Optical Cell Retrieval by Spatiotemporal Imaging and Phototagging
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Solution Overview
Problem
Current high-throughput screening methodologies are limited in their ability to monitor complex phenotypes with spatiotemporal resolution and are specialized for specific cell types, often requiring custom microfluidics or optical hardware, and cannot screen cells within biofilms, tissue, or in vivo.
Innovation Solution
A microscopy-based all-optical screening platform that uses selective illumination of target structures labeled with phototransformable molecules, followed by retrieval using FACS or microfluidics-based sorting, enabling high-throughput imaging and isolation of cellular, subcellular, or multicellular structures.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If FACS is used for high-throughput sorting, then sorting rate is improved, but the ability to conduct dynamic measurements and monitor cells with subcellular resolution is lost
Solution Approach 1:
The patent merges FACS sorting capability with microscopy imaging capability into a single integrated platform. The system combines a flow cytometer with a microscope, allowing cells to be imaged with high spatiotemporal resolution and then sorted based on the imaging data, thus achieving both high throughput and high measurement precision simultaneously
Solution Approach 2:
The integrated platform performs multiple functions: it can conduct dynamic measurements, monitor cells with subcellular resolution, and perform high-rate sorting all within the same system. This multi-functional approach eliminates the need to choose between FACS and microscopy-based methods
2Measurement precision
If standard microscopy-based approaches are used for high spatiotemporal resolution imaging, then measurement precision is improved, but throughput is limited
Solution Approach 1:
The patent combines standard microscopy imaging with FACS sorting in an integrated platform. The microscopy component provides high spatiotemporal resolution imaging, while the FACS component enables high-throughput sorting based on the imaging data, thus achieving both high measurement precision and high productivity
3Measurement precision
If existing microscopy-based single-cell isolation methods are used, then measurement precision is improved, but versatility across different cell types and three-dimensional structures is limited
Solution Approach 1:
The integrated FACS-microscopy platform is universally applicable to various cell types including bacteria, yeast, and mammalian cells. It can handle cells in different configurations such as monolayers, biofilms, and three-dimensional tissue structures, making it highly versatile across different biological systems
4Manufacturing precision
If custom microfluidics or optical hardware is used for specialized sorting, then sorting precision is improved, but device complexity and cost increase
Solution Approach 1:
The patent combines commercially available FACS hardware with microscopy hardware into an integrated system. This approach achieves high sorting precision through the coordinated operation of both systems without requiring custom-designed complex microfluidics or optical hardware, thus reducing device complexity while maintaining sorting precision
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
The platform is versatile, capable of screening various cell types, including those in dense monolayers or three-dimensional structures, and can be implemented with commercially available hardware, achieving high-content/high-throughput screening both in vitro and in vivo.
Implementation Method 1
Each target structure is selectively illuminated by an excitation light, thereby causing one or more taggable markers within the target structure to be phototransformed
Data Source
AI summary
Provided herein are embodiments of methods and systems for screening cellular, subcellular, and multicellular structures. In one embodiment, a method for screening is provided comprising the steps of introducing a plurality of cellular, subcellular, or multicellular structures, or a combination thereof, to an imaging system, wherein one or more structures of the plurality comprise one or more taggable markers; imaging the plurality of structures using the imaging system; identifying one or more target structures among the plurality of structures based on one or more properties of the target structures; tagging the target structures to produce tagged target structures, wherein each target structure is selectively illuminated by an excitation light, thereby causing one or more taggable markers within the target structure to be phototransformed to produce one or more phototransformed taggable markers within the target structure; and isolating one or more tagged target structures from the plurality of structures.