Microfluidic Cell Imaging With Quantitative Phase Refocusing
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Solution Overview
Problem
Conventional microfluidic devices face challenges in maintaining focus on cells flowing through channels due to inherent distribution in axial position, operator variability, focus shift from sample size differences, mechanical vibrations, and flow instabilities, leading to underfocused or overfocused images, and difficulties in distinguishing cells with similar appearances.
Innovation Solution
A device using quantitative phase imaging and numerical refocusing techniques, such as interferometric quantitative phase imaging, to obtain a phase distribution map, allowing for computational focusing without physical movement of optics, and distinguishing cells based on phase shift information, including dry mass density analysis.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional optical imaging is used to analyse flowing cells, then cell morphology and internal structure can be observed, but focus is lost due to axial position distribution, operator variability, and mechanical vibrations
Solution Approach 1:
The patent replaces the mechanical focusing system with a computational approach. Instead of physically moving the objective lens to maintain focus on cells at different axial positions, the system captures optical information (intensity and phase) and performs numerical refocusing through computational propagation. This substitution eliminates mechanical vibrations and operator variability while maintaining measurement precision across the entire axial range of flowing cells.
Solution Approach 2:
The patent changes the parameter space from real-space optical focusing to phase-space computational processing. By measuring both intensity and phase information and propagating these parameters numerically, the system achieves focus at any axial position without mechanical adjustment. This parameter transformation enables reliable, consistent imaging throughout the channel depth.
2Measurement precision
If the optics are moved to maintain focus on flowing cells, then clear images can be obtained, but the device complexity and cost increase due to powerful and precise motors
Solution Approach 1:
The patent eliminates the mechanical positioning system entirely by replacing it with computational refocusing. The system captures optical information at a fixed optical configuration and uses numerical algorithms to achieve focus at any desired axial position, thereby removing the need for powerful and precise motors while maintaining focus accuracy.
Solution Approach 2:
The patent creates a computational copy of the optical focusing process. Instead of physically moving the optics to achieve focus, the system numerically propagates the captured optical field to reconstruct focused images at different axial positions, effectively copying the focusing effect through computation rather than mechanics.
3Measurement precision
If the sample flow speed is reduced to improve focusing, then focus can be maintained, but the productivity and throughput of cell analysis decrease
Solution Approach 1:
The patent replaces mechanical focusing (which requires slow sampling to track cell positions) with computational refocusing that works at any flow speed. The system captures optical information and numerically propagates it to achieve focus, eliminating the need to slow down the sample flow while maintaining focus stability throughout the axial range.
4Loss of information
If bright field imaging is used to obtain cell images, then cell shape and deformation can be measured, but cells with similar appearances cannot be distinguished
Solution Approach 1:
The patent changes from measuring only intensity (amplitude) to measuring both intensity and phase parameters. This additional phase information provides insights into cell internal structure and composition that are not visible in conventional bright field imaging, enabling distinction between cells with similar appearances while preserving all morphological information.
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 reliable, high-throughput cell analysis with focused images and improved distinction between cell types, overcoming the limitations of conventional imaging by providing clear, focused images and enabling real-time diagnostic capabilities.
Implementation Method 1
An imaging means is arranged so as to obtain optical information of the bodies as they are flowing through the channel
Implementation Method 2
an analysis means is arranged which uses the optical information obtained by the imaging means to obtain a phase distribution map of the spatial distribution of the phase shift of light as it passes through the bodies
Implementation Method 3
A device using quantitative phase imaging and numerical refocusing techniques, such as interferometric quantitative phase imaging, to obtain a phase distribution map, allowing for computational focusing without physical movement of optics
Data Source
Figure 1A~2B
Figure 3
Figure 4A~4C
AI summary
The present invention relates a device for analysing bodies, preferably cells, suspended in a fluid, the device comprising: a microfluidic channel arranged for allowing the fluid containing the bodies to flow therethrough, an imaging means arranged so as to obtain optical information of the bodies as they are flowing through the channel, an analysis means which uses the optical information obtained by the imaging means to obtain a phase distribution map of the spatial distribution of the phase shift of light as it passes through the bodies.