Resonant and shaped photonics for understanding the physical and biomedical world

Lead Research Organisation: University of St Andrews
Department Name: Physics and Astronomy

Abstract

Light has been used for centuries to image the world around us, and continues to provide profound insights across physics, chemistry, biology, materials science and medicine. However, what are the limits of light as a measurement tool? For example, we can use light to image single bacteria, but can we also use light to trap a single bacterium, identify the bacterial strain and assess its susceptibility to antibiotics? How can we image over multiple length scales, from single cells to multiple cellular tissue, in order to comprehensively map all the neuronal connections in the brain? Can we use a combination of resonance with the wave nature and momentum of light to measure the forces associated with the natural and stimulated motion of a single neuronal cell, or even the extremely small forces associated with phenomena at the classical-quantum interface?

This proposal aims to answer these questions by exploring new and innovative ways in which we can use light to measure the natural world. This research builds on our recent advances in photonics - the science of generating, controlling and detecting light - and in particular will exploit resonant structures and shaped light. These provide us with tools for controlling the interaction of light and matter with exquisite sensitivity and accuracy. We will run three research strands in parallel and by combining their outputs, we aim to address major Global Challenges in antimicrobial resistance, neurodegenerative disease, multimodal functional imaging and next generation force, torque and microrheology.

Our work is supported by a suite of UK and International project partners (both academic and industry) who are enthused to work with us and have committed over £0.5M in kind to the programme.

Planned Impact

The impact of Photonics is felt across many disciplines - physics, chemistry, information technology, as well as the biological and medical sciences. The inter-disciplinarity of our innovations is reflected in the wide range of potential future applications, industries and stakeholders that will benefit from our research. We anticipate particular impact within healthcare and associated industries; the key biomedical issues of neurodegenerative disease and antimicrobial resistance, present major challenges to patients and healthcare providers around the world. We anticipate other areas of impact beyond healthcare, such as in situ monitoring of environmental contamination and water quality, rapid screening of bacteria for the production of high value chemicals, the detection of infectious agents for defence and security and on a fundamental level exquisite force sensing at the quantum-classical interface.

Potential stakeholders include:
1) Healthcare providers (including NHS) and patients; Department of Health; Home Office; Ministry of Defense; Environment Agency/DEFRA.
2) Business/industry including Medical Devices manufacturers; Diagnostics companies; Pharmaceutical/Biotech companies; Research equipment manufacturers; suppliers of optical and photonic systems and components.

A number of mechanisms have been put in place to engage with potential stakeholders throughout the course of the project and beyond. These include:

Healthcare impact: We will regularly review progress and consider which technology may offer opportunities for translation. We will be supported in this through our strong clinical links (Medical School of Ninewells Hospital, Institute of Medical Science and Technology, Dundee, and the York Hospital NHS Trust) who will provide advice on technology development, clinical samples and access to their laboratories. We also have direct input from the Wellman Centre for Photomedicine at Mass General Hospital, USA; Albert Einstein College of Medicine, USA; Max-Planck Institute for the Science of Light, Germany. We will participate in UK healthcare meetings to ensure that a wider range of researchers are aware of our research. These activities will lead to contacts with whom we could work to take forward new diagnostics or treatments arising from our research.

Intellectual property: There is a significant prospect of intellectual property arising from this proposal. The investigators have a strong track record of patenting their research. Protection and exploitation of intellectual property arising from the project will be supported by the University of St Andrews and Research & Innovation Services at York. The input from project partners IP Group, M Squared Lasers, Phillips and Almac will also be invaluable, as between them they have a wide IP portfolio including the Healthcare technology space and will be able to advise on the most promising opportunities.

Commercialisation strategy: Our research is relevant to a wide range of companies. We will use our contacts in these companies to bring relevant developments to their attention. Workshops in years 3 and 5 will be used to disseminate our research to an audience (50-80 attendees) that represents the full range of beneficiaries, i.e. researchers across the physical and life sciences, from both academia and industry. The input from project partners will be invaluable and will support us throughout the Programme, providing commercialisation advice and market intelligence. Their support includes direct investment, commercial and technical due diligence, market research, customer engagement, business plan development and investment proposition, and ultimately facilitation of the spin out process and subsequent business building.
 
