Biological Probe Array Scanning with Auto-Focus and Position Correction
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Solution Overview
Problem
Current optical scanners face challenges in accurately imaging small feature sizes on biological probe arrays due to positioning errors and the need for precise focus adjustment, which affects the accuracy of data collection from high-density arrays like Affymetrix GeneChip arrays.
Innovation Solution
A scanning system that includes optical elements for directing an excitation beam, detectors for receiving reflected intensity data, an auto-focuser to determine the best plane of focus, and a transport frame for adjusting the focusing distance, along with a method for associating pixel intensity values with image pixel positions using position correction values, enabling precise imaging of small features with minimal error.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional optical scanners are used to image small features on high-density probe arrays, then the system structure is simple, but the imaging precision deteriorates due to positioning errors and focus adjustment issues
Solution Approach 1:
The system performs preliminary actions by pre-determining the best plane of focus using reflected intensity data before actual imaging, and pre-calculating position correction values based on fiducial markers. This preliminary preparation eliminates the need for repeated focus adjustments and positioning corrections during imaging, thereby improving measurement precision without proportionally increasing system complexity
Solution Approach 2:
The system implements feedback mechanisms by using detectors to receive reflected intensity data and determine the best plane of focus, then using position correction values derived from fiducial markers to correct imaging positions. This closed-loop feedback ensures high imaging precision for small features on high-density arrays while maintaining manageable system complexity through automated control
2Productivity
If manual focus adjustment is used, then the device complexity is low, but the productivity deteriorates due to time-consuming focus adjustment
Solution Approach 1:
The system performs self-service by automatically determining the best plane of focus using reflected intensity data from detectors, without requiring manual intervention. The auto-focuser mechanism independently adjusts the focusing distance based on real-time feedback, significantly improving productivity while the automated nature keeps the added complexity manageable
Solution Approach 2:
The system replaces manual mechanical focus adjustment with an automated optical-electrical system that uses detectors to measure reflected intensity and an auto-focuser to adjust focusing distance. This substitution eliminates time-consuming manual operations, improving data collection efficiency while the integration of these components maintains reasonable system complexity
3Measurement precision
If the excitation beam is focused tightly to resolve small features, then the measurement precision improves, but the reliability deteriorates due to sensitivity to positioning errors
Solution Approach 1:
The system performs preliminary determination of the best plane of focus using reflected intensity data before actual feature imaging. This preliminary focusing action ensures that when tight focus is applied for high-resolution imaging, the system is already positioned optimally, reducing sensitivity to positioning errors and improving reliability
Solution Approach 2:
The system uses feedback from detectors measuring reflected intensity data to continuously monitor and adjust the focus position. This feedback mechanism ensures that tight focusing maintains both high measurement precision for small features and high reliability by compensating for positioning variations in real-time
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 system achieves accurate imaging of probe array features with an error of ±1 pixel or less, improving data collection efficiency and accuracy from high-density biological arrays by optimizing focus and positioning.
Implementation Method 1
emissions from biological probe arrays having small features that may be arranged in high densities on the arrays
Implementation Method 2
a transport frame that adjusts the focusing distance in a direction with respect to the probe array
Data Source
AI summary
An embodiment of a scanning system is described including optical elements that direct an excitation beam at a probe array, detectors that receive reflected intensity data responsive to the excitation beam, where the reflected intensity data is responsive to a focusing distance between an optical element and the probe array, a transport frame that adjusts the focusing distance in a direction with respect to the probe array, an auto-focuser that determines a best plane of focus based upon characteristics of the reflected intensity data of at least two focusing distances where the detectors further receive pixel intensity values based upon detected emissions from a plurality of probe features disposed on the probe array at the best plane of focus, and an image generator that associates each of the pixel intensity values with at least one image pixel position of a probe array based upon one or more position correction values.