Double-Clad Fiber Endomicroscope for Multiphoton Imaging

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Solution Overview

Problem

Conventional endomicroscopes face challenges in achieving high detection sensitivity due to miniaturization, leading to inadequate image quality and the need for high excitation power, while also being too large to fit through standard medical scopes, and suffer from nonlinear background emission and focal shift issues.

Innovation Solution

A miniature endomicroscope using a single double-clad optical fiber with a pure silica core and a customized micro-objective lens with diffractive elements to reduce background noise and focal shift, along with a dispersion management unit to maintain short pulse widths, enabling high signal-to-noise ratio imaging within a compact 2.1 mm probe.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Volume of moving object

If a single double-clad optical fiber is used for both excitation light delivery and emission light collection, then the probe size is reduced to fit through standard medical scopes, but the signal collection efficiency may be compromised

Engineering Contradiction:
Improveprobe sizeVSAvoidsignal collection efficiency
Core Design Contradiction:
Volume of moving objectVSMeasurement precision

Solution Approach 1:

The optical fiber is segmented into functional regions: the core delivers excitation light while the cladding collects emission light. This segmentation allows simultaneous optimization of excitation delivery and signal collection within a single fiber structure, resolving the contradiction between compact probe size and signal collection efficiency.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The single double-clad fiber performs multiple functions: the core transmits excitation light while the cladding collects emission light. This multi-functionality eliminates the need for separate fibers, reducing probe size while maintaining signal collection capability through the cladding's large numerical aperture.

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

2Volume of moving object

If miniaturization is applied to reduce probe size, then the device can fit through access channels of commercial scopes, but detection sensitivity and image quality deteriorate

Engineering Contradiction:
Improveprobe sizeVSAvoiddetection sensitivity
Core Design Contradiction:
Volume of moving objectVSReliability

Solution Approach 1:

The system changes key optical parameters including using 700-980 nm excitation wavelengths optimized for deep tissue penetration, employing a numerical aperture of 0.35 for the fiber, and using a 2.1 mm outer diameter probe. These parameter optimizations maintain detection sensitivity despite miniaturization, enabling high-SNR imaging through standard medical scope channels.

Inventive Principle:
Principle #35Parameter changes

3Measurement precision

If high excitation power is used to improve image quality, then adequate signal is obtained, but photodamage and safety concerns increase

Engineering Contradiction:
Improveimage qualityVSAvoidphotodamage
Core Design Contradiction:
Measurement precisionVSObject-affected harmful factors

Solution Approach 1:

The system replaces mechanical scanning with acoustic radiation force-based sample manipulation, enabling high-resolution imaging at lower excitation powers. This substitution reduces photodamage while maintaining image quality through non-mechanical, optically-driven sample positioning and stabilization.

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

4Use of energy by moving object

If conventional optical fibers are used, then excitation light delivery is achieved, but nonlinear background emission and focal shift occur

Engineering Contradiction:
Improveexcitation light deliveryVSAvoidnonlinear background emission
Core Design Contradiction:
Use of energy by moving objectVSObject-generated harmful factors

Solution Approach 1:

The cladding acts as an intermediary that collects emission light before it can generate nonlinear background emission in the core. By providing a separate light collection pathway through the cladding, the system separates excitation delivery and emission collection, eliminating cross-contamination and focal shift issues.

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

The solution achieves unprecedented detection sensitivity, allowing for clear visualization of subcellular structures using only intrinsic two-photon signals and moderate excitation power, demonstrating potential for in vivo optical biopsy with improved image quality and reduced photodamage.

Implementation Method 1

one single-mode fiber for excitation light delivery

Methodology Applied
Scientific EffectTotal internal reflection: Total Internal Reflection

Implementation Method 2

one large-diameter multimode fiber for signal collection

Methodology Applied
Scientific EffectTotal internal reflection: Total Internal Reflection

Implementation Method 3

a piezoelectric tube (PZT) configured to function as an actuator

Methodology Applied
Scientific EffectPiezoelectric effect: Piezoelectric Effect

Implementation Method 4

an achromatic objective lens configured for collecting the emission light with a short wavelength (e.g. 350-600 nm) mainly generated from the focal volume of the excitation light of a long wavelength (e.g. 750-1060 nm)

Methodology Applied
Scientific EffectChromatic aberration:

Implementation Method 5

two-photon fluorescence (TPF) and second harmonic generation (SHG)

Methodology Applied
Scientific EffectTwo-photon fluorescence:

Implementation Method 6

two-photon fluorescence (TPF) and second harmonic generation (SHG)

Methodology Applied
Scientific EffectSecond harmonic generation: Second Harmonic Generation

Data Source

PatentUS9915819B2Fiber-optic methods and devices enabling multiphoton imaging with improved signal to-noise ratio
Publication Date: 2018.03.13 JOHNS HOPKINS UNIVERSITY
  • US9915819B2 patent drawing
  • US9915819B2 patent drawing
  • US9915819B2 patent drawing

AI summary

The present invention is directed to a fiber optic device that enables multiphoton imaging with improved signal-to-noise ratio having a single piece of double-clad fiber (DCF). The device also includes all components for focusing, scanning and signal collection within an endomicroscope probe of 2.1 mm outer diameter (OD). The unprecedented imaging capability of this miniature endomicroscope is demonstrated herein via both ex vivo and in vivo experiments.