Flow Cytometer 3D Morphology Extraction via Coherent Diffraction Imaging

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Solution Overview

Problem

Conventional flow cytometers face challenges in accurately analyzing three-dimensional morphology parameters of particles due to their reliance on two-dimensional imaging techniques, which are complex and labor-intensive, and are limited by high flow speeds and poor signal-to-noise ratios.

Innovation Solution

A flow cytometer assembly that uses a coherent light source to illuminate particles, detecting spatially coherent distributions of elastically scattered light to extract three-dimensional morphology parameters, combined with non-coherent light source imaging for enhanced data acquisition and analysis.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Difficulty of detecting and measuring

If conventional two-dimensional imaging techniques are used in flow cytometers, then imaging capability is provided, but analysis complexity increases and three-dimensional morphology extraction becomes labor-intensive

Engineering Contradiction:
Improveimaging capabilityVSAvoidanalysis complexity
Core Design Contradiction:
Difficulty of detecting and measuringVSDevice complexity

Solution Approach 1:

The patent replaces conventional two-dimensional bright-field microscopy with diffraction imaging technology that uses spatially coherent light distributions. This substitution enables automatic extraction of three-dimensional morphology parameters through mathematical analysis of diffraction patterns, eliminating the need for complex manual analysis of two-dimensional images while providing genuine three-dimensional structural information.

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

Solution Approach 2:

The patent changes the fundamental imaging parameter from intensity-based two-dimensional imaging to spatially coherent diffraction pattern detection. By measuring the angular distribution of scattered light intensities and applying diffraction theory, the system extracts three-dimensional morphological parameters directly, transforming the measurement approach to achieve both simplicity and three-dimensional capability.

Inventive Principle:
Principle #35Parameter changes

2Productivity

If high flow speeds are used in flow cytometers, then productivity increases, but signal-to-noise ratio deteriorates

Engineering Contradiction:
Improveflow speedVSAvoidsignal-to-noise ratio
Core Design Contradiction:
ProductivityVSMeasurement precision

Solution Approach 1:

The patent replaces conventional intensity-based scattering detection with diffraction imaging that measures spatially coherent light distributions. This substitution inherently improves signal-to-noise ratio because diffraction patterns provide structured information that is more resistant to noise, enabling accurate three-dimensional morphology measurement even at high flow speeds where conventional methods fail.

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

Solution Approach 2:

The patent introduces spatially coherent light as an intermediary between the particle and detector. The coherent light creates diffraction patterns that encode three-dimensional morphological information in a way that is more robust to flow speed variations and noise, effectively mediating the measurement process to maintain precision at high productivity.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Difficulty of detecting and measuring

If conventional fluorescence or bright-field microscopy is used, then two-dimensional images are acquired, but three-dimensional structural information is lost due to focal depth compression

Engineering Contradiction:
Improveimaging capabilityVSAvoidthree-dimensional information
Core Design Contradiction:
Difficulty of detecting and measuringVSLoss of information

Solution Approach 1:

The patent replaces conventional microscopy with diffraction imaging that inherently captures three-dimensional information. By measuring the angular distribution of scattered light in the diffraction pattern and applying diffraction theory, the system reconstructs three-dimensional morphological parameters directly, eliminating the information loss that occurs when three-dimensional structures are compressed into two-dimensional focal planes.

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

Solution Approach 2:

The patent transitions from two-dimensional intensity imaging to three-dimensional diffraction pattern measurement. The diffraction pattern contains spatial frequency information that encodes three-dimensional structural data, effectively adding a dimensional aspect to the measurement that conventional microscopy cannot provide, allowing full three-dimensional reconstruction without focal depth compression.

Inventive Principle:
Principle #17Another dimension (Dimensionality change)

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

Enables the extraction of detailed three-dimensional morphology parameters from particles, improving analysis efficiency and accuracy, and increasing the signal-to-noise ratio for enhanced imaging capabilities.

Implementation Method 1

A detector is configured to detect a spatially coherent distribution of elastically scattered light from the particle excited by the coherent light source

Methodology Applied
Scientific EffectElastic scattering: Scattering

Data Source

PatentUS9013692B2Flow cytometer apparatus for three dimensional difraction imaging and related methods
Publication Date: 2015.04.21 HU XIN HUA
  • US9013692B2 patent drawing
  • US9013692B2 patent drawing
  • US9013692B2 patent drawing

AI summary

A flow cytometer assembly includes a fluid controller configured to form a hydrodynamically focused flow stream including an outer sheath fluid and an inner core fluid. A coherent light source is configured to illuminate a particle in the inner core fluid. A detector is configured to detect a spatially coherent distribution of elastically scattered light from the particle excited by the coherent light source. An analyzing module configured to extract a three-dimensional morphology parameter of the particle from a spatially coherent distribution of the elastically scattered light.