SCAPE Microscopy Single-Objective Volumetric Imaging

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Solution Overview

Problem

Current 3D volumetric optical microscopy techniques, such as light-sheet and two-photon microscopy, face limitations in speed, resolution, and field of view due to dual-objective geometries and the need for physical sample translation or complex synchronization, making it challenging to capture high-speed, in-vivo neuronal activity and dynamic processes in diverse samples.

Innovation Solution

The Swept, Confocally-Aligned Planar Excitation (SCAPE) microscopy method uses a single objective to sweep an oblique light sheet across the sample, allowing for ultra-fast, translationless volumetric imaging by aligning the detection plane with the illumination sheet and using image rotation optics to maintain a stationary camera, enabling high-speed capture of 3D dynamics in intact samples without physical sample movement.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If conventional light-sheet imaging uses dual-objective geometry with side-on illumination and physical sample translation, then 3D volumetric imaging can be achieved, but imaging speed is limited and sample mounting becomes highly challenging

Engineering Contradiction:
Improvevolumetric imaging speedVSAvoidsample mounting and positioning
Core Design Contradiction:
ProductivityVSEase of operation

Solution Approach 1:

The patent inverts the conventional light-sheet geometry by rotating it 45 degrees and implementing it through a single objective lens rather than dual objectives. This allows the light sheet to sweep across the sample volume while the detection plane remains stationary, eliminating the need for physical sample translation and complex mounting arrangements.

Inventive Principle:
Principle #13The other way round (Inversion)

Solution Approach 2:

The patent replaces the mechanical sample translation system with an optical scanning system. Instead of physically moving the sample through the detection plane, a scanning mirror deflects the light sheet across the sample volume, achieving volumetric imaging without mechanical movement of the sample or detection objective.

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

2Productivity

If piezoelectric objective scanning is used for volumetric imaging, then 3D imaging can be achieved, but acquisition speeds are limited

Engineering Contradiction:
Improveacquisition speedVSAvoidobjective scanning mechanism
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The patent replaces piezoelectric objective scanning with a stationary objective and a scanning light sheet system. A scanning mirror deflects the excitation light sheet across the sample volume while the detection objective remains fixed, eliminating the need for fast piezoelectric scanning and enabling higher acquisition speeds.

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

Solution Approach 2:

The patent introduces a scanning mirror as an intermediary element between the light source and the sample. This mirror deflects the light sheet across the sample volume, enabling volumetric scanning without moving the detection objective, thus decoupling the scanning function from the detection system.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Measurement precision

If two-photon microscopy uses sequential point scanning to generate volumetric images, then high resolution can be achieved, but imaging speed forces trade-offs between 3D imaging speed, resolution and field of view

Engineering Contradiction:
Improveimaging resolutionVSAvoid3D imaging speed
Core Design Contradiction:
Measurement precisionVSProductivity

Solution Approach 1:

The patent transitions from sequential point scanning (1D time dimension) to planar light sheet illumination (2D spatial dimension). By illuminating an entire plane simultaneously with a light sheet and detecting it with a 2D camera, the system achieves parallel acquisition of multiple points, dramatically increasing volumetric imaging speed while maintaining resolution through optical sectioning.

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

Solution Approach 2:

The patent enables continuous illumination of the entire sample volume with a swept light sheet, allowing the camera to continuously capture images at every position along the sweep. This continuous acquisition method eliminates the sequential nature of point scanning, enabling high-speed volumetric imaging without sacrificing resolution or field of view.

Inventive Principle:
Principle #20Continuity of useful action

4Productivity

If coordinated scanning of the light sheet with translation of the detection focal plane is used, then higher frame rate light sheet imaging can be achieved, but the dual-objective geometry remains limiting

Engineering Contradiction:
Improveframe rateVSAvoiddual-objective configuration
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The patent inverts the conventional approach by keeping the detection objective stationary and scanning the light sheet instead. This single-objective configuration eliminates the need for coordinated translation of the detection focal plane and removes the limitations of dual-objective geometry while maintaining high frame rates through optical scanning.

Inventive Principle:
Principle #13The other way round (Inversion)

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

SCAPE achieves significantly higher volumetric imaging speeds than conventional methods, exceeding 20 volumes per second, and can image spontaneous neuronal firing in awake mice and freely moving Drosophila larvae, providing detailed 3D dynamics with sufficient spatiotemporal resolution to resolve different onset and decay dynamics within a single dendritic branch.

Implementation Method 1

projecting sheets of light into a sample

Methodology Applied
Scientific EffectLight: Light

Implementation Method 2

detecting light emission elicited from the swept light sheets

Methodology Applied
Scientific EffectFluorescence: Fluorescence

Data Source

PatentEP3095001B1Systems and methods for three-dimensional imaging
Publication Date: 2023.04.26 THE TRUSTEES OF COLUMBIA UNIV IN THE CITY OF NEW YORK
  • EP3095001B1 patent drawingFigure 1A~1B
  • EP3095001B1 patent drawingFigure 1C~1E
  • EP3095001B1 patent drawingFigure 1F

AI summary

The present disclosure is directed to new 3D imaging techniques. For example, in certain embodiments, the instant disclosure is directed to a technique for the volumetric imaging of living samples at ultra-high speeds identified herein as swept, confocally-aligned planar excitation (SCAPE) imaging.