Variable-Zone Sample Tilt Adjustment for High-NA Imaging Focus
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Solution Overview
Problem
Increasing the numerical aperture (NA) of optical imaging systems improves resolution but reduces the depth of field (DoF), making it difficult to maintain focus as the sample is translated, leading to poor data quality due to local tilts or tips within the sample.
Innovation Solution
Implementing intelligent sample tilt or tip adjustment using zones of variable size, calculated based on surface profile data to associate detilt or detip values with each zone, adjusting the relative tilt or tip between the sample and image sensor before imaging.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If the numerical aperture (NA) of the optical imaging system is increased to improve resolution, then the imaging resolution is improved, but the depth of field (DoF) is reduced making it difficult to maintain focus
Solution Approach 1:
The sample is divided into multiple zones based on surface profile data, with each zone having its own detilt/detip values. This segmentation allows different regions of the sample to be focused independently, resolving the contradiction between high NA (narrow DoF) and focus maintenance across the entire sample area.
Solution Approach 2:
Different detilt/detip adjustment values are applied to different zones of the sample based on their local topography. This local quality approach ensures that each region receives the appropriate focus adjustment, maintaining image quality across the entire sample even with reduced DoF from high NA.
2Reliability
If global detilt is applied to the entire sample to maintain focus, then the overall focus is improved, but local tip or tilt variations within the sample still cause DoF excursions and out-of-focus regions
Solution Approach 1:
The sample area is segmented into multiple zones, each with independently calculated detilt/detip values based on local surface profile data. This allows precise local focus adjustment while maintaining overall focus, resolving the contradiction between global and local focus uniformity.
Solution Approach 2:
Each zone receives customized detilt/detip values tailored to its specific local topography, ensuring that local tip or tilt variations are compensated. This local quality approach maintains focus uniformity across the entire sample area, eliminating out-of-focus regions caused by local variations.
3Ease of manufacture
If the depth of field is reduced by increasing NA to enable lower sequencing costs, then cost is reduced, but it becomes more difficult to ensure the sample remains in focus during translation
Solution Approach 1:
Surface profile data is obtained and detilt/detip zones are calculated before imaging begins. This preliminary action prepares the focus adjustment parameters in advance, allowing the system to maintain focus during sample translation without requiring complex real-time adjustments, thus easing operation despite reduced DoF.
Solution Approach 2:
The system applies dynamic detilt/detip adjustments across different zones during sample translation, adapting to local topography variations. This dynamic approach maintains focus control ease while enabling the use of high NA optics for cost-effective sequencing.
Data Source
AI summary
Some implementations of the disclosure describe an imaging instrument, including: an image sensor to image a sample; and one or more processors configured to cause the imaging instrument to: obtain surface profile data of a swath of the sample, the swath divided into multiple regions, and the surface profile data including surface profile data for each region; calculate, based at least on a threshold residual and the surface profile data of the swath, one or more zones of the swath that include the multiple regions, each zone including a respective one or more of the regions that are adjacent; and associate, based on the surface profile data of the one or more regions of each zone, a detilt or detip value with each zone, the detilt or detip value indicating an amount to adjust, before imaging the zone, a relative tilt or tip between the sample and image sensor.