Multichannel SPR Instrument Using Multiple Reflections for High Sensitivity
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Solution Overview
Problem
Current SPR instruments are limited in their ability to perform high-throughput screening and proteomics analysis due to low sensitivity, particularly in detecting small molecules with low binding affinities, which hinders their utility in drug discovery and small molecule research.
Innovation Solution
A multichannel SPR instrument utilizing a planar light guide configuration with multiple reflections to amplify reflected light intensity changes near the resonance angle, enabling simultaneous multichannel detection with high sensitivity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If traditional SPR detection modes (angular or wavelength detection) are used, then sensitivity can be maintained, but the optical complexity increases and multichannel implementation becomes cumbersome
Solution Approach 1:
The patent replaces complex angular or wavelength detection mechanisms with a simplified intensity detection scheme. By using a fixed-angle illumination and detecting intensity changes at the resonance angle, the system eliminates the need for complex angular scanning or wavelength tuning mechanisms, thereby reducing optical complexity while maintaining sensitivity.
Solution Approach 2:
The patent divides the detection system into multiple independent channels, each capable of simultaneous intensity detection. This segmentation allows for multichannel SPR measurements without requiring complex optical switching or scanning mechanisms, as each channel operates independently with simple intensity detection.
2Reliability
If SPR angle or wavelength detection modes are used for multichannel detection, then reference channels can be used to normalize for instrument errors, but the optical complexity and difficulty of implementation increase significantly
Solution Approach 1:
The patent replaces complex angular or wavelength detection with simple intensity detection at a fixed angle. This substitution allows reference channels to be implemented as simple intensity measurement channels, eliminating the need for complex optical switching or scanning mechanisms while maintaining the ability to normalize for instrument errors.
3Productivity
If current SPR instruments are used for high throughput screening, then multiple channels can be detected simultaneously, but sensitivity is insufficient for detecting small molecules with low binding affinities
Solution Approach 1:
The patent changes the detection parameter from angular or wavelength detection to intensity detection at a fixed angle. This parameter change enables simultaneous multichannel detection while improving sensitivity for small molecule detection, as the intensity detection mode provides sufficient signal change detection for low binding affinity interactions.
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 instrument achieves an order of magnitude higher sensitivity than existing systems, allowing for the detection of small molecules with low binding affinities without the need for fluorescence labeling, enhancing the drug discovery process and small molecule research.
Implementation Method 1
Surface plasmon resonance (SPR) spectroscopy is a key enabling technology in the analysis of molecular interactions
Implementation Method 2
utilizing a planar light guide configuration with multiple reflections to amplify reflected light intensity changes near the resonance angle
Implementation Method 3
SPR spectroscopy is an optical technique that detects changes in the refractive index in the immediate vicinity of a thin film of metal deposited on a glass substrate
Data Source
AI summary
A robust multichannel SPR instrument with exceptionally high sensitivity (<pg/mm2). The instrument utilizes an SPR detection scheme providing multiple reflections from a planar light guide configuration to amplify the reflected light intensity changes near the resonance angle. This SPR approach is amenable to simultaneous multichannel detection while maintaining high sensitivity with a simple, cost-effective design. The idea of using multiple reflections to excite multiple surface plasmon waves seems counterintuitive at first because the SPR resonance will be broadened; the broadened resonance will diminish sensitivity for angle or wavelength detection modes. However, changes in reflected light intensity near the resonance angle will be amplified by the multiple reflections, thereby increasing the sensitivity of SPR utilizing intensity detection at a fixed angle of incidence.