DNA Nanostructure Tethered Diffusion for Versatile Electrochemical Detection
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Solution Overview
Problem
Current electrochemical sensors for biomarker quantification are target-focused and lack generalizability, making them inefficient for detecting a range of molecular classes such as small molecules, nucleic acids, and proteins, and require laborious and expensive probe preparation.
Innovation Solution
A DNA-nanostructure composed of a single continuous DNA molecule with hairpin structural motifs, an anchor recognition moiety, and a signal moiety, which changes its tethered diffusion rate upon analyte binding, allowing for versatile detection of multiple analyte classes through changes in signal output.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If target-focused electrochemical sensors are used, then detection precision for specific biomarkers is improved, but adaptability to detect multiple molecular classes deteriorates
Solution Approach 1:
The patent employs a universal aptamer scaffold that can bind to multiple different analytes including small molecules, nucleic acids, and proteins. The aptamer backbone remains constant while only the recognition moiety needs to be changed, allowing a single sensor platform to detect diverse molecular classes with high precision without requiring target-specific sensor redesign
2Measurement precision
If target-focused sensor methods are used, then detection precision for specific analytes is improved, but device complexity increases due to separate probe preparation for each target
Solution Approach 1:
The patent utilizes a universal aptamer scaffold structure that serves multiple detection functions. The same basic scaffold can be used to detect different analytes by simply changing the recognition moiety, eliminating the need for separate complex probe preparations for each target and significantly reducing device complexity
Solution Approach 2:
The aptamer is divided into modular components: a constant scaffold structure and a variable recognition moiety. This segmentation allows the scaffold to be reused across different applications while only the recognition portion needs to be customized for each specific analyte, simplifying overall sensor preparation
3Measurement precision
If target-focused electrochemical sensors are used, then measurement precision for specific biomarkers is improved, but productivity deteriorates due to laborious probe preparation
Solution Approach 1:
The universal aptamer scaffold enables a single sensor platform to detect multiple analyte classes including small molecules, nucleic acids, and proteins. This multi-functionality increases productivity by allowing researchers to screen for multiple targets using the same prepared sensor, eliminating the need to prepare separate sensors for each analyte class
Solution Approach 2:
The aptamer scaffold automatically adapts to different analytes through its modular design, where the constant scaffold structure provides the detection capability and only the recognition moiety needs to be exchanged. This self-service characteristic allows the same sensor platform to serve multiple detection purposes without requiring re-engineering of the core detection mechanism
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
Enables efficient and cost-effective detection of various analytes by measuring changes in tethered diffusion rates, providing a streamlined and economic method for quantitative readouts across different molecular classes.
Implementation Method 1
The signal moiety can be a redox molecule... The electrochemical detection nanostructure... measuring changes in tethered diffusion rates
Data Source
AI summary
Described herein are DNA-nanostructures that can be used in an assay to detect and/or quantify an analyte of interest. Aspects of the DNA-nanostructure can include a single DNA molecule composed of hairpin structural motifs, an anchor recognition moiety, and a signal moiety, where the anchor recognition moiety and the signal moiety are in effective proximity to each other such that the tethered diffusion of the signal molecule can be altered based upon binding status of the anchor recognition moiety. Also described herein are methods of making and using the DNA-nanostructures.