Microarray Characterization Using Lens Array and Immersion Fluid
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Solution Overview
Problem
Current fluorescence characterization systems face challenges in detecting multiple target molecules with high sensitivity and reproducibility, particularly in medical diagnostics, due to background noise and the need for efficient immobilization and excitation of labels without bleaching, especially when dealing with diluted samples and multiplexing measurements.
Innovation Solution
A compact system combining confocal scanning with imaging, using an aperture array and lens array for direct focusing and efficient luminescence collection, with immersion liquid to enhance excitation and collection efficiency, and a scanning mechanism for relative movement between excitation radiation and the substrate, allowing focused excitation and collection of luminescence over a large surface area.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional fluorescence detection systems are used, then multiple target molecules can be detected, but background noise reduces measurement sensitivity
Solution Approach 1:
The system segments the detection process by using a lens array to create multiple independent focal spots, each detecting a specific sub-region of the substrate. This spatial segmentation allows confocal detection that rejects out-of-focus background noise while maintaining sensitivity to specific target molecules at each location.
Solution Approach 2:
An immersion liquid is introduced as an intermediary medium between the lens array and substrate. This intermediary increases the numerical aperture of the optical system, enhancing both excitation light delivery and emission light collection efficiency, thereby improving signal-to-noise ratio without requiring additional complex noise filtering components.
2Measurement precision
If high excitation intensity is used to improve detection sensitivity, then label bleaching occurs
Solution Approach 1:
The system applies excitation light locally at each focal spot created by the lens array, concentrating energy only where needed at the substrate surface. This localized excitation provides sufficient intensity for sensitive detection while limiting total exposure and preventing label bleaching across the entire sample area.
Solution Approach 2:
The scanning mechanism moves the focal spots periodically across different sub-regions of the substrate, allowing each location to be excited only during its specific time window. This periodic scanning enables sensitive detection at each position while distributing the total excitation exposure over time, preventing cumulative label damage.
3Productivity
If scanning is used to improve measurement speed, then system complexity increases
Solution Approach 1:
The system merges imaging and scanning functions into a unified confocal detection approach. The lens array creates multiple focal spots simultaneously, and the scanning mechanism simply repositions these spots across sub-regions, combining parallel detection capability with spatial scanning in a single integrated system rather than requiring separate imaging and scanning subsystems.
Solution Approach 2:
The lens array serves multiple functions simultaneously: it focuses excitation light onto the substrate, collects emission light from focal spots, and enables confocal detection to reject background noise. This multi-functionality reduces the need for additional specialized components, maintaining measurement speed while limiting system complexity.
4Manufacturing precision
If additional lensing elements are added to improve focusing, then device complexity and cost increase
Solution Approach 1:
Instead of using a single complex objective lens, the system uses an array of simple lenses that replicate the focusing function across multiple locations. Each lens in the array creates a focal spot corresponding to a sub-region, providing sufficient focusing accuracy for detection without requiring a single high-precision objective lens, thereby reducing overall system complexity and cost.
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 approach enables high sensitivity and speed in detecting multiple analytes with reduced background noise, efficient luminescence collection, and the ability to perform multiplexing measurements without the need for additional lensing elements, maintaining label integrity and improving signal-to-noise ratio.
Implementation Method 1
a lens array adapted for directly focusing the excitation sub-beams on a sub-region of the substrate surface
Implementation Method 2
Each of the sub-regions being adapted to bind to different analytes and/or to different luminescent labels
Implementation Method 3
The numerical aperture of the optical system is increased by using an immersion liquid for collection
Data Source
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AI summary
A system and method is described for detecting a plurality of analytes in a sample. The characterization system (100) comprises an aperture array (108) and a lens array (110) for generating and focusing a plurality of excitation sub-beams on different sub-regions of a substrate. These sub-regions can be provided with different binding sites for binding different analytes in the sample. By detecting the different luminescent responses in a detector, the presence or amount of different analytes can be determined simultaneously. Alternatively or in addition thereto collection of the luminescence radiation can be performed using the lens array for directly collecting the luminescence response and for guiding the collected luminescence response to corresponding apertures. In a preferred embodiment, the excitation sub-beams are focused at the side of the substrate opposite of the lens array and an immersion fluid is provided between the lens array and the substrate to increase the collection efficiency of the luminescence radiation.