Time-domain diffuse optics (TD-DO) is a powerful technique to non-invasively study diffusive media (e.g., biological tissues). In GAP lab, we work to bring the TD-DO towards its future. GAP lab is pursuing this journey exploiting the recent technological advancements to push the DO to its ultimate performances. The activity is divided into several topics which, however, have a strong interplay since they focus on specific tasks of the same mainstream research: the development of new approaches and instruments for TD-DO.
For all research topics (detailed in the following), strong and continuous collaborations with national and international institutions/universities are carried on, reaching highest level of research quality and international impact.

LARGE AREA DETECTOR

To reach the ultimate performances of the TD-DO technique (i.e., penetration depth > 6 cm) a huge number of late photons (i.e., those that travelled longer in the medium, thus reaching deeper layer) is needed. Therefore, a detector with large light harvesting capability must be employed [2015DallaMoraBOEx]. In 2015 GAP lab firstly introduced Silicon PhotoMultipliers (SiPMs) in the diffuse optics achieving the best timing performances ever reported for single-photon detection [2015DallaMoraOptExpr]. SiPMs have a large light harvesting capability thanks to the large active area (> 1 mm², comparable to the classical PhotoMultiplier Tubes) and the possibility to be put directly in contact with the sample. Moreover, they exhibit all the other advantages of the solid-state detectors such as ruggedness, insensibility to electromagnetics fields, low cost, relatively low biasing voltage [DallaMora2020NIMA]. GAP lab had successfully introduced both SiPM-based cooled modules (active area < 2 mm²) as well probe-hosted ones (active area from 1 to 9 mm²) [2016MartinenghiRSI, 2016ReNeuroph, 2020Di SienoBOEx]. The suitability of all the realized detectors was validated firstly using well-assessed protocols for DO and then directly on-field for several applications (from brain imaging to tomography passing through fruit quality assessment).
Moreover, within the SP-LADOS project (funded thanks to the Attract project promoted by the EU) GAP inspired and participated in the realization the largest detector ever reported for diffuse optics with an active area up to 1 cm² has been realized, allowing to reach a penetration depth of more than 40 mm [2020_Acerbi_Instru; 2021_Behera_JSTQE].

(Fig.1) Example of different arrangement of SiPMs. (a) miniaturized 1 mm² probe-hosted SiPM; (b) and (c) 36 mm² and 1 cm² SiPM module developed within the ATTRACT project SP-LADOS; (d) 1 mm² SiPM module.

FAST-GATING TECHNIQUE

Another condition to reach the ultimate performance of TD-DO is the use of the so-called “fast-gating” detector (i.e., detector that can be turned on and off in few hundreds of ps) [2015_DallaMora_BOEx]. Indeed, acquiring only given slices of the TD-DO curves, it is possible to enhance the information given by late photons and, adjusting the power injected to reach a given number of counts in all slices, the dynamic range of the measurements can be increased by several decades [2010_Dalla Mora_JSTQE]. GAP lab, thanks to the strong collaboration with the DEIB of PoliMi, developed the “null source-detector distance approach” and applied it in several applications (tomography, non-contact imaging, functional near infrared spectroscopy) with both phantom and in-vivo measurements [2016_DiSieno_JBO, 2013_Mazurenka_BOEx,2019_DiSieno_ApplSci]. Measurements were conducted using Single-Photon Avalanche Diodes (SPADs) enabled in fast-gated mode exploring the potentialities of this technique (improved spatial resolution, possibility to have non-contact measurements, improvement in the visibility of deep inhomogeneities) but also enlightening the bottlenecks (low light harvesting capability of the detectors due to their small active area -about 0.007 mm²- and a previously undiscovered noise source related to the number of photons impinging on the detector when it is off [2015_DallaMora_JAP]). In the last years, the issue of the small active area was overcome thanks to the development (in collaboration with PoliMi/DEIB) of a large-area SiPM having a tunable active area (from few μm2 up to 8.6 mm²) to adapt to the level of signal detected [2021_DiSieno_OptLett, 2020_Conca_JSSC].

(Fig.2) Schematic representation of the time-gating technique. The reconstructed curve with high dynamic range is obtained by dividing it in many slices and by progressively increasing the optical power to improve the signal-to-noise ratio along the tail.

HIGH THROUGHTPUT

(Fig.3) Schematic representation of the improvement in the penetration depth (reported as the organs that can be reached) given by the high-throughput.

To reach the ultimate limits of TD-DO all detected photons need to be analyzed. If detectors with large light harvesting capability are employed, a wide number of photons is available. However not all of them are exploited when working in the so-called “single-photons statistics” (i.e., count-rate of recorded photons lower than 5% of the laser repetition rate) which allows not to distort the recorded curve. Indeed, if lots of photons arrived, the earlier (i.e., those that travelled in shallower layer) have larger probability to be detected, thus giving rise to curve distortion. Exploiting the innovative instruments for timing electronics, GAP lab did pioneer studies on the possibility to work well-beyond single-photon statistics, provided that a suitable correction for the pile-up effect is applied.
Such a new working regime will allow to exploit all photons recorded, thus improving the achievable performances. Indeed, it is possible to enhance the visibility of the deep inhomogeneity (whether the integration time is kept fixed) or decreasing substantially the acquisition time of the measurements (if the overall numbers of counts is maintained). Both those achievements will open the way to new disruptive applications of the TD-DO (e.g., capability to follow fast dynamics or improve penetration depth of the systems).