Description We have developed new methods for imaging at depth, new methods for measuring forces cells exert and methods for monitoring cell secretion.
Exploitation Route This is too early to say
Sectors Electronics,Healthcare,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology

 
Description Work on TRAFIX method for multiphoton imaging has been filed as patent and we are exploring setting up a spin-off company. We have secured funds from Scottish Enterprise for a High Growth Spin Off Programme to look at commercialisation
Sector Electronics,Manufacturing, including Industrial Biotechology
Impact Types Societal

 
Title "Is Laser Repetition Rate Important for Two-Photon Light Sheet Microscopy?" (dataset) 
Description  
Type Of Material Database/Collection of data 
Year Produced 2020 
Provided To Others? Yes  
URL https://risweb.st-andrews.ac.uk:443/portal/en/datasets/is-laser-repetition-rate-important-for-twopho...
 
Title Data Underpinning: Deep learning enabled laser speckle wavemeter with a high dynamic range 
Description  
Type Of Material Database/Collection of data 
Year Produced 2019 
Provided To Others? Yes  
URL https://risweb.st-andrews.ac.uk:443/portal/en/datasets/data-underpinning-deep-learning-enabled-laser...
 
Title Data set: Optical binding of two cooled micro-gyroscopes levitated in vacuum 
Description  
Type Of Material Database/Collection of data 
Year Produced 2018 
Provided To Others? Yes  
 
Title Data set: Optical trapping of ultrasmooth gold nanoparticles in liquid and air 
Description  
Type Of Material Database/Collection of data 
Year Produced 2018 
Provided To Others? Yes  
 
Title Data underpinning " Through-Bottle Whisky Sensing and Classification using Raman Spectroscopy in an Axicon-Based Backscattering Configuration" 
Description  
Type Of Material Database/Collection of data 
Year Produced 2020 
Provided To Others? Yes  
URL https://risweb.st-andrews.ac.uk:443/portal/en/datasets/data-underpinning--throughbottle-whisky-sensi...
 
Title Data underpinning - "Analysis of the Precision, Robustness and Speed of Elastic Resonator Interference Stress Microscopy" 
Description 05.05.2017 St Andrews, Philipp Liehm Requirements: 1. Install the python package Anaconda 2.3 (not tested with other versions, likely to work with newer versions as well) https://www.continuum.io/downloads 2. To run ERISM_Calc_3.0.py you need to have a compiled version of the additional cython package. (cython_all_fit.pyx --> compile -->cython_all_fit.pyd) 3. To compile under WINDOWS you need the setup_normal_win7.py and run from the command line: "python setup_normal_win7.py build_ext --inplace" You may be required to install the free C++ Compiler for Python 2.7: http://aka.ms/vcpython27 
Type Of Material Database/Collection of data 
Year Produced 2018 
Provided To Others? Yes  
 
Title Data underpinning - "Flexible and Ultra-lightweight Polymer Membrane Lasers" 
Description Data for each figure panel from the paper that displays numerical data are provided in the form of ASCII text-formatted data (.txt). 
Type Of Material Database/Collection of data 
Year Produced 2018 
Provided To Others? Yes  
 
Title Data underpinning - "Ultrastrong coupling of electrically pumped near-infrared exciton-polaritons in high mobility polymers" 
Description The attached data files underpin the publication "Ultrastrong coupling of electrically pumped near-infrared exciton-polaritons in high mobility polymers". The following file types and formats are included: - data used for line graphs ending with -modes.txt or -data.txt (can be opened with a text editor) - data used for reflectivity/PL/EL contour plots ending with R/PL/EL-2D.txt (can be opened with a text editor); in these files the first column contains the energy in eV and the first row the angle in deg 
Type Of Material Database/Collection of data 
Year Produced 2018 
Provided To Others? Yes  
 
Title Data underpinning: A label-free optical hemogram of granulocytes enhanced by artificial neural networks 
Description  
Type Of Material Database/Collection of data 
Year Produced 2019 
Provided To Others? Yes  
 
Title Data underpinning: Femtometer-resolved simultaneous measurement of multiple laser wavelengths in a speckle wavemeter 
Description  
Type Of Material Database/Collection of data 
Year Produced 2020 
Provided To Others? Yes  
URL https://risweb.st-andrews.ac.uk:443/portal/en/datasets/data-underpinning-femtometerresolved-simultan...
 
Title Data underpinning: Light sheet microscopy with acoustic sample confinement 
Description Research data associated with the publication: Light sheet microscopy with acoustic sample confinement. The data files are not yet publicly available. Enquiries and requests for data should be directed to the publication's corresponding authors. 
Type Of Material Database/Collection of data 
Year Produced 2018 
Provided To Others? Yes  
 
Title Data underpinning: Light-sheet microscopy with attenuation-compensated propagation-invariant beams 
Description The data will be available soon. In the meantime, if you would like to access the dataset, please, email research-data@st-andrews.ac.uk. 
Type Of Material Database/Collection of data 
Year Produced 2017 
Provided To Others? Yes  
 
Title Data underpinning: Optimal compressive multiphoton imaging at depth using single-pixel detection 
Description  
Type Of Material Database/Collection of data 
Year Produced 2019 
Provided To Others? Yes  
 
Title Data underpinning: Real-time monitoring of live mycobacteria with a microfluidic acoustic-Raman platform 
Description  
Type Of Material Database/Collection of data 
Year Produced 2020 
Provided To Others? Yes  
URL https://risweb.st-andrews.ac.uk:443/portal/en/datasets/data-underpinning-realtime-monitoring-of-live...
 
