Microscope Control Device for Automated Laser Pulse Sequences

Resolve Bottlenecks,
Find Innovative Solutions
Generate Solutions

Solution Overview

Problem

Current luminescence microscopy techniques face challenges in automating the examination of different samples with various luminophores over time, as they struggle to prevent crosstalk between luminescence responses and require manual adjustment of laser pulse sequences, which limits their flexibility and accuracy.

Innovation Solution

A microscope system with a control device that allows user interaction to adjust pulse parameters, including the assignment of trigger signals and time intervals for laser pulses, enabling flexible and automated illumination of samples using multiple laser systems, which can be externally triggered, and a trigger generator for generating temporally successive trigger signals based on these parameters.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Adaptability or versatility

If manual adjustment of laser pulse sequences is used, then flexibility in examining different samples is improved, but productivity and automation are worsened

Engineering Contradiction:
ImproveflexibilityVSAvoidautomation
Core Design Contradiction:
Adaptability or versatilityVSProductivity

Solution Approach 1:

The system dynamically adapts the laser pulse sequence parameters based on the specific sample and luminophore being examined. The control device automatically adjusts pulse intervals, trigger signals, and laser activation timing according to the detected luminescence characteristics, enabling both high flexibility for different samples and automated operation without manual reconfiguration.

Inventive Principle:
Principle #15Dynamics

Solution Approach 2:

The invention changes multiple parameters of the laser pulse sequence simultaneously including pulse intervals, trigger signal timing, and laser activation sequences based on the sample type and luminophore properties. This parameter optimization is performed automatically by the control device, providing both adaptability to different samples and automated operation.

Inventive Principle:
Principle #35Parameter changes

2Ease of operation

If constant time interval between laser pulses is used, then simplicity of operation is improved, but measurement precision is worsened due to crosstalk

Engineering Contradiction:
ImprovesimplicityVSAvoidaccuracy
Core Design Contradiction:
Ease of operationVSMeasurement precision

Solution Approach 1:

The system uses periodic laser pulse sequences with specifically optimized intervals that correspond to the luminescence decay characteristics of different luminophores. The control device automatically determines and applies these periodic patterns, maintaining operational simplicity while achieving high measurement precision by preventing crosstalk through scientifically optimized pulse timing.

Inventive Principle:
Principle #19Periodic action

3Productivity

If multiple laser systems are used simultaneously, then productivity is improved, but crosstalk between luminophores increases

Engineering Contradiction:
Improveexamination speedVSAvoidcrosstalk
Core Design Contradiction:
ProductivityVSObject-generated harmful factors

Solution Approach 1:

The examination process is segmented into distinct temporal phases, with each laser system activated in a specific sequence rather than simultaneously. The control device divides the multi-laser operation into separate pulse trains with appropriate intervals, allowing each luminophore to be excited and measured without interference from others, thus eliminating crosstalk while maintaining high productivity through parallel capability.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The control device acts as an intermediary that coordinates the operation of multiple laser systems. It introduces controlled time intervals and trigger signal sequences between laser activations, mediating the interaction between multiple luminophores to prevent crosstalk while enabling the productivity benefits of using multiple laser systems.

Inventive Principle:
Principle #24Intermediary (Mediator)

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 solution allows for precise control over laser pulse sequences and intervals, optimizing the excitation of luminophores and reducing crosstalk, enabling flexible and automated examination of different samples with varying luminophores, improving the accuracy and efficiency of luminescence microscopy.

Implementation Method 1

PIE uses two or more lasers that generate laser pulses with different spectral excitation frequencies

Methodology Applied
Scientific EffectLaser: Laser

Implementation Method 2

The luminescence of the dyes is usually only excited in a specific spectral band and includes fluorescence, i.e. a short afterglow in the range of less than one millisecond

Methodology Applied
Scientific EffectFluorescence: Fluorescence

Implementation Method 3

and phosphorescence, i.e. a longer afterglow of at least one millisecond

Methodology Applied
Scientific EffectPhosphorescence: Phosphorescence

Data Source

PatentEP3615976B1Microscope, more particularly confocal or light sheet microscope, having a freely programmable laser pulse sequence, and corresponding method
Publication Date: 2024.06.05 LEICA MICROSYSTEMS CMS GMBH
  • EP3615976B1 patent drawingFigure 1~2
  • EP3615976B1 patent drawingFigure 3A~3B
  • EP3615976B1 patent drawingFigure 4

AI summary

The invention relates to a microscope (30), more particularly a confocal or light sheet microscope, having an illumination system (32) for illuminating a sample region (34) containing a sample (36). The invention further relates to a method for illuminating the sample region in the field of luminescence microscopy. The problem addressed by the invention is that of providing a microscope and a method which simplify the adaptability and automation of luminescence microscopy. To achieve this, according to the invention the illumination system (32) has a control device (60) with illumination parameters (112) that can be modified by user interaction. The control device also has trigger outputs (70), to each of which an externally triggerable laser system (72) can be connected. A trigger generator (81) generates temporally successive trigger signals (10) which trigger the laser systems (72) that are connected to the trigger outputs (70). The assignment of the trigger signals (10) to the trigger outputs (70) and/or a temporal interval (∆T) between successive trigger signals (10) is dependent on the illumination parameters (112). The variable generation and assignment of the trigger signals allow the laser systems to be freely controlled and to be adapted to a wide range of measuring tasks. The use of the illumination parameters stored in the control device allows the measuring tasks to be automated.