LED-based interferometric reflectance imaging sensor for the detection of amyloid-β aggregation
Xin R Cheng1, George G Daaboul, M Selim Ünlü
1Dept. of Physical and Environmental Sciences, University of Toronto at Scarborough, 1265 Military Trail, Toronto, ON M1C 1A4, Canada. kagan.kerman@utoronto.ca.
The Analyst
|November 7, 2013
Summary
This study introduces a novel sensor platform for real-time detection of amyloid-β (Aβ) fibril formation. The system screens potential Alzheimer's disease therapeutics by monitoring Aβ aggregation influenced by compounds like EGCG and Zn(ii).
Area of Science:
- Biochemistry
- Neuroscience
- Biomedical Engineering
Background:
- Amyloid-β (Aβ) self-aggregation is a key factor in Alzheimer's disease (AD) pathogenesis.
- Small molecules inhibiting Aβ fibril formation offer potential therapeutic strategies for AD.
- (-)epigallocatechin-3-gallate (EGCG) and Zn(ii) are known modulators of Aβ aggregation.
Purpose of the Study:
- To develop and validate a novel high-throughput, real-time platform for detecting Aβ fibril formation.
- To investigate the interaction of Aβ with modulators EGCG and Zn(ii) using the developed sensor.
- To demonstrate the platform's utility in screening small molecules for potential AD therapeutics.
Main Methods:
- Utilized a LED-based interferometric reflectance imaging sensor (LED-IRIS) for real-time detection.
- Employed a nucleation-based fibril growth strategy with covalently immobilized Aβ seeds.
- Used microfluidics to expose Aβ oligomers to the immobilized seeds and monitor fibril elongation.
Main Results:
- Successfully detected and monitored Aβ fibril elongation in real-time.
- Quantified the impact of EGCG and Zn(ii) on Aβ fibril growth.
- Demonstrated the platform's capability to assess the efficacy of modulators in inhibiting or facilitating Aβ aggregation.
Conclusions:
- Introduced a novel LED-IRIS based platform for high-throughput, real-time screening of Aβ aggregation inhibitors.
- The platform facilitates the discovery of potential therapeutic agents for Alzheimer's disease.
- This approach offers a promising avenue for accelerating the development of new AD treatments.
