Chirped-Wavelength Optical Imaging for High-Speed Single-Cell Analysis

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Solution Overview

Problem

Current quantitative phase-contrast imaging (QPI) techniques face limitations in high-throughput single-cell analysis due to speed constraints, mechanical instability, and computational intensity, particularly in label-free imaging of biological cells and tissues, which hinders efficient high-speed real-time analysis.

Innovation Solution

The implementation of a chirped-wavelength-encoding mechanism using wavelength-swept laser sources and optical time-stretch, eliminating the need for classical interferometric approaches, enables high-speed single-pixel quantitative phase contrast optical imaging without the use of conventional image sensors, allowing for flexible system design and ultrafast multiplexing of phase-contrast images.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If classical interferometric or holographic QPI techniques are used, then quantitative phase contrast imaging is achieved, but imaging speed is limited and mechanical stability is compromised

Engineering Contradiction:

Improvequantitative phase contrast measurementVSAvoidimaging speed

Core Design Contradiction:

Measurement precisionVSSpeed

Solution Approach 1:

The patent extracts and eliminates the interferometric component from QPI techniques, using direct detection of phase-modulated light intensity instead. This removes the mechanical instability and speed limitations inherent in interferometric systems while preserving quantitative phase contrast measurement capability

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The patent replaces mechanical interferometric systems with an optical modulation approach where phase information is encoded in light intensity variations. This substitution eliminates moving parts and mechanical stability requirements while enabling high-speed imaging

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

2Measurement precision

If CCD/CMOS sensors are used for image acquisition, then quantitative phase imaging is performed, but a trade-off between imaging sensitivity and speed occurs

Engineering Contradiction:

Improveimaging sensitivityVSAvoidimage acquisition rate

Core Design Contradiction:

Measurement precisionVSProductivity

Solution Approach 1:

The patent changes the detection parameter from direct intensity measurement to phase-modulated intensity measurement. By encoding phase information in the intensity signal through optical modulation, the system achieves both high sensitivity and high acquisition rates without being constrained by sensor limitations

Inventive Principle:

Principle #35Parameter changes

3Measurement precision

If phase-retrieval algorithms are applied, then quantitative phase information is obtained, but computational intensity increases and real-time analysis is hindered

Engineering Contradiction:

Improvequantitative phase informationVSAvoidcomputational complexity

Core Design Contradiction:

Measurement precisionVSDevice complexity

Solution Approach 1:

The patent extracts and removes the computationally intensive phase-retrieval step from the imaging process. By directly measuring phase-modulated intensity signals, the system obtains quantitative phase information without requiring iterative computational algorithms, enabling real-time analysis

Inventive Principle:

Principle #2Taking out (Extraction)

4Loss of information

If imaging capability is added to flow cytometry, then spatial information of cells is accessed, but imaging throughput decreases to orders of magnitude slower than non-imaging flow cytometers

Engineering Contradiction:

Improvespatial informationVSAvoidimaging throughput

Core Design Contradiction:

Loss of informationVSProductivity

Solution Approach 1:

The patent enables continuous high-speed imaging of flowing cells by eliminating the speed limitations of conventional QPI and imaging flow cytometry. The direct detection method maintains imaging capability while achieving throughput comparable to non-imaging flow cytometry through ultrafast data acquisition

Inventive Principle:

Principle #20Continuity of useful 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 achieves high-speed optical imaging with higher contrast and information content, enabling high-throughput label-free quantitative imaging of biological cells and tissues, significantly enhancing single-cell analysis capabilities, including rare cancer cell detection, with imaging speeds orders of magnitude faster than conventional methods.

Implementation Method 1

wavelength-swept laser sources

Methodology Applied

Scientific EffectWavelength sweeping: Laser

Implementation Method 2

optical time-stretch

Methodology Applied

Scientific EffectDispersion: Dispersion (of waves)

Implementation Method 3

detected by a photodetector

Methodology Applied

Scientific EffectPhotoelectric detection: Photoelectric Effect

Implementation Method 4

phase-gradient modulation

Methodology Applied

Scientific EffectPhase modulation: Phase Modulation

Data Source

PatentUS10365465B2Apparatus and method for quantitative phase-gradient chirped-wavelength-encoded optical imaging

Publication Date: 2019.07.30 VERSITECH LTD

AI summary

Systems and method for high-speed single-pixel quantitative phase contrast optical imaging are provided. This imaging technique can bypass the use of conventional image sensors and their associated speed limitations. The quantitative phase images can be acquired much faster than conventional quantitative phase imaging by a chirped-wavelength-encoding mechanism via wavelength-swept laser sources or optical time-stretch based on optical fibers, without the need for interferometric approaches.