Aptamer Probes for Ultrasensitive Biomarker Detection in Serum
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Solution Overview
Problem
Existing methods for detecting biomarkers, such as SiMREPS using antibody query probes, face challenges in sensitivity and cost-effectiveness, and require complex signal differentiation due to fast dissociation kinetics.
Innovation Solution
Utilizing aptamers as detection probes in SiMREPS assays, optimized through systematic evolution and chemical synthesis, with modified bases for enhanced stability and binding kinetics, allowing for rapid and accurate detection of biomarkers like VEGF165 and IL-8 in serum matrices.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If antibody query probes are used in SiMREPS assays, then detection sensitivity is achieved, but cost and complexity increase
Solution Approach 1:
The patent replaces expensive antibodies with cheaper aptamers as detection probes. Aptamers are synthetic oligonucleotides that can be produced at lower cost through chemical synthesis rather than complex biological production methods required for antibodies. This substitution maintains detection functionality while reducing assay cost and simplifying the overall system.
2Productivity
If antibody query probes with fast dissociation kinetics are used, then signal differentiation becomes complex, but detection speed is maintained
Solution Approach 1:
The patent modifies the kinetic parameters of the detection probes by using aptamers with different dissociation rate constants compared to antibodies. By selecting aptamers with appropriate binding kinetics, the system achieves both rapid detection and simplified signal interpretation. The kinetic fingerprinting approach leverages these parameter differences to distinguish specific from nonspecific binding events more easily.
3Stability of the object's composition
If aptamers with modified bases are used, then stability and nuclease resistance increase, but synthesis complexity increases
Solution Approach 1:
The patent incorporates modified nucleotide bases into the aptamer structure to create a composite oligonucleotide material with enhanced properties. These modifications (such as 2′-fluoro or 2′-O—CH3 groups) increase thermal stability and resistance to nuclease degradation. While the synthesis process becomes slightly more complex, it remains feasible through solid-phase chemical synthesis methods, achieving a balance between stability and manufacturability.
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
Aptamers provide ultrasensitive detection in the low femtomolar range with reduced noise and cost, enabling efficient characterization and quantification of biomarkers with improved signal distinction and kinetic fingerprinting.
Implementation Method 1
Aptamers are synthetic single-stranded DNA (ssDNA) or RNA oligonucleotides that fold into unique three-dimensional structures and bind their targets specifically
Implementation Method 2
aptamers comprised modified bases (e.g., modified with 2′-fluoro or 2′-O—CH3 groups) to increase their stability and resistance to nuclease degradation
Data Source
AI summary
Provided herein is technology relating to detecting analytes and particularly, but not exclusively, to methods, compositions, systems, and kits for detecting analytes using aptamer technologies.