Quantitative Matrix Microscopy: Non-Invasive Imaging of Oocytes and Embryos (M/F)

Job Description

Thesis Subject

Infertility affects one in six couples worldwide, and the use of Assisted Reproductive Technologies (ART) keeps increasing, with over four million cycles performed annually. Yet, success rates remain low, as only one in four transferred embryos leads to a live birth. Current methods for assessing oocyte and embryo quality rely on subjective 2D morphological evaluation, which has limited predictive power. There is therefore a strong need for non-invasive, objective, and quantitative tools to assess embryonic competence.

The thesis will build on a label-free, real-time 3D imaging technology developed at the Langevin Institute [1,2] and now being transferred by the deeptech start-up OWLO [3]. Based on ultra-fast measurement of the optical reflection matrix, this approach combines advanced algorithms that correct optical aberrations and multiple scattering, enabling the acquisition of high-resolution, deeply penetrating 3D images of biological samples.

The goal of this PhD thesis is to show that matrix imaging can go beyond a simple image of the sample reflectivity and can pave a route towards a quantitative optical imaging of oocytes and embryos.
(i) The high frame rate of OWLO technology allows us to capture the temporal variations of reflectivity. These rapid fluctuations generally rely on active transport within the cell's cytoplasm, in particular mitochondrial transport [4,5]. Our hypothesis is that the dynamics contrast will be an extremely valuable tool to monitor the lipids and organelles motion at the different steps of the oocyte maturation and to yield a better contrast for cell and nuclei counting at different stages of embryonic development.
(ii) Our ability to probe the dynamics at work in the sample will also allow us to monitor the propagation of elastic waves[6] in oocytes and embryos. Our interferometric set up actually provides a strong phase sensitivity to the axial displacement of the sample. By monitoring the deformations throughout the oocyte/embryo volume, we will be able to measure their visco-elastic properties[7}. The biomechanical properties of oocytes and embryos undergo a dynamic, characteristic transformation from oocyte maturation[8] through zygotic stage and then blastocyst formation[9]. A biomechanical assessment of oocytes and embryos is therefore crucial to predict their developmental potential.
(iii) While sample-induced aberrations are generally seen as a barrier for conventional microscopy, they can actually be exploited to map the refractive index inside the biological specimen. A recent experimental work in ultrasound[10] and a theoretical study in the context of optical microscopy[11] have paved the route towards this ambitious aim using the matrix imaging framework. The objective in QUANTIFY will be to use these tools to go beyond a simple reflectivity image and get a complementary image of the refractive index distribution inside oocyte and embryo.
(iv) While multiple scattering is generally seen as a nightmare for imaging, it can also be used for characterization purposes. Once again, a recent ultrasound study [12] has shown how the evolution of the multiple scattering contribution with depth can provide a measurement of the scattering mean free path, the typical distance between two successive scattering events. This physical parameter is potentially a relevant bio-marker of the lipid concentration, an indicator of the oocyte maturation state and embryo quality [13].

The goal of this PhD thesis is therefore to take a decisive step forward: to move from qualitative imaging to quantitative, noninvasive characterization of live oocytes and embryos.

Your Work Environment

The position is based at the Institut Langevin laboratory (https://www.institut-langevin.espci.fr/home). This is a full-time position. The thesis is funded through the ANR QUANTIFY project, which focuses on quantitative optical imaging of oocytes and embryos.

Constraints and risks

N/A

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.

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