Creatinine-Responsive DNA Aptamers for Accurate Ion-Resistant Detection
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Existing techniques for measuring creatinine levels in bodily fluids are not sensitive enough to detect low levels accurately and are hindered by the presence of other molecules such as magnesium, potassium, and calcium, requiring further buffering solutions that decrease accuracy.
Innovation Solution
Development of single-stranded DNA aptamers with specific oligonucleotide sequences, capable of binding creatinine with a dissociation constant between 10−9 and 10−3 M, which can be immobilized on substrates like gold or quartz to form stem-loop structures, altering conductance or fluorescence upon binding, and are insensitive to interfering ions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional measurement techniques are used, then measurement can be performed, but sensitivity is insufficient to detect low levels of creatinine accurately
Solution Approach 1:
The patent employs aptamers with specifically optimized sequences and structures that exhibit enhanced binding affinity to creatinine, achieving dissociation constants in the range of 10^-9 to 10^-6 M. This parameter optimization of the binding molecule enables detection at clinically relevant low concentrations while maintaining accuracy despite the presence of interfering ions.
2Object-affected harmful factors
If buffering solutions are added to handle interfering molecules, then interference from ions like magnesium, potassium, calcium, or sodium can be managed, but measurement accuracy decreases
Solution Approach 1:
The patent uses aptamers as selective intermediary binding molecules that specifically recognize and bind to creatinine with high affinity while exhibiting minimal binding to interfering ions. This selective intermediary approach allows direct measurement in complex biological matrices without requiring buffering solutions, thereby maintaining measurement accuracy while achieving interference resistance.
3Ease of operation
If direct measurement without buffering is attempted, then measurement simplicity is improved, but accuracy decreases due to interfering molecules
Solution Approach 1:
The aptamer-based measurement system enables self-service direct measurement by inherently resisting interference from common ions through its selective binding properties. The system requires no external buffering or sample preparation modifications, allowing direct measurement of creatinine in complex biological samples while maintaining both simplicity and accuracy.
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
Enables accurate and direct measurement of creatinine levels in clinical samples without additional buffering, providing sensitivity across a wide range of concentrations and resistance to interfering ions, facilitating diagnosis and treatment of kidney diseases.
Implementation Method 1
the aptamer can be configured to bind the target molecule/analyte with a dissociation constant between about 10−9 and about 10−3 M
Implementation Method 2
The stem region can be configured to be positioned to transform a second conformation into a stem-loop structure of the aptamer, or stem-loop structure into a second conformation when the oligonucleotide sequence binds to the target molecule/analyte
Implementation Method 3
altering conductance or fluorescence upon binding
Data Source
AI summary
Aptamers and methods for detecting a target molecule/analyte in a sample are disclosed herein. The aptamer can include a single-stranded deoxyribonucleic acid (DNA) strand that includes an oligonucleotide sequence with bases identical at least about 60% to TAATTGTGGTTCGTGTAAA (SEQ ID NO: 1). The aptamer can be configured to bind the target molecule/analyte with a dissociation constant between about 10−9 and about 10−3 M.