ESR Probe Molecule Thioether Linkages for Biosensor Detection
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Solution Overview
Problem
Current biosensor technologies face challenges in providing rapid, point-of-care, multiplexed, matrix-insensitive, and in-situ/implantable solutions for detecting specific analytes, particularly in complex mediums like whole blood, often requiring surface preparation and suffering from issues like non-specific binding and surface-related problems.
Innovation Solution
An electron spin resonance (ESR) analytical method using a probe molecule with a paramagnetic moiety bound via two thioether linkages, allowing selective binding to targets such as antibodies or aptamers, which generates distinct ESR signals for bound and unbound states, enabling direct measurement of binding without surface immobilization.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If surface preparation is used in biosensors, then detection capability is improved, but surface-related problems and non-specific binding increase
Solution Approach 1:
The invention extracts the probe molecule from surface-based detection systems and implements solution-phase detection. The paramagnetic probe molecule freely diffuses in solution to bind with target analytes, eliminating all surface-related problems including non-specific binding, surface preparation requirements, and surface-induced artifacts while maintaining high detection capability through ESR signal measurement.
Solution Approach 2:
The invention introduces a paramagnetic probe molecule as an intermediary that mediates between the target analyte and the ESR detection system. The probe molecule binds selectively to the target in solution, transferring the binding information to the ESR detector without requiring direct surface interaction, thus resolving the contradiction between detection capability and surface-related issues.
2Productivity
If optical techniques are used for detection, then real-time monitoring is enabled, but interference from complex mediums like whole blood increases
Solution Approach 1:
The invention substitutes optical detection with electron spin resonance (ESR) detection. ESR operates in the microwave frequency range and detects the magnetic properties of paramagnetic species, making it insensitive to optical interference from complex biological mediums like whole blood while maintaining real-time monitoring capability through continuous ESR signal acquisition.
Solution Approach 2:
The invention changes the detection parameter from optical properties (absorbance, fluorescence) to magnetic spin properties detectable by ESR. This parameter change allows detection in complex mediums where optical techniques fail, as ESR signals are not affected by turbidity, color, or other optical interferences present in whole blood and similar samples.
3Measurement precision
If competition assays relying on displacement are used, then target detection is achieved, but assay complexity and time requirements increase
Solution Approach 1:
The invention inverts the traditional competition assay approach. Instead of using displacement competition where a labeled analyte competes with the target for binding sites (requiring multiple steps and time), the method directly measures the binding of the paramagnetic probe to the target in solution. This direct binding measurement achieves the same detection accuracy while significantly reducing assay time and complexity.
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
This method allows for sensitive detection of targets at low concentrations in complex mediums like whole blood, minimizing surface-related issues, providing solution-phase binding constants, and enabling real-time monitoring with potential for high throughput and automation, while avoiding the limitations of optical techniques.
Implementation Method 1
electron spin resonance (ESR) analytical method comprising: providing a probe molecule capable of binding selectively to a target, wherein a paramagnetic moiety is bound to the probe molecule via two thioether linkages
Data Source
Figure 1a~1e
Figure 2(a)~2(c)
Figure 2(d)
AI summary
The present application relates to an electron spin resonance (ESR) analytical method comprising: providing a probe molecule capable of binding selectively to a target, wherein a paramagnetic moiety is bound to the probe molecule via two thioether linkages, and an electron spin resonance signal of the probe molecule bound to the target is different from an electron spin resonance signal of the probe molecule that is not bound to the target, contacting the probe molecule with a first sample, which may or may not comprise the target, to form a mixed sample and obtaining an electron spin resonance signal of the mixed sample. Probe molecules, molecules for producing the probe molecules, and an apparatus is also described.