Multifocal Imaging System Microlens Array Parallel Detection

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Solution Overview

Problem

Current multiphoton microscopy systems have limited imaging speed, which restricts their application in capturing detailed, high-resolution images of large biological structures and tissues, particularly in deep tissue imaging where scattering of light leads to reduced signal quality and increased noise.

Innovation Solution

The development of a multifocal imaging system using a plurality of optical pathways and focusing optics, combined with a scanning system for relative movement, allows for efficient light collection from multiple focal locations within a biological sample, increasing imaging speed and reducing cross-talk due to light scattering by increasing the distance between focal spots.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If multiple focal spots are used to increase imaging speed, then productivity is improved, but light scattering causes cross-talk between adjacent focal spots reducing measurement precision

Engineering Contradiction:
Improveimaging speedVSAvoidimage resolution
Core Design Contradiction:
ProductivityVSMeasurement precision

Solution Approach 1:

The patent divides the imaging field into multiple independent focal spots using a microlens array, allowing parallel imaging across different regions. This segmentation enables simultaneous capture of multiple areas, dramatically increasing imaging speed while maintaining resolution through proper spacing of the segmented focal regions

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent transitions from single-point sequential scanning to multi-point parallel imaging by introducing spatial multiplexing through a microlens array. This dimensional change from 1D scanning to 2D/3D parallel focal spots resolves the contradiction by enabling both high speed and high resolution through coordinated multi-dimensional imaging

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

2Measurement precision

If focal spots are spaced closely to improve resolution, then measurement precision is improved, but light scattering increases cross-talk between adjacent spots

Engineering Contradiction:
Improveimage resolutionVSAvoidlight scattering cross-talk
Core Design Contradiction:
Measurement precisionVSObject-generated harmful factors

Solution Approach 1:

The patent optimizes the spacing parameter between adjacent focal spots to balance resolution and cross-talk reduction. By carefully selecting the distance between microlenses in the array, the system achieves sufficient spatial resolution while maintaining adequate separation to minimize light scattering interference between neighboring focal regions

Inventive Principle:
Principle #35Parameter changes

3Productivity

If scanning speed is increased to improve productivity, then imaging speed is improved, but motion blur and signal quality deteriorate

Engineering Contradiction:
Improveimaging speedVSAvoidsignal quality
Core Design Contradiction:
ProductivityVSReliability

Solution Approach 1:

The patent uses a microlens array to pre-establish multiple focal spots before scanning begins, enabling parallel signal acquisition from multiple regions simultaneously. This preliminary spatial configuration allows the system to capture sufficient signal from each region before motion occurs, maintaining signal quality while achieving high imaging speed through parallel processing

Inventive Principle:
Principle #10Preliminary action

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 enables high-speed, high-resolution 3D imaging of large biological samples, improving the statistical accuracy and precision of biomedical assays, and facilitating the visualization of complex tissue structures and vasculature, while minimizing the impact of light scattering on image quality.

Implementation Method 1

The multifocal optical element can comprise a micro lens array... such that a plurality of beams are provided that can be focused onto a plurality of focal locations

Methodology Applied
Scientific EffectLight refraction and focusing: Lens

Implementation Method 2

The multifocal optical element can comprise... a diffractive optical element, such that a plurality of beams are provided that can be focused onto a plurality of focal locations

Methodology Applied
Scientific EffectLight diffraction: Diffraction

Implementation Method 3

Multiphoton microscopy is based on the nonlinear excitation of fluorophores in which fluorescence generation is localized at the focus of excitation light

Methodology Applied
Scientific EffectFluorescence emission: Fluorescence

Implementation Method 4

An important issue in the collection of light from discrete focal spots or locations within a turbid medium such as tissue is the cross talk that can occur due to the scattering of light

Methodology Applied
Scientific EffectLight scattering: Scattering

Data Source

PatentUS10598597B2Multifocal imaging systems and method
Publication Date: 2020.03.24 MASSACHUSETTS INST OF TECH
  • US10598597B2 patent drawing
  • US10598597B2 patent drawing
  • US10598597B2 patent drawing

AI summary

In the systems and methods of the present invention a multifocal multiphoton imaging system has a signal to noise ratio (SNR) that is reduced by over an order of magnitude at imaging depth equal to twice the mean free path scattering length of the specimen. An MMM system based on an area detector such as a multianode photomultiplier tube (MAPMT) that is optimized for high-speed tissue imaging. The specimen is raster-scanned with an array of excitation light beams. The emission photons from the array of excitation foci are collected simultaneously by a MAPMT and the signals from each anode are detected using high sensitivity, low noise single photon counting circuits. An image is formed by the temporal encoding of the integrated signal with a raster scanning pattern. A deconvolution procedure taking account of the spatial distribution and the raster temporal encoding of collected photons can be used to improve decay coefficient. We demonstrate MAPMT-based MMM can provide significantly better contrast than CCD-based existing systems.