Experimental equipment at UCL

Lead Research Organisation: University College London
Department Name: Office of Vice Provost Research

Abstract

This is a UCL-wide bid to invest in a range of equipment items to refresh and upgrade our experimental facilities which will help to maintain a cutting-edge in internationally leading research. Each of the bundles included in this proposal contributes to one or more strategic themes, in which UCL, as well as national and international funders, has invested significantly in recent years: Health technologies, Advanced functional materials, Sustainable built environment and Novel information and communication technologies. UCL has considerable strengths in these areas, and we have experienced significant growth in terms of staff and student numbers, and breadth and impact of research activity. This additional investment will therefore provide an ideal platform to ensure the sustained growth of the highest quality research, as well as supporting the early career researchers.

Each bundle identifies a set of items that underpin a range of research activities, often reaching across department and discipline boundaries, which are of strategic importance for UCL and EPSRC. The specific items identified within the bundles have been selected in close collaboration with senior management and individuals and groups working in the area, to ensure that they are aligned with their current needs and have the greatest potential to support maximum impact of their research activities. Each bundle has been allocated a Lead Investigator who will be responsible for regular reporting to the Vice-Provost for Research on progress against objectives.

The four EPSRC challenge themes addressed by this proposal are: Health technologies [bundles 1, 2, 3, 6]; Advanced functional materials [bundles 1, 3, 4, 5, 6]; Sustainable built environments [bundle 7]; and Novel information and communication technologies [bundles 5, 8].

Planned Impact

This proposal aims at acquiring eight bundles of capital equipment items, to upgrade and complement existing experimental resources and facilities within UCL labs, across the Engineering and Physical Sciences Domain. Broadly speaking, we can divide the impact of this proposal into two types: a "direct" impact (on researchers and students, both at UCL and beyond, and on their research) and an "indirect" impact that will be determined by the research enabled by the equipment.

Impact of the first type will be visible on a shorter time-scale, and can be easily measured in terms of improved research capability and performance. In identifying the items requested in this proposal, priority has been given to items supporting areas of high strategic importance for both EPSRC and UCL, in which there is a high level of internationally leading research activity and where UCL hosts a critical mass of researchers at all stages of their career. The benefits will be visible in terms of: training and skills upgrade (PhD students/junior postdocs); supporting the development of independent research careers (senior postdocs/lecturers); and enhanced capability for world-leading, transformative research programmes (established career).

Access to state-of-the-art equipment is also extremely valuable for industry and users, and is often one of the drivers for new collaborations. At UCL we have significant experience in sharing equipment resources with collaborators from both academia and industry, and the bundles included in the proposals will benefit from the presence of all the necessary mechanisms and structures. By upgrading our experimental facilities, therefore, this proposal will enable our research activity to have an impact on UK R&D activity beyond the academic environment.

Impact of the second type will be harder to measure, since it will be both longer term and mediated by the research process itself. Given the timeliness and importance of the challenges we address in the proposal, though, we are confident that there will be a significant benefit to the UK society and economy including (but not limited to) the following:

Developments in health technology [1,2,3,6] have the potential to benefit the UK society and economy (and are in line with the priorities outlined in the EPSRC Healthcare Technologies theme, as well as with the RCUK Lifelong Health and Wellbeing Programme);

Research in advanced functional materials [1,3,4,5,6] has the potential to impact on a variety of sectors, including healthcare (e.g. drug development), energy (e.g. batteries and fuel cells), and ICT (e.g. new devices);

Investigation of novel information and communication technologies [5,8] is crucial to support modern-day society, which relies more and more on high-speed communication and information processing;

Advances in the built environments [7] are crucial in developing a sustainable future, where we are able to balance the requirements of a modern society with the constraints imposed by energy and resource limitations.
 
Description Bundle 1: UCL cross-disciplinary advanced X-ray imaging centre

The instrument we developed thanks to this grant allowed a new understanding of the implications of scaling our proprietary laboratory based x-ray phase contrast techniques to higher x-ray energies. We published two papers on this subject, and are continuing to develop this area in collaboration with Nikon including as part of our Prosperity Partnership programme (EP/T005408/1). This increased knowledge will allow us to target even higher x-ray energies which will allow exploring currently inaccessible areas such as novel battery technology and additive manufacturing. Through a subsequent development, we have started to explore low monochromatic x-ray energies (which have applications in histology and biomedicine in general), which also cast new lights on some of the basic challenges associated with very low energy laboratory based x-ray phase contrast imaging and how to overcome these. This has led to an extension of our collaboration with Rigaku, and to the award of a joint NIH grant ("A soft X-Ray Phase-Based Microscope for Biomedical Applications", NIBIB/NIH, $1.8M, UCL share £277,010).