Title Data underpinning: Speckle-based determination of the polarisation state of single and multiple laser beams 
Description  
Type Of Material Database/Collection of data 
Year Produced 2020 
Provided To Others? Yes  
URL https://risweb.st-andrews.ac.uk:443/portal/en/datasets/data-underpinning-specklebased-determination-...
 
Title Data underpinning: Three-photon light-sheet fluorescence microscopy 
Description Research data related to publication: Three-photon light-sheet fluorescence microscopy. The data files are not yet publicly available. Enquiries and requests for data should be directed to the publication's corresponding authors. 
Type Of Material Database/Collection of data 
Year Produced 2019 
Provided To Others? Yes  
 
Title Direct measurement of vertical forces shows correlation between mechanical activity and proteolytic ability of invadopodia (dataset) 
Description The data files attached are linked to the publication with title: "Direct measurement of vertical forces shows correlation between mechanical activity and proteolytic ability of invadopodia". The data set contains a zip folder (Figures_OpenData_aax6912) with all the figures of the publication in .tif, .jpg and .png formats. These files can be opened and analysed with ImageJ. There is also a file (Plots and graphs_OpenData_aax6912) with the data needed to generate the plots and graphs of the publication. This file is in .opj format and can be opened using the OriginPro software. 
Type Of Material Database/Collection of data 
Year Produced 2019 
Provided To Others? Yes  
URL https://risweb.st-andrews.ac.uk:443/portal/en/datasets/direct-measurement-of-vertical-forces-shows-c...
 
Title Non-obstructive intracellular nanolasers (dataset) 
Description  
Type Of Material Database/Collection of data 
Year Produced 2018 
Provided To Others? Yes  
URL https://risweb.st-andrews.ac.uk:443/portal/en/datasets/nonobstructive-intracellular-nanolasers-datas...
 
Title Podocyte injury elicits loss and recovery of cellular forces (dataset) 
Description NULL 
Type Of Material Database/Collection of data 
Year Produced 2018 
Provided To Others? Yes  
 
Title Widefield light sheet microscopy using an Airy beam combined with deep-learning super-resolution (dataset) 
Description  
Type Of Material Database/Collection of data 
Year Produced 2020 
Provided To Others? Yes  
URL https://risweb.st-andrews.ac.uk:443/portal/en/datasets/widefield-light-sheet-microscopy-using-an-air...
 
Title Willin/FRMD6 influences mechanical phenotype and neuronal differentiation in mammalian cells by regulating ERK1/2 activity (dataset) 
Description Willin/FRMD6 is part of a family of proteins with a 4.1 ezrin-radixin-moesin (FERM) domain. It has been identified as an upstream activator of the Hippo pathway and, when aberrant in its expression, is associated with human diseases and disorders. Even though Willin/FRMD6 was originally discovered in the rat sciatic nerve, most studies have focused on its functional roles in cells outside of the nervous system, where Willin/FRMD6 has been shown to be involved in the formation of apical junctional cell-cell complexes and in regulating cell migration. Here, we investigate the biochemical and biophysical role of Willin/FRMD6 in neuronal cells, employing the commonly used SH-SY5Y neuronal model cell system and combining biochemical measurements with Elastic Resonator Interference Stress Micropscopy (ERISM). We present the first direct evidence that Willin/FRMD6 expression influences both the cell mechanical phenotype and neuronal differentiation. By investigating cells with increased and decreased Willin/FRMD6 expression levels, we show that Willin/FRMD6 not only affects proliferation and migration capacity of cells, but also leads to changes in cell morphology and to an enhanced neurite formation. These changes were accompanied by alterations of biophysical parameters such as cell force, the organization of actin stress fibers and the formation of focal adhesions. At the biochemical level, changes in Willin/FRMD6 expression inversely effected the activity of the extracellular signal-regulated kinases (ERK) pathway and downstream transcriptional factor, NeuroD1. 
Type Of Material Database/Collection of data 
Year Produced 2020 
Provided To Others? Yes  
URL https://risweb.st-andrews.ac.uk:443/portal/en/datasets/willinfrmd6-influences-mechanical-phenotype-a...