High-speed timE Resolved fluorescence iMaging with no pilE-up diStortion

Introduction

The overarching goal of HÈRMES is to establish a new methodology for time-resolved imaging by means of Time-Correlated Single Photon Counting (TCSPC). Since its debut in the literature, the potential of TCSPC as a non-invasive, ultra-sensitive, and extremely precise imaging tool has been manifest. Numerous applications have benefited from it so far, but a key limitation still prevents its wide use in many other crucial applications: the speed of a TCSPC acquisition chain must be kept low (few Mcount/s in the best case) to avoid distortion due to pile-up of events.

Current Limitations

Up to now, researchers in this field have tried to work around this limit mainly by posing multiple channels in parallel, but they still face severe limitations mainly due to:

1. Efficiency
2. Fill factor
3. Precision
4. Linearity
5. Readout complexity

Proposed Methodology

I propose an innovative methodology for removing all constraints on TCSPC, promising a change in the paradigm of how TCSPC systems are conceived and how time-resolved measurements are carried out. To achieve such an ambitious goal, a radical change is necessary.

Development of Mathematical Model

I expect to develop a comprehensive mathematical model showing that pile-up distortion can be avoided with any combination of single photon detector and laser excitation power if additional picosecond-precision information on the status of the system in each time bin is acquired at run-time.

Ultrafast Electronics

I will develop ultrafast electronics for Single Photon Avalanche Diodes to move from theory to the real experimental world. Moreover, I will empower the new constraint-less TCSPC by developing an innovative computational imaging framework, opening the way to the real-time acquisition of 4D images.

Applications

Next-generation TCSPC systems based on the HÈRMES methodology will allow the exploitation of this powerful tool in crucial applications such as, for example:

• Intraoperative imaging
• Neuron imaging

These applications require an ultrafast but still linear acquisition to enable complex operations like image-assisted brain surgery and spike analysis of neurons.