Emitter Position Estimation Using Rotational Probe Arrays
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Solution Overview
Problem
Existing super-resolution fluorescence microscopy techniques face challenges in accurately estimating the position of emitters due to high levels of background emission and fluctuating background emission, leading to biased results and uncertainty dependent on the emitter's actual position.
Innovation Solution
A method for estimating the position of an emitter using a set of six or more probe positions arranged rotationally symmetric on a circle without a central position, allowing real-time background correction and reducing the dependency on the emitter's exact position, by determining a value representative of background noise and adapting the estimator in real-time.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If a central probe position is used in the coordinate pattern, then the localization precision is improved by having a reference point at the emitter position, but the measurement becomes biased and uncertain when background emission is present
Solution Approach 1:
The patent removes the central probe position from the coordinate pattern, extracting the problematic element that causes bias in the presence of background emission. By using only peripheral probe positions arranged symmetrically around the expected emitter location, the method eliminates the systematic error that arises when the central position is contaminated by background noise, while maintaining localization precision through the symmetric arrangement of surrounding probes.
Solution Approach 2:
The patent employs symmetric arrangement of probe positions around the center (rotational symmetry) rather than including the center itself. This symmetric peripheral arrangement creates an asymmetric solution to the problem: the probe pattern is symmetric, but the central position is deliberately excluded, creating a annular pattern that is symmetric about the center but has no measurement at the center, thereby eliminating bias while maintaining precision.
2Productivity
If background correction is performed using conventional methods, then the processing is simple and fast, but the results are biased and uncertain under high background emission conditions
Solution Approach 1:
The patent performs background correction as a preliminary step before position estimation by fitting a constant background level to the measured photon counts at the symmetric probe positions. This preliminary background subtraction eliminates the bias that would otherwise propagate through the localization calculation, ensuring that subsequent position estimation is based on background-corrected data. This approach maintains computational efficiency while significantly improving measurement accuracy under high background conditions.
3Loss of time
If fewer probe positions are used, then the measurement time and photon exposure are reduced, but the robustness and accuracy of position estimation decrease
Solution Approach 1:
The patent changes the geometric parameter of the probe arrangement by using six or more probe positions distributed symmetrically around the center at a defined radius. This specific geometric configuration optimizes the balance between measurement speed and accuracy: the symmetric distribution provides robust position estimation through multiple angular samples, while the finite number of positions (six or more) keeps the measurement time and total photon exposure manageable. The radius of the probe circle is also optimized to balance sensitivity to emitter position with robustness against background noise.
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 improves the robustness and accuracy of emitter position estimation by minimizing bias and uncertainty, enabling faster and more efficient localization with reduced photon exposure.
Implementation Method 1
acquiring photons, in particular fluorescence photons, for the sets of probe positions
Data Source
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AI summary
The invention relates to a method for estimating a position of an emitter (2) in a sample (1) comprising illuminating the sample (1) with light at one or more sets of probe positions (Pi), acquiring photons for the sets of probe positions (Pi), and determining vectors of photon counts or sums of photon counts for the sets of probe positions from the acquired photons, and-estimating the position of the emitter (2) from the vectors of photon counts or sums of photon counts, wherein the one or more sets of probe positions (Pi) each comprise six or more probe positions (Pi), which are arranged rotationally symmetric on a circle around a center, wherein the one or more sets of probe positions lacks a central probe position. The invention further relates to an apparatus (40) for implementing the method, a microscope (10) using the apparatus (40) and a computer program implementing the method.