Cell Imaging via Inclined Light Sheet and Phase Modulation

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Solution Overview

Problem

Current cell imaging methods face challenges in obtaining clear images of cells that deviate from the focal position of the object lens, particularly when imaging multiple cells or cell aggregates, leading to reduced throughput and image quality.

Innovation Solution

A cell imaging method that forms a light sheet inclined with respect to the flow cell, using a phase modulation element to extend the depth of focus and correct distortion, allowing for simultaneous imaging of multiple cells across the light sheet and generating high-quality, three-dimensional images.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If multiple cells are simultaneously imaged to increase throughput, then productivity is improved, but image quality deteriorates due to focus deviation for cells away from the focal position

Engineering Contradiction:
ImprovethroughputVSAvoidimage quality
Core Design Contradiction:
ProductivityVSMeasurement precision

Solution Approach 1:

The patent changes the optical parameter by introducing a phase modulation element that extends the depth of focus. This allows multiple cells at different positions along the optical axis to remain in focus simultaneously, maintaining image quality while enabling simultaneous imaging of multiple cells to increase throughput

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The phase modulation element acts as an intermediary component in the optical path that modifies the light waves to extend the depth of focus. This intermediary element enables the system to capture clear images of multiple cells at different depths without compromising image quality

Inventive Principle:
Principle #24Intermediary (Mediator)

2Productivity

If the light sheet is positioned to capture multiple cells, then productivity is improved, but manufacturing precision deteriorates due to distortion in taken images

Engineering Contradiction:
ImprovethroughputVSAvoidimage accuracy
Core Design Contradiction:
ProductivityVSManufacturing precision

Solution Approach 1:

The patent implements a feedback mechanism where distortion correction information is calculated based on the known geometry of the light sheet inclination and phase modulation. This feedback is applied to the captured images to correct distortion, ensuring manufacturing precision is maintained while allowing simultaneous imaging of multiple cells for improved productivity

Inventive Principle:
Principle #23Feedback

3Measurement precision

If a phase modulation element is introduced to extend depth of focus, then image quality is improved, but device complexity increases

Engineering Contradiction:
Improveimage qualityVSAvoidsystem complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent replaces complex mechanical focusing mechanisms with a phase modulation element that achieves extended depth of focus through optical phase manipulation. This substitution reduces mechanical complexity while maintaining or improving image quality through non-mechanical means

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

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 enables clear cross-sectional images of cells regardless of their position, increasing throughput and image quality by extending the depth of focus and correcting distortion, thereby obtaining high-quality images of multiple cells simultaneously.

Implementation Method 1

via an element (55) configured to extend a depth of focus... the element (55) configured to extend the depth of focus may be a phase modulation element (55) configured to modulate a point spread function

Methodology Applied
Scientific EffectPhase modulation: Phase Modulation

Implementation Method 2

receiving lights generated from the plurality of cells passing through the light sheet (11)

Methodology Applied
Scientific EffectFluorescence: Fluorescence

Data Source

PatentUS11366097B2Cell imaging method, cell imaging apparatus, particle imaging method, and particle imaging apparatus
Publication Date: 2022.06.21 SYSMEX CORP
  • US11366097B2 patent drawing
  • US11366097B2 patent drawing
  • US11366097B2 patent drawing

AI summary

Disclosed is a cell imaging method including: forming a light sheet with respect to a flow cell; causing a measurement sample containing a plurality of cells to flow in the flow cell; and receiving lights generated from the plurality of cells passing through the light sheet, by an imaging device via an element configured to extend a depth of focus, and taking images of the plurality of cells by the imaging device.