
Silk
Peptides
Hematologic Tests
Biocompatible Materials
Serum
Neuroimaging
Positron-Emission Tomography
Oxidation-Reduction
Disease Progression
Electrophoresis
Limit of Detection
Equipment and Supplies
Water
Behavior Rating Scale

Keywords

  • Alzheimer's disease
  • Amyloid-beta (Aβ)
  • MicroPET
  • Point-of-care testing (PoCT)
  • Silk fibroin

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Pharmacology, Toxicology and Pharmaceutics (miscellaneous)

Cite this

Highly sensitive/selective 3D nanostructured immunoparticle-based interface on a multichannel sensor array for detecting amyloid-beta in Alzheimer's disease. / Liu, Ta Chung; Lee, Yi Chao; Ko, Chiung Yuan; Liu, Ren Shyan; Ke, Chien Chih; Lo, Yu Chun; Hong, Pei Sung; Chu, Chao Yi; Chang, Ching Wen; Wu, Pu Wei; Chen, You Yin; Chen, San Yuan.

In: Theranostics, Vol. 8, No. 15, 01.01.2018, p. 4210-4225.

Research output: Contribution to journalArticle

Liu, Ta Chung ; Lee, Yi Chao ; Ko, Chiung Yuan ; Liu, Ren Shyan ; Ke, Chien Chih ; Lo, Yu Chun ; Hong, Pei Sung ; Chu, Chao Yi ; Chang, Ching Wen ; Wu, Pu Wei ; Chen, You Yin ; Chen, San Yuan. / Highly sensitive/selective 3D nanostructured immunoparticle-based interface on a multichannel sensor array for detecting amyloid-beta in Alzheimer's disease. In: Theranostics. 2018 ; Vol. 8, No. 15. pp. 4210-4225.
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AU - Liu, Ren Shyan

AU - Ke, Chien Chih

AU - Lo, Yu Chun

AU - Hong, Pei Sung

AU - Chu, Chao Yi

AU - Chang, Ching Wen

AU - Wu, Pu Wei

AU - Chen, You Yin

AU - Chen, San Yuan

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AB - Accumulation of β-amyloid (Aβ) peptides is highly associated with Alzheimer's disease (AD) progression in prevailing studies. The successful development of an ultrasensitive detection assay for Aβ is a challenging task, especially from blood-based samples. Methods: We have developed a one-step electrophoresis/electropolymerization strategy for preparing a CSIP hierarchical immunoelectrochemical interface that is easily integrated into a PoCT device. The interface includes conductive silk fibroin-based immunoparticles (CSIPs) via electropolymerized Poly(3,4-ethylenedioxythiophene) (PEDOT) bridging to enable on-site electrochemical detection of serum amyloid-β42 (Aβ42) and -β40 (Aβ40) peptides from an AD blood test. In addition, micro-positron emission tomography (microPET) neuroimaging and behavioral tests were simultaneously performed. Results: This nanostructured conductive interface favors penetration of water-soluble biomolecules and catalyzes a redox reaction, providing limits of detection (LOD) of 6.63 pg/mL for Aβ40 and 3.74 pg/mL for Aβ42. Our proof-of-concept study confirms that the multi-sensing electrochemical immunosensor array (MEIA) platform enables simultaneous measurement of serum Aβ42 and Aβ40 peptide levels and is more informative in early stage AD animals than amyloid-labeling Aβ plaque PET imaging and behavioral tests. Conclusion: We believe this study greatly expands the applications of silk fibroin-based materials, is an important contribution to the advancement of biomaterials, and would also be valuable in the design of new types of multichannel electrochemical immunosensor arrays for the detection of other diseases.

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KW - Amyloid-beta (Aβ)

KW - MicroPET

KW - Point-of-care testing (PoCT)

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