Pinhole-Modulated Autofocusing for Whole Slide Imaging

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Solution Overview

Problem

Current whole slide imaging systems face inefficiencies in maintaining optimal focal position due to topographical variations, particularly in digital pathology, where existing auto-focus methods either fail to adapt quickly or require time-consuming z-stacking for accurate focusing.

Innovation Solution

The implementation of pinhole-modulated cameras at the eyepiece ports of a microscope, using one-pinhole or two-pinhole masks at the Fourier plane, allows for instant focal plane detection by analyzing translational shifts in images, eliminating the need for z-scanning and enabling rapid auto-focusing across large fields of view.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If image contrast based methods are used to track sample topography variations, then optimal focal position can be identified, but total scanning time increases due to z-stacking

Engineering Contradiction:
Improvefocal position accuracyVSAvoidscanning time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The patent extracts the focus detection function from the main imaging path by using a separate detection camera with a pinhole mask. This allows simultaneous acquisition of focus information and imaging data without requiring z-stacking, thereby resolving the contradiction between focal position accuracy and scanning time.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The pinhole mask acts as an intermediary element that modulates light to create translational shifts in the detection camera image. This intermediary mechanism enables focus detection through a single z-position image, eliminating the need for time-consuming z-stacking while maintaining accurate focal position identification.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Speed

If laser reflection based methods are used to determine distance, then focusing speed is improved, but the method fails when sample location varies from the glass surface

Engineering Contradiction:
Improvefocusing speedVSAvoidsample position adaptability
Core Design Contradiction:
SpeedVSAdaptability or versatility

Solution Approach 1:

The detection camera with pinhole mask uses the sample's own light transmission properties to generate focus detection signals. The method is self-adapting to sample position variations because it directly measures the optical path through the actual sample, rather than relying on fixed-distance laser reflection assumptions.

Inventive Principle:
Principle #25Self-service

Solution Approach 2:

The patent replaces the mechanical laser distance measurement system with an optical-based image analysis system. The pinhole-modulated detection camera captures optical information that directly reflects sample position and focus state, providing both speed and adaptability without the limitations of laser reflection methods.

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

3Measurement precision

If multiple images are acquired by moving the sample along the z direction, then optimal focal position can be calculated, but system throughput decreases

Engineering Contradiction:
Improvefocal position determinationVSAvoidsystem throughput
Core Design Contradiction:
Measurement precisionVSProductivity

Solution Approach 1:

The pinhole mask is pre-positioned in the detection camera to create the necessary optical modulation. This preliminary setup enables focus detection from a single image capture, eliminating the need for preliminary or subsequent z-direction image acquisitions, thereby maintaining high system throughput while achieving accurate focal position determination.

Inventive Principle:
Principle #10Preliminary action

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 significantly reduces acquisition time, enhances image quality by ensuring all regions are in-focus, and provides a cost-effective solution for high-throughput whole slide imaging, suitable for digital pathology and other biomedical applications.

Implementation Method 1

pinhole-modulated cameras... using one-pinhole or two-pinhole masks at the Fourier plane

Methodology Applied
Scientific EffectDiffraction: Diffraction

Implementation Method 2

one-pinhole or two-pinhole masks at the Fourier plane, allows for instant focal plane detection by analyzing translational shifts in images

Methodology Applied
Scientific EffectFourier optics:

Data Source

PatentUS10330906B2Imaging assemblies with rapid sample auto-focusing
Publication Date: 2019.06.25 UNIV OF CONNECTICUT
  • US10330906B2 patent drawing
  • US10330906B2 patent drawing
  • US10330906B2 patent drawing

AI summary

Advantageous instruments, assemblies and methods are provided for undertaking imaging techniques (e.g., microscopic imaging techniques). The present disclosure provides improved imaging techniques, equipment and systems. More particularly, the present disclosure provides advantageous microscopy/imaging assemblies with rapid sample auto-focusing (e.g., microscopy/imaging assemblies having instant focusing for rapid sample imaging with auto-focusing). The present disclosure provides for high-throughput whole slide imaging with instant focal plane detection. A whole slide imaging platform/assembly that uses instant focusing systems/methods for high-speed sample autofocusing is provided. Such exemplary platforms/assemblies can be used for digital pathology or the like, and can provide improved, faster and cheaper diagnosis/prognosis of ailments/diseases. At least two exemplary rapid-focus systems for whole slide imaging are provided, a first system including two pinhole-modulated cameras mounted on the eyepiece ports of a microscope platform/assembly, and a second system including one pinhole-modulated camera mounted on the epi-illumination arm for auto-focusing.