Microscope System Combining Diffraction-Limited and Superresolution Imaging
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Solution Overview
Problem
Current optical microscopy techniques, including superresolution microscopy, are limited in their ability to efficiently screen and observe drug targets at the nanoscale in living materials, particularly in terms of high throughput and time-resolved monitoring of reaction dynamics.
Innovation Solution
The method combines diffraction-limited imaging for low and high magnification overview images with MINFLUX and/or MINSTED superresolution microscopy to screen specific compounds of interest, utilizing intelligent algorithms to define regions of interest and track compounds dynamically.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional optical microscopy is used, then the imaging process is simple and fast, but the resolution is limited by diffraction and cannot achieve nanoscale observation
Solution Approach 1:
The imaging process is segmented into two stages: first, low-resolution overview imaging to identify regions of interest; second, high-resolution nanoscale imaging only of selected regions. This segmentation allows the system to achieve nanoscale resolution without continuously operating complex superresolution microscopy, thus resolving the contradiction between resolution and complexity.
Solution Approach 2:
The method performs preliminary low-resolution imaging before high-resolution imaging to pre-identify regions of interest. This preliminary action filters out irrelevant areas, allowing the complex superresolution microscopy to be applied only where needed, thereby achieving high resolution without proportionally increasing overall system complexity.
2Productivity
If superresolution microscopy is used to observe nanoscale structures, then resolution improves, but the number of compounds that can be observed is limited and throughput decreases
Solution Approach 1:
The imaging workflow is segmented into screening phase (low-resolution, high throughput) and analysis phase (high-resolution, low throughput). By segmenting the observation process, the system can maintain high throughput during screening while achieving high resolution only for compounds of interest, resolving the contradiction between productivity and measurement precision.
Solution Approach 2:
The method applies superresolution microscopy partially - only to regions and compounds that show interest during low-resolution screening. This partial application of the high-resolution technique allows the system to maintain high overall throughput while achieving nanoscale resolution where necessary, rather than attempting to observe all compounds at high resolution simultaneously.
3Productivity
If multiple compounds are screened simultaneously, then throughput increases, but the ability to monitor reaction dynamics and observe specific interactions is reduced
Solution Approach 1:
The imaging process segments compounds into two groups: those requiring detailed dynamic analysis (selected through low-resolution screening) and those that can be observed at lower resolution. This segmentation allows the system to maintain high throughput by not requiring superresolution imaging for all compounds, while still capturing reaction dynamics information for selected compounds of interest.
Solution Approach 2:
The method applies different imaging qualities to different compounds based on their relevance. Compounds showing interest during screening receive high-resolution, time-resolved imaging to capture reaction dynamics, while other compounds are observed at lower resolution. This local quality differentiation maintains overall throughput while preserving critical dynamic information for relevant compounds.
4Measurement precision
If high-resolution imaging is applied to the entire sample, then observation detail improves, but the time required for screening increases
Solution Approach 1:
The method performs preliminary low-resolution imaging of the entire sample to identify regions and compounds of interest before applying high-resolution imaging. This preliminary action filters out irrelevant areas, reducing the time required for high-resolution screening by focusing only on promising targets rather than scanning the entire sample at high resolution.
Solution Approach 2:
The imaging process is segmented into a quick screening phase using low-resolution imaging and a detailed analysis phase using high-resolution imaging. This segmentation allows the system to maintain fast screening by not applying high-resolution imaging to the entire sample, while still achieving detailed observation of selected compounds of interest.
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 enables faster and more detailed observation of drug targets and their interactions, allowing for earlier and more informed decision-making in drug development, with improved resolution and throughput compared to conventional methods.
Implementation Method 1
The MINFLUX principle enables the precise localisation of a fluorescence marker through a donut-shaped focus of a laser beam used to excite the fluorescence
Implementation Method 2
In this case, the fluorescence inhibition light is preferably focused in such a way that the focus is at such a minimum that the stimulation light can be focused
Data Source
AI summary
In a first aspect, the invention relates to a method for imaging and screening a component of interest in a sample based on different types of imaging. In particular, the method comprises first acquiring low or high magnification images of the sample and, after determining the region of interest, MINFLUX and/or MINSTED superresolution microscopy of the region of interest to screen the compound of interest. A system is further described for imaging and screening a compound of interest in a sample, the system comprising a microscope system combining diffraction-limited imaging techniques with at least one of MINFLUX or MINSTED superresolution techniques. The system optionally comprises a database of properties of known compounds. Finally, a computer program product resided on a computer-readable medium is provided to enable the method of the invention to be carried out for controlling a microscope system.