Light-Field Tomographic FLIM With SPAD Arrays for Fast 3D Acquisition
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Solution Overview
Problem
Conventional fluorescence lifetime imaging microscopy (FLIM) techniques require extensive scanning, leading to prolonged acquisition times for high-resolution two-dimensional (2D) and three-dimensional (3D) imaging, particularly in time-domain FLIM systems, which are costly and limited by the need for large-format gated image sensors.
Innovation Solution
The implementation of light-field tomographic fluorescence lifetime imaging microscopy (LIFT-FLIM) using a linear single-photon avalanche diode (SPAD) array and computational imaging methods to capture en-face projections of 3D objects, transforming volumetric images into lines, allowing for reduced scanning steps and simultaneous spectral-lifetime multiplex imaging.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional time-domain FLIM uses pointwise scanning like confocal microscope, then measurement precision is improved, but productivity deteriorates due to slow data acquisition
Solution Approach 1:
The patent transforms the detection approach from pointwise scanning in 3D space to capturing light field projections in 4D phase space (x, y, angle, angle). By using a light field microscope to capture directional information and subsequently performing tomographic reconstruction, the system obtains volumetric FLIM data without mechanical scanning, thus achieving high productivity while maintaining measurement precision through computational reconstruction.
Solution Approach 2:
The patent replaces the mechanical scanning system with a computational imaging system. Instead of physically moving the detector or sample to scan through 3D space, the system uses a light field microscope to capture angular information and applies tomographic reconstruction algorithms to generate volumetric images, eliminating mechanical scanning limitations and achieving high-speed volumetric acquisition.
2Productivity
If conventional time-domain FLIM uses widefield imaging with gated image sensor, then productivity is improved through parallel measurement, but device complexity increases due to costly large-format sensors
Solution Approach 1:
The patent introduces a light field microscope as an intermediary optical system between the sample and the detector. This intermediary captures the angular distribution of light rays, encoding 3D spatial information into 2D projection images. The subsequent tomographic reconstruction algorithm acts as a computational intermediary to recover volumetric data, enabling the use of simpler, lower-cost detectors while achieving high-speed parallel acquisition.
Solution Approach 2:
The patent creates optical copies of the sample from different angular perspectives simultaneously through the light field microscope. By capturing the light field information that contains directional data, the system effectively creates multiple virtual views of the sample in a single exposure, enabling tomographic reconstruction without mechanical scanning or expensive large-format gated sensors.
3Measurement precision
If conventional FLIM performs extensive scanning for high-resolution imaging, then measurement precision is improved, but loss of time increases significantly
Solution Approach 1:
The patent performs preliminary action by capturing the complete light field information (including angular distributions) in a single exposure or minimal scans. The light field microscope records directional information for all rays simultaneously, preparing the data in advance for tomographic reconstruction. This preliminary capture of comprehensive optical information enables high-resolution volumetric reconstruction without subsequent time-consuming scanning.
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
LIFT-FLIM significantly reduces the number of scanning steps required for 3D imaging, enabling high-speed, high-dimensional data acquisition with low-cost detectors, and provides high temporal bandwidth for both lifetime and spectral information, suitable for high-content multiplexed imaging.
Implementation Method 1
a linear single-photon avalanche diode (SPAD) array
Implementation Method 2
an array of Dove prisms configured to receive light from the field stop
Implementation Method 3
a plurality of cylindrical lenses, the cylindrical lenses optically coupled to at least one lenslet
Implementation Method 4
Fluorescence lifetime imaging microscopy (FLIM) is a powerful imaging technique that enables the visualization of biological samples at the molecular level by measuring the fluorescence decay rate of fluorescent probes
Data Source
AI summary
A light field tomography fluorescence lifetime imaging microscopy (LIFT-FLIM) apparatus with an objective, a field stop, and a fluorescence lifetime imager. The imager includes an array of Dove prisms configured to receive light from the field stop, a plurality of lenslets where each lenslet is optically coupled to at least one Dove prism in the array of Dove prisms, and a plurality of cylindrical lenses that are optically coupled to at least one lenslet, and an image sensor configured to image light received from the cylindrical lenses.