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A Method for Selecting Structure-switching Aptamers Applied to a Colorimetric Gold Nanoparticle Assay
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Modular Aptamer Switches for the Continuous Optical Detection of Small-Molecule Analytes in Complex Media
Amani A Hariri1, Alyssa P Cartwright2, Constantin Dory2
1Department of Radiology, Stanford University, Stanford, CA, 94305, USA.
Advanced Materials (Deerfield Beach, Fla.)
|November 17, 2023
Summary
Researchers developed a novel aptamer switch design for biosensors. This innovation allows for tunable properties without needing prior knowledge of the target binding site, enabling faster, multi-biomarker detection in complex samples.
Area of Science:
- Biotechnology and Biomedical Engineering
- Molecular Biology and Biochemistry
- Analytical Chemistry and Sensor Technology
Background:
- Aptamers are valuable affinity reagents for biosensing due to integrated signal transduction capabilities.
- Integrating signal transduction into aptamers is challenging, often requiring extensive optimization and knowledge of target binding sites, potentially compromising affinity and specificity.
Purpose of the Study:
- To develop a universal design architecture for converting existing aptamers into 'reversible aptamer switches'.
- To enable tuning of aptamer switch kinetic and thermodynamic properties without prior knowledge of the ligand binding domain or structure.
- To demonstrate a novel optical biosensor system for continuous, real-time multiplexed biomarker detection in complex biological samples.
Main Methods:
- Designed a novel architecture to create 'reversible aptamer switches' from existing aptamers.
- Combined aptamer switches with evanescent-field-based optical detection hardware.
- Utilized minimized sample autofluorescence for enhanced signal detection.
Main Results:
- Successfully converted existing aptamers into tunable, reversible aptamer switches.
- Demonstrated the first optical biosensor capable of continuous, multiplexed detection of dopamine and cortisol.
- Achieved second and subsecond-scale time responses in complex samples like artificial cerebrospinal fluid and undiluted plasma at physiologically relevant concentrations.
Conclusions:
- The developed design architecture provides a versatile method for creating aptamer-based biosensors with tunable properties.
- The novel optical biosensor system enables rapid, continuous, and multiplexed detection of biomarkers in complex biological matrices.
- This approach overcomes limitations of traditional aptamer engineering and opens new avenues for real-timePoint-of-care diagnostics.

