Plasmon Resonance Biosensor Arrays for Multiplexed Detection
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Solution Overview
Problem
Current microarray assay techniques face challenges in sensitivity, particularly at high sensitivities where non-specific binding events can swamp genuine signals, and there is a need for improved detection of refractive index changes beyond 10^-4 RIU to enhance diagnostic capabilities for pathological conditions.
Innovation Solution
A plasmon resonance-based biosensor array employing discrete metallic nanoparticles with functionalising molecules on a transparent substrate, utilizing total internal reflection to modulate scattering of light by binding targets, and incorporating control spots to compensate for non-specific binding and refractive index variations, allowing for simultaneous detection of multiple biological targets with enhanced sensitivity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If fluorescence labelling is employed to detect binding events, then detection capability is provided, but sensitivity is limited and non-specific binding swamps genuine signals at high sensitivities
Solution Approach 1:
The patent replaces fluorescence-based optical detection with plasmon resonance-based detection. Instead of using fluorescent labels that emit light, the invention uses changes in refractive index at the metal surface to detect binding events. This substitution enables label-free detection with higher sensitivity (down to 10^-7 RIU) and better ability to distinguish specific from non-specific binding, as the plasmon resonance signal is highly sensitive to molecular mass and configuration changes at the sensor surface.
Solution Approach 2:
The patent changes the detection parameter from fluorescence intensity to refractive index changes. By monitoring the resonance condition of surface plasmons, which is highly sensitive to the refractive index of the surrounding medium, the system achieves superior detection limits. The resonance angle or wavelength shifts provide a direct measure of binding events without the background noise that plagues fluorescence methods at high sensitivities.
2Productivity
If continuous metal surface is used for SPR sensing, then label-free detection is achieved, but array format for multiplexed detection is not realized
Solution Approach 1:
The patent divides the continuous metal surface into discrete metallic islands or nanoparticles arranged in an array format. Each island can be independently functionalized with different probes, enabling multiplexed detection of multiple targets simultaneously. This segmentation maintains the plasmon resonance sensing capability while providing the spatial resolution and parallelism needed for high-throughput applications.
Solution Approach 2:
The patent applies different functional properties to different regions of the array by functionalizing each metallic island or nanoparticle with specific probes. This local functionalization allows each spot in the array to detect a specific target while maintaining the overall array structure. The local quality approach enables customization of each sensing element for different applications while using the same underlying plasmon resonance technology.
3Measurement precision
If refractive index sensitivity is increased beyond 10^-4 RIU, then detection capability improves, but non-specific binding events swamp genuine signals
Solution Approach 1:
The patent employs reference spots or control channels that provide feedback for correcting non-specific binding effects. By comparing the signal from functionalized spots with that from reference spots (which lack specific probes or contain control probes), the system can subtract background signals and isolate genuine binding events. This feedback mechanism maintains high sensitivity while eliminating the interference from non-specific binding.
Solution Approach 2:
The patent uses control probes or blocking agents as intermediaries to prevent or detect non-specific binding. These control elements compete for non-specific binding sites or provide a reference signal that accounts for non-specific interactions. By introducing these intermediary elements, the system can distinguish between specific and non-specific binding even at high sensitivity levels.
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 approach enables extremely sensitive detection of specific binding events against a high background of non-specific binding, achieving refractive index sensitivity of up to 2 x 10^-7, effectively distinguishing specific from non-specific interactions and providing a detailed 'fingerprint' of pathological conditions through kinetic analysis.
Implementation Method 1
total internal reflection of light is used to generate an evanescent wave which excites plasmons
Implementation Method 2
excites plasmons (a collective electronic excitation) in a metallic conductor, which are modified by the presence of a target molecule
Implementation Method 3
total internal reflection of light at said surface at a wavelength at or near a said plasmon resonance results in scattering of said light away from said surface, said scattering being modulated by said binding
Data Source
Figure 1~2a
Figure 2b~2c
Figure 2d~2e
AI summary
This invention relates to photonic biosensor arrays in particular employing plasmon resonance based sensing, and to methods and apparatus for reading such arrays. A biosensor array for plasmon resonance-based sensing of a plurality of different biological targets simultaneously, the array comprising a transparent substrate having a surface bearing a plurality of assay spots for plasmon resonance sensing, each of said assay spots comprising a discrete metallic island, a said metallic island comprising a plurality of metallic nanoparticles to which are attached functionalising molecules for binding to a said biological target, different said islands bearing different said functionalising molecules for binding to different ones of said biological targets, and wherein total internal reflection of light at said surface at a wavelength at or near a said plasmon resonance results in scattering of said light away from said surface, said scattering being modulated by said binding of said biological targets.