CE42 - Capteurs, instrumentation

Temporally Heterodyned Theta Tomographic Microscopy – THTTM

THTTM – Temporally Heterodyned Theta Tomographic Microscope

THTTM Project aims at characterizing moving samples using Tomographic Diffraction Microscopy (TDM). These aspects will be studied through two main axes:<br /><br />- discrimination of static/dynamic areas of a sample using laser Doppler 3D imaging<br />- Moving object characterization using TDM

Aims and Goals

Coupling heterodyne holography with true 3D imaging might allow to:<br />- Focus on selected features. Selective 3D reconstruction of the studied bio-sample will be possible.<br />- Functionalize conventional TDM by adding new modalities like 3D laser Doppler imaging.<br />To the best of our knowledge these imaging properties have never been brought together and will be a major scientific breakthrough in the field of marker-less 3D imaging.<br /><br />One of the interest of the project is to propose a way to image and analyze internal mechanisms leading, for instance to cellular (e.g. macrophage) motion.<br />The proposed Doppler Tomographic Diffractive microscopy technique (DTDM) is expected to have the following properties: High resolution without contrast agent, Multifunctional imaging, High-speed imaging, True 3D Imaging. <br /><br />In order to attain these ambitious objectives, we propose to address three gradual challenges aiming at validating the proposed concept to slowly varying samples, speeding-up the acquisition process using a theta configuration, and finally building a routine high-speed DTDM for either slowly or rapidly flowing samples.

Building of a «slow DTDM« demonstrator with sample rotation, that would be used for characterization of slowly moving scattering samples (e.g. bio-vegetal samples, microfluidic channels …), and that will allow to validate the reconstruction algorithms that will be developed during the other tasks.

Building a «multiview« DTDM for acquisition speeding-up. Combining the viewing angle will help parallelizing the acquisition, thus speeding-up image grabbing. At the end of this stage, we will be able to characterize rapidly flowing sample in 3D, but with a degraded resolution, due to the limitation of the viewing angles.

At the end of the project, hardware speeding-up, based on the use of very high-speed cameras coupled with high-throughput illumination sweep device (DMD), will lead to a high-speed full-resolution DTDM device.

At the end of THTTM project we expect to have two types of products:
- Multimodal Tomographic Diffractive Microscopes (associated with experimental challenges)
- High-end reconstruction algorithms (associated with data processing challenges)
We do hope that the DTDM device developed during THTTM project, as well as the associated data reconstruction methods will help the scientific imaging community by proposing a novel and innovative imaging modality.

It should be noted that the scientific coordinator team recently became a member of the joint network MIAP (Microscopy and Image Analysis Platform: miap.eu/), which make available innovative imaging device and data processing resources. This might be a great opportunity to spread out the developed device to a larger community.

Moreover, a study has been started to identify the detection limit of the proposed configuration. Heterodyne detection has been proved to be a coherent detection method limited to shot-noise. We can therefore expect to reach an extremely high sensitivity in the refractive index estimation.

* Published Journal Articles *
7. A.M. Taddese et al., Opt. Express 31 9034-9051 (2023)
6. N. Verrier et al., J. Microsc. 289 pp 128-133 (2023)
5. R. Abbessi et al., J. Microsc. 288 pp 193-206 (2022)
4. J.-B. Courbot et al., IEEE Signal Process. Lett. pp 2702-2706 (2023)
3. A.M. Taddese et al., Appl. Opt. 60 pp 7745-7753 (2021) doi.org/10.1364/AO.435721
2. A.M. Taddese et al., Appl. Opt. 60 pp 1694-1704 (2021) doi.org/10.1364/AO.417061
1. J.-B. Courbot et al., Inverse Problems 37 025002 (2021) doi.org/10.1088/1361-6420/abd29c

* Oral Presentations *
16. N. Verrier et al. Focus on Microscopy 2023 :
15. N. Verrier et al. , Journées d’imagerie optique non conventionnelle (GdR ISIS) 2023
14. N. Verrier et al., HoloPhi6 2022
13. R. Abbessi et al. HoloPi6 2022
12. A.M. Taddese et al., Focus on Microscopy 2022 :
11. R. Abbessi et al., Focus on Microscopy 2022 :
10. A.M. Taddese et al., Journées Optique SFO 2022
9. R. Abbessi et al., SPIE Photonics Europe 2022 :
8. N. Verrier et al. ISOT 2021
7. S. Laroche et al., Journées Optique SFO 2021
6. A.M. Taddese et al., Journées Optique SFO 2021
5. A.M. Taddese et al. Focus on Microscopy 2021 : www.focusonmicroscopy.org/2021/PDF/1042_Taddese.pdf
4. S. Laroche et al., Journées d’imagerie optique non conventionnelle (GdR ISIS) 2021
3. A.M. Taddese et al., Journées d’imagerie optique non conventionnelle (GdR ISIS) 2021
2. N. Verrier et al., SPIE Photonics Europe 2020 : doi.org/10.1117/12.2559200
1. A.M. Taddese et al., Journées d’imagerie optique non conventionnelle (GdR ISIS) 2020

High-resolution microscopy techniques are one of the fundamental tools in biomedical imaging studies.
"Nobelized" work of Bertzig and Hell in PALM/STED/STORM have paved the way to high-resolution microscopy (down to 50 nm).
However, these methods need the addition of a fluorescent dye to operate, which can be a limiting factor when in-vivo imaging is considered.
Recently, the development of interferometric methods like tomographic diffractive microscopy has shown that it was possible to exact a 3D structural information without using contrast agent. Moreover, using heterodyne interferometry makes it possible to obtain a dynamic information about the sample (2D Doppler effect) and thus discriminating static from dynamic structures.

We here propose to couple both techniques in a new imaging device aiming at imaging, without contrast agent, cellular dynamics (3D Doppler effect). In order to cope with the acquisition time issue, stress will be put to both experimental improvement (use of high-speed cameras and illumination scanning device), and numerical aspects (improvement of the reconstruction algorithms so as to limit the amount of acquired images for full resolution characterization).

At the end of THTTM project, it will be possible to perform 3D + Doppler contrast imaging, without contrast agent, and on moving object with a frame rate around 10 Hz. We hope these developments will be insightful for living sample characterization.

Project coordination

Nicolas Verrier (Institut de Recherche en Informatique Mathématiques Automatique Signal (IRIMAS) - EA 7499)

The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.


IRIMAS Institut de Recherche en Informatique Mathématiques Automatique Signal (IRIMAS) - EA 7499
LP2N Laboratoire Photonique, Numérique, Nanosciences

Help of the ANR 260,712 euros
Beginning and duration of the scientific project: December 2019 - 48 Months

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