The goal of FLASH (FLuorescence Analysis Speedup to extremely High rates) project is to develop a new detection system that combines single-photon sensitivity, picosecond temporal resolution, and unprecedented high throughput to acquire time-resolved fluorescence images. A similar system holds great promise to have a revolutionary impact on several fields of biology and medicine.
For example, one of the most time/cost-consuming stages of drug discovery is the identification of drug leads. This requires the measurement of hundreds of thousands of samples, which have been treated with varied dosages of a large number of drug leads. Fluorescence Lifetime IMaging (FLIM) widely demonstrated its potential in this field, but it is intrinsically too slow to be extended to a large scale. The main challenge in achieving fast FLIM has been in the lack of high-speed electronics combined with high-performance detectors.
FLASH aims at overcoming this limitation by combining in a single system three key elements:
• a high-performance Single-Photon Avalanche Diode (SPAD)
• fast, picosecond-precision front-end and processing electronics
• a new solution to guarantee zero-distortion at very high speed
The coordinator’s research group in 2017 demonstrated that a completely different approach with respect to what is currently used in this field can increase by an order of magnitude the acquisition rate in fluorescence imaging. The proposed solution guarantees zero-distortion at high-rates.
Now, several aspects need to be addressed to make this solution available to end users. In particular, high-performance front-end electronics developed on purpose is of the utmost importance. The FLASH project aims at the development of a new complete Time Correlated Single Photon Counting (TCSPC) single-channel module providing both the theoretically estimated speedup by almost an order of magnitude with respect to classic pile-up limited acquisition chains and very high performance. In principle, the same result could be achieved exploiting several channels operating in parallel. Numerous multichannel SPAD-based acquisition systems have been presented in literature so far. Unfortunately, the performance of most of them, especially those featuring a very high number of channels, are quite poor compared to the best results achieved with single-channel systems. Even worse, acquisition speed has not increased accordingly to the number of channels. Therefore, FLASH can provide for the first time both unprecedented measurement speed and high performance with a TCSPC acquisition system.
Moreover, the FLASH approach can be extended to multichannel systems to reduce the duration of fluorescence measurements by more than two orders of magnitude.