Physics-Life Sciences Interface C-DIP Fellowship Fund, EPSRC Leadership Fellowship Dr. Paola Borri

Lead Research Organisation: Cardiff University
Department Name: School of Biosciences

Abstract

As a physicists appointed to the School of Biosciences at Cardiff University I have direct experience of the benefits but also of the challenges associated with working at the interface between physics and the life sciences. While at Cardiff University there is growing interest in this cross-disciplinary research, an organised mechanism is missing to create awareness of the available expertise, to connect researchers from physics and the life sciences both within UK and internationally, and to initiate new cross-disciplinary research.I propose to make use of the C-DIP fund to overcome this shortfall and support organised activities which will promote and stimulate cross-disciplinary research at the physics-life science interface at Cardiff University and in the wider scientific community. These activities will comprise:i) a series of one-day topical meetings held at Cardiff University covering research subjects at the physics-life science interfaceii) a mini-symposium to provide a forum in which leading scientists and early-career researchers can meet and interactiii) visits from/to outstanding overseas scientists working at the physics-life sciences interface iv) seed corn funding to complete a piece of research or to carry out initial research at the physics-life sciences interface.

Planned Impact

Who will benefit from this programme? The networking activities supported by this Cross-Disciplinary Interfaces Programme Fellowship Fund will provide an organised mechanism to promote and stimulate cross-disciplinary research at the physics-life science interface at Cardiff University and in the wider scientific community. Researchers from physics and the life sciences within UK and internationally will greatly benefit from this support. Although the networking activities are primarily targeted to the academic community, the planed one-day workshop series a the physics-life sciences interface will be open to the industrial sector through invited speakers from companies working in e.g. physics-based technologies applied to biomedicine. How will they benefit from this research? The contribution of this programme to these beneficiaries will be mainly through: - Knowledge: via the dissemination at the symposium and workshop topical meetings of cutting edge scientific achievements and latest advances, and via the scientific outputs which will be enabled by the seed corn funding to complete a piece of research or to carry out initial research at the physics-life sciences interface. - People: The visit fund for distinguished cross-disciplinary researchers will support outstanding overseas scientists working at the physics-life sciences interface to visit a research group at Cardiff University or researchers from Cardiff to visit distinguished cross-disciplinary overseas research groups. Moreover, the mini-symposium will provide a forum in which leading scientists and early-career researchers will meet and interact. By creating such a forum, the early-career scientists will be encouraged to explore new cross-disciplinary directions and make contacts that will help them push forward the frontiers of cross-disciplinary science at the physics-life sciences interface. What will be done to ensure that they benefit from this research? As EPSRC cross-disciplinary leadership fellow I will lead the organization of these events and activities. An Advisory Board will be formed comprising national and international distinguished researchers to help and advice in the selection of invited speakers and in the overall organization of the activities. Cross-School calls for applications to the Distinguished Researcher Visit Fund and the Seed Corn Funding will be announced within Cardiff University and funding decisions will be taken by a Committee chaired by myself, with members from the Research Committees in the Schools of Physics and Biosciences. Specialised staff has also been appointed in the School of Biosciences as Innovation and Engagement Officers with whom I will liaise to engage with industry and the wider public.

Publications

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Sayers EJ (2014) Distal phenylalanine modification for enhancing cellular delivery of fluorophores, proteins and quantum dots by cell penetrating peptides. in Journal of controlled release : official journal of the Controlled Release Society

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Masia F (2015) Hyperspectral image analysis for CARS, SRS, and Raman data. in Journal of Raman spectroscopy : JRS

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Tarrés M (2014) Imaging in living cells using ?B-H Raman spectroscopy: monitoring COSAN uptake. in Chemical communications (Cambridge, England)

 
Title Contemporary Dance OPTO-NANO 
Description The professional dancer and choreographer Jack Philp created a dance piece inspired by the research in my laboratory, with funding from the Arts Council Wales. This resulted in a showcase performance at the National dance House in Cardiff in November 2019 and in a video posted in social media. 
Type Of Art Performance (Music, Dance, Drama, etc) 
Year Produced 2019 
Impact The work has attracted considerable interest in social media. Several members of the general public attended the performance showcase which was followed by a question and answer session in which I had the opportunity to explain my research to the wider public. With the coreographer we plan to bring this forward into a dance tour and we are seeking further funding. 
URL http://www.jackphilpdance.co.uk/opto-nano
 
