DNA Switch Nucleic Acid Sensor for Rapid PCR-Free Biomarker Detection
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Solution Overview
Problem
Conventional diagnostic tests for biomarkers are slow and complex, struggling to keep pace with rapid mutations in nucleic acids associated with diseases and public health threats, necessitating a novel, agile, and sensitive method for biomarker detection.
Innovation Solution
An agile nucleic acid sensor using DNA nanostructures and AI frameworks for label-free, PCR-free biomarker detection, producing unique molecular signatures decoded by AI to quantify measurement errors and uncertainties.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional PCR methods are used for biomarker detection, then detection sensitivity can be achieved, but the process is time-consuming and complex due to sample enrichment requirements
Solution Approach 1:
The patent extracts and eliminates the time-consuming sample enrichment step entirely. Instead of using PCR to amplify and enrich biomarkers before detection, the invention directly detects biomarkers in their native form using DNA switches that bind to specific biomarker sequences, achieving detection without prior enrichment.
Solution Approach 2:
The patent replaces the mechanical/chemical amplification process of PCR with a direct biochemical binding system. DNA switches bind to biomarkers through complementary base pairing, and this binding event is directly transduced into an electrical signal, eliminating the need for thermal cycling and enzymatic amplification steps.
2Adaptability or versatility
If conventional diagnostic methods are used, then biomarker detection is possible, but multiplexing capability is limited due to method complexity
Solution Approach 1:
The patent segments the detection system into multiple independent DNA switch units, each capable of detecting different biomarkers. These segmented units can be simultaneously present in the same assay mixture, allowing multiplexed detection of multiple biomarkers parallelly without increasing overall system complexity.
Solution Approach 2:
The patent creates a universal detection platform where the same basic DNA switch-component architecture can be used to detect various different biomarkers by simply changing the DNA sequence. This multi-functional system allows a single assay to simultaneously detect multiple types of biomarkers using the same operational principles.
3Speed
If rapid detection is implemented, then detection speed improves, but accuracy may be compromised due to lack of enrichment
Solution Approach 1:
The patent changes the fundamental detection parameter from signal amplification (PCR-based) to direct binding affinity (DNA switch-based). By optimizing the DNA switch-biomarker binding interaction through sequence complementarity and thermodynamic parameters, the system achieves both rapid detection and high accuracy without relying on enrichment processes.
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
The sensor provides high sensitivity and flexibility for rapid reprogramming, enabling efficient and accurate biomarker detection in medical diagnostics and public health surveillance without the need for polymerase chain reaction.
Implementation Method 1
a DNA switch that contacts and selectively duplexes with a chemical analyte comprising the biomarker
Implementation Method 2
an analysis substrate in electrostatic communication with the DNA switch that is disposed on the analysis substrate, such that when the chemical analyte duplexes with the DNA switch, the analysis substrate produces a biomarker electrical signal
Implementation Method 3
a sensor reference electrode in electrical communication and capacitively coupled to the analysis substrate and that produces a feedback signal based on electrical interactions with a composition that is in fluid contact with the feedback signal and the analysis substrate
Data Source
AI summary
An agile nucleic acid sensor includes: a DNA switch; an analysis substrate in electrostatic communication with the DNA switch and that produces a biomarker electrical signal; a transduction member that receives the biomarker electrical signal and produces a transduction signal; a sensor counter electrode in electrical communication with and capacitively coupled to the analysis substrate and that receives a counter electrode voltage; a sensor reference electrode in electrical communication and capacitively coupled to the analysis substrate and that produces a feedback signal based on electrical interactions with a composition that is in fluid contact with the feedback signal and the analysis substrate; and a voltage follower in electrical communication with the sensor counter electrode and the sensor reference electrode and that receives the feedback signal from the sensor reference electrode and produces the counter electrode voltage for the sensor counter electrode based on the feedback signal.