Multi-Aperture Autofocus for Uneven IMS Sample Imaging
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Solution Overview
Problem
Existing autofocus systems for imaging mass spectrometry and imaging mass cytometry often fail when dealing with biological samples due to issues like varying composition, uneven topology, or voids, which can obstruct the detection of focus using a single aperture.
Innovation Solution
The implementation of an autofocus system with a plurality of apertures, allowing radiation to pass through multiple openings, provides redundancy and improves the robustness of focus detection by compensating for failures in individual aperture measurements.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If a single aperture is used in the autofocus system, then the device complexity is reduced, but the reliability of focus detection deteriorates due to failures caused by varying sample composition, uneven topology, or voids
Solution Approach 1:
The autofocus system is segmented into multiple independent aperture channels instead of using a single aperture. Each aperture provides an independent measurement path, so that if one aperture fails to detect focus properly due to sample characteristics (varying composition, uneven topology, or voids), other apertures can still provide valid measurements. This segmentation increases reliability without requiring a completely different system architecture.
Solution Approach 2:
Different apertures are positioned at different locations in the optical path, allowing each aperture to sample different local regions of the beam. This local quality variation means that apertures at different positions experience different interactions with the sample, increasing the probability that at least one aperture will successfully detect focus despite sample heterogeneity.
2Reliability
If multiple apertures are used in the autofocus system, then the reliability of focus detection is improved through redundancy, but the device complexity increases
Solution Approach 1:
The multiple apertures share common optical components including the illumination source, detection sensor, and signal processing electronics. This multi-functionality approach allows the system to achieve redundant measurement paths without proportionally increasing overall system complexity, as many components serve multiple aperture channels simultaneously.
Solution Approach 2:
The autofocus system merges multiple aperture measurements into a single integrated focus determination process. The signals from multiple apertures are combined through the detection sensor and processing electronics to produce a unified focus metric, reducing the operational complexity despite having multiple physical apertures.
3Productivity
If a single aperture is used for autofocus, then the system is simpler to operate, but the productivity decreases due to unsuccessful autofocus attempts on complex biological samples
Solution Approach 1:
The system implements feedback by continuously monitoring focus quality metrics from multiple aperture channels and automatically adjusting the focus position based on the combined information. This feedback mechanism increases productivity by reducing unsuccessful autofocus attempts, while the automation maintains ease of operation as users simply initiate the process without manual intervention.
Solution Approach 2:
The autofocus system performs self-service by automatically selecting the optimal focus position based on measurements from multiple apertures. The system autonomously handles the complexity of coordinating multiple aperture measurements and determining the best focus point, freeing the user from manual focus adjustment while improving productivity through more reliable automated focusing.
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 the reliability and efficiency of autofocus systems by reducing the number of unsuccessful autofocus attempts and improving data quality and sample integrity, especially when dealing with complex biological samples.
Implementation Method 1
an autofocus sensor arranged to receive radiation reflected from the sample
Implementation Method 2
an objective lens disposed in the optical path of the radiation to focus the radiation towards the sample
Implementation Method 3
A laser in the sampling and ionisation system acts to remove material from the sample in the sample chamber
Data Source
AI summary
We describe in this application systems and methods for autofocusing in imaging mass spectrometry. The present application describes improvements over current IMS and IMC apparatus and methods through an autofocus component including a plurality of apertures in the autofocus system, such as a plurality of apertures arranged in 2 dimensions. As a plurality of apertures is used, the autofocus system provides redundancy in the event that measurement of focus on the sample from the illuminating radiation passed through one or more of the apertures fails so as to reduce the number of unsuccessful autofocus attempts.