We have extended our unique, proprietary laboratory based x-ray phase contrast techniques into both higher (with the initial tungsten target) and lower (with the copper target we have installed later) x-ray energies, opening the way to new applications that were previously inaccessible. We now aim to further extend applications at the high-energy end to target areas such as novel battery technology and additive manufacturing, and further develop the low energy methods to target digital histology and other biomedical applications. We have developed a deeper understanding of the requirements associated with designing imaging system suitable to perform phase contrast imaging at higher and lower x-ray energies than we previously had used, and are currently pursuing applications in both areas with two different industrial collaborators.

Bundle 2: A capability for the rapid formulation and manufacturing process development of novel freeze-dried biological therapies

All of the equipment obtained has been used extensively by PhD students across the CDT in Emergent Macromolecular Therapies and from different collaborating HEIs, as well as by other PhD / EngD students and PDRAs across UCL. The AKTA is used extensively for protein purification prior to formulation research, as well as for analytical chromatography to support fermentation and downstream processing research.
The Agilent UPLC provides rapid and small sample analysis of proteins by SEC, IEX and RP-HPLC, and is coupled to the liquid handling and resin screening work in 0.5-1ml columns, undertaken on the Tecan Evo, while also providing standalone analysis of protein aggregates and charge variants in product formulations.
The high-resolution fluorometer measures protein fluorescence lifetimes in the ns time range, and is opening new frontiers for the analysis of product quality in microscale bioprocesses, and product formulations for protein stability and heterogeneity.

Bundle 6: Atomic Force Microscopy for materials characterisation at the nanoscale

- Main key finding to day is the "Elucidation of biomolecular dynamics involved in immune response to bacteria and can cancer cells".
- That the formation of quadruply folded DNA structures strongly depend on the rest of the DNA molecule in which they are formed. Such DNA quadruplexes are intensively studied in the context of anticancer therapies.
- That an attack mechanism of the immune system, operating by punching holes, becomes dysfunctional if only a fraction of its hole-punching proteins ("perforin") is deficient.
- the instrumentation has contributed to understanding protein assemblies relevant in health and disease at a molecular level, such as antimicrobial proteins and peptides that punch holes in bacteria, and the nature of the transport gate that determines how, e.g., viruses such as Hepatitis B virus and HIV gain access to the cell nucleus.

Bundle 8: Advanced test equipment for future wireless and optical systems research

Included instrumentation providing the ability to make extremely high resolution measurements on optical and microwave signals.
This has enabled optical frequency synthesis of terahertz signals, including the first demonstration of optically injection locked quantum cascade lasers, where the frequency is exactly related to a primary frequency standard, such as Caesium. This has fully met the objective of controlling the terahertz spectrum with the same accuracy that is possible at radio frequencies. It has also been possible to show that the phase noise of optical comb synthesised terahertz signals is limited by the multiplied phase noise of the microwave reference used. We have used the equipment to make a proof of principle demonstration of THz spectroscopy with unprecedented resolution and frequency accuracy. We have also used the equipment to characterize the first monolithically integrated dual DFB laser source and UTC device, with up to 100 µW generated at 120 GHz (through an international collaboration with III-V Laboratories, France.)

The DAC system along with the multiwavelength sources has enabled a state-of-the art digital transmitter to be set up. This has given us a world-leading capability to undertake optical transmission research. Working in collaboration with Oclaro, who have provided the high-bandwidth modulators, the resulting system has given us a unique capability to generate high bandwidth signals. To date we have carried out experiments with both 64QAM and 256QAM modulation formats inc joint experiment with Xtera which has resulted in a world-record 120Tbit/s capacity transmitted over a single fibre: https://www.xtera.com/2018/03/14/xtera-ucl-smash-transmission-world-record/. Used both as a research tool for the study of limits in capacity over single-mode fibres in a variety of regimes, the test-bed also provides a service to industry for the testing of different subsystems, components and algorithms, both in the UK and internationally. The impact has already been significant - for example, we have been approach to host a researcher from KDDI (Japan) - themselves leaders in high-capacity transmission and also a Memorandum of Understanding has been signed with NICT (Japan). The system will be used to underpin the experimental activity in the programme grant proposal TRANSNET, recently approved for funding by EPSRC.
Exploitation Route The equipment has been set up and is now running, as per our original submission. The capabilities thus enable will facilitate the delivery of new research which is likely to be either taken forward by us (or put to use by others), but it is still early to give details.