MINIATURIZATION

One final field of research of GAP lab is the miniaturization of the components of TD-DO systems. Indeed, the reduction the dimensions of the components is the first step to reach two objectives: i) the creation of a dense distribution of sources and detectors to reach the ultimate performances of the TD-DO and ii) the possibility to have wearable devices for consumers’ market (e.g., monitoring of sportsmen parameters such as oxygenation, etc.). In 2016 we demonstrated the possibility to have miniaturized light sources suitable for TD-DO applications [2017_DiSieno_JBO] and, in the same period, we published also the capability to have probe-hosted SiPM detector which can be put directly in contact with the sample (e.g., the muscle or the head of the subject to be monitored) [2016_Re_Neuroph, 2020_Di Sieno_BOEx].
More recently, thanks to the SOLUS project (funded by the European Commission) GAP lab was involved in the design and following validation of the so called “smart-optode”, which is the first multi-wavelength, complete and miniaturized system for TD-DO applications featuring the most advanced strategies for detection (such as the fast gating). Indeed, in the dimensions of few cm³, it embeds 8 laser sources (at different wavelengths for probing several chromophores), a wide area (up to 8.6 mm²) SiPM that can be enabled in fast-gating and an integrated timing electronics. This reduction of dimensions is of more than three orders of magnitude if considering state-of-the-art compact eight wavelength spectroscopy system. The possibility to arrange several optodes in different geometries makes them the perfect solution for the new generation of tomographic systems.

(Fig.4) Example of miniaturized components and/or system. (a) Probe containing the 9 mm² probe-hosted SiPM; (b) integrated CMOS laser drive; (c) arrangement of 4 smart optodes and a picture of the boards embedding the optics and the lasers.

PERSPECTIVES AND FUTURE ACTIVITY

Regarding the activities presented before, in the next future, GAP lab will explore several possibilities in some cases mixing the above-described fields.
For example, in the next months, large area detectors (such as the 1 cm²) will be operated in high-throughput regime to exploit all the photons detected. First measurements will be conducted on phantoms and then in-vivo applications will be explored.
Regarding the high throughput activity, several other steps will be studied. Indeed, new algorithms for the correction of distortion will be explored and/or proposed to improve the achievable performances. Moreover, the possibility to enhance the late photons working with very high count-rate at short source-detector separation will be studied. Indeed, in principle, boosting the overall count-rate implies the increase of the overall number of late arriving photons, thus possibly leading to results similar to the fast-gating technique. Moreover, new multichannel systems can be realized using the newly developed technologies and exploiting the high throughput technique to simplify the signal equalization procedure.
Currently, GAP lab is also working to the exploitation of fast-gated SiPMs for different applications through the validation and characterization of devices realized using new technologies. Another field which needs to be exploited is the smart-optode whose potential application fields range from brain imaging to wood characterization passing through tomography. Moreover, thanks with collaborations with international institutions, other integrated systems (embedding sources, detectors and timing electronics) are currently under study to assess their potential suitability for TD-DO applications.
The road to new disruptive applications of TD-DO has just started!

EQUIPMENTS

• high-throughput detection system based on high power laser at 670 and 830 nm and advanced timing electronics.
• 1-9 mm² SiPMs (both probe hosted and Peltier cooled module)
• large area SiPM modules (36 and 100 mm²)
• fast-gated SPAD module (active area of 100 µm diameter)
• fast-gated SiPM system (active area up to 8.6 mm²)
• complete miniaturized TD-DO optode (8 laser drivers, fast gated SiPM detector and integrated timing electronics)

COLLABORATIONS

• Commissariat à l’énergie atomique et aux énergies alternatives (CEA-LETI), Grenoble (France):
• Physikalisch-Technische Bundesanstalt (PTB), Berlin (Germany)
• University of Oulu, Oulu (Finland)
• Institut de Ciències Fotòniques (ICFO), Castelldefels (Spain)
• University College London, London (UK)
• Politecnico di Torino, Torino (Italy)
• Università di Firenze, Florence (Italy)
• Politecnico di Milano, DEIB, Milan (Italy)
• Centre Hospitalier Universitaire-Grenoble, Grenoble (France)
• Medical Photonics Research Center, Hamamatsu (Japan)
• Fondazione Bruno Kessler, Trento (Italy)
• PIONIRS s.r.l., Milano (Italy)

THESIS INFO

GAP lab is available to host master thesis students interested to work in the research fields above described. Examples of available thesis (together with other practical details) are reported in this Link.
At any rate, we warmly invite the interested students to contact the scientific responsibles of the lab (prof. A. Dalla Mora and Dr. L. Di Sieno) to get information about the last advancement of the research in which a thesis activity can be framed.