Optical microresonators for next generation biophotonics
Lead Research Organisation:
University of St Andrews
Department Name: Physics and Astronomy
Abstract
In this postgraduate project optically stable, small resonators for the investigation of biological processes in living cells will be developed.
In the beginning of this project, there will be an introduction to cell biology and training on cell culture techniques, so that the student can broaden her knowledge on biology and familiarize herself with biological concepts. Apart from this, great emphasis will be given to the development of experimental physics skills. Initially the student will work on two research projects developed in the group, with the aim to use the basics of these projects to combine them into a novel optical technique, during her postgraduate studies.
Optical resonators are essential for the generation of laser light and the laser spectra change significantly when small changes happen in the medium with which the laser light interacts. By implementing micro-lasers into living cells, we can study in detail the different processes that cells undergo. Small changes in the cell or different types of cells, emit a different and unique laser light, which provides information about the cell and provides an opportunity for cell tracking.
Another aspect that will be studied during this PhD project is the mechanism that the cells exert force, in particular measuring cell forces and understand the mechanism behind them. Cell forces play a very important role for cell motility, proliferation, apoptosis as well as in certain types of cancer. The weak nature of these forces makes the measurement particularly challenging. In the very first months of this project, force measurement will be taken using a stress microscopy technique, based on an elastic resonator, which has already been developed in our group. In that way, the PhD student will get familiar with our novel optical technique and study photonics, biology and physics even further.
During the postgraduate studies, and after the student has acquired all the necessary knowledge and skills from our research projects, she will attempt to create a deformable optical resonator for cell force measurements. The light emitted from the resonators will be analysed to take useful information about the cells investigated. In addition, except cells, measurements can be taken in a living organism such as in the Drosophila larvae, with the aim to understand the behaviour of cells during the transition of this organism from larvae into an adult fly. The challenges are many, from fabricating these optical resonators to introducing them into the cell assay and taking a light signal, making this PhD project quite demanding as well as interesting. Quantitative measurement and explanation of biological processes will be attempted and at the same time, the student will develop skills from various fields, given the multidisciplinary character of this project.
Training will be provided by researchers in the group, in the beginning of the PhD studies. Also, the first 2 years, the student should take a few courses related to the project. These courses are provided by the Scottish Universities Physics Alliance (SUPA) and the ones chosen are:
1. Biophotonics (semester 1)
2. Problem solving skills for physicists (semester 1)
3. Ultrafast photonics (semester 2)
Keywords: optical resonators, elastic resonator, living cells
In the beginning of this project, there will be an introduction to cell biology and training on cell culture techniques, so that the student can broaden her knowledge on biology and familiarize herself with biological concepts. Apart from this, great emphasis will be given to the development of experimental physics skills. Initially the student will work on two research projects developed in the group, with the aim to use the basics of these projects to combine them into a novel optical technique, during her postgraduate studies.
Optical resonators are essential for the generation of laser light and the laser spectra change significantly when small changes happen in the medium with which the laser light interacts. By implementing micro-lasers into living cells, we can study in detail the different processes that cells undergo. Small changes in the cell or different types of cells, emit a different and unique laser light, which provides information about the cell and provides an opportunity for cell tracking.
Another aspect that will be studied during this PhD project is the mechanism that the cells exert force, in particular measuring cell forces and understand the mechanism behind them. Cell forces play a very important role for cell motility, proliferation, apoptosis as well as in certain types of cancer. The weak nature of these forces makes the measurement particularly challenging. In the very first months of this project, force measurement will be taken using a stress microscopy technique, based on an elastic resonator, which has already been developed in our group. In that way, the PhD student will get familiar with our novel optical technique and study photonics, biology and physics even further.
During the postgraduate studies, and after the student has acquired all the necessary knowledge and skills from our research projects, she will attempt to create a deformable optical resonator for cell force measurements. The light emitted from the resonators will be analysed to take useful information about the cells investigated. In addition, except cells, measurements can be taken in a living organism such as in the Drosophila larvae, with the aim to understand the behaviour of cells during the transition of this organism from larvae into an adult fly. The challenges are many, from fabricating these optical resonators to introducing them into the cell assay and taking a light signal, making this PhD project quite demanding as well as interesting. Quantitative measurement and explanation of biological processes will be attempted and at the same time, the student will develop skills from various fields, given the multidisciplinary character of this project.
