Shortwave Infrared Photothermal Microscopy for Deep Tissue Imaging
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Solution Overview
Problem
Conventional vibrational microscopy techniques face limitations in imaging depth and spatial resolution when probing cellular activities in intact tissue due to water absorption and tissue scattering, which restricts their ability to map chemical content in organoids or tissues without altering the natural microenvironment.
Innovation Solution
A short-wave infrared photothermal (SWIP) microscopy system and method utilizing a pump-probe approach with shortwave infrared excitation and probe light to achieve millimeter-deep vibrational imaging with micron lateral resolution by optically sensing refractive index changes from absorption sites, eliminating signal loss during propagation and eliminating the need for sample contact.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional infrared spectroscopy-based approaches are used, then chemical contrast from biomolecules is obtained, but imaging depth is restricted to tens of micrometers due to strong water absorption
Solution Approach 1:
The patent introduces a photothermal intermediary mechanism where infrared excitation light is absorbed by biomolecules, converting optical energy to thermal energy, which then modulates the refractive index of the surrounding medium. This thermal-optical intermediary allows indirect detection of molecular vibrations without direct infrared transmission through deep tissue, overcoming water absorption limitations while maintaining chemical contrast.
Solution Approach 2:
The patent replaces direct infrared transmission (optical detection) with a photothermal-refractive index modulation mechanism (thermal-optical detection). Instead of detecting transmitted or reflected infrared light directly, the system detects refractive index changes caused by localized heating, substituting direct optical interaction with indirect thermal-optical interaction to achieve deeper penetration.
2Length of stationary object
If spontaneous or coherent Raman microscopy with visible or near-infrared excitation is used, then imaging depth reaches around 100 μm, but spatial resolution is limited due to large tissue scattering
Solution Approach 1:
The patent changes the detection parameter from direct Raman scattering intensity to photothermal-induced refractive index modulation. By measuring refractive index changes rather than scattered photons, the system achieves both deep imaging capability (through infrared excitation) and high spatial resolution (through localized thermal lens effects), resolving the depth-resolution trade-off.
3Length of stationary object
If spatially offset Raman spectroscopy or spontaneous Raman tomography is used, then imaging depth exceeds millimeter levels, but spatial resolution degrades to millimeter-level resolution
Solution Approach 1:
The patent segments the detection process into two independent components: infrared excitation for deep penetration and probe light detection for high-resolution imaging. The infrared excitation light penetrates deeply to reach millimeter-level depths, while the visible/near-infrared probe light detects localized refractive index changes with high spatial resolution, allowing both deep imaging and fine resolution simultaneously.
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
SWIP microscopy achieves subcellular spatial resolution and millimeter-level imaging depth in highly scattering mediums, enabling imaging of single 1-μm polystyrene beads through 800-μm thick scattering phantoms and resolving intracellular lipids in intact tumor spheroids and thick tissues.
Implementation Method 1
absorption-induced thermo-optic selective heating
Implementation Method 2
SWIP signal generated by absorption-induced thermo-optic selective heating
Implementation Method 3
optically sensing refractive index changes from absorption sites
Data Source
AI summary
A short-wave infrared photothermal (SWIP) microscopy system and method for vibrational imaging of a sample generates shortwave infrared excitation light probe light. The excitation light and the probe light are combined to generate a combined beam, which is focused to generate a focused combined beam, which is directed onto the sample to obtain a SWIP signal generated by absorption-induced thermo-optic selective heating of the sample. The SWIP signal is collected through an aperture in a condenser and detected.