Description This grant was supporting cross-disciplinary research at the Physics Life Science interface within a collaborative network linked to Prof Borri Leadership Fellowship. The funds were used on several projects, including supporting the research of a cohort of PhD students in Bioimaging. The funds were also used to run a series of scientific symposia in BioNanoPhotonics at Cardiff University, and to support research exchange trough visits.
Exploitation Route In terms of scientific outputs, this grant supported the research of a number of PhD students in Bioimaging covering areas from novel technology developments in optical micro-spectroscopy to drug discovery to developmental biology. It resulted in several published papers in international journals. Several strands of the research are being taken forward by other PhD projects and are planned to be the subject of future collaborative grant proposals.

In terms of the series of BioNanoPhotonics scientific symposia, they generated a lot of interest and were attended by 50-100 delegates. They provided a key platform for very useful knowledge exchange within the community and the formation of new collaborations. The intention is to maintain the momentum generated by this series and to run subsequent events through various sponsorships.
Sectors Chemicals,Healthcare,Pharmaceuticals and Medical Biotechnology

 
Description Some of the finding in drug delivery as well as nanoparticle characterization analysis funded by this research are being taken forward toward commercial impact. We have established a specific collaboration with pharmaceutical companies (GSK) and particle manufacturers (BBI Solutions), which have led to recent iCASE studentships. We are now working with biotech companies and manufacturers of analytical instrumentation toward establishing a knowledge transfer partnership. Also of interest is that a bright PhD student supported by this award was appointed by a firm as a patent attorney. This shows that the research training he has received has stimulated his interest in innovation and business and has resulted in a professional career path which is key to scientific entrepreneurship.
First Year Of Impact 2011
Sector Chemicals,Healthcare,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology
Impact Types Economic

 
Description Life Sciences Bridging Fund
Amount £5,000 (GBP)
Funding ID LSBF/R4-004 
Organisation Government of Wales 
Sector Public
Country United Kingdom
Start 08/2016 
End 10/2016
 
Description Science Committee - Multidisciplinary Project Award
Amount £403,597 (GBP)
Funding ID C368/A22099 
Organisation Cancer Research UK 
Sector Charity/Non Profit
Country United Kingdom
Start 08/2016 
End 07/2019
 
Title Heterodyne CARS microscopy 
Description We have developed a novel label-free technique based on chemical imaging via coherent anti-Stokes Raman scattering microscopy using a dual-polarization balanced heterodyne detection in epi-geometry (eH-CARS). This technique provides a unique combination of background-free chemically-specific image contrast for nanoparticles and interfaces, shot-noise limited detection, and phase sensitivity. 
Type Of Technology New/Improved Technique/Technology 
Year Produced 2015 
Impact This new technique could prove instrumental to investigate the chemical composition of thin films with high spatial resolution, topographic sensitivity, and label-free. It could be a powerful tool to study single lipid bilayers, including model and cellular membranes, as well as single nanoparticles. 
 
Title Quantitative Extinction analysis 
Description We have developed an optical extinction microscopy analysis method to quantify the optical extinction cross-section s_ext of single nanoparticles using wide-field microscopy. The method utilities the simultaneous acquisition of hundreds of nanoparticles for statistical analysis. The method is simple, rapid, and quantitative. We have demonstrated a sensitivity of s_ext below 1nm^2 corresponding to the detection of a single gold nanoparticle of 2nm diameter, using only ~1min total acquisition time. From the measurement of s_ext and its dependence on the light polarization, an accurate quantification of particle sizes and asymmetries at the single particle level is rapidly obtained for a statistically-relevant number (>100) of particles. An Extinction Suite Macro for ImageJ was also developed, for quantitative data analysis. 
Type Of Technology New/Improved Technique/Technology 
Year Produced 2013 
Impact This technique has generated commercial interested with our industrial collaborators BBI Solution, a world leading nanoparticle manufacturer. Precise characterisation of nanoparticle sizes and shapes is key to manufacturing quality control. Current techniques for particle characterisation are dynamics light scattering (DLS), which is easy to use but not very accurate and provides only the effective mean size (hydrodynamic radius), and transmission electron microscopy (TEM) which is time consuming and expensive. The optical extinction microscopy method developed by us overcomes these limitations and effectively complements these analysis techniques. Malvern Panalytical Ltd manufacturing analytical instrumentation including DLS, is interested in a knowledge transfer partnership on this technology. 
URL http://langsrv.astro.cf.ac.uk/Crosssection/Extinction_Suite/Extinction_Suite.html
 
