Biomimetic Nanophotonic Sensors for Immunotherapy Evaluation

Abstract

This PhD thesis focuses on the development of innovative nanophotonic biosensors aimed at improving the evaluation of immunotherapies for cancer and infectious diseases, particularly through the use of monoclonal antibodies (mAbs). Current methods for assessing mAb interactions with immune cells or pathogens rely on labor-intensive techniques like cell culture and colorimetric assays, leading to delays in developing effective therapies and increasing costs. To address these limitations, this thesis introduces advanced nanophotonic biosensors designed to streamline and accelerate the selection and evaluation of mAbs, especially as immune checkpoint inhibitors or antiviral agents. The research emphasizes the creation of label-free, real-time biosensors capable of analyzing biomolecular and cellular interactions. These sensors, designed for point-of-care use, offer significant improvements over traditional methods. The work involves the fabrication of plasmonic nanostructures from gold and silver and dielectric nanoresonators from high-refractive-index materials like silicon. These nanostructures function as highly sensitive refractometric sensors, capable of detecting minute changes in the refractive index that occur during biomolecular interactions. A novel biofunctionalization protocol is also developed in this thesis, enabling the formation of artificial cell membranes directly on the sensor surface. Using lipid bilayers, this biomimetic approach creates a biologically relevant microenvironment on the sensors, allowing them to anchor specific ligands and receptors. By mimicking natural cellular environments, the sensors provide more reliable and biologically accurate data. This protocol enhances the sensors' ability to evaluate the therapeutic potential of mAbs and other immunotherapy candidates. Two specific applications of these biosensors are explored: first, in the screening of mAbs as potential antiviral therapies, including treatments for COVID-19. The ability to quickly assess mAb interactions with viral proteins offers critical advantages in responding to emerging infectious diseases. Second, the biosensors are used to evaluate immune checkpoint inhibitors targeting the PD-1 pathway, which is vital in cancer immunotherapy. These sensors contribute to faster and more accurate assessments of inhibitors, improving the selection process for therapeutic candidates and leading to more effective cancer treatments. Overall, this thesis represents a significant advancement in nanophotonic biosensor technology, offering faster, simpler, and more reliable methods for evaluating mAbs and other therapeutic candidates. The technological innovations in sensor design and biochemical functionalization presented here hold potential for a range of biomedical applications, including precision diagnostics and personalized medicine. By addressing key challenges in immunotherapy evaluation, these nanophotonic biosensors are poised to become essential tools in future biomedical research and therapeutic development.

Date of Award	11 Nov 2024
Original language	English
Supervisor	Laura Lechuga Gómez (Director) & María Soler Aznar (Director)