Description of Ph.D. project in EXSS for Oct 2021 Entry Project title: Quantum Cascade Laser s-SNOM for intracellular imaging Principal Prof Chris Phillips Project No: CCP_1 Supervisor: Email: [email protected] Telephone x47575 Other Dr Holger Auner, Prof Alexandra Porter, Prof Charles Coombes. supervisors: Aims of the project: Very recently we gave found out how to use a Solid- State near field imaging technique, so- called s-SNOM, to look inside cells for the first time. It beats the diffraction limits of ordinary microscopy by a factor of ~3000, and the spatial resolution it gives (~3nm) already rivals the very best of electron microscopy at a fraction of the time effort and cost. We believe it has the potential to transform the biomedical sciences. We have shown how it can image the organelles inside a cell optically for the first time first time ever. Also , because it works at mid-IR wavelengths where chemical bonds have characteristic vibrational absorption bands that give them spectral “fingerprints” , the technique can be used to provide nanoscal chemical maps that, e.g. reveal where drugs bind inside the cell. The initial aims of the project will be to trail and develop the technology with Imperial cinicians, with a focus on themes, (1) the pathology pf Breast Cancer, (2) Drug resistance in multiple myeloma, and (3) the nanoscale causes of osteporosis. However, the potential applications are limitless and we will likely establish more collaborations as the programme progresses. Also Recent developments in the field of quantum imaging have demonstrated new methods of imaging objects by detecting photons that have not actually interacted with it. In collaboration with colleagues in the optics groups we plan to investigate extending the wavelength of this technique into the mid-IR. There will also be collaboration with the team developing the diffraction-limited “Digistain” imager for Cancer diagnosis. Techniques, activities, and equipment used: The s-SNOM signal is small (1 in 10^7) so we will have to use a challenging interferometric phase-sensitive heterodyning method to detect it. This requires ultra-stable operation from the QCL's; difficult to achieve whilst maintaining the wide tunability that is required to do the chemical spectroscopy. Mechanical vibrations will have to be excluded throughout the equipment, at the sub-nanometre level. Ethical issues associated with studying Human tissue will have to be navigated, and the whole project relies on being able to work together and effectively with clinically trained personnel. This is a technically challenging project, but with a potentially very high scientific payoff. Locations of equipment / collaborators Level 9 Blackett; Hammersmith and Charing Cross Hospitals. Description of Ph.D. project in EXSS for Oct 2021 Entry Project title: Mid-IR imaging for Biomedical Applications Principal Prof Chris Phillips Project No: CCP_2 Supervisor: Email: [email protected] Telephone x47575 Other Prof Charles Coombs, Prof Chris Bakal supervisors: Aims of the project: Mid-IR imaging has proven to be capable of detecting the chemical changes in human tissue biopsies that accompany the onset of cancer. This project will build on this discovery in 3 directions 1) Further refinement and clinical evaluation of a diffraction limited “Digistain” prototype tissue imager. 2) Development of near-field imaging techniques for cancer pathology. Very recently we gave found out how to use a Solid- State near field imaging technique, so-called s-SNOM to look inside cells for the first time. It beats the diffraction limits of ordinary microscopy by a factor of ~3000, and the spatial resolution it gives (~3nm) already rivals the very best of electron microscopy at a fraction of the time effort and cost. We believe it has the potential to transform the biomedical sciences. We have shown how it can image the organelles inside a cell optically for the first time first time ever. The initial aims of the project will be to trail and develop the technology with Imperial clinicians, with a focus on the pathology of Breast Cancer, and mapping out the proteosome in Myeloma cancer cells. Techniques, activities, and equipment used The digistan imager will need trailing and evaluating for high-frequency low drift amage acquisition, with improved optical throughput and thermal drift.The s-SNOM signal is small (1 in 10^7) so we will have to use a challenging interferometric phase-sensitive heterodyning method to detect it. This requires ultra-stable operation from the QCL's; difficult to achieve whilst maintaining the wide tunability that is required to do the chemical spectroscopy. Locations of equipment / collaborators Level 9 Blackett; Hammersmith and Charing Cross Hospitals. Description of Ph.D. project in EXSS for Oct 2021 Entry Project title: Better mobilities through better theories Principal Jarvist Moore Frost Project No: JMF_1 Supervisor: Email: [email protected] Telephone x41167 Other Collaborators: J. Skelton (University of Manchester) supervisors: Aims of the project: Humanity could really do with some new energy materials. If these are to be more efficient than what we have already, they are likely to be more complex; if they are to be cheaper, then they are likely to be more disordered. Solid-state theory, mostly dating from the 1950s and 1960s, is really best at predicting the behaviour of perfect infinite crystals at zero temperature. So let's make some better theories! Semiconductors are required for a number of applications: they often form one of the electrodes of a battery, they are used as the active material in solar cells, LEDs and solid-state lasers, low-thermal conductivity semiconductors can be used as thermoelectrics to generate electricity from temperature difference. A key (and highly technologically relevant) character of a semiconductor is the charge-carrier mobility. Generally you want this mobility to be as high as possible, and there are mobility thresholds for using a semiconductor in certain devices (e.g. a solid-state laser needs a higher mobility than that required by a solar cell). Charge carrier mobility is a phenomenological quantity, it is a product of a competition between processes with the semiconductor. It is not a direct ground state property of the material, and is strongly temperature dependent. Most theories of semiconductor charge carrier mobility have an empirical parameter (often an effective scattering time, in a Drude like model of mobility). This means that while relative mobility can be predicted within one material class, absolute predictions of mobility are lacking. The situation is not entirely hopeless though. As electronic structure techniques are getting more sophisticated, it is possible to calculate more subtle aspects of a material, such as the electron phonon coupling (This electron-phonon coupling is between the nuclear and electronic degrees of freedom, which is adiabatically separated and ignored once you apply the Born-Oppenheimer approximation.) Recently we implemented a 1960s theory of polaron mobility[1,2], in a modern (2017) computer code [3], written in the Julia programming language. These codes can be combined with electron-phonon coupling and effective-mass parameters for real materials calculated with standard electronic structure methods and packages (typically using the density functional theory) to predict the polaron character, and polaron response functions, of technologically relevant semiconductors. There are a number of different avenues to explore, depending on the interests of the student, and the existence of new experimental data to explain. The model polaron Lagrangian could be extended (while retaining analytic solution) to attempt to increase the accuracy of the approximation, perhaps by extending the Gaussian form to a set of correlated Gaussian processes. The effective Lagrangian could be extended to provide greater material specific detail. Diagrammatic Monte-Carlo can provide direct evaluation of the effective Lagrangian, and a code for this could be written to compare to the Feynman variational results. Further response functions of the polaron variation state could be computed, which enable comparison to experimental observables. For instance, the optical absorption of the polaron state could be compared to transient absorption measurements on these materials; the frequency dependent mobility could be calculated and compared to Terahertz and microwave conductivity measurements.There are theoretical models built on a compatible path integral basis to describe disorder that exists in non-crystalline systems, but so far these have not been interfaced to polaron mobility theories. As well as immediate method development, there is a large scope to apply these codes to material groups and classes. This requires the characterisation of materials, either by recourse to the material databases of synthetic data derived from electronic structure calculations, such as the Materials Project [4], and through the use of standard electronic structure packages such as VASP and Gaussian.The central aim is to develop methods which can offer fully predictive temperature-dependent mobilities for a wide variety of systems of technical interest, and thereby offer design clues for, and methods to computationally screen, new materials. Though this project is envisaged as theoretical and computational, it will require a deep familiarisation and contact with experimental methods, material specific properties,