Miniature Two-Photon Brain Probe With Resonant 3D Scanning

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Solution Overview

Problem

Existing imaging technologies struggle to provide real-time, high-resolution, 3D imaging of deep tissue structures without causing harm to the specimen, particularly in the vertical plane of brain tissue, and lack the ability to track neuronal activity in moving animals over sustained periods at millisecond scales.

Innovation Solution

A handheld multi-photon endomicroscope system utilizing miniature vertical actuators with electrostatic, thin-film piezoelectric, or electrothermal actuators for fast axial scanning, combined with lateral scanning, enabling real-time 3D imaging and high spatiotemporal resolution without damaging the subject.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Volume of moving object

If conventional endomicroscopes are used for imaging, then imaging capability is provided, but the device is bulky and cannot repetitively pass into brain regions

Engineering Contradiction:

Improvedevice sizeVSAvoidrepetitive imaging capability

Core Design Contradiction:

Volume of moving objectVSReliability

Solution Approach 1:

The imaging system is divided into separate functional modules: a compact endomicroscope probe for insertion, an external laser source for excitation, and an external detector for signal collection. This segmentation allows the imaging function to be performed by a small insertable device while relying on external equipment for heavy-duty components.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The endomicroscope probe is designed with universal applicability to image multiple brain regions by being repeatedly inserted and repositioned. The same probe structure can access different cortical areas, making it a multi-functional tool for various imaging locations rather than requiring dedicated devices for each region.

Inventive Principle:

Principle #6Universality (Multi-functionality)

2Speed

If fast axial scanning is implemented for real-time 3D imaging, then imaging speed is improved, but device complexity increases

Engineering Contradiction:

Improveaxial scanning speedVSAvoidscanner complexity

Core Design Contradiction:

SpeedVSDevice complexity

Solution Approach 1:

The axial scanning system uses dynamic resonance scanning where the scanner operates at its resonant frequency to achieve high-speed scanning. By exploiting the natural resonant properties of the mechanical system, fast scanning is achieved without requiring overly complex control mechanisms or high-power actuators.

Inventive Principle:

Principle #15Dynamics

Solution Approach 2:

The axial scanner utilizes mechanical resonance and vibration to achieve high-speed scanning. The scanner is designed to oscillate at its resonant frequency, converting small actuator movements into large-amplitude rapid scanning motions, thereby achieving fast scanning with minimal device complexity.

Inventive Principle:

Principle #18Mechanical vibration

3Measurement precision

If intense pulses of long wavelength light are used for multi-photon imaging, then imaging depth and resolution are improved, but photobleaching and tissue damage increase

Engineering Contradiction:

Improveimaging resolutionVSAvoidphotobleaching and tissue damage

Core Design Contradiction:

Measurement precisionVSObject-affected harmful factors

Solution Approach 1:

The system uses periodic pulsed laser illumination rather than continuous wave illumination. The ultrafast pulsed delivery method provides intense peak power for multi-photon excitation during brief moments, then allows tissue recovery during the intervals between pulses, reducing cumulative thermal damage and photobleaching while maintaining high imaging resolution.

Inventive Principle:

Principle #19Periodic action

4Adaptability or versatility

If fiber bundles and electrowetting lenses are used for 3D imaging, then three-axis imaging capability is provided, but frame rates and spatial resolution are limited

Engineering Contradiction:

Improvethree-axis imaging capabilityVSAvoidframe rate

Core Design Contradiction:

Adaptability or versatilityVSProductivity

Solution Approach 1:

The system replaces fiber bundle-based light delivery with free-space optical paths and replaces electrowetting lens-based focal adjustment with MEMS mirror-based axial scanning. This substitution eliminates the frame rate and resolution limitations of fiber bundles while achieving three-axis imaging capability through coordinated lateral and axial mirror scanning.

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

Data Source

PatentUS20260023253A1Three-Dimensional Two Photon Miniature Microscope Brain Imaging in Freely-Behaving Animals

Publication Date: 2026.01.22 THE RGT UNIV OF MICHIGAN

AI summary

An implantable multi-photon optical probe includes a probe housing having a proximal end and a distal end implantable on a sample. The probe housing adapted to provide excitation energy to the sample and to collect emitted radiation from the sample. The probe housing includes scanning optics configured to receive excitation radiation, and to laterally and axially scan the excitation radiation over a field-of-view of the optical probe. A scanning lens is disposed in the probe housing configured to receive the excitation radiation from the scanning optics, and an objective lens reshapes and focuses the excitation radiation. A focusing lens is disposed to receive the excitation radiation and to focus the excitation radiation into the sample.