Bundle 1: Some of the research allowed by the new instrument is at the basis of the pre-commercial prototype developed with Nikon X-Tek Systems. The research conducted after the anode was swapped from W to Cu for softer x-rays was at the basis of a successful NIH bid led by Rigaku, on which UCL is a partner (details are being defined as I write). Should this new project be as successful as we hope, Nikon and Rigaku would discuss an agreement for exploitation of our technology in soft x-ray applications. EPSRC has recently funded a £10M National Research Facility in x-ray CT, and our spoke will offer the new technologies we have been developing to external users (both academic and industrial) for the first time.
Sectors Chemicals,Digital/Communication/Information Technologies (including Software),Electronics,Energy,Healthcare,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology,Security and Diplomacy,Other

URL https://www.ucl.ac.uk/medical-physics-biomedical-engineering/research/research-groups/advanced-x-ray-imaging-group-axim
 
Description Bundle 1: UCL cross-disciplinary advanced X-ray imaging centre Although there may be the need to wait a bit longer for commercial exploitation, this grant has provided a significant step forward towards the development of the first pre-commercial prototypes, and re-enforced industry's confidence on the commercial viability of our technique. Two prototypes have been built by Nikon, one is being built by Rigaku, and one is being designed by Perkin Elmer.It also provided ground for some of the public engagement events listed elsewhere in this submission (Made @ UCL, UCL Minds and UCL Physics and Engineering in Medicine Podcast) Bundle 2: A capability for the rapid formulation and manufacturing process development of novel freeze-dried biological therapies All of the equipment obtained has been used extensively by PhD students across the CDT in Emergent Macromolecular Therapies and from different collaborating HEIs, as well as by other PhD / EngD students and PDRAs across UCL. The AKTA is used extensively for protein purification prior to formulation research, as well as for analytical chromatography to support fermentation and downstream processing research. The Agilent UPLC provides rapid and small sample analysis of proteins by SEC, IEX and RP-HPLC, and is coupled to the liquid handling and resin screening work in 0.5-1ml columns, undertaken on the Tecan Evo, while also providing standalone analysis of protein aggregates and charge variants in product formulations. The high-resolution fluorometer measures protein fluorescence lifetimes in the ns time range, and is opening new frontiers for the analysis of product quality in microscale bioprocesses, and product formulations for protein stability and heterogeneity. The specific use by EPSRC CDT students has formed either part of either their core PhD research, or has been used within their Pilot Plant week training. Bundle 6: Atomic Force Microscopy for materials characterisation at the nanoscale The award has facilitated the study of antibody drugs as they bind to their targets located on the cell surface, which has given our industrial collaborator MedImmune scientific insights that may facilitate their drug development and approval. I has also helped Bruker to market their instruments This grant is for equipment that has served and is serving a wide community of academic and industrial researchers, with e.g. 40~50 users in a 3-month period. It has widely benefitted scientific endeavours across UCL, Imperial College and King's College, and to industry as per Collaborations & Partnerships. For the imaging equipment - Impact is mostly academic for the time being; the activities are based around developing new imaging techniques, so translation takes time Bundle 8: Advanced test equipment for future wireless and optical systems research Demonstrations of high data rate wireless transmission enabled by the equipment funded by this grant have increased interest in the use of THz frequencies for future wireless systems. The technology is now under active investigation by companies such as Huawei for use in 5G+ communications systems.
Sector Chemicals,Digital/Communication/Information Technologies (including Software),Electronics,Healthcare,Pharmaceuticals and Medical Biotechnology
Impact Types Societal,Economic

 
Description "Micro-radian x-ray scattering: transformative technology for industrial and medical diagnostics", Royal Academy of Engineering Chair in Emerging Technology
Amount £2,780,000 (GBP)
Organisation Royal Academy of Engineering 
Sector Charity/Non Profit
Country United Kingdom
Start  
 
Description BBSRC Standard Grant
Amount £458,449 (GBP)
Funding ID BB/N015487/1 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 09/2016 
End 10/2019
 
Description Dynamics of bacterial killing by the membrane attack complex
Amount £449,429 (GBP)
Funding ID MR/R000328/1 
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 06/2018 
End 06/2021
 
Description EPSRC Future formulation of complex products
Amount £2,500,000 (GBP)
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Public
Country United Kingdom
Start  
 
Description Enabling rapid liquid and freeze-dried formulation design for the manufacture and delivery of novel biopharmaceuticals
Amount £1,519,555 (GBP)
Funding ID EP/N025105/1 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Public
Country United Kingdom
Start 06/2016 
End 06/2021
 
Description Enabling rapid liquid and freeze-dried formulation design for the manufacture and delivery of novel biopharmaceuticals
Amount £2,380,872 (GBP)
Funding ID EP/N025105/1 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Public
Country United Kingdom
Start 06/2016 
End 06/2021
 
Description FUTURE TARGETED HEALTHCARE MANUFACTURING HUB
Amount £10,317,090 (GBP)
Funding ID EP/P006485/1 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Public
Country United Kingdom
Start 01/2017 
End 12/2023
 
