Aptamer Sequence Optimization for Sensitive Small Molecule Detection
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Solution Overview
Problem
Current methods for detecting small molecules, such as endocrine-disrupting compounds, are cumbersome, time-consuming, and require specialized equipment, limiting their use for rapid on-site assessment in environmental testing.
Innovation Solution
Optimization of polynucleotide sequences, specifically aptamers, to include additional nucleotide bases beyond the ligand binding domain for enhanced signal transduction and binding to nanoparticles, enabling sensitive and selective detection of small molecules in assays.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional detection methods (HPLC, GCMS) are used, then detection accuracy is improved, but device complexity and time consumption increase
Solution Approach 1:
The patent introduces aptamers as intermediary molecules that specifically bind to target small molecules, translating their presence into detectable signals. These aptamers act as mediators between the target analytes and the detection system, enabling simplified detection without complex chromatographic separation equipment while maintaining high detection accuracy through specific molecular recognition
Solution Approach 2:
The patent replaces complex mechanical chromatographic separation systems with a molecular recognition-based detection approach. Instead of using HPLC or GCMS equipment for separation and detection, the invention uses aptamer-target binding interactions followed by signal amplification techniques, substituting mechanical separation with biochemical recognition and signal transduction
2Measurement precision
If aptamer sequences are optimized with additional nucleotide bases, then signal transduction is improved, but sequence complexity increases
Solution Approach 1:
The patent segments the aptamer sequence into functional domains: a ligand-binding domain for target recognition and additional nucleotide bases for signal transduction. This segmentation allows independent optimization of each domain's function, where the binding domain maintains high affinity for the target while the additional bases enhance signal amplification without interfering with binding activity
Solution Approach 2:
The patent optimizes sequence parameters by adding specific numbers of nucleotide bases (e.g., 1-10 bases) to the standard aptamer sequence. This parameter change enhances signal transduction efficiency by providing additional bases for hybridization or structural formation, while the changes are controlled and quantified to avoid excessive complexity
3Measurement precision
If sample concentration is required for chromatographic techniques, then detection sensitivity is improved, but loss of time and portability increase
Solution Approach 1:
The patent enables the detection system to perform its own sample concentration function through the high affinity of aptamers for target molecules. The aptamer-target binding occurs directly in the sample without requiring external concentration steps, as the binding itself effectively concentrates the target analytes onto the aptamer-coated particles, eliminating time-consuming pre-concentration procedures while maintaining detection sensitivity
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 optimized aptamer sequences provide detection limits in the pM range with improved selectivity and sensitivity, allowing for quick and accurate detection of small target molecules in environmental samples using colorimetric assays.
Implementation Method 1
coating of a nanoparticle with the polynucleotide sequence
Implementation Method 2
the additional nucleotide bases are selected to provide optimal signal transduction
Data Source
AI summary
The present invention provides for a method of optimisation of a polynucleotide sequence for use in an aptamer based assay, comprising adding additional bases to the ligand binding domain. The invention also covers methods of detecting target molecules in a sample using 5 optimised polynucleotide sequences in a suitable detection assay.