Microarray Imaging System with Chromatic Correction
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Solution Overview
Problem
Current microarray imaging systems face challenges in achieving high uniformity and spectral consistency for quantitative analysis, particularly in minimizing residual spatial variations in sensitivity and reducing stray light, which affects the accuracy of signal intensity measurements over a wide dynamic range.
Innovation Solution
The proposed imaging system employs a broad-band excitation light source with Kohler illumination, a chromatically corrected detection lens system, and a telecentric or substantially telecentric configuration to ensure consistent intensity and spectral accuracy across the microarray, using a combination of lenses and filters to minimize chromatic aberrations and stray light, allowing for precise comparison of signal intensities without computational correction.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If a CCD detector with imaging lens is used to illuminate the entire array simultaneously, then light detection efficiency and measurement precision are improved, but residual spatial variations in sensitivity and stray light increase
Solution Approach 1:
The patent segments the wide field of view into multiple smaller fields by using a microlens array that divides the incoming light into separate channels, each corresponding to a specific region of the microarray. This segmentation allows each detector element to receive light from a restricted angular range, reducing stray light and spatial sensitivity variations while maintaining overall measurement precision
Solution Approach 2:
The patent introduces a field lens and microlens array as intermediary optical elements between the sample plane and the detector. These intermediaries condition the light paths to ensure that only light from specific directions reaches each detector element, thereby eliminating stray light and uniformizing spatial sensitivity across the array without compromising detection efficiency
2Measurement precision
If multiple dyes are detected by alternating excitation laser wavelength and optical filter switching, then spectral discrimination is improved, but measurement time and device complexity increase
Solution Approach 1:
The patent employs periodic switching of excitation wavelengths and optical filters to detect multiple dyes sequentially. By rapidly alternating between different excitation lines and corresponding emission filters, the system achieves spectral discrimination for multiple fluorophores while minimizing measurement time through efficient time-multiplexed detection
Solution Approach 2:
The patent uses dynamic control of laser wavelength switching and filter wheel rotation to adapt the optical configuration for detecting different dye combinations. This dynamic adjustment allows the system to optimize spectral discrimination for each detection cycle while maintaining high throughput by minimizing the time spent in each configuration state
3Measurement precision
If the incident angle of excitation light is increased to reduce stray light, then spectral consistency is improved, but illumination uniformity across the array deteriorates
Solution Approach 1:
The patent applies local quality by using a microlens array to provide different incident angles for different regions of the array. Each microlens directs light at an optimized angle for its specific location, ensuring that all regions benefit from stray light reduction while maintaining appropriate illumination uniformity across the entire array through localized angular control
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 configuration provides high uniformity and spectral consistency, enabling accurate comparison of signal intensities across the microarray without software correction, enhancing the detection of slight variations in nucleic acid expression and composition, and improving hybridization efficiency and quality control in microarray analysis.
Implementation Method 1
a broad band excitation light source that provides Kohler illumination of the microarray at an incident angle that ranges from about 30 degrees to about 75 degrees from the normal to said microarray
Implementation Method 2
the detection of fluoresced light resulting from one or more fluorophores upon exposure of the fluorophores to an excitation light
Implementation Method 3
a detection lens system that is chromatically corrected so the apparent position of the microarray or a feature comprising the microarray varies by less than 10 μm as the detection wavelength varies from about 400 to about 800 nm
Implementation Method 4
design of filters to obtain adequate spectral discrimination of multiple wavelengths and to reduce stray light, and reduction of 'ghost' images due to reflections within the optical system
Data Source
AI summary
This invention provides an imaging system for high-accuracy quantitative analysis of a microarray. In certain embodiments, the system comprises a broad band excitation light source that provides Kohler illumination of said microarray at an incident angle that ranges from about 30 degrees to about 75 degrees from the normal to the microarray, and that has less than about ±25 percent variation in intensity over the array at all wavelengths ranging from 400 to 800 nm; a support for holding a microarray; a detection lens system that is chromatically corrected so the apparent position of the microarray or a feature comprising the microarray varies by less than 10 μm as the detection wavelength varies from about 400 to about 800 nm; and a detection device for detecting and optionally recording an image produced by said detection lens system.