Microarray Imaging Fiducial Surface Fitting

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Solution Overview

Problem

Current methods for imaging biological probe arrays face challenges in achieving optimal image sharpness due to surface non-flatness, requiring manual adjustment of multiple fiducials and complex optical parameters.

Innovation Solution

A method involving the use of fiducials to determine the sharpest image at various z positions, employing surface fitting algorithms to calculate a surface fit profile, and adjusting parameters to improve image flatness, along with a tilt stage and motorized lens adjustments for precise focusing.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If manual adjustment of multiple fiducials and optical parameters is performed, then image sharpness can be optimized, but device complexity and operation time increase

Engineering Contradiction:

Improveimage sharpnessVSAvoidcomplexity of optical parameter adjustment

Core Design Contradiction:

Measurement precisionVSDevice complexity

Solution Approach 1:

The system automatically focuses by detecting fiducials and using image processing algorithms to determine the optimal focal plane without requiring manual intervention. The software autonomously adjusts optical parameters based on detected fiducial positions and image sharpness metrics, eliminating the need for operator expertise in manual focusing.

Inventive Principle:

Principle #25Self-service

Solution Approach 2:

Manual mechanical adjustment of fiducials and optical parameters is replaced by automated image processing algorithms. The system uses computational methods to analyze image sharpness and determine optimal focusing, substituting physical manual operations with digital image analysis and automated control.

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

2Measurement precision

If multiple images are taken at various z positions to determine sharpness, then image quality improves, but acquisition time increases

Engineering Contradiction:

Improveimage sharpnessVSAvoidtime for focusing adjustment

Core Design Contradiction:

Measurement precisionVSLoss of time

Solution Approach 1:

The system performs preliminary detection of fiducials and automated focusing before actual data acquisition. By pre-determining the optimal focal plane and adjusting optics in advance, the system eliminates the need for time-consuming manual focusing during the measurement process, allowing rapid sequential imaging at multiple z-positions.

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The automated focusing system continuously monitors and adjusts the focal plane without interrupting the imaging workflow. Once the optimal focus is determined through algorithmic analysis, the system maintains this focus state throughout data acquisition, enabling continuous imaging at multiple z-positions without repeated manual refocusing.

Inventive Principle:

Principle #20Continuity of useful action

3Manufacturing precision

If surface non-flatness is present on the probe array, then imaging accuracy decreases, but correcting it requires complex adjustments

Engineering Contradiction:

Improveimage flatnessVSAvoidease of focusing

Core Design Contradiction:

Manufacturing precisionVSEase of operation

Solution Approach 1:

The system uses image processing algorithms to continuously monitor image sharpness and fiducial positions, providing feedback to automatically adjust the focal plane. This closed-loop control compensates for surface non-flatness by dynamically adapting the focus position based on detected variations in image quality and fiducial alignment, eliminating the need for manual correction.

Inventive Principle:

Principle #23Feedback

Solution Approach 2:

The system automatically changes optical parameters such as focal plane position and camera positioning to compensate for surface non-flatness. By algorithmically determining the optimal parameter settings based on detected fiducials and image sharpness, the system adapts to varying surface conditions without requiring manual intervention or complex mechanical adjustments.

Inventive Principle:

Principle #35Parameter changes

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 efficient and accurate imaging of biological probe arrays by optimizing image sharpness and flatness, improving the quality of data acquisition for genetic information and diagnostics.

Implementation Method 1

focusing on a plurality of fiducials on a surface of an array. A plurality of images is taken at a plurality of various z positions

Methodology Applied

Scientific EffectFocusing: Focusing

Implementation Method 2

detecting the responsive emitted light from fluorescent labels associated with target molecule hybridized to the probes

Methodology Applied

Scientific EffectFluorescence: Fluorescence

Data Source

PatentUS10977478B2Methods and devices for reading microarrays

Publication Date: 2021.04.13 AFFYMETRIX INC

AI summary

In one embodiment of the invention, a method to image a probe array is described that includes focusing on a plurality of fiducials on a surface of an array. The method utilizes obtaining the best z position of the fiducials and using a surface fitting algorithm to produce a surface fit profile. One or more surface non-flatness parameters can be adjusted to improve the flatness image of the array surface to be imaged.