Single-Particle Localization Microscopy With Asymmetric Test Patterns
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Solution Overview
Problem
Existing methods for single-particle localization in light microscopy suffer from ambiguity in determining the actual particle position due to symmetry in light patterns, leading to inefficient and time-consuming solutions that involve mechanical repositioning and high photon usage.
Innovation Solution
A single-particle localization microscope that uses a sequence of symmetrical light patterns followed by an asymmetrical test pattern to unambiguously locate a particle, leveraging electro-optical or acousto-optical devices for fast pattern generation without mechanical repositioning.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If a sequence of symmetrical light patterns is used for localization, then measurement precision is improved, but ambiguity in determining actual particle position occurs
Solution Approach 1:
The patent applies asymmetry by introducing at least one asymmetrical light pattern into the sequence of illumination patterns. This asymmetrical pattern breaks the symmetry that causes multiple potential positions to have equal likelihood, thereby resolving the position ambiguity while maintaining the high precision achieved through the sequence of measurements.
2Measurement precision
If mechanical repositioning is used to verify particle position, then position accuracy is improved, but time consumption increases
Solution Approach 1:
The patent replaces mechanical repositioning with an optical solution. Instead of physically moving the microscope or scanning device to verify particle positions, the system uses asymmetrical light patterns to optically distinguish between potential positions, eliminating mechanical movement and significantly reducing measurement time.
3Reliability
If repeated measurement sequences are performed to resolve ambiguity, then position certainty is improved, but photon budget is depleted
Solution Approach 1:
The patent performs preliminary action by incorporating asymmetrical light patterns into the initial measurement sequence. This allows the system to resolve position ambiguity during the first pass of measurements, eliminating the need for repeated measurement sequences and conserving the photon budget while achieving reliable position determination.
4Speed
If electro-optical or acousto-optical devices are used for pattern generation, then speed is improved, but device complexity increases
Solution Approach 1:
The patent replaces mechanical scanning devices with electro-optical or acousto-optical devices for generating light patterns. These devices use electrical or acoustic fields to modulate light, enabling fast pattern generation without mechanical movement. While the optical system becomes more complex, the elimination of mechanical components and the speed improvement represent a favorable trade-off for dynamic localization applications.
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 fast and efficient localization of single particles with reduced photon usage by distinguishing between potential positions using an asymmetrical test pattern, eliminating the need for mechanical repositioning and improving precision.
Implementation Method 1
illuminate a sample region with a sequence of light patterns having spatially different distributions of illumination light adapted to cause a single particle located in the sample region to emit detection light
Implementation Method 2
a detector configured to detect a sequence of intensities of the detection light emerging from the sample region in response to the sequence of illuminating light patterns
Data Source
Figure 1
Figure 2
Figure 3~4
AI summary
A single-particle localization microscope (100) comprises an optical system (102) configured to illuminate a sample region (120) with a sequence of light patterns (124-1, 124-2, 124-3) having spatially different distributions of illumination light (110) adapted to cause a single particle (122) located in the sample region (120) to emit detection light (112), a detector (116) configured to detect a sequence of intensities (11, 12, 13) of the detection light (112) emerging from the sample region (120) in response to the sequence of illuminating light patterns (124-1, 124-2, 124-3), and a processor (132) configured to determine, based on the sequence of intensities (I1, I2, 13) of the detection light (112), an arrangement of potential positions (446a, 446b, 448a, 448b) for locating the particle (4) in the sample region (120). The processor (132) is further configured to cause the optical system (102) to illuminate the sample region (120) with at least one subsequent light pattern (524) having a spatial distribution of the illumination light (110) which is asymmetrical with respect to the arrangement of the multiple potential positions (446a, 446b, 448a, 448b, to cause the detector (116) to detect at least one subsequent intensity (14) of the detection light (112) emerging from the sample region (120) in response to the at least one subsequent light pattern (524), and to decide, based on the at least one subsequent intensity (14) of the detection light (112), which one of the multiple potential positions (446a, 446b, 448a, 448b) represents an actual position of the particle (122) in the sample region (120).