Bond-Selective Intensity Diffraction Tomography for Fast 3D Chemical Imaging
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Solution Overview
Problem
Existing label-free microscopy methods lack molecular specificity and suffer from limitations such as photodamage, slow volumetric imaging speed, and low depth resolution, hindering the full exploration of volumetric chemical imaging.
Innovation Solution
A non-interferometric computational MIP microscopy system, Bond-Selective Intensity Diffraction Tomography (BS-IDT), integrates a time-gated pump-probe MIP microscopy with pulsed-laser-based Intensity Diffraction Tomography, enabling high-resolution, high-speed volumetric quantitative chemical imaging and mid-infrared fingerprint spectroscopy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If Raman scattering microscopy is used for vibrational imaging, then molecular specificity is achieved, but photodamage risk increases due to tightly-focused laser beams with large excitation power
Solution Approach 1:
The patent changes the fundamental imaging parameter from Raman scattering to mid-infrared photothermal absorption. This parameter change enables molecular specificity through IR absorption spectroscopy while avoiding the need for tightly-focused high-power laser beams, thereby reducing photodamage risk to biological samples
Solution Approach 2:
The patent replaces the mechanical focusing requirement of Raman microscopy with a wide-field photothermal detection system. By using mid-infrared illumination that penetrates deeper and requires less focusing, the system substitutes the mechanical constraint with an optical-thermal mechanism that inherently reduces photodamage
2Measurement precision
If conventional IR micro-spectroscopy is used for chemical imaging, then chemical sensitivity is improved, but imaging speed and resolution are limited
Solution Approach 1:
The patent merges the advantages of wide-field IR illumination with photothermal detection and computational imaging. By combining these three approaches, the system achieves both high chemical sensitivity from IR absorption and high imaging speed from wide-field parallel detection, overcoming the limitations of conventional sequential scanning methods
Solution Approach 2:
The patent transitions from 2D surface imaging to 3D volumetric imaging by capturing depth-resolved information through optical sectioning and tomographic reconstruction. This dimensional enhancement provides depth resolution of approximately 3 μm while maintaining high imaging speed through wide-field illumination
3Measurement precision
If ODT-based MIP microscopy is used for depth-resolved chemical imaging, then depth resolution is improved, but system complexity and acquisition time increase
Solution Approach 1:
The patent extracts and eliminates the complex interferometric components from the optical system. By removing the two-arm interferometer and specialized optics, the system achieves depth-resolved chemical imaging through a simplified wide-field photothermal microscopy approach combined with computational reconstruction, reducing both device complexity and phase noise
Solution Approach 2:
The patent uses computational imaging to create a virtual copy of the depth-resolved chemical information. Instead of relying on complex optical interferometry to directly measure depth, the system captures intensity variations and computationally reconstructs the 3D chemical distribution, simplifying the optical path while preserving depth resolution
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
BS-IDT provides high-speed (up to 6 Hz) and high-resolution (350 nm laterally, 1.1 μm axially) 3D hyperspectral imaging with a large FOV, improving imaging speed by 40 times, depth resolution by 3 times, and FOV by 3 times compared to state-of-the-art ODT-based MIP microscopy, while recovering mid-IR fingerprint spectroscopic information.
Implementation Method 1
The emerging mid-infrared photothermal (MIP) microscopy inherits IR absorption spectroscopy's advantages
Implementation Method 2
IR absorption offers a cross-section ( ̃10−18 cm2) that is ten orders of magnitude larger than Raman scattering
Implementation Method 3
pulsed-laser-based Intensity Diffraction Tomography
Implementation Method 4
quantitative label-free microscopy based on elastic scattering
Data Source
AI summary
An example microscope includes a pump laser for providing a first illumination to a sample. A laser array provides a second illumination to the sample. The laser array may include a plurality of laser elements, each providing oblique illuminations to the sample. An illumination collecting source collects the first illumination and the second illumination from the sample. The illumination collecting source may capture transient 3D refractive index (RI) variations in the sample due to the first illumination and second illumination.