PhD in Biomedical Photoacoustic sensing: Quantifying the nanoscale “hotspot” effect of photothermal nanoagents (M/F)

Job Description

Thesis Subject

Photothermal therapeutic nanoagents aim at converting optical energy into heat to induce hyperthermia and a stress response in targeted biological tissues. From an external optical excitation, the energy is absorbed by the nanoagents, transformed into heat and then transferred to the surrounding medium. At the macroscopic scale, a continuous laser excitation of a collection of nanoagents leads to a global heating until a steady state is reached. However, this macroscopic point-of-view ignores the nanoscale spatial heterogeneity of the temperature distribution while strong thermal gradients could induce localized therapeutic effects. This nanometric hyperthermia, also named “hotspot” effect, could be more precise (Nicolas-Boluda et al., 2021) and would require less particles than a macroscopic hyperthermia. However, while the hotspot effect starts to focus attention, its experimental quantification without any modification of the nanoagent (luminescence reporter or destructive method) is currently an unmet need to characterize the efficiency of promising nanoagents.
The objective of this doctoral project is to develop an innovative method for sensing and quantifying the hotspot effect in aqueous suspensions of optically absorbing nanoagents, without any chemical modification of the nanoagents, prior (temperature reporter) or during the measurement (degradation). We make the hypothesis that quantitative photoacoustics operating at mesoscopic scale (several μL of solution) can measure the steady-state temperature gradient in a nanoscale shell around the nanoagents when the nanoagent suspension is concurrently heated with an additional external stimulus.
Photoacoustic sensing (introductory video: https://youtu.be/2f3V0DQNLYg ) is based on a transformation of absorbed optical energy into ultrasound waves, when a transient optical excitation is used. The optical energy transformed into heat induces a transient pressure increase in the nanoscale layer surrounding each nanoagent. Recently, we demonstrated that the macroscopic light-to-heat conversion efficiency of photothermal nanoagents can be precisely measured with quantitative photoacoustic spectroscopy (Lucas et al., 2023). For this purpose, we determined the photoacoustic coefficient of nanoparticle suspensions with a home-build photoacoustic spectrometer (Lucas et al., 2022). To characterize the nanoscale temperature distribution, we propose to combine the pulsed excitation of photoacoustic imaging with a continuous heating of the nanoagents in suspension, and to benefit from the nanometric sensing length of the photoacoustic pulse. This novel nanothermometry method is expected to pave the way for a systematic evaluation of photothermal particles regarding their capacity to induce efficient nanoscale heating.
The doctoral project is part of a collaborative research project funded by the ANR in 2025. Our partner, laboratory PHENIX (Sorbonne Université, Inorganic Colloids groupt) will design and elaborate several nanoagents (Benassai et al., 2024) to strongly modulate the hotspot effect at the nanoscale. The doctoral project aims at (1) developing the instrument and the methods to quantify the hotspot effect, (2) performing an experimental and parametric investigation of the hotspot quantification with the nanoagent size and the optical fluence for instance, and (3) numerically modeling the hotspot measurement with the photoacoustic method to link the mesoscopic measurement with nanometric temperature levels and gradients.
The indicative timetable for this doctoral project is:
0 to 12 months: Experimental development of the photoacoustic instrument and automated acquisition sequences. Development the analysis method and algorithm.
12 to 24 months: Photothermal, photoacoustic and hotspot characterization of several nanoagents with a significantly different hotspot effect. Parametric study in different experimental conditions to modulate the hotspot effect and its quantification.
24 to 36 months: Modeling both the photoacoustic signal generation by a heated nanoagent and the experimental method using the experimental parametric study. Validation of the hotspot efficiency of tested nanoagents in cell culture (in collaboration with PHENIX)

Bibliography
Benassai, E., Hortelao, A.C., Aygun, E., Alpman, A., Wilhelm, C., Saritas, E.U., Abou-Hassan, A., 2024. High-throughput large scale microfluidic assembly of iron oxide nanoflowers@PS- b -PAA polymeric micelles as multimodal nanoplatforms for photothermia and magnetic imaging. Nanoscale Adv. 6, 126–135. https://doi.org/10.1039/D3NA00700F
Lucas, T., Linger, C., Naillon, T., Hashemkhani, M., Abiven, L., Viana, B., Chaneac, C., Laurent, G., Bazzi, R., Roux, S., Becharef, S., Avveduto, G., Gazeau, F., Gateau, J., 2023. Quantitative, precise and multi-wavelength evaluation of the light-to-heat conversion efficiency for nanoparticular photothermal agents with calibrated photoacoustic spectroscopy. Nanoscale 15, 17085–17096. https://doi.org/10.1039/D3NR03727D
Lucas, T., Sarkar, M., Atlas, Y., Linger, C., Renault, G., Gazeau, F., Gateau, J., 2022. Calibrated Photoacoustic Spectrometer Based on a Conventional Imaging System for In Vitro Characterization of Contrast Agents. Sensors 22, 6543. https://doi.org/10.3390/s22176543
Nicolas-Boluda, A., Yang, Z., Guilbert, T., Fouassier, L., Carn, F., Gazeau, F., Pileni, M.P., 2021. Self-Assemblies of Fe3O4 Nanocrystals: Toward Nanoscale Precision of Photothermal Effects in the Tumor Microenvironment. Advanced Functional Materials 31, 2006824. https://doi.org/10.1002/adfm.202006824

Profile and skills expected:
- Master 2 (or equivalent) with knowledge of wave physics, instrumentation and a taste for multiphysics
- Strong interest in experimental techniques and analysis of experimental data
- Skills in programming and signal and image processing
- Taste for interdisciplinary environment: physics, chemistry and biology
- Good interpersonal skills (enthusiasm for research), able to work independently as well as in a team, taking initiatives
- Good command of English (involving good communication skills)


To apply, please send:
• A resume
• A cover letter
• A copy of the transcripts of Master 1, Master 2 and / or School of Engineering
• A description of previous work (max. 3 pages)
• Letters of recommendations, if any

Your Work Environment

The doctoral student will be appointed by Sorbonne University. This doctoral project is funded by the ANR project Hotspot 2025, which is a collaborative project between two research teams working in biomedical photoacoustic imaging (Team: Medicine and ultrasound, Laboratoire d'imagerie Biomedical, LIB , https://www.lib.upmc.fr/) and nanoparticle engineering ( PHENIX Laboratory https://phenix.cnrs.fr/). The LIB is located in the Centre de Recherche des Cordeliers (CRC, Paris). The laboratory has a strong expertise in the development of ultrasound-based imaging modalities, such as pulse-echo ultrasound imaging and photoacoustic imaging. The project will benefit from state-of-the-art equipment (tunable nanosecond laser, programmable research ultrasound machine) and from the experience gained in previous implementations of quantitative photoacoustic spectroscopy with this equipment.

Compensation and benefits

Compensation

2300 € gross monthly

Annual leave and RTT

44 jours

Remote Working practice and compensation

Pratique et indemnisation du TT

Transport

Prise en charge à 75% du coût et forfait mobilité durable jusqu’à 300€

About the offer

About the CNRS

The CNRS is a major player in fundamental research on a global scale. The CNRS is the only French organization active in all scientific fields. Its unique position as a multi-specialist allows it to bring together different disciplines to address the most important challenges of the contemporary world, in connection with the actors of change.

CNRS

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