Training will be provided by researchers in the group, in the beginning of the PhD studies. Also, the first 2 years, the student should take a few courses related to the project. These courses are provided by the Scottish Universities Physics Alliance (SUPA) and the ones chosen are:
1. Biophotonics (semester 1)
2. Problem solving skills for physicists (semester 1)
3. Ultrafast photonics (semester 2)
Keywords: optical resonators, elastic resonator, living cells
Organisations
People |
ORCID iD |
| Malte Gather (Primary Supervisor) | |
| Eleni Dalaka (Student) |
Studentship Projects
| Project Reference | Relationship | Related To | Start | End | Student Name |
|---|---|---|---|---|---|
| EP/N509759/1 | 01/10/2016 | 30/09/2021 | |||
| 1795537 | Studentship | EP/N509759/1 | 01/07/2016 | 31/12/2019 | Eleni Dalaka |
| Description | My research focuses on cancer mechanobiology and the study of optical techniques that can be used to measure/image cellular forces. I used Elastic Resonator Interference Stress Microscopy (ERISM), a novel technique developed in our group based on light interference, to measure the forces exerted by small, subcellular protrusions. These protrusions are called invadopodia, have a diameter of 1-2 µm and facilitate cancer invasion and metastasis. I measured invadopodial forces for the first time and I found that cancer cells are more likely to invade the neighbouring tissue when these forces are over 5pN. These cancer protrusions are highly oscillatory, with cycles of protrusions and contraction against their substrate. Studying the temporal dynamics of these forces showed that dynamic and persistent protrusions contribute and facilitate cancer invasion. I was also interested to see if a tumour (instead of individual cells) is able to form these protrusions. Therefore, I developed tumour spheroids, 3D spherical structures of cell aggregates that simulate tumour conditions. Using the same stress microscopy technique (ERISM), I imaged the formation of dynamic protrusions at the interface between tumour and substrate. The forces and the dynamics of the protrusions are similar to the ones observed at the single-cell level. Moreover, the force exertion by the tumour interface is not uniform under its surface, but it's rather localised at certain, random areas under the spheroid. The tumour forces are also dynamic and oscillatory and they increase over time. I have also imaged the mechanical behaviour of tumour spheroids and quantified the forces needed for either a single cell or many cells (collective cancer invasion) to escape the tumour. To complete the force imaging of cancer, we need to image the forces inside the 3D tumour spheroid. For this reason, I'm developing a new technique that uses deformable, optical micro-resonators as 3D force sensor. We have generated oil droplets doped with a fluorescent dye, which gives rise to lasing spectra (whispering gallery mode lasing) upon laser-light excitation. Cellular force exertion, deforms the droplets, resulting in changes in the spectra, from which the mechanical force can be calculated. I calibrate these resonators by deforming them with a known force using Atomic Force Micrscopy (AFM) and measuring the separation of the lasing peaks, due to uniaxial deformation. I found that there is a linear correlation between the amount of deformation and the exerted force. These laser droplets have been introduced in 3D tumour and benign spheroids and I have mapped the mechanical forces in the spheroid volume over the course of several hours. Moreover, I managed to functionalised the laser droplets with antibodies, targeting specific proteins in the tumour environment. Perturbation of physical forces with chemical reagents will also be performed. |
| Exploitation Route | Cancer invasion and metastasis are very complicated processes, for which very little is known. My data provide new and crucial knowledge on the physical aspect of cancer growth, invasion and metastasis. The high sensitivity of the Elastic Resonator Interference Stress Microscopy (ERISM) technique gave me the opportunity to investigate subcellular cancer protrusions, identifying for the first time how much force is needed for these small features to degrade their environment. In addition, the mechanical behaviour of tumour will shed light on their mechanical aspects and their physical interactions, providing novel routes for the development of cancer treatments that target the mechanics of cancer. The new knowledge created in this project is beneficial to both basic and applied research, as academics could use these data to complete their understanding on cancer invasion and clinicians could use the physical forces measured at different cell levels to assess the metastatic ability of cancer, giving a more precise and efficient treatment to cancer patients. Lastly, the optical 3D force sensor will create a new tool to study mechanobiology with high sensitivity, in-vivo and under natural conditions, providing valuable information on the mechanics of tissue development, wound healing, cancer etc. |
| Sectors | Healthcare,Pharmaceuticals and Medical Biotechnology |