Ion Beam Focus Control for Tilted Sample Imaging
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Solution Overview
Problem
Conventional multiplexed immunohistochemical techniques face challenges in visualizing protein expression in biological samples due to limitations in signal amplification, spectral signature discrimination, and antibody compatibility, leading to compromised quantitative information and diagnostic utility.
Innovation Solution
The use of multiplexed ion beam imaging methods, where biological samples are tagged with antibodies conjugated to lanthanide elements and exposed to a primary ion beam, generating secondary ions for spatially-resolved analysis to determine protein expression and other biological events, with focal length adjustment of the ion source to maintain sample regions within the focal plane, reducing imaging artifacts and enhancing spatial resolution.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If the sample is tilted relative to the ion beam to enhance secondary ion yield, then the yield of secondary ions is improved, but imaging artifacts and blurring arise due to regions being out of focal plane
Solution Approach 1:
The patent applies dynamic focal length adjustment during ion beam scanning. The focal length is continuously modified based on the beam position relative to the tilted sample surface, allowing the system to adapt to the changing geometry and maintain focus across the entire scanned area, thereby resolving the contradiction between tilted-sample ion yield and spatial resolution
Solution Approach 2:
The patent changes the focal length parameter of the ion source as a function of beam position. By dynamically adjusting this critical parameter, the system compensates for the geometric distortion introduced by sample tilting, maintaining optimal focus and spatial resolution while preserving the benefits of the tilted configuration for secondary ion generation
2Area of stationary object
If the ion beam is translated across an extended sample region, then the coverage area is improved, but focal plane deviations cause blurring and compromised spatial resolution
Solution Approach 1:
The system dynamically adjusts the focal length during scanning operations. As the ion beam is translated across extended sample regions, the focal length is continuously modified to compensate for geometric deviations, ensuring that all scanned areas remain in focus and maintaining high spatial resolution across the entire coverage area
Solution Approach 2:
The patent implements a feedback mechanism where the focal length adjustment is based on the position of the ion beam relative to the sample. This closed-loop control ensures that focal plane deviations are continuously corrected during scanning, maintaining spatial resolution across extended regions
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 allows for high-sensitivity, quantitative assessment of multiple mass tags with parts-per-billion sensitivity and dynamic range of 10^5, achieving imaging resolution comparable to optical microscopy, enabling detailed analysis of tumor viability and progression.
Implementation Method 1
exposing a biological sample to an ion beam that is incident on the sample at a first angle to a plane of the sample by translating a position of the ion beam on the sample
Implementation Method 2
adjusting a focal length of an ion source that generates the ion beam; after each translation of the ion beam in the first direction, adjusting a focal length of an ion source that generates the ion beam
Data Source
AI summary
The disclosure features systems and methods that include: exposing a biological sample to an ion beam that is incident on the sample at a first angle to a plane of the sample by translating a position of the ion beam on the sample in a first direction relative to a projection of a direction of incidence of the ion beam on the sample; after each translation of the ion beam in the first direction, adjusting a focal length of an ion source that generates the ion beam; and measuring and analyzing secondary ions generated from the sample by the ion beam after adjustment of the focal length to determine mass spectral information for the sample, where the sample is labeled with one or more mass tags and the mass spectral information includes populations of the mass tags at locations of the sample.