Description Healthcare Impact Partnership
Amount £948,478 (GBP)
Funding ID EP/P023231/1 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Public
Country United Kingdom
Start 07/2017 
End 01/2021
 
Description Low-complexity transceivers
Amount £219,500 (GBP)
Organisation Huawei Technologies 
Sector Private
Country China
Start 03/2017 
End 02/2018
 
Description MERL 4-year donation
Amount $100,000 (USD)
Organisation Mitsubishi Electric 
Sector Private
Country Japan
Start 03/2016 
End 03/2020
 
Description Microsoft studentship
Amount £71,650 (GBP)
Organisation Microsoft Research 
Department Microsoft Research Cambridge
Sector Private
Country United Kingdom
Start 09/2016 
End 10/2019
 
Description National Research Facility for Lab X-ray CT
Amount £10,097,652 (GBP)
Funding ID EP/T02593X/1 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Public
Country United Kingdom
Start 11/2020 
End 10/2025
 
Description Nikon-UCL Prosperity Partnership on Next-Generation X-Ray Imaging
Amount £2,283,598 (GBP)
Funding ID EP/T005408/1 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Public
Country United Kingdom
Start 12/2019 
End 11/2024
 
Description Programme Grant
Amount £6,517,861 (GBP)
Funding ID EP/P021859/1 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Public
Country United Kingdom
Start 05/2017 
End 05/2022
 
Description RAEng Early Career Fellowship
Amount £500,000 (GBP)
Organisation Royal Academy of Engineering 
Sector Charity/Non Profit
Country United Kingdom
Start 12/2016 
End 11/2021
 
Description UK IC Postdoctoral Research Fellowship
Amount £188,396 (GBP)
Organisation Royal Academy of Engineering 
Sector Charity/Non Profit
Country United Kingdom
Start  
 
Title Optical test bed software-defined network optical transmission 
Description Software-defined test bed for experimental investigation of long-haul fibre optical transmissions systems. 
Type Of Material Improvements to research infrastructure 
Year Produced 2015 
Provided To Others? Yes  
Impact Extended test-bed infrastructure used for a number of key experiments and evaluation of of new components/fibres/devices/subsystems. This now includes 16 ECL lasers and an SS-ASE, digital transceiver with 12x92 GSample/s 8-bit digital-to-analogue converters (DAC). This means we can generat signals with a symbol rate up to 64GBd, compared to 10GBd previously. We can also now perform high order modulation formats up to 256QAM. The test bed has been updated for full C-band transmission capability using the following: - Spectrally shaped amplifier spontaneous emission noise (SS-ASE) to emulate the generation of full C-band transmission - 3xHigh power (33 dBm output power) optical amplifiers (EDFAs) to transmit full C-band - A recirculating optical loop with state-of-the-art optical fibres is used for long haul C-band transmissions. Specialist fibres now include Corning® Vascade® EX2000. We also have use of anti-resonant hollow core fibre produced by Southampton University Optical Research Centre. Mitsubishi Electric Research Laboratories used the test bed for a joint MERL-UNLOC paper on a dual-carrier 1Tb/s signal generation, suitable for current commercial systems. Aston University, as part of the UNLOC programme, have also used this test bed for joint work to analyse nonlinearity. Joint work with Southampton University to characterise the new anti-resonant hollow core fibre. The test bed was used for joint work with Corning on a single span transmission, where we achieved a record spectral efficiencyxdistance product. Joint work underway with Xtera to extend transmission bandwidth beyond C and L band. Numerous resulting publications presented at OFC and ECOC during 2015/16/17. 
URL http://unloc.net/index.php/research/facilities
 
