Bi-Modal Optical Microscope for Drift-Corrected Single-Molecule Imaging
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Solution Overview
Problem
Current optical microscopes, particularly super resolution microscopes, are complex, require significant user knowledge, and are sensitive to minute environmental movements, limiting their precision and ability to observe molecular-scale interactions like drug-receptor binding and protein-protein interactions effectively.
Innovation Solution
A bi-modal optical microscope combining confocal and TIRF microscopy modes, with automated sample preparation and image capture, corrects for positional drift using fiducial markers and real-time Z-direction focus, enabling high spatial and temporal resolution imaging of molecular interactions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If a conventional optical microscope is used to observe live cells, then the cells remain alive, but the image quality deteriorates due to insufficient light intensity reaching the sensor
Solution Approach 1:
The patent implements a nested optical system where a first optical system (objective lens) and a second optical system (tube lens) are arranged in sequence. The first optical system forms an intermediate image that is then magnified by the second optical system, creating a nested configuration that increases overall magnification and light intensity at the sensor without requiring higher illumination that would harm live cells
Solution Approach 2:
The patent introduces a spectral dimension by using a spectral image sensor that detects light in multiple wavelength bands simultaneously. This dimensional expansion allows the system to capture more information from the same light source, effectively increasing the utility of available light without increasing illumination intensity that would damage live cells
2Illumination intensity
If light intensity is increased to improve image quality, then image quality improves, but the live cells are damaged by excessive light
Solution Approach 1:
The nested optical system with first and second optical systems allows progressive magnification where the intermediate image formed by the first system is further magnified by the second system. This multi-stage approach achieves high overall magnification and improved image quality without requiring excessive illumination intensity that would damage live cells
Solution Approach 2:
By utilizing the spectral dimension with a spectral image sensor that captures multiple wavelength bands, the system extracts more information from the same light input. This dimensional expansion improves image quality and provides more data about the sample without increasing light intensity to harmful levels
3Measurement precision
If magnification is increased to observe cellular structures, then observation detail improves, but light intensity at the sensor decreases
Solution Approach 1:
The patent employs a nested configuration where a first optical system with its own magnification is combined with a second optical system that provides additional magnification of the intermediate image. This nested arrangement achieves high total magnification for detailed cellular structure observation while maintaining adequate light intensity at the sensor through the distributed magnification stages
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 direct observation of single molecule interactions with resolutions as low as 15-20nm and time-resolutions of 1ms or less, providing accurate kinetic data for drug development and molecular-scale monitoring.
Implementation Method 1
a spectral image sensor, which detects light in multiple wavelength bands, is arranged in the optical path
Implementation Method 2
a first optical system and a second optical system are arranged in sequence in the optical path
Implementation Method 3
first optical system and a second optical system are arranged in sequence in the optical path of a light beam passing through the sample
Data Source
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AI summary
An optical microscope (10) comprising a first optical microscope (R); and a second optical microscope (Q) with a different mode of operation to the first optical microscope (R). The optical microscope (10) is configured such that the first optical microscope (R) and the second optical microscope (Q) simultaneously view a sample on a sample stage (I).