Development of three-dimensional diamond photonics platforms for neuronal research
- Autores: Beatriz Neves Leal Costa
- Directores de la Tesis: Jana Berit Nieder (dir. tes.)
- Lectura: En la Universidade de Vigo ( España ) en 2025
- Idioma: inglés
- Tribunal Calificador de la Tesis: Romana Schirhagl (presid.), Stefano Chiussi (secret.), Enrico Domenico Lemma (voc.)
- Programa de doctorado: Programa de Doctorado en Láser, Fotónica y Visión por la Universidad de A Coruña; la Universidad de Santiago de Compostela y la Universidad de Vigo
- Calificación: Sobresaliente Cum Laude
- Materias:
- Enlaces
- Tesis en acceso abierto en: Investigo
- Resumen
Technological developments in the field of 3D cell culture are revolutionizing biomedical research by offering advanced instruments for creating models that mimic tissues complex architecture and environment, while simultaneously tackling the ethical concerns associated with animal experimentation. Numerous fields of study, including neurological illnesses, cardiovascular research, and cancer research, can benefit from these 3D model applications.
However, this work focuses specifically on applications for neurological diseases, particularly neurodegenerative disorders. Since the prevalence of neurodegenerative disorders is increasing globally, it is essential to raise awareness of these conditions, as well as their treatment and prevention. Furthermore, a thorough investigation of the signaling networks underlying intricate brain functions is required.
Quantum sensing has arisen as an innovative method for measuring physical quantities like magnetic fields, temperature, and strain, offering unmatched spatial and temporal accuracy.
Among quantum sensing technologies, nitrogen-vacancy (NV) centers in fluorescent nanodiamonds (FNDs) offer distinct benefits because of their compatibility with biological systems and their responsiveness to small variations in temperature and magnetic fields.
These characteristics establish NV centers as a valuable resource for analyzing intricate biological systems.
Even with recent advancements, creating intricate models that go beyond the constraints of 2D cell cultures and traditional sensing methods is still essential. Furthermore, methods for the early identification of illnesses need to be investigated. The scientific community believes that single-cell mapping of neural activity may be crucial to these methods. Combining cutting-edge 3D cell culture methods with quantum metrology can create a more efficient platform for researching brain function and understanding the causes and progression of various diseases.
The aim of this work is to integrate quantum metrology in novel 3D cellular models.
In order to address the challenges of combining quantum sensing with bioengineered 3D systems, bioinspired 3D scaffolds capable of supporting precise quantum measurements were developed. These scaffolds are made of photosensitive materials via Two-Photon Polymerization (TPP), a process that can produce nanometric 3D structures. The structures will later be functionalized with FNDs, where the NV centers in FNDs exhibit spin-state changes that can be detected using Optically Detected Magnetic Resonance (ODMR) experiments. The analysis of the ODMR curves can potentially allow the readout of biological signals, such as local temperature gradients, magnetic field variations, and neural activity signatures.
The study begins with the development of radio frequency antennas, testing their performance through ODMR experiments, and optimizing cell culture protocols on the antennas for subsequent studies. Following this, FNDs were evaluated in 2D cultures to assess their sensing capabilities in simplified systems. This provides initial insights when 3D scaffolds or confocal ODMR are not viable options. Building upon these findings, the next stage focuses on fabricating scaffolds via TPP and integrating FND-functionalized scaffolds with embryoid bodies (EBs) to study complex cellular interactions. By bringing neurons in close proximity to the functionalized scaffolds, low biophysical signals, such as neural activity, have an increased probability of being recorded. These scaffolds are tailored to expand the understanding of neurodegenerative diseases such as Parkinson s disease (PD), where early diagnosis and treatment options remain limited.
Our findings reveal that this innovative approach challenges the limitations of traditional 2D cultures and provides a promising platform for broader studies beyond neuronal research.
The results indicate the feasibility of developing FND-functionalized scaffolds that may enable detailed insights into neuronal biophysical properties. Applying these platforms to 3D organoids opens new possibilities for studying disease mechanisms and identifying biomarkers for early diagnosis, particularly significant for PD.
In conclusion, the study showcased here may aid in early diagnostic platform creation or customized treatment developments. Although research on neurons and neurodegenerative diseases has received extensive attention, these 3D models can be extended to a wide range of sectors, and measuring biological temperature variations has many potential uses. Quantum metrology and 3D scaffolding together hold great potential for advancements in medical science.