Title Atomic force microscopy and atomistic molecular dynamics simulation data to resolve structures of negatively-supercoiled DNA minicircles at base-pair resolution. 
Description This data record consists 2 zipped folders: Full AFM raw data set.zip, and Source data .zip.The zipped folder Full AFM raw data set.zip contains all raw AFM data including repeats and experiments carried out in alternative conditionsThe primary subfolder names correspond to the method of DNA immobilisation:Nickel - use of 3 mM NiCl2 in Ph7.4 20 mM HEPES bufferPLLNaOAc - use of PLL and pH 5.4 50 mM NaOAc bufferHR images - high resolution images, obtained also using the nickel conditions.The secondary subfolder names correspond to the superhelical density as shown in figure 3 in the article, and these contain the raw AFM images as .spm isles, the sub folders within those are created by the program TopoStats, and are processed data from the raw AFM images. File formats included in the zipped folder: .spm, .tiff, .json, .txt and .pdf.The zipped folder Source data .zip comprises all relevant data, pdbs of all the structures depicted in the paper obtained from simulations and AFM. See below for details on each sub folder within Source data 2.zip. Each folder contains the data used to generate each figure ad supplementary figure in the article. Figure 1: AFM data: the AFM raw files for the high-resolution images shown in figure 1, and calculations of their aspect ratios as aspectratiomanual.xlsxAFM movie: the AFM raw files for the time-lapse images shown in figure 1.MD data: the MD images used for the high-resolution images shown in figure 1 and .tar files - the MD files used to generate the snapshots MD movie: the MD snapshots files for the time-lapse images shown in figure 1 and .tar files - the MD files used to generate the snapshotsFile formats included in the Figure 1 sub folder: 0## files where ## represent numbers, .gwy, .txt, .eps, .mpg and .xlsx.Figure 2: Kink and defect measurements - the measured bend angles shown in Fig 2 and an AFM image showing how the FAM bends were measuredMD Radgyr Writhe - measurements of radius of gyrations and writhe for each topoisomer.tar files - the MD files used to generate the snapshots in 2a.txt file - the profile shown in fig 2bFile formats included in the Figure 2 sub folder: .tiff, .txt and .datFigure 3: The subfolder names correspond to the superhelical density as shown in figure 3, and these contain the raw AFM images as '.spm' isles, the sub folders within those are created by the program TopoStats, and are processed data from the raw AFM images. The '.json' file contains the data used to make the plots shown in Figure 3File formats included in the Figure 3 sub folder: .spm, .tiff, .txt, .json and .pdfFigure 4: '.dat' files contain information from MD simulations used to create the subfigure they are labelled with.The '.spm' and '.037' files are the raw AFM images used in this figure.The .tar files are MD simulations data used to generate the snapshots shown in figure 4.File formats included in the Figure 4 sub folder: .spm, .txt, .pdf and .datFigure S1: Simulations data generated using the SerraLine program, showing the average and maximum deviations from planarity in relative and absolute numbers.Data were plotted suing the distributions_plot.py script.File formats included in the Figure S1 sub folder: .csv, .pdf, and .txtFigure S2a: MD measurement of the writhe over time as a '.dat file' and snapshots as '.pdb' files. File formats included in the Figure S2a sub folder: .pdb and .dat.Figure S2b: MD measurement of the writhe over time as a '.dat file' and snapshots as '.pdb' files.File formats included in the Figure S2b sub folder: .pdb and .dat.Figure S3: The AFM and MD measurements of bending angles including all profiles for MD simulations, generated using Serraline A, FM images and measurements in the form '251angles' '339 angles'.File formats included in the Figure S3 sub folder: .tiff, .txt and .pdb.Figure S4: AFM length analysis of the position of the triplex on linearised minicircles. 'Csv' file contains the length data measured by hand using the IMOD software.Plots: plots of the data raw AFM data: AFM data files used in the analysisFile formats included in the Figure S4 sub folder: .csv, .xlsx, .pdf and 0## files where ## represent numbers.Figure S5: Surface plasmon resonance (SPR) data show the effect of ions on the affinity of the triplex for varying superhelical densities of DNA minicircles, plotted using the script 'sprplot'. '.pdf' files are the plots of the various excel files.File formats included in the Figure S5 sub folder: .json, .pdf and .xlsx.Figure S6: SPR data in showing the affinity of the triplex for varying superhelical densities of DNA minicircles, plotted using the script 'sprplot'. '.pdf' files are the plots of the various excel files.File formats included in the Figure S6 sub folder: .json, .pdf, .xlsx and .pdf.Figure S7: An MS '.tar' file containing the snapshots shown in figure S7File formats included in the Figure S7 sub folder: .pdbFigure S8: AFM data used in figure s8, the '.gwy' files are AFM images of the wide view, and each of the time-lapse images. The '.txt' files are the profiles taken in those images and plotted in the figure.File formats included in the Figure S8 sub folder: .gwy and .txt.Figure S9: Simulations data showing the difference between the OL$ and BSC1 forcefields.File formats included in the Figure S9 sub folder: .datSimulations: The simulations data File formats included in the Simulations sub folder: .gro and .xtcSupp videos: The supplementary videosFile formats included in the SuppVideods sub folder: .pdb and .mpgSoftware needed to access data: 20151103_251_NAT_17ng_Ni_20mm_052DX.058 or AFM_339_TFO_HR_cs.037, spm files & all files included in the "Raw AFM data" sub folder - Gwyddion, Nanoscope Analysiseps files - illustrator/ pdf software.mpg - any movie player.gro - gromacs files- GRO files may be viewed on a computer using a supporting HP calculator emulator, such as Emu48.xtc files - gromacs files- a suitable software like XTrkCADsee http://manual.gromacs.org/documentation/2018/user-guide/file-formats.html for more information on gromacs files.Study aims and methodology: In the cell, DNA is arranged into highly-organised and topologically-constrained (supercoiled) structures. It remains unclear how this supercoiling affects the detailed double-helical structure of DNA, largely because of limitations in spatial resolution of the available biophysical tools. In this study, the authors combined high-resolution atomic force microscopy (AFM) with molecular dynamics (MD) simulations to reveal how supercoiling affects global and local DNA conformation, structure and dynamics in DNA minicircles of length 250-340 bp. The following procedures are described in more detail in the related article: generation and purification of small DNA circles, preparation and analysis of different topological species of minicircles, S1 nuclease digestions, atomic force microscopy, atomistic simulations and surface plasmon resonance. 
Type Of Material Database/Collection of data 
Year Produced 2021 
Provided To Others? Yes  
URL https://springernature.figshare.com/articles/dataset/Atomic_force_microscopy_and_atomistic_molecular...
 
