Multiphoton Imaging System for High-Speed Cellular Dynamics
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current biomedical technologies lack a high-resolution imaging technique capable of recording the dynamics of cellular or biochemical processes in biological samples at the single-cell level and high speeds, particularly for small or large groups of cells, which is essential for understanding activities like neuronal connectivity and brain functions.
Innovation Solution
The development of a system using a pulsed laser beam with a spectrum of different wavelengths, dispersed and re-overlapped to create a multiphoton excitation area in a biological sample, allowing for high-speed recording of cellular and biochemical changes through molecular reporters that emit light based on properties like calcium concentrations, membrane voltage, and enzymatic activity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Speed
If conventional imaging techniques are used to record cellular processes, then the system is simpler to operate, but the recording speed and resolution are insufficient for capturing fast cellular dynamics at single-cell level
Solution Approach 1:
The patent employs pulsed laser illumination with periodic timing to excite molecular reporters in different regions of the biological sample. By using periodic pulsed action rather than continuous illumination, the system achieves high-speed sequential imaging of multiple cell regions while maintaining single-cell resolution, directly addressing the speed limitation of conventional techniques.
Solution Approach 2:
The system uses dynamic control of laser beam positioning and timing to adaptively track and image fast-moving cellular processes. The illumination pattern and detection timing are dynamically adjusted to capture rapid cellular dynamics, enabling the system to record fast biological events that static conventional methods cannot capture.
2Measurement precision
If high-resolution single-cell imaging is implemented, then measurement precision improves, but the ability to record large populations of cells simultaneously decreases
Solution Approach 1:
The patent divides the biological sample into multiple discrete regions or fields of view that can be independently illuminated and imaged. By segmenting the sample and using sequential or parallel imaging of these segments, the system maintains single-cell resolution while expanding the total number of cells that can be recorded across the entire sample population.
Solution Approach 2:
The system transitions from two-dimensional planar imaging to three-dimensional volumetric imaging by adding the depth dimension. This enables simultaneous recording of multiple cell layers at single-cell resolution, dramatically increasing the total number of cells that can be imaged while maintaining high measurement precision through optical sectioning techniques.
3Loss of time
If fast recording of cellular dynamics is achieved, then the time resolution improves, but the complexity of dispersing and re-overlapping laser spectra increases
Solution Approach 1:
The patent introduces dispersive optical elements (such as gratings or prisms) as intermediaries to separate the laser spectrum into different wavelengths, which are then directed to different spatial regions. These intermediary elements enable time-resolved imaging by spatially encoding spectral information, achieving high time resolution while managing optical complexity through well-established dispersive components.
Solution Approach 2:
The system creates multiple spectral copies of the laser beam at different spatial locations by dispersing the spectrum and re-overlapping selected wavelength ranges. This copying approach allows simultaneous excitation of different molecular reporters with different spectral requirements, achieving high time resolution for tracking multiple cellular processes without requiring a completely complex custom optical system.
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
Enables simultaneous or near-simultaneous imaging of cellular or biochemical changes within seconds to picoseconds, capturing information at a single-cell resolution for populations ranging from tens to millions of cells, applicable in neuroscience, drug discovery, stem cell research, and cancer research.
Implementation Method 1
one or more dispersive elements that are configured to receive a pulsed laser beam with a spectrum of different wavelengths and disperse the spectrum of the pulsed laser beam
Implementation Method 2
generate a multiphoton excitation area in a biological sample by re-overlapping in time and space the dispersed spectrum of the pulsed laser beam
Implementation Method 3
molecular reporters that emit light based on properties like calcium concentrations, membrane voltage, and enzymatic activity
Data Source
AI summary
Devices and methods for recording dynamics of cellular and/or biochemical processes, including a device including one or more dispersive elements configured to receive a pulsed laser beam with a spectrum of different wavelengths and disperse the spectrum of the pulsed laser beam; and one or more first elements configured to receive the dispersed spectrum of the pulsed laser beam, and generate a multiphoton excitation area in a biological sample by re-overlapping in time and space the dispersed spectrum of the pulsed laser beam on an area in the biological sample, wherein the device is configured to record at high speed changes of cellular and biochemical processes of a population of cells of the biological sample based on generation of the multiphoton excitation area in the biological sample.