Microlens Array Multi-Focal Point Fluorescence Microscopy

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Solution Overview

Problem

Existing laser scanning fluorescence microscopes are limited by the diffraction limit in achieving high spatial resolution and have restricted imaging rates due to the structure of light distribution defined by interference patterns.

Innovation Solution

The method involves concentrating optical signals at multiple focal points, which can be focused arbitrarily into various sample sites, allowing for flexible light distribution and parallel scanning, thereby increasing resolution and imaging rate. This is achieved through the use of phase filters and microlens arrays to produce intensity zero points and modulate light distribution, enabling subdiffraction resolution imaging.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If interference patterns are used to define light distribution in the sample, then spatial resolution can be improved beyond the diffraction limit, but imaging rate is restricted and device complexity increases

Engineering Contradiction:
Improvespatial resolutionVSAvoidimaging rate
Core Design Contradiction:
Measurement precisionVSProductivity

Solution Approach 1:

The patent segments the optical signal into multiple focal points using a microlens array, allowing parallel illumination of multiple sample regions. This segmentation enables simultaneous acquisition of multiple spatial locations, thereby increasing imaging rate while maintaining super-resolution capability through controlled interference at each focal point

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent employs periodic modulation of the optical signal intensity to create time-varying interference patterns that enable temporal separation of signal acquisition. By using periodic action in the form of modulated illumination cycles, the system can extract high-resolution information over multiple periods, increasing effective imaging rate without sacrificing resolution

Inventive Principle:
Principle #19Periodic action

2Measurement precision

If interference patterns are used to define light distribution in the sample, then spatial resolution can be improved beyond the diffraction limit, but device complexity increases

Engineering Contradiction:
Improvespatial resolutionVSAvoiddevice complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent introduces a microlens array as an intermediary optical element that simplifies the generation of multiple focal points compared to complex spatial light modulators or acousto-optic devices. This intermediary component enables parallel focal point generation with simpler optics, reducing overall device complexity while maintaining super-resolution capability

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent uses a microlens array to create multiple copies of the optical signal at different focal points in parallel. Each lens in the array produces a copied and focused version of the input signal, enabling simultaneous multi-point illumination without requiring complex programmable optical systems, thus reducing device complexity

Inventive Principle:
Principle #26Copying

3Productivity

If optical signals are concentrated at multiple focal points for parallel scanning, then imaging rate increases, but light distribution control becomes more challenging

Engineering Contradiction:
Improveimaging rateVSAvoidlight distribution control
Core Design Contradiction:
ProductivityVSEase of operation

Solution Approach 1:

The patent controls light distribution by changing the optical parameters (wavelength, numerical aperture, lens positioning) of the microlens array system. By adjusting these parameters, the system can dynamically control focal point positions and intensities, enabling flexible light distribution control that adapts to different imaging requirements while maintaining parallel scanning capability

Inventive Principle:
Principle #35Parameter changes

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

The approach significantly enhances spatial resolution and imaging speed by allowing for flexible light distribution and parallel scanning, particularly beneficial in STED and GSD microscopy, while maintaining a structurally simple and cost-effective design.

Implementation Method 1

the optical signal is simultaneously concentrated at a number of focal points, and the focal points are focused into various sites of the sample

Methodology Applied
Scientific EffectOptical focusing: Focusing

Implementation Method 2

This is achieved through the use of phase filters and microlens arrays to produce intensity zero points and modulate light distribution

Methodology Applied
Scientific EffectPhase modulation: Phase Modulation

Implementation Method 3

the first state is a fluorescence-capable state (named state A below), and the second state is a nonfluorescence-capable state (named state B below)

Methodology Applied
Scientific EffectFluorescence: Fluorescence

Implementation Method 4

The physical process of fluorescence suppression can be of a very different nature in this case. Thus, for example, stimulated emission from the previously excited state

Methodology Applied
Scientific EffectStimulated emission:

Data Source

PatentUS7619732B2Method and microscope for high spatial resolution examination of samples
Publication Date: 2009.11.17 LEICA MICROSYSTEMS CMS GMBH
  • US7619732B2 patent drawing
  • US7619732B2 patent drawing
  • US7619732B2 patent drawing

AI summary

A method and a microscope, in particular a laser scanning fluorescence microscope, for high spatial resolution examination of samples, the sample (1) to be examined comprising a substance that can be repeatedly converted from a first state (Z1, A) into a second state (Z2, B), the first and the second states (Z1, A; Z2, B) differing from one another in at least one optical property, comprising the steps that the substance in a sample region (P) to be recorded is firstly brought into the first state (Z1, A), and that the second state (Z2, B) is induced by means of an optical signal (4), spatially delimited subregions being specifically excluded within the sample region (P) to be recorded, are defined with regard to increasing resolution in any desired direction and with regard to an increased imaging rate by the fact that the optical signal (4) is simultaneously concentrated at a number of focal points, and the focal points are focused into various sites of the sample (1).