Molecular Sensor Linear Dichroism Multiplexing
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Solution Overview
Problem
Current methods for detecting nucleic acid molecules, especially during amplification reactions like PCR, face limitations such as requiring long amplimer sequences and lack of multiplexing capability, and are not efficient for quantifying or detecting specific nucleic acid sequences in complex samples.
Innovation Solution
A molecular sensor utilizing alignable scaffold/receptor complexes with high aspect ratios, where the receptor moiety is complementary to the target nucleic acid, allowing for detection through linear dichroism (LD) changes induced by binding, enabling multiplexing and efficient detection of multiple targets in a single assay.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If conventional detection methods are used for nucleic acid molecules during amplification reactions, then detection can be performed, but the methods require long amplimer sequences and lack multiplexing capability
Solution Approach 1:
The detection system is segmented into multiple independent scaffold/receptor complexes, each designed to detect a specific target sequence. This segmentation enables multiplexing by allowing simultaneous detection of multiple different nucleic acid targets in a single assay, while each individual complex maintains high detection specificity through its unique receptor design
Solution Approach 2:
The scaffold structure serves as a universal platform that can be functionalized with different receptor sequences. This multi-functional scaffold design allows the same basic detection mechanism to be applied across multiple different target sequences, enabling multiplexed detection without requiring different detection methodologies for each target
2Productivity
If conventional detection methods are used, then detection can be performed, but they are not efficient for quantifying or detecting specific nucleic acid sequences in complex samples
Solution Approach 1:
The system incorporates real-time feedback through linear dichroism signal monitoring during the amplification reaction. The alignment state of the scaffold/receptor complexes provides continuous feedback on target binding, enabling both efficient detection and accurate quantification by correlating signal intensity with target concentration
Solution Approach 2:
The patent replaces conventional mechanical or chemical detection methods with an optical detection system based on linear dichroism. This substitution enables non-invasive, real-time monitoring of nucleic acid amplification with high efficiency and precision, as the optical signals can be detected without disrupting the reaction and provide direct quantitative information
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
This approach allows for sensitive and specific detection of nucleic acid molecules, including during amplification reactions, with the ability to quantify and differentiate between multiple targets, overcoming the limitations of existing methods by using LD to monitor alignment changes caused by target binding.
Implementation Method 1
using linear dichroism (LD) to detect a change in the alignment of the scaffold/receptor complexes effected by binding of the target nucleic acid molecule
Implementation Method 2
Due to the elongate nature of the molecules, alignment arises as a result of shear forces generated by the flow
Data Source
Figure 1
Figure 2a~2b
Figure 3
AI summary
A molecular sensor that utilises dichroism can be used to identify the presence of a target nucleic acid molecule in a sample, for example during or after amplification reactions such as PCR/thermocyling reactions and isothermal reactions. A sensor element for use in the molecular sensor may comprise an alignable scaffold/receptor complex, the receptor of said complex comprising a nucleic acid sequence which is complementary to at least a portion of a target nucleic acid molecule.