Fabry-Pérot Scanning Microscope for Low-Background Tissue Lasing
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Solution Overview
Problem
Biological lasers face challenges in generating predictable and trackable laser emission signals from tissues due to strong background emissions, leading to undesirable signal-to-background ratios, limiting their practicality and applicability for scanning and detection in tissue samples, especially for detecting multiple targets with high sensitivity.
Innovation Solution
A scanning microscope device with a Fabry-Pérot resonator cavity and a lasing pump source is used to generate a two-dimensional scan of tissue samples, featuring a first and second reflection surface with a quality factor greater than 10^2, capable of detecting emissions from lasing energy responsive species like fluorophores, and allowing for multiplexed emissions from multiple species.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If biological lasers are used to detect targets in tissue samples, then detection sensitivity is improved, but signal-to-background ratio deteriorates due to strong background emissions
Solution Approach 1:
The patent introduces a Fabry-Pérot resonator cavity as an intermediary optical element between the biological laser source and the detector. This resonator selectively enhances laser emissions at specific wavelengths while suppressing background emissions, thereby improving the signal-to-background ratio without sacrificing detection sensitivity. The resonator acts as a wavelength-selective mediator that filters and amplifies the desired laser signals.
Solution Approach 2:
The patent utilizes the threshold behavior parameter of biological lasers to achieve selective detection. By controlling the pump power to exceed the lasing threshold, the system transforms the gain media from emitting broad-spectrum fluorescence to emitting narrow-line laser radiation. This parameter change enables discrimination between specific targets and background emissions, improving both signal-to-background ratio and detection sensitivity.
2Measurement precision
If biological lasers are used for tissue scanning, then detection sensitivity is improved, but predictability and trackability of laser emission signals deteriorate
Solution Approach 1:
The Fabry-Pérot resonator cavity provides optical feedback to the biological laser system by reflecting specific wavelengths back into the gain media. This feedback mechanism stabilizes the laser emission process, ensuring predictable and trackable signals. The resonator's defined cavity length and mirror reflectivities create discrete resonant modes that guide the laser emission characteristics, making the output signals reliable and reproducible for scanning applications.
3Adaptability or versatility
If multiple lasing energy responsive species are detected simultaneously, then multiplexing capability is improved, but spectral overlap and differentiation difficulty increase
Solution Approach 1:
The patent segments the spectral detection space by using a Fabry-Pérot resonator that supports multiple discrete longitudinal modes at different wavelengths. Each mode can be selectively tuned to match the emission wavelength of a specific lasing energy responsive species. This segmentation of the spectral domain allows simultaneous detection of multiple species without overlap, as each species is assigned to a distinct resonant mode of the cavity.
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
The device achieves high sensitivity and specificity in detecting and differentiating targets in tissues, providing clear laser emission signals with spatial resolution of less than 0.7 micrometers and enabling multiplexed scans of tissue samples.
Implementation Method 1
At least a portion of the scanning cavity corresponds to a Fabry-Pérot resonator cavity defined between the first reflection surface and the second reflection surface having a quality factor (Q) of greater than or equal to about 1 x 10^2
Implementation Method 2
detecting emissions from one or more lasing energy responsive species (e.g., fluorophores) in a tissue sample
Implementation Method 3
Biolasers lase from biological and biochemical materials such as proteins, vitamins, luciferins, DNAs, cells, and blood, when they are labelled with external fluorophores
Implementation Method 4
a first reflection surface that is planar, a second reflection surface, and a scanning cavity
Data Source
Figure 1a~1b
Figure 2~3(b)
Figure 4a~4g
AI summary
Laser emission based microscope devices and methods of using such devices for detecting laser emissions from a tissue sample are provided. The scanning microscope has first and second reflection surfaces and a scanning cavity holding a stationary tissue sample with at least one fluorophore/lasing energy responsive species. At least a portion of the scanning cavity corresponds to a high quality factor (Q) Fabry-Pérot resonator cavity. A lasing pump source directs energy at the scanning cavity while a detector receives and detects emissions generated by the fluorophore(s) or lasing energy responsive species. The second reflection surface and/or the lasing pump source are translatable with respect to the stationary tissue sample for generating a two-dimensional scan of the tissue sample. Methods for detecting multiplexed emissions or quantifying one or more biomarkers in a histological tissue sample, for example for detection and diagnosis of cancer, or other disorders/diseases are provided.