Development of photo-printed interferometric biosensors on multi-core optical fibers for molecular diagnostics
Optical fibers are minimally invasive devices commonly used in medicine for in vivo tissue imaging by endoscopy. However, at present, they only provide images and no molecular information about the tissues observed. The proposed thesis is part of a project aimed at giving optical fibers the ability to perform molecular recognition in order to develop innovative biosensors capable of performing real-time, remote, in situ, and multiplexed molecular analysis. Such a tool could lead to significant advances in the medical field, particularly in the study of brain pathologies, where knowledge of the tumor environment, which is difficult to access using conventional biopsies, is essential.
The proposed approach is based on 2-photon polymerization printing of interferometric structures at the end of each core of a multifiber assembly. The detection principle is based on the interference occurring in these structures and their modification by the adsorption of biological molecules. Each fiber in the assembly will act as an individual sensor, and measuring the intensity of the light reflected at the functionalized end will provide information about the biological interactions occurring on that surface. By modeling the interference phenomenon, we determined parameters to optimize the shape and sensitivity of interferometric structures (PTC InSiBio 2024-2025). These results enabled the printing and characterization of the sensitivity of interferometric structures on single-core fibers. The objectives of the thesis are to continue this optical characterization on new samples and to develop original photochemical functionalization methods in order to graft several biological probes onto the surface of the fiber assemblies. This multi-functionalization will enable multiplexed detection, which is essential for future medical applications. Depending on the progress of the thesis, the biosensors will be validated through the detection of biological targets in increasingly complex environments, up to and including a brain tissue model.
Modeling of a magnonic diode based on spin-wave non-reciprocity in nanowires and nanotubes
This PhD project focuses on the emerging phenomenon of spin wave non-reciprocity in cylindrical magnetic wires, from their fundamental properties, to their exploitation towards realizing magnonic diode based devices. Preliminary experiments conducted in our laboratory SPINTEC on cylindrical wires, with axial magnetization in the core and azimuthal magnetization on the wire surface, revealed a giant non-symmetrical effect (non-symmetrical dispersion curves with different speeds and periods for left- and right-propagating waves), up to an extent of creating a band gap for a given direction of motion, related to the circulation of magnetization (right or left). This particular situation has not been yet described theoretically or modeled, which sets an unexplored and promising ground for this PhD project. To model spin-wave propagation and derive dispersion curves for a given material we plan to use different numerical tools: our in-home 3D finite element micromagnetic software feeLLGood and open source 2D TetraX package dedicated to eigen modes spectra calculations. This work will be conducted in tight collaboration with experimentalists, with a view both to explain experimental results and to guide further experiments and research directions.
Chemical biology approaches to rare earth toxicology in Humans
Recent technological developments have expanded and intensified the use of lanthanides in domains as diverse as renewable energy, computing, and medicine. Increasing usage of these metals raises the question of their impact on the environment and human health. However, the potential toxicity of these metal ions, and its underlying molecular mechanisms, are still little known and rarely investigated in human cell models. The goal of the PhD will be to investigate the human cells response to exposure to Ln ions, and to systematically identify the proteins involved in this response, using a set of chemical and biological tools. In particular, we want to address the following questions: which protein networks are activated or deactivated following Ln exposure? Do Ln ions affect phosphorylation of proteins? Which proteins are directly interacting with Ln ions? will thus decipher what are the key biological interactors of lanthanides, their roles in living systems and the features that enable efficient binding to metals. We expect that our findings will give insights into the toxicology of those elements and inform environmental and occupational safety policies. On the longer term, new bio-inspired strategies for their extraction, recycling, decorporation and remediation will arise from the molecular understanding of metal-life interactions, enabling a well thought-out usage of these elements to support the environmental and numerical transitions.s
Ultra-fast pathogenic bacteria detection in human blood
This project aims to develop a versatile and easy-to-use surface plasmon resonance imaging (SPRi) instrument for the rapid and broad-spectrum detection of low concentrations of pathogenic bacteria in complex samples, particularly blood. SPRi is a label-free technique that allows real-time probing of a sample (regardless of its optical transparency). Due to the high sensitivity of the plasmon phenomenon, the dynamic range of measurable index variation is limited by SPRi detection when reading is performed at a fixed angle, as is the case in commercially available devices. This reduces the use of such optical instruments to the study of environments whose index remains relatively stable during the experiment and whose molecular probes have molecular weights comparable to the targets (monitoring of bimolecular interactions).
This considerably limits the detection of growing bacteria in complex environments. Our laboratory has developed original solutions for the detection of very low levels of contamination in food matrices (creation of a start-up in 2012), but SPRi is unsuitable for the detection of bacteria in blood, partly due to the very high intrinsic variability of this matrix.
These limitations will be overcome by integrating five complementary components:
1. The design of an instrument optimized for real-time recording of SPR images over a defined range of illumination angles;
2. The development of dedicated SPR data analysis and processing to extract the most relevant information for each probe from the images in real time;
3. The functionalization of biochips through a combination of appropriate probes (series of peptides such as antimicrobial peptides (AMPs), antibodies, and even bacteriophages) to optimize the number of possible identifications with a reduced set of probes;
4. The learning of specific “4D-SPRi signatures” of model strains in blood matrices;
5. Validation of the performance of the new “4D-SPRi” instrument as a tool for detecting and characterizing bacteria from hospital strains compared to reference techniques.