All-Solid-State Lock-In Imager for Fluorescence Lifetime Imaging
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
The widespread application of fluorescence lifetime imaging microscopy (FLIM) is limited by high costs and the need for specialized knowledge in maintaining and operating existing systems, particularly due to the use of multi-channel-plate detectors which are expensive and prone to noise, and the sub-optimal performance of CCD cameras in frequency-domain detection for nanosecond decays.
Innovation Solution
The use of an all-solid-state lock-in imager, originally developed for 3D vision, is adapted for FLIM, enabling cost-effective and user-friendly wide-field frequency-domain imaging with solid-state light sources, achieving high modulation frequencies up to 100 MHz and video-rate imaging capabilities.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If multi-channel-plate detectors are used for FLIM detection, then detection sensitivity is improved, but system cost increases and noise level increases
Solution Approach 1:
The patent replaces expensive and noisy multi-channel-plate detectors with inexpensive solid-state detectors that have longer operational lifetimes and lower noise characteristics. The invention uses standard CCD or CMOS cameras that can be readily replaced if needed, eliminating the need for costly MCP detectors while maintaining adequate detection performance for fluorescence lifetime imaging.
Solution Approach 2:
The patent substitutes the mechanical and electronic complexity of multi-channel-plate detectors with solid-state semiconductor detectors. The MCP detector system is replaced by a solid-state camera system that uses photodiode arrays, eliminating the mechanical vacuum tube components and their associated noise and reliability issues.
2Measurement precision
If multi-channel-plate detectors are used for FLIM detection, then detection sensitivity is improved, but system cost increases
Solution Approach 1:
The patent replaces expensive multi-channel-plate detectors with inexpensive solid-state detectors that can be easily replaced. The invention uses standard CCD or CMOS cameras that are significantly cheaper than MCP detectors and can be obtained through standard purchasing channels, making the system more accessible to laboratories with limited budgets.
Solution Approach 2:
The patent creates a simplified copy of the detection function using solid-state technology instead of the original MCP detector system. The solid-state camera provides sufficient detection capability for FLIM applications while costing a fraction of the original system, effectively copying the essential function at lower cost.
3Ease of manufacture
If CCD cameras are used for frequency-domain detection, then system cost is reduced, but measurement precision for nanosecond decays deteriorates
Solution Approach 1:
The patent changes the operational parameters of the solid-state detector by using high-speed mode with reduced exposure times and increased frame rates. The camera is operated at modulation frequencies up to 100 MHz with exposure times optimized for nanosecond fluorescence lifetime measurements, enabling precise detection despite the solid-state technology limitations.
Solution Approach 2:
The patent employs periodic modulation of the excitation light at high frequencies (up to 100 MHz) and synchronizes the detector readout with this modulation. The camera captures multiple frames per modulation period, and the fluorescence lifetime is extracted from the phase and amplitude modulation of the periodic signal, enabling precise nanosecond timing measurements.
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 results in a more sensitive and cost-effective FLIM system with improved noise characteristics, capable of robust nanosecond lifetime measurements, potentially outperforming multi-channel-plate systems and enabling broader application in life sciences and diagnostics.
Implementation Method 1
at least one pixel of the detector means comprises a radiation-sensitive element for converting incident radiation into an electric signal
Implementation Method 2
The use of an all-solid-state lock-in imager, originally developed for 3D vision, is adapted for FLIM, enabling cost-effective and user-friendly wide-field frequency-domain imaging
Data Source
AI summary
Fluorescence lifetime imaging microscopy (FLIM) is a powerful technique increasingly used in the life sciences during the past decades. An all-solid-state fluorescence-lifetime-imaging microscope (1) with a simple lock-in imager (4) for fluorescence lifetime detection is described. The lock-in imager (4), originally developed for 3D vision, embeds all the functionalities required for FLIM in a compact system. Its combination with a light-emitting diode (2) yields a cost-effective and user-friendly FLIM unit for wide-field microscopes. The system is suitable for nanosecond lifetime measurements and achieves video-rate imaging capabilities.