Polymer Dye Probes for Nucleic Acid Detection
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Solution Overview
Problem
Conventional nucleic acid detection methods using solid surfaces for immobilization of target nucleic acids are hindered by reduced hybridization speed, interference with signal, and noise, as well as the inability for in vivo detection and real-time monitoring.
Innovation Solution
Development of compounds with polymeric chromophores covalently bound to polynucleotides, which form probes that can enhance brightness and reduce signal-to-noise ratio, allowing for improved detection without the need for solid surfaces, enabling in vivo analysis and real-time monitoring.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Loss of time
If solid surfaces are used to immobilize target nucleic acids, then detection can be performed, but hybridization time increases and signal-to-noise ratio deteriorates
Solution Approach 1:
The patent extracts the target nucleic acid from solid surface immobilization and keeps it in solution phase. The probe is designed to hybridize with target nucleic acid in solution without requiring solid support, thereby eliminating the negative effects of solid surfaces on hybridization kinetics and signal quality.
Solution Approach 2:
The patent introduces a soluble probe molecule as an intermediary that carries the detection function into the solution phase. This probe mediates the detection process by hybridizing with target nucleic acid in solution, eliminating the need for solid surface immobilization while maintaining detection capability.
2Reliability
If solid surfaces are used for immobilization, then probe-target hybridization can occur, but access and mobility of target nucleic acids are restricted
Solution Approach 1:
The patent removes the solid surface immobilization step entirely, allowing both probe and target nucleic acid to remain in solution during hybridization. This extraction of the solid support element eliminates mobility restrictions while preserving hybridization efficiency through optimized soluble probe design.
3Illumination intensity
If conventional probes are used, then detection is possible, but brightness is insufficient and noise is high
Solution Approach 1:
The patent employs composite probe structures combining polynucleotide sequences with fluorescent reporter molecules. This composite design integrates the specific binding capability of nucleic acids with the high brightness and low noise characteristics of fluorescent materials, achieving superior detection performance.
Solution Approach 2:
The patent optimizes parameters of the probe molecule including fluorescent label selection, probe sequence design, and molecular structure to maximize brightness and minimize noise. By changing these parameters, the probe achieves enhanced optical properties for superior signal quality.
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 described compounds provide enhanced detection capabilities with increased brightness and reduced noise, enabling efficient and accurate nucleic acid detection without the limitations of solid surface immobilization, facilitating in vivo analysis and real-time monitoring.
Implementation Method 1
compounds comprising polymer fluorophore moieties bound to a nucleotide probe
Implementation Method 2
enhance brightness and produce a lower signal-to-noise ratio
Data Source
AI summary
Compounds useful as probes are disclosed. The compounds have the following structure (II): or a stereoisomer, tautomer or salt thereof, wherein M, L1a, L1b, L2, L3, L4, L5, L6, L7, L8, L9-R1, R2, R3, R4, R5, m, n, q, and w areas defined herein. Additionally, compositions, kits, and methods useful for detecting a target analyte are also described.