Autofocus with Variable Angle Illumination for Microscopy

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Solution Overview

Problem

Current autofocus techniques in microscopy face limitations in accuracy and reliability due to interference structures and weakly contrasting samples, which hinder precise Z-positioning of the sample stage.

Innovation Solution

A method that involves acquiring images under multiple angle-variable illumination geometries, separating the measurement object from interference structures using a priori knowledge, and determining object displacement to adjust the Z-position of the sample stage for precise focusing.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If angle-variable illumination is used for autofocus, then Z-positioning capability is provided, but reliability and accuracy are limited due to interfering structures and low-contrast samples

Engineering Contradiction:
Improveautofocus reliabilityVSAvoidobject displacement detection accuracy
Core Design Contradiction:
ReliabilityVSMeasurement precision

Solution Approach 1:

The image is segmented into multiple components: the measurement object, interfering structures, and background. This is achieved by capturing images at multiple illumination angles and using the fact that the measurement object exhibits angle-dependent displacement while interfering structures remain relatively static. The segmentation allows selective analysis of object displacement without interference from other structures.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The illumination angle is varied as a parameter to induce differential displacement between the measurement object and interfering structures. By changing the illumination angle, the measurement object's image position changes predictably, while interfering structures remain stationary or change minimally, enabling reliable separation and accurate displacement measurement.

Inventive Principle:
Principle #35Parameter changes

2Measurement precision

If traditional autofocus with angle-variable illumination is used, then Z-positioning is achieved, but accuracy deteriorates due to interfering structures captured alongside the measurement object

Engineering Contradiction:
Improvedefocus position determination accuracyVSAvoidinterference structures
Core Design Contradiction:
Measurement precisionVSObject-affected harmful factors

Solution Approach 1:

The measurement object's signal is extracted from the composite image by analyzing its unique response to angle-variable illumination. The object's image displacement pattern with respect to illumination angle changes is distinct from interfering structures, allowing selective extraction of object-related information while eliminating interference from other structures.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The illumination angle serves as an intermediary parameter that differentiates between the measurement object and interfering structures. By using angle-variable illumination as a mediator, the system can selectively enhance the measurement object's signal while suppressing interfering structures, improving defocus position determination accuracy.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Measurement precision

If autofocus is performed on low-contrast samples with little absorption and phase shift, then Z-positioning is attempted, but signal separation becomes insufficient preventing accurate object displacement detection

Engineering Contradiction:
Improvesignal separation qualityVSAvoidsample contrast
Core Design Contradiction:
Measurement precisionVSIllumination intensity

Solution Approach 1:

The system introduces dynamic angle-variable illumination to create temporal and spatial variations in the image signal. Even low-contrast samples exhibit dynamic displacement patterns when illuminated from different angles, transforming a static low-contrast problem into a dynamic high-contrast problem that can be reliably detected and measured.

Inventive Principle:
Principle #15Dynamics

Data Source

PatentEP3557306B1Autofocus with variable angle illumination
Publication Date: 2024.11.27 CARL ZEISS MICROSCOPY GMBH
  • EP3557306B1 patent drawingFigure 1
  • EP3557306B1 patent drawingFigure 2
  • EP3557306B1 patent drawingFigure 3~4

AI summary

Several aspects of the invention relate to techniques for enabling autofocus techniques for a measurement object (499) using angle-variable illumination. Images are captured under a variety of angle-variable illumination geometries (301, 302). The captured images are then evaluated to determine the Z-position.