Spatial Light Modulator Hyperspectral Confocal Microscope

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Solution Overview

Problem

Conventional confocal microscopy techniques face limitations in rapid image acquisition and efficient utilization of excitation light, particularly due to the use of Nipkow disks with fixed pinhole arrays, which restricts the speed and flexibility of optical sectioning.

Innovation Solution

The implementation of spatial light modulators (SLMs), such as micromirror devices or liquid crystal devices, allows for programmable artificial pinholes with adjustable size and spacing, enabling simultaneous capture of light from multiple locations at a focal plane and flexible adjustment of optical sectioning.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If Nipkow disk with fixed pinhole array is used for parallel scanning, then image acquisition speed is improved, but excitation light utilization efficiency deteriorates

Engineering Contradiction:
Improveimage acquisition speedVSAvoidexcitation light utilization efficiency
Core Design Contradiction:
ProductivityVSLoss of energy

Solution Approach 1:

The patent replaces the fixed pinhole array of the Nipkow disk with a dynamic spatial light modulator (SLM) that can programmably adjust pinhole positions, sizes, and patterns. This dynamic control allows the system to optimize light utilization by adapting the pinhole configuration to match the excitation beam profile and detection requirements, thereby resolving the contradiction between fast parallel scanning and efficient light use.

Inventive Principle:
Principle #15Dynamics

Solution Approach 2:

The invention changes the parameters of the pinhole array from fixed to programmably variable. By using an SLM, the system can dynamically modify pinhole size, spacing, and pattern to optimize both the speed of parallel acquisition and the efficiency of excitation light utilization, allowing adaptation to different imaging conditions and objectives.

Inventive Principle:
Principle #35Parameter changes

2Reliability

If Nipkow disk with fixed pinhole spacing is used, then optical sectioning is maintained, but adaptability to different numerical apertures deteriorates

Engineering Contradiction:
Improveoptical sectioning qualityVSAvoidadaptability to different numerical apertures
Core Design Contradiction:
ReliabilityVSAdaptability or versatility

Solution Approach 1:

The spatial light modulator enables dynamic reconfiguration of the pinhole array to match different numerical apertures of objectives. The system can programmably adjust pinhole size and spacing to optimize optical sectioning for each specific objective, replacing the static, one-size-fits-all approach of the Nipkow disk with an adaptive system that maintains high reliability across varying conditions.

Inventive Principle:
Principle #15Dynamics

Solution Approach 2:

The SLM-based system provides universal adaptability to work with multiple objective types and numerical apertures. By programmably configuring the pinhole pattern, a single system can optimize performance for various objectives without requiring physical disk changes, achieving multi-functionality while maintaining optical sectioning quality.

Inventive Principle:
Principle #6Universality (Multi-functionality)

3Reliability

If physical removal and replacement of Nipkow disk is required to change pinhole configuration, then optical sectioning can be optimized, but device complexity and operation difficulty increase

Engineering Contradiction:
Improveoptical sectioning optimizationVSAvoidease of pinhole configuration adjustment
Core Design Contradiction:
ReliabilityVSEase of operation

Solution Approach 1:

The patent replaces the mechanical Nipkow disk system with a spatial light modulator that uses electronic control to adjust pinhole configurations. This substitution eliminates the need for physical disk removal and replacement, allowing rapid, software-controlled reconfiguration of pinhole patterns while maintaining optimized optical sectioning, thereby dramatically improving ease of operation.

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

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 significantly enhances the speed and throughput of confocal imaging by allowing for efficient excitation light utilization and easy adjustment of optical sectioning, enabling rapid acquisition of high-resolution images and hyperspectral datasets.

Implementation Method 1

A confocal imaging system uses a light source to provide an excitation light beam and a first spatial light modulator to structure the excitation light beam into a two-dimensional excitation pattern

Methodology Applied
Scientific EffectLight modulation and focusing: Lens

Implementation Method 2

The structured excitation light beam is directed towards a sample. The excitation light beam is focused to a spot and scanned across the sample or the sample is translated in the transverse direction with the laser spot being fixed

Methodology Applied
Scientific EffectLight focusing: Lens

Implementation Method 3

Fluorescence microscopy uses principles of fluorescence to highlight structures for examination instead of light absorption, phase or interference effects. In fluorescence microscopy, fluorophores or other optical labels in a sample are excited by an excitation light beam directed towards the sample. Upon excitation, the fluorophores emit fluorescent light

Methodology Applied
Scientific EffectFluorescence: Fluorescence

Implementation Method 4

The fluorescent light collected from the sample then passes through a single pinhole to produce an optical section of the sample. A two-dimensional (2-D) image is generated by translating the pinhole or sample laterally on a point-by-point basis

Methodology Applied
Scientific EffectOptical sectioning through pinhole filtering: Filter (optical)

Implementation Method 5

A confocal imaging system uses a light source to provide an excitation light beam, a first spatial light modulator to structure the excitation light beam into a two-dimensional excitation pattern, and a two-dimensional detector to detect emission light from the sample in a given lateral direction after the emission light has been spectrally dispersed in a given lateral direction

Methodology Applied
Scientific EffectSpectral dispersion: Prism

Data Source

PatentEP3465158B1Spatial light modulator based hyperspectral confocal microscopes and methods of use
Publication Date: 2020.11.25 VERILY LIFE SCIENCES LLC
  • EP3465158B1 patent drawingFigure 1
  • EP3465158B1 patent drawingFigure 2
  • EP3465158B1 patent drawingFigure 3

AI summary

Systems and methods for confocal imaging are described. In one implementation, a confocal imaging system (100) includes a light source (110) configured to emit excitation light (10) having one or more wavelengths, a sample holder (180) configured to hold a sample, a two-dimensional (2-D) imaging device (190), and an optical system comprising: a first spatial light modulator (140) and a second spatial light modulator (150), wherein the optical system is configured to (i) collimate the excitation light (10); (ii) apply, using the first spatial light modulator (140), a predetermined phase modulation pattern to the collimated excitation light (12); (iii) use the phase-modulated collimated excitation light (14) as an excitation pattern to illuminate the sample, wherein the excitation pattern is located at a Fourier plane relative to a focal plane within the sample; (iv) collect emission light (18) from the focal plane within the sample; and (v) direct the collected emission light (20) to the imaging device (190) via the second spatial light modulator (150) such that the focal plane within the sample is conjugate to a pinhole pattern formed by pixels of the second spatial light modulator (150).