Title Atomic force microscopy and atomistic molecular dynamics simulation data to resolve structures of negatively-supercoiled DNA minicircles at base-pair resolution. 
Description This data record consists 2 zipped folders: Full AFM raw data set.zip, and Source data .zip.The zipped folder Full AFM raw data set.zip contains all raw AFM data including repeats and experiments carried out in alternative conditionsThe primary subfolder names correspond to the method of DNA immobilisation:Nickel - use of 3 mM NiCl2 in Ph7.4 20 mM HEPES bufferPLLNaOAc - use of PLL and pH 5.4 50 mM NaOAc bufferHR images - high resolution images, obtained also using the nickel conditions.The secondary subfolder names correspond to the superhelical density as shown in figure 3 in the article, and these contain the raw AFM images as .spm isles, the sub folders within those are created by the program TopoStats, and are processed data from the raw AFM images. File formats included in the zipped folder: .spm, .tiff, .json, .txt and .pdf.The zipped folder Source data .zip comprises all relevant data, pdbs of all the structures depicted in the paper obtained from simulations and AFM. See below for details on each sub folder within Source data 2.zip. Each folder contains the data used to generate each figure ad supplementary figure in the article. Figure 1: AFM data: the AFM raw files for the high-resolution images shown in figure 1, and calculations of their aspect ratios as aspectratiomanual.xlsxAFM movie: the AFM raw files for the time-lapse images shown in figure 1.MD data: the MD images used for the high-resolution images shown in figure 1 and .tar files - the MD files used to generate the snapshots MD movie: the MD snapshots files for the time-lapse images shown in figure 1 and .tar files - the MD files used to generate the snapshotsFile formats included in the Figure 1 sub folder: 0## files where ## represent numbers, .gwy, .txt, .eps, .mpg and .xlsx.Figure 2: Kink and defect measurements - the measured bend angles shown in Fig 2 and an AFM image showing how the FAM bends were measuredMD Radgyr Writhe - measurements of radius of gyrations and writhe for each topoisomer.tar files - the MD files used to generate the snapshots in 2a.txt file - the profile shown in fig 2bFile formats included in the Figure 2 sub folder: .tiff, .txt and .datFigure 3: The subfolder names correspond to the superhelical density as shown in figure 3, and these contain the raw AFM images as '.spm' isles, the sub folders within those are created by the program TopoStats, and are processed data from the raw AFM images. The '.json' file contains the data used to make the plots shown in Figure 3File formats included in the Figure 3 sub folder: .spm, .tiff, .txt, .json and .pdfFigure 4: '.dat' files contain information from MD simulations used to create the subfigure they are labelled with.The '.spm' and '.037' files are the raw AFM images used in this figure.The .tar files are MD simulations data used to generate the snapshots shown in figure 4.File formats included in the Figure 4 sub folder: .spm, .txt, .pdf and .datFigure S1: Simulations data generated using the SerraLine program, showing the average and maximum deviations from planarity in relative and absolute numbers.Data were plotted suing the distributions_plot.py script.File formats included in the Figure S1 sub folder: .csv, .pdf, and .txtFigure S2a: MD measurement of the writhe over time as a '.dat file' and snapshots as '.pdb' files. File formats included in the Figure S2a sub folder: .pdb and .dat.Figure S2b: MD measurement of the writhe over time as a '.dat file' and snapshots as '.pdb' files.File formats included in the Figure S2b sub folder: .pdb and .dat.Figure S3: The AFM and MD measurements of bending angles including all profiles for MD simulations, generated using Serraline A, FM images and measurements in the form '251angles' '339 angles'.File formats included in the Figure S3 sub folder: .tiff, .txt and .pdb.Figure S4: AFM length analysis of the position of the triplex on linearised minicircles. 'Csv' file contains the length data measured by hand using the IMOD software.Plots: plots of the data raw AFM data: AFM data files used in the analysisFile formats included in the Figure S4 sub folder: .csv, .xlsx, .pdf and 0## files where ## represent numbers.Figure S5: Surface plasmon resonance (SPR) data show the effect of ions on the affinity of the triplex for varying superhelical densities of DNA minicircles, plotted using the script 'sprplot'. '.pdf' files are the plots of the various excel files.File formats included in the Figure S5 sub folder: .json, .pdf and .xlsx.Figure S6: SPR data in showing the affinity of the triplex for varying superhelical densities of DNA minicircles, plotted using the script 'sprplot'. '.pdf' files are the plots of the various excel files.File formats included in the Figure S6 sub folder: .json, .pdf, .xlsx and .pdf.Figure S7: An MS '.tar' file containing the snapshots shown in figure S7File formats included in the Figure S7 sub folder: .pdbFigure S8: AFM data used in figure s8, the '.gwy' files are AFM images of the wide view, and each of the time-lapse images. The '.txt' files are the profiles taken in those images and plotted in the figure.File formats included in the Figure S8 sub folder: .gwy and .txt.Figure S9: Simulations data showing the difference between the OL$ and BSC1 forcefields.File formats included in the Figure S9 sub folder: .datSimulations: The simulations data File formats included in the Simulations sub folder: .gro and .xtcSupp videos: The supplementary videosFile formats included in the SuppVideods sub folder: .pdb and .mpgSoftware needed to access data: 20151103_251_NAT_17ng_Ni_20mm_052DX.058 or AFM_339_TFO_HR_cs.037, spm files & all files included in the "Raw AFM data" sub folder - Gwyddion, Nanoscope Analysiseps files - illustrator/ pdf software.mpg - any movie player.gro - gromacs files- GRO files may be viewed on a computer using a supporting HP calculator emulator, such as Emu48.xtc files - gromacs files- a suitable software like XTrkCADsee http://manual.gromacs.org/documentation/2018/user-guide/file-formats.html for more information on gromacs files.Study aims and methodology: In the cell, DNA is arranged into highly-organised and topologically-constrained (supercoiled) structures. It remains unclear how this supercoiling affects the detailed double-helical structure of DNA, largely because of limitations in spatial resolution of the available biophysical tools. In this study, the authors combined high-resolution atomic force microscopy (AFM) with molecular dynamics (MD) simulations to reveal how supercoiling affects global and local DNA conformation, structure and dynamics in DNA minicircles of length 250-340 bp. The following procedures are described in more detail in the related article: generation and purification of small DNA circles, preparation and analysis of different topological species of minicircles, S1 nuclease digestions, atomic force microscopy, atomistic simulations and surface plasmon resonance. 
Type Of Material Database/Collection of data 
Year Produced 2021 
Provided To Others? Yes  
URL https://springernature.figshare.com/articles/dataset/Atomic_force_microscopy_and_atomistic_molecular...
 
