Multi-Plane Microarrays for High-Density Analyte Detection
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Solution Overview
Problem
Conventional fluorescent-detection protocols for nucleic acid arrays face limitations in resolution due to the number of pixels in detection devices, leading to increased costs and decreased accuracy, especially when detecting large collections of analytes.
Innovation Solution
The use of multi-plane microarrays with features at different elevations allows for increased packing density and resolution, enabling the distinction of analytes by altering the depth of focus, utilizing techniques like epi-illumination and waveguide excitation to selectively detect features at different z-planes.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional fluorescent-detection protocols are used to detect large collections of analytes, then detection capability is maintained, but resolution decreases and cost increases
Solution Approach 1:
The patent transitions from a two-dimensional planar array to a three-dimensional multi-plane structure by incorporating features at different z-heights (first z-height and second z-height). This vertical dimensionality allows multiple analyte collections to be stacked, increasing packing density while maintaining resolution through selective plane detection, thereby avoiding the need for complex high-resolution optics.
Solution Approach 2:
The array is segmented into multiple distinct planes or layers at different elevations. Each plane can be detected independently, allowing the system to handle large collections of analytes across multiple planes without requiring a single complex high-resolution detection system for the entire surface.
2Measurement precision
If higher resolution optics are used to detect dense analyte collections, then measurement precision improves, but cost increases
Solution Approach 1:
By utilizing the vertical dimension to stack multiple analyte planes at different z-heights, the system achieves high effective density without requiring expensive high-resolution optics. The detection can be performed at lower resolution by focusing on specific planes, reducing overall system cost while maintaining analytical precision.
Solution Approach 2:
The patent changes the spatial arrangement parameter from a two-dimensional dense packing to a three-dimensional distributed packing across multiple planes. This parameter change allows standard detection equipment to achieve high effective resolution by selectively focusing on individual planes, thereby reducing the need for expensive high-resolution optical components.
3Productivity
If more analytes are packed per square centimeter, then productivity increases, but signal overlap and interference increase
Solution Approach 1:
The patent resolves signal overlap by introducing the vertical dimension. Features at the first z-height and second z-height are spatially separated in the vertical direction, allowing signals from different planes to be distinguished through selective focusing or optical sectioning. This enables high throughput with reduced signal interference.
Solution Approach 2:
The analyte collection is segmented into distinct vertical planes. By detecting each plane separately through optical sectioning or focus stacking, the system can process large numbers of analytes across multiple planes without signal overlap, as each plane's signal can be isolated and analyzed independently.
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 enhances throughput and reduces costs by allowing for higher resolution detection of analytes without the need for high-resolution optics, enabling more dense packing of features on the array surface.
Implementation Method 1
an optical system is used to direct an excitation light onto fluorescently-labeled analytes and to also detect the fluorescent signals that may emit from the analytes
Data Source
Figure 1A~1B
Figure 2~4
Figure 5
AI summary
An array including a solid support having a plurality of contours along its exterior surface. A first subset of contours is positioned along the exterior surface of the solid support to form a first pattern of features and a second subset of contours is positioned along the exterior surface to form a second pattern of features. The contours of the first subset are juxtaposed with the second subset along the exterior surface, whereby the first and second patterns form an interleaved pattern. The features of the first pattern occur at a first elevation z1 and the features of the second pattern occur at a second elevation z2. The features of the first pattern are configured to attach analytes at a different elevation relative to analytes attached to the features of the second pattern.