Refractive Index-Matched Flow Cell for High-Throughput Microscopy
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Solution Overview
Problem
The bottleneck in using multi-cellular constructs for pharmaceutical research is the lack of efficient in-depth validation methodologies due to the complexity of imaging large and opaque constructs, which limits their use in high-throughput screening.
Innovation Solution
A flow cell unit with a castable light-transparent flow cell body, formed from a refractive index-matching gel, allows for high-throughput imaging of multicellular constructs under flow using light microscopy, facilitating automated and efficient screening.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If traditional imaging methods are used for multicellular constructs, then image quality is maintained, but imaging speed and throughput are limited
Solution Approach 1:
The patent introduces a flow cell body as an intermediary medium between the sample carrier liquid and the imaging system. This flow cell body with refractive index matching acts as a mediator that enables high-throughput imaging by resolving the optical interference caused by the sample container, thereby increasing productivity without compromising measurement capability
Solution Approach 2:
The patent changes the refractive index parameter of the flow cell body to match that of the sample carrier liquid. This parameter change eliminates optical distortion and enables rapid imaging, directly addressing the contradiction between imaging speed and imaging complexity by making the system optically transparent to the imaging wavelengths
2Measurement precision
If light microscopy is used for multicellular constructs, then cellular resolution is achieved, but imaging time is too long for high-throughput screening
Solution Approach 1:
The flow cell body serves as an optical intermediary that enables light microscopy to achieve both cellular resolution and high speed. By matching the refractive index, it allows light to pass through without distortion, maintaining measurement precision while enabling rapid acquisition suitable for high-throughput screening
Solution Approach 2:
By changing the refractive index parameter of the imaging medium to match the sample carrier liquid, the system achieves optimal light transmission. This parameter optimization allows light microscopy to maintain cellular resolution while dramatically reducing imaging time, resolving the contradiction between precision and speed
3Measurement precision
If refractive index matching is implemented, then image quality is improved, but device complexity increases
Solution Approach 1:
The patent implements refractive index matching by selecting materials with specific optical parameters. This parameter-based solution improves image quality through a single material selection criterion rather than complex structural modifications, minimizing the increase in device complexity while achieving superior optical performance
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 rapid and high-throughput imaging of multicellular constructs, overcoming the limitations of traditional imaging methods by providing a refractive index-matched environment for improved image quality and compatibility with various sample types.
Implementation Method 1
the castable flow cell body (120) has a refractive index matching a refractive index of the sample carrier liquid
Data Source
Figure 1A~1C
Figure 2A~2C
Figure 3A~3C
AI summary
Provided herein is a flow cell unit (100) for imaging of a sample of at least one multicellular construct under flow, wherein: the sample comprises one or more multicellular constructs suspended in a sample carrier liquid; and the imaging is by light microscopy; the flow cell unit (100) comprising: - a castable flow cell body (120) formed from a settable light-transparent casting substance, a casting substance, having a set state in the castable flow cell body (120), wherein the castable flow cell body (120) has a refractive index matching a refractive index of the sample carrier liquid; and - a flow cell channel (140) in the castable flow cell body (120) for flow of the sample through at least a light-interacting portion (130) of the castable flow cell body (120) such that sample is in contact with the casting substance in the set state in the light-interacting portion (130).