Title Example GMI database 
Description The metric generalised mutual information (GMI) can be used to estimate the performance of a soft-decision binary forward error correction algorithm. This research brought the metric to the attention of the optical networks community, and provided an example set of GMI-BER (bit error rate) relations. 
Type Of Material Database/Collection of data 
Provided To Others? No  
Impact The work has already informed the development of coded modulation in optical communications systems, and has been referenced 38 times in the literature to date (March 2017). 
 
Title Reduced subset of probabilistically shaped constellations for finite penalty 
Description A methodology and reference example for the design of practical probabilistically shaped modulation formats was developed. It was shown that, for the reference example, that just four constellations could be used to approximate the continuous distribution of shaped constellations for <0.1 dB SNR penalty. 
Type Of Material Database/Collection of data 
Provided To Others? No  
Impact This methodology has been used in a range of subsequent optical communications research investigating probabilistic shaping. 
 
Title Transceiver noise-Gaussian noise model 
Description This model enables the accurate prediction of an optical fibre communication system performance when nonlinearity has been compensated in the presence of transceiver (transmitter and/or receiver) noise. This allows both better transmission system design, but also opens an avenue of research into signal-to-noise ratio improved transceivers. 
Type Of Material Computer model/algorithm 
Provided To Others? No  
Impact Within our group, this research has informed transmission experiments, as well as research direction. 
 
