Line Scanning Mechanical Streak System for Phosphorescence Lifetime Imaging
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Solution Overview
Problem
Conventional phosphorescence lifetime imaging techniques face challenges with long emission lifetimes, leading to low signal accumulation rates and high noise due to the use of point scanning methods, which are inefficient for collecting weak signals in biological tissues.
Innovation Solution
A line scanning mechanical streak system utilizing a camera and a scanning mirror to spread phosphorescence emission onto a 2D sCMOS camera, allowing for high-throughput, low-noise imaging by converting pixel positions to time and performing exponential curve fitting to determine decay lifetimes, thereby reducing 2D streak images into 1D phosphorescence lifetime images.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If point scanning methods are used for phosphorescence lifetime imaging, then the system can effectively collect emitted photons from thick scattering tissue, but the signal accumulation rate is very low due to long emission lifetimes
Solution Approach 1:
The patent transitions from point scanning (1D spatial sampling) to line scanning with mechanical streaking (2D spatial-temporal mapping). By spreading the phosphorescence emission temporally across a line scan and mapping time to spatial position on the detector, the system accumulates signals from multiple excitation cycles simultaneously, dramatically increasing the signal accumulation rate while maintaining compatibility with long emission lifetimes.
2Productivity
If laser focal intensity is increased to speed up signal accumulation, then the signal accumulation rate improves, but photobleaching and measurement artifacts occur
Solution Approach 1:
The patent implements continuous line scanning that repeatedly samples the same spatial location over many excitation cycles. This continuous action allows signal accumulation without requiring high instantaneous laser intensity, as the weak signals from each cycle are coherently summed over time. The system maintains low laser power throughout the measurement process, avoiding photobleaching while achieving high signal accumulation rates through temporal integration.
3Productivity
If PMT array detector is used for parallel recording, then the detection capability is improved, but the cost increases and detector noise aggregates through multiple readout processes
Solution Approach 1:
The patent replaces the electronic readout mechanism of PMT arrays with a mechanical scanning system combined with a single-photon counting detector. Instead of using multiple noisy detectors in parallel, the system uses a single high-sensitivity detector that sequentially samples different spatial positions along a line. This mechanical approach eliminates the need for multiple independent readout channels, thereby avoiding the aggregation of detector noise while maintaining parallel recording capability through rapid sequential measurement.
4Productivity
If intensified camera with many pixels is used for parallel detection, then the number of detection channels increases, but the time domain recording becomes highly lossy due to gating for defined time points
Solution Approach 1:
The patent introduces dynamic temporal mapping through mechanical streaking, where the detector integrates photons continuously over the entire phosphorescence decay period. The scanning mirror dynamically deflects photons arriving at different times to different spatial positions on the detector, creating a temporal-spatial mapping without requiring time-gating. This dynamic approach captures the full time domain information without loss, while still enabling parallel detection across multiple spatial channels.
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 enables simultaneous recording of hundreds to thousands of pixels with high quantum efficiency and low read noise, simplifying lifetime measurement and improving signal-to-noise ratios, suitable for imaging samples with lifetimes ranging from tens of nanoseconds to hundreds of microseconds.
Implementation Method 1
phosphorescence lifetime imaging based on mechanical streaking... a light source (which may be configured to excite phosphorescence emission)... receiving light energy from the first target location with a detector, the light energy being indicative of the excitation level
Implementation Method 2
a scanner (which may be a scanning mirror in view of the light source, the camera and/or the slit)... the scanning mirror reflects a phosphorescence emission passing back through the slit and directs it to the camera
Implementation Method 3
a detector (which may be a camera configured to receive the phosphorescence emission from a sample)... receiving light energy from the first target location with a detector
Data Source
AI summary
Systems and methods for analyzing samples, such as tissue samples, and measuring the emissions when these samples are exposed to light are disclosed. Embodiments include illuminating multiple target locations on a sample with laser light, which may first be manipulated by a scanner, and receiving decaying emissions from the target location. At least some embodiments include the emissions traveling backwards along a substantial portion of the laser light pathway and being received by a detector. Additional embodiments include converting the received emissions into streak lines of position versus time, converting the streak lines to plots of signal strength versus time, and curve fitting the plots to determine representative decay times. In some embodiments, the decay times are presented as plots of position on the surface of the sample versus emission strength, which may be color coded. Some embodiment dwell on each target location for multiple scans of the laser.