Multi-view reflector microscope 3D orientation

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Solution Overview

Problem

Current imaging systems are unable to simultaneously and accurately determine the 3D position and 3D orientation of dipole-like emitters, such as biological molecules, due to limitations in resolution, alignment, and optical efficiency, particularly for low-light imaging and in environments with aberrations.

Innovation Solution

An imaging system utilizing a multi-view reflector (MVR) that splits incoming light into multiple beams, directing each beam to separate detection elements to create multiple images, allowing for the precise determination of 3D position and orientation, and incorporating polarizing elements for improved polarization separation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If multi-lens array is used to image position and angle of light rays, then both position and orientation can be imaged, but resolution is limited and alignment/aberration difficulties arise

Engineering Contradiction:
Improveposition and orientation measurementVSAvoidalignment and aberration control
Core Design Contradiction:
Measurement precisionVSManufacturing precision

Solution Approach 1:

The patent replaces the mechanical multi-lens array system with a single-lens system combined with a multi-spot point spread function engineering approach. This substitution eliminates the alignment and aberration problems inherent in multi-lens systems while maintaining the capability to measure both position and orientation through optical field distribution analysis

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

Solution Approach 2:

The patent changes the optical field parameters by engineering the point spread function to create multi-spot patterns. By manipulating the optical field distribution and intensity patterns in the image plane, the system can encode both position and orientation information in a single lens system, avoiding the need for complex multi-lens arrangements

Inventive Principle:
Principle #35Parameter changes

2Measurement precision

If signal photons are split into multiple spots to encode orientation information, then molecular orientation can be determined, but signal-to-background ratio deteriorates

Engineering Contradiction:
Improvemolecular orientation determinationVSAvoidsignal-to-background ratio
Core Design Contradiction:
Measurement precisionVSLoss of information

Solution Approach 1:

The patent segments the optical field into multiple intensity spots within the point spread function, where each spot's position and intensity encodes specific information about molecular orientation. This segmentation allows orientation determination while maintaining a favorable signal-to-background ratio through optimized spot distribution and intensity modulation

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent encodes orientation information in the intensity distribution dimension rather than solely relying on spatial separation. By using the relative intensities of multiple spots within the PSF pattern, the system determines molecular orientation without requiring large spatial separations that would dilute the signal in any single location

Inventive Principle:
Principle #17Another dimension (Dimensionality change)

3Measurement precision

If existing PSF engineering methods are used, then single-molecule orientation localization can be achieved, but depth of field is poor and aberration robustness is limited

Engineering Contradiction:
Improvesingle-molecule orientation localizationVSAvoiddepth of field and aberration robustness
Core Design Contradiction:
Measurement precisionVSReliability

Solution Approach 1:

The patent designs a universal point spread function engineering approach that simultaneously provides orientation localization, depth of field extension, and aberration robustness. The multi-spot PSF pattern is engineered to maintain its information-encoding capability across a range of depths and in the presence of optical aberrations, making the system universally applicable to various imaging conditions

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

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 MVR system achieves robust and precise measurement of 3D orientation and position, maintaining a favorable signal-to-background ratio and improving photon efficiency, enabling accurate imaging of single molecules and bulk fluorescent samples.

Implementation Method 1

the MVR reflects the at least two beams of light in different directions such that each of the at least two beams of light impinge on a separate detection element

Methodology Applied
Scientific EffectLight reflection: Reflection

Implementation Method 2

the MVR splits the incoming light into at least two beams of light

Methodology Applied
Scientific EffectLight refraction: Refraction

Implementation Method 3

a polarizing beam splitter (PBS) positioned between the MVR and the detector, wherein the PBS is configured to provide x- and y-polarization separation to the MVR

Methodology Applied
Scientific EffectPolarization separation: Polarisation

Implementation Method 4

a vortex wave or half-wave plate configured to convert radially- and azimuthally-polarized light at the BFP to x- and y-polarized light

Methodology Applied
Scientific EffectPolarization conversion: Polarisation

Data Source

PatentUS20240210671A1Multi-view reflector microscope
Publication Date: 2024.06.27 WASHINGTON UNIV IN SAINT LOUIS
  • US20240210671A1 patent drawing
  • US20240210671A1 patent drawing
  • US20240210671A1 patent drawing

AI summary

An imaging system uses a multi-view reflector (MVR) to simultaneously measure the three-dimensional (3D) position and orientation of a light emitter. The MVR is positioned at a back focal plane (BFP) of a light collecting optical system, and uses pyramid reflectors and/or conical reflectors to reflect light in at least two regions of the BFP to at least two detection channels of a detector. The at least two detection channels produce images that are used to determine the 3D position and orientation of a light emitter. The system may be used, for example, to image the structure of molecules or organelles in a cell, track the movement of molecules in a cell, or to study the interaction of molecules within a cell.