Title Resonant FWM imaging 
Description We have developed a novel optical microscopy technique to visualise small single metallic nanoparticels (NPs), without the need of any fluorophore labelling, in a very specific and background free way, even in highly scattering environments such as cells and tissues. In this method individual small (radii below 20nm) metallic NPs are visualised with high contrast and photo-stability, free from background and at powers corresponding to negligible photothermal heating, via their coherent nonlinear optical emission called Four-Wave Mixing (FWM) in resonance with the NP surface plasmon. The technique has been implemented to work both in transmission and reflection geometry. It includes a polarisation resolved analysis to detect particle asymmetry, a phase resolved analysis for biosensing, and a time-resolved analysis to quantify thermal and mechanical couplings of NPs with their environments. 
Type Of Technology New/Improved Technique/Technology 
Year Produced 2012 
Impact The technique is being utilized extensively over several research projects, including a collaborative project with Bristol University with interest in correlative light-electron microscopy . It is planned to become part of an imaging facility at Cardiff University. 
URL http://www.cardiff.ac.uk/people/view/81122-borri-paola
 
Title Single particle tracking via four-wave-mixing optical vortex interferometry 
Description We have developed and demonstrated a new four-wave-mixing interferometry technique, whereby the position of a single nonfluorescing gold nanoparticle is determined with nanometric precision in 3D from rapid single-point measurements at 1-ms acquisition time by exploiting optical vortices. The technique is also uniquely sensitive to particle asymmetries of only 0.5% ellipticity, corresponding to a single atomic layer of gold, as well as particle orientation. This method opens new ways of unraveling single-particle trafficking within complex 3D architectures. 
Type Of Technology New/Improved Technique/Technology 
Year Produced 2015 
Impact Ultimately, this new method paves the way towards a new form of single-particle tracking, where not only the nanoparticle position but also its asymmetry, orientation, and chirality are detected with submillisecond time resolution, revealing much more information about the nanoparticle and its complex dynamics (e.g., hindered rotation) while moving and interacting within a disordered 3D environment. As such it can have many applications in physical science systems (e.g. diffusion in complex liquids and gels, liquid crystals) and in the life sciences (single-molecule intra-cellular trafficking). 
 
Title quantitative DIC microscopy 
Description We have developed an analysis technique to quantify the thickness of thin transparent objects using optical microscopy, based on quantitative differential interference contrast. The method was demonstrated on giant unilamellar lipid vesicles. It is generally applicable to many other structures, for example nanoparticles, thin films and waveguides. 
Type Of Technology New/Improved Technique/Technology 
Year Produced 2013 
Impact Since its introduction the technique has been widely used (by our and other labs) to 1) measure the volume of transparent particles, such as nanodiamonds 2) measure the thickness of lipid bilayers both suspended and surface attached 3) measure the thickness of thin dielectric layers for waveguide design and processing 
URL http://dx.doi.org/10.1016/j.bpj.2013.07.048
 
Description BioNanoPhotonics Symposium 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Industry/Business
Results and Impact This is a scientific symposium that I organise every two years, with international invited speakers and participation from industry and postgraduate students. We started having 40 delegates in 2011 and reached 80 delegates in 2015. The event has sparked many scientific discussions and further collaboration with industry among the delegates.
Year(s) Of Engagement Activity 2011,2013,2015,2017
URL http://www.bionanophoto.org.uk/
 
Description Contemporary Dance project OPTO NANO 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact In collaboration with a contemporary dance professional choreographer Jack Philp, an outreach project was started aimed at creating a dance piece inspired by the biophotonics research in my lab. Jack was awarded a grant from the Arts Council Wales to work on the creation of the piece which was showcased at an open rehearsal to the public at the National Dance House in Cardiff in November 2019. The work is titled OPTO-NANO and resulted in a promotional video and posting on social media. Jack is working toward expanding the work into a tour and we are seeking further funding.
Year(s) Of Engagement Activity 2019
URL http://www.jackphilpdance.co.uk/opto-nano