Nuc-Macromolecules for Signal Detection in Nucleic Acid Analysis
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Solution Overview
Problem
Conventional modified nucleotides lose their substrate properties when coupled with large molecules, leading to inefficient signal detection and amplification in nucleic acid analysis, and existing labeling methods suffer from low yield and signal distortion due to multiple, uncontrolled steps.
Innovation Solution
Development of 'nuc-macromolecules' with nucleotide components attached to signal-giving or signal-transmitting macromolecular markers via a long linker, allowing retention of substrate properties and improved signal intensity upon incorporation into nucleic acids.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Illumination intensity
If conventional modified nucleotides are coupled with large molecules for signal detection, then signal intensity is improved, but substrate properties are lost leading to inefficient incorporation
Solution Approach 1:
The modified nucleotide is divided into separate functional components: a nucleotide portion that maintains substrate properties for enzymatic incorporation, and a separate macromolecular signal-giving portion. This segmentation allows each component to perform its designated function independently, resolving the contradiction between signal intensity and substrate properties.
Solution Approach 2:
A linker molecule serves as an intermediary between the nucleotide and the macromolecular signal portion. This linker mediates the connection while allowing the nucleotide to maintain its substrate properties and the macromolecule to provide signal intensity, enabling both functions to coexist without interference.
2Measurement precision
If multiple labeling steps are used for signal amplification, then signal detection capability is improved, but manufacturing precision deteriorates due to uncontrolled steps
Solution Approach 1:
The signal-giving macromolecule is pre-attached to the nucleotide before the nucleic acid synthesis process. This preliminary action ensures that the labeling is controlled and uniform, eliminating the need for multiple subsequent labeling steps that would reduce manufacturing precision while still achieving signal amplification.
Solution Approach 2:
The labeling function and the nucleotide function are merged into a single integrated molecule. The macromolecular signal portion is directly coupled to the nucleotide, combining signal detection capability with precise control in one step, thereby improving both measurement precision and manufacturing precision simultaneously.
3Illumination intensity
If multiple signal multiplication steps are performed, then signal intensity is improved, but loss of time increases due to multiple incubation steps
Solution Approach 1:
Signal multiplication is achieved through pre-attachment of macromolecules containing multiple signal-giving units to the nucleotide before incorporation. This preliminary action provides signal amplification in advance, eliminating the need for multiple time-consuming incubation steps during detection while maintaining high signal intensity.
Data Source
AI summary
The invention relates to novel classes of nucleotides that can be used as substrates for enzymes, e.g. for labeling nucleic acids.