Non-contact Coherent Raman Spectrometric Imaging Method
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Existing Raman spectrometric imaging technologies face challenges in achieving accurate spatial super-resolution, particularly in complex molecular systems like biological cells, due to limitations in fluorescent labeling methods and contact-based surface-enhanced Raman technologies, which restrict their application in biomedicine.
Innovation Solution
A non-contact spatial super-resolution coherent Raman spectrometric imaging method using a 'pump-deplete-probe' measurement with femtosecond optical comb pulses, where a pump light beam, a depletion light beam delayed by less than 10 ps, and a probe light beam generate a coherent anti-Stokes Raman scattering (CARS) signal, breaking the optical diffraction limit and enabling broadband molecular characterization without fluorescent labeling or contact with the sample.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If fluorescent labeling method is used for spatial super-resolution imaging, then spatial resolution is improved, but application range is limited and broadband molecular characteristic spectral information cannot be provided
Solution Approach 1:
The patent replaces the mechanical/chemical fluorescent labeling system with an optical field-based coherent Raman scattering system. By using focused laser beams to excite Raman scattering in specific spatial regions, the method achieves super-resolution without requiring fluorescent labels, thereby expanding application range to various molecular systems including biological cells and materials.
Solution Approach 2:
The patent changes the fundamental operating parameters by using ultrafast laser pulses (femtosecond to picosecond duration) with specific frequency characteristics to induce coherent Raman scattering. This parameter change enables both spatial super-resolution through focused beam geometry and broadband spectral information acquisition through frequency-modulated continuous wave (FMCW) or frequency-resolved optical gating (FROG) techniques.
2Power
If surface-enhanced Raman technology is used, then Raman signal strength is improved, but contact with sample surface is required which increases difficulty of sample preparation
Solution Approach 1:
The patent replaces the mechanical contact-based surface-enhanced Raman technique with a non-contact optical field-based coherent Raman scattering method. By using focused laser beams that can be precisely positioned and controlled without physical contact, the method eliminates the need for complex sample preparation while maintaining sufficient Raman signal strength through optical field concentration and coherent signal enhancement.
3Device complexity
If single fingerprint peak measurement is used, then measurement simplicity is maintained, but accurate determination of type, state and dynamic process is difficult in complex molecular systems
Solution Approach 1:
The patent segments the molecular characterization process by measuring multiple Raman scattering components with different frequency characteristics (e.g., vibrational modes, rotational transitions) separately and systematically. Through frequency-resolved detection and spectral analysis, the method decomposes the complex molecular spectrum into identifiable components, enabling accurate determination of molecular type, state, and dynamic processes.
Solution Approach 2:
The patent adds the frequency dimension to the measurement by using frequency-modulated continuous wave (FMCW) or frequency-resolved optical gating (FROG) techniques. This transforms the measurement from a single-point frequency measurement to a multi-dimensional spectral analysis, enabling comprehensive molecular characterization while maintaining measurement simplicity through automated spectral processing.
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 method achieves spatial super-resolution imaging and broadband coherent Raman spectroscopy, suitable for various sample components, by using ultrashort pulses and a dual-comb 'pump-probe' technology, allowing for precise molecular analysis without the need for fluorescent labels or contact with the sample surface.
Implementation Method 1
emitting a second light beam as a probe light beam by a second optical comb light source to the remaining excited molecules to generate a coherent anti-Stokes Raman scattering (CARS) signal
Implementation Method 2
guiding the depletion light beam to the region of the sample to make excited molecules at a periphery of the region to return into a vibrational ground state
Data Source
AI summary
A Raman spectrometric imaging method, including: placing a sample on a two-dimensional translation stage; emitting a first light beam by a first optical comb light source; dividing the first light beam into a pump light beam and a depletion light beam to illuminate the sample; guiding the pump light beam to illuminate a region of the sample to excite molecules of the sample in the region; guiding the depletion light beam to the region of the sample to make excited molecules at a periphery of the region to return into a vibrational ground state; emitting a second light beam as a probe light beam by a second optical comb light source to the remaining excited molecules to generate a CARS signal; recording the CARS signal for imaging; moving the two-dimensional translation stage to scan other regions of the sample to form an image of the sample.