Adaptive MINFLUX Scanning for Fast Dye Molecule Localization

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Solution Overview

Problem

The MINFLUX method for high-resolution localization microscopy is inefficient and time-consuming due to the need for successive scanning of individual dye molecules, leading to prolonged illumination and potential sample damage from phototoxic effects.

Innovation Solution

Adapt the scanning parameters for each dye molecule based on its type and environment, using a scanning rule determined from a raster image to optimize photon efficiency and scanning speed, avoiding unnecessary steps and reducing illumination.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If successive scanning of individual dye molecules is performed to achieve high-resolution localization, then measurement precision is improved, but productivity deteriorates due to time-consuming sequential measurement

Engineering Contradiction:

Improvelocalization accuracyVSAvoidscanning speed

Core Design Contradiction:

Measurement precisionVSProductivity

Solution Approach 1:

The patent segments the measurement process by identifying and localizing individual dye molecules separately rather than attempting to measure all molecules simultaneously. This segmentation enables the system to achieve high localization accuracy for each molecule while managing the overall measurement time through efficient sequential processing of discrete molecular targets.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The patent applies preliminary action by first identifying candidate dye molecule locations and pre-screening them before performing the full localization measurement sequence. This preliminary identification step filters out non-target regions, allowing the system to focus scanning resources on actual dye molecules and reduce unnecessary measurement time.

Inventive Principle:

Principle #10Preliminary action

2Measurement precision

If prolonged illumination is applied to scan individual dye molecules sequentially, then measurement precision is improved, but object-affected harmful factors worsen due to phototoxic effects

Engineering Contradiction:

Improvelocalization accuracyVSAvoidphototoxic damage

Core Design Contradiction:

Measurement precisionVSObject-affected harmful factors

Solution Approach 1:

The patent applies local quality by concentrating illumination only at the specific locations of individual dye molecules rather than illuminating the entire sample uniformly. This localized scanning approach delivers sufficient light intensity for accurate localization while minimizing total light exposure to the sample, thereby reducing phototoxic effects and photobleaching.

Inventive Principle:

Principle #3Local quality

Solution Approach 2:

The patent implements skipping by rapidly moving the illumination beam between dye molecule locations and minimizing dwell time at each position. This rushed scanning approach collects sufficient photons for localization while reducing the cumulative light dose delivered to the sample, thereby mitigating photodamage.

Inventive Principle:

Principle #21Skipping (Rushing through)

3Device complexity

If uniform scanning parameters are used for all dye molecules, then device complexity is reduced, but adaptability deteriorates due to varying dye types and environments

Engineering Contradiction:

Improvescanning parameter uniformityVSAvoidoptimization for different dyes

Core Design Contradiction:

Device complexityVSAdaptability or versatility

Solution Approach 1:

The patent applies dynamics by making scanning parameters adaptive rather than fixed. The system dynamically adjusts scanning parameters such as dwell time, laser power, and scan step size based on the specific properties of each dye molecule type and its environmental context. This dynamic adaptation optimizes measurement efficiency and accuracy for different dye molecules without requiring complete redesign of the scanning system.

Inventive Principle:

Principle #15Dynamics

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

Achieves accurate and rapid localization of dye molecules with minimal photon usage, minimizing bleaching and sample damage while enhancing scanning efficiency.

Implementation Method 1

fluorescent dye molecules... in which each of the individual dye molecules is scanned by excitation light... the fluorescence emission excited by the excitation light is registered

Methodology Applied

Scientific EffectFluorescence: Fluorescence

Implementation Method 2

scanned by excitation light at different positions with an intensity distribution exhibiting an intensity minimum

Methodology Applied

Scientific EffectLight intensity distribution: Light

Implementation Method 3

the fluorescence emission excited by the excitation light is registered, and the location of the respective molecule is inferred from the course of the intensity of the fluorescence light

Methodology Applied

Scientific EffectPhoton detection: Photoelectric Effect

Data Source

PatentUS12523607B2Method and fluorescence microscope for determining the location of individual fluorescent dye molecules by means of adaptive scanning

Publication Date: 2026.01.13 ABBERIOR INSTR GMBH

AI summary

The present invention is a method for spatially highly accurate location determination of individual dye molecules of a fluorescent dye by scanning with an intensity distribution of a scanning light having a local minimum. The invention is characterized by the fact that the scanning is not performed uniformly for all dye molecules, but is individually adapted to the dye molecule to be scanned and, if necessary, to its environment in the sample, in order to achieve the most accurate location determination possible with the smallest possible number of fluorescence photons.