Spatial Light Modulator Probe Identification via Temporal Frequency
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Solution Overview
Problem
Current imaging technologies face limitations in identifying probes within biological samples due to the restricted number of distinguishable fluorophores and their spectral or temporal resolving abilities, which restricts the simultaneous imaging of multiple analytes.
Innovation Solution
The system employs a spatial light modulator with a refractive layer that varies its refractive index spatially, combined with light sensors and optical systems to determine the identity of probes based on the colors and locations of multiple fluorophores by generating and correlating time-varying waveforms of light emitted from different locations and wavelengths.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If traditional optical imaging systems are used to image fluorophores, then the system structure is simple and easy to operate, but the measurement precision and distinguishability of probes are limited due to spectral overlap and diffraction limits
Solution Approach 1:
The patent transforms the imaging problem from 2D spatial detection to 3D phase space detection by incorporating temporal frequency dimension. Multiple light sensors detect fluorophores at different temporal frequencies, creating a three-dimensional detection space (spatial position, wavelength, temporal frequency) that resolves spectral overlaps and enables precise probe identity determination beyond traditional diffraction limits
Solution Approach 2:
The system dynamically modulates the excitation light frequency over time and detects fluorophores at corresponding temporal frequencies. This dynamic temporal frequency modulation allows the system to distinguish between fluorophores with overlapping spectra by detecting their unique temporal frequency signatures, thereby improving measurement precision without requiring complex spatial separation
2Productivity
If the number of distinguishable fluorophores is increased to image multiple analytes simultaneously, then the productivity and information content increase, but the spectral resolving ability and signal-to-noise ratio deteriorate due to spectral overlap
Solution Approach 1:
The system employs periodic modulation of excitation light at different temporal frequencies for different fluorophores. By detecting emitted light at these distinct temporal frequencies, the system can simultaneously image multiple analytes with high signal distinguishability, as each fluorophore's temporal frequency signature acts as a unique identifier that prevents spectral confusion
Solution Approach 2:
Temporal frequency serves as an intermediary dimension that mediates between multiple fluorophores with overlapping spectra. By introducing this temporal frequency mediator, the system can resolve spectral overlaps and maintain high signal distinguishability when imaging multiple analytes simultaneously, effectively expanding the distinguishable fluorophore capacity
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 allows for the identification of probes with increased distinguishability, enabling the simultaneous imaging of multiple analytes by correlating spatial and spectral information, beyond the diffraction limit of traditional optical systems.
Implementation Method 1
a spatial light modulator that includes a reflective layer disposed beneath a refractive layer and that is operable to have a refractive index that varies spatially across the spatial light modulator according to a controllable gradient
Implementation Method 2
The refractive layer is chromatically dispersive
Implementation Method 3
determining, based on a plurality of images, locations and colors of two or more fluorophores in the target
Data Source
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AI summary
Methods are provided to identify spatially and spectrally multiplexed probes in a biological environment. Such probes are identified by the ordering and color of fluorophores of the probes. The devices and methods provided facilitate determination of the locations and colors of such fluorophores, such that a probe can be identified. In some embodiments, probes are identified by applying light from a target environment to a spatial light modulator that can be used to control the direction and magnitude of chromatic dispersion of the detected light; multiple images of the target, corresponding to multiple different spatial light modulator settings, can be deconvolved and used to determine the colors and locations of fluorophores. In some embodiments, light from a region of the target can be simultaneously imaged spatially and spectrally. Correlations between the spatial and spectral images over time can be used to determine the color of fluorophores in the target.