Description Bruker 
Organisation Bruker Corporation
Country United States 
Sector Private 
PI Contribution We have provided technical feedback on equipment and produced data and protocols that helped Bruker to promote their equipment.
Collaborator Contribution Bruker has provided a cash contribution of £30,000 to a PhD studentship and provided extensive technical support and guidance (hard to exactly quantify, but I guess that £20,000 monetary value would not be unreasonable)
Impact N/A
Start Year 2009
 
Description EMBL European Molecular Biology Laboratory Heidelberg 
Organisation European Molecular Biology Laboratory
Department European Molecular Biology Laboratory Heidelberg
Country Germany 
Sector Academic/University 
PI Contribution We have adapted one of our imaging methods so that it can be used on their samples without any staining - so far all their imaging is based on staining and there are significant advantages in avoiding this
Collaborator Contribution They provided specialised biological samples to test the above concept
Impact joint grant ""UTXuCT X-ray phase contrast micro CT as a bridging imaging modality", EU ATTRACT Scheme, € 100,000 led by my colleague Dr M Endrizzi
Start Year 2018
 
Description Freeze drying of COVID vaccines 
Organisation University of Oxford
Country United Kingdom 
Sector Academic/University 
PI Contribution Freeze drying optimisation of COVID vaccine formulations
Collaborator Contribution Donation of COVID vaccine materials from Oxford University
Impact This is still in data form at present. Note last year we happened to be working with oxford on their ChAdOx system for rabies vaccines. Then covid happened, and so we immediately switched to working on their Covid vaccine version of ChAdOx, with a view to making them more accessible to LMICs through freeze drying. This was funded through a 3100k Vax-Hub (UCL/Oxford) feasibility study.
Start Year 2019
 
Description Huawei 
Organisation Huawei Technologies
Country China 
Sector Private 
PI Contribution Development of next generation low complexity transceivers for future access networks.
Collaborator Contribution Funding agreement and provision of optical and electronic components. This follows a series of previous collaborations with Huawei in digital signal processing and coherent optical communication systems
Impact Agreement signed.
Start Year 2016
 
Description Hyperhighway 
Organisation National Institute for Health Research
Department NIHR Southampton Respiratory Biomedical Research Centre
Country United Kingdom 
Sector Academic/University 
PI Contribution We have used UNLOC equipment and expertise to characterise antiresonant hollow core fibre
Collaborator Contribution Provision of antiresonant hollow core fibre for characterisation and exerimentation.
Impact Publications in submission
Start Year 2016
 
Description IMASENIC 
Organisation IMASENIC Advanced Imaging S.L.
Country Spain 
Sector Private 
PI Contribution We are providing input to new sensor design and making our labs available for testing
Collaborator Contribution They are training us on and providing access to their unique sensor technology
Impact We have won a joint Proof-of-Concept grant (2019 "XCOL: Low-cost, large area x-ray colour image sensors", EU ATTRACT Scheme, € 100,000, co-I (47.5k€ UCL), see below)
Start Year 2019
 
Description ISDI 
Organisation Indian School of Design and Innovation
Country India 
Sector Academic/University 
PI Contribution We are providing input to new sensor design and making our labs available for testing
Collaborator Contribution They are training us on and providing access to their unique sensor technology, and are co-funding a PhD student in the group
Impact None unless contributing to a CASE PhD studentship counts.
Start Year 2019
 
Description LCN/Bruker Partnership 
Organisation Bruker Corporation
Department Bruker Nano
Country Germany 
Sector Private 
PI Contribution The LCN AFM lab has been designated as Bruker's key partner in the development of high-resolution, high-speed AFM imaging for biological applications.
Collaborator Contribution The LCN AFM labs have been equipped to include the latest Bruker AFM technology. Broker is also co-sponsoring a 4-year PhD studentship
Impact This collaboration tackles key challenges at the interface between physical sciences and life sciences
Start Year 2015
 
Description Los Alamos National Labs 
Organisation Los Alamos National Laboratory
Country United States 
Sector Public 
PI Contribution We have provided lectures and practicals on the use of our technology
Collaborator Contribution They have given us access to, and trained on the use of, their unique facilities
Impact No output yet, pilot experiment conducted
Start Year 2019
 
Description MERL 
Organisation Mitsubishi Electric Research Laboratories
Country United States 
Sector Private 
PI Contribution Occasionally we provide our research facilities and lab equipment to partners from MERL to conduct a variety of testing.
Collaborator Contribution MERL is a valuable research partner with which we exchange and share ideas particularly in the area of DSP for high-capacity optical receivers. Recently our collaboration was features in an official press release from Mitstubishi, one of 15 highly competitve press news to come out of the company during a press conference in Japan in Feb 2016 ( see http://www.mitsubishielectric.com/news/2016/0215.h tml?cid=rss). MERL also provides a yearly charitable donation of $20 000 to the Optical Networks Group. In March 2016, MERL pledged to donate $25,000 to the UCL Optical Networks Group every year for a 4-year period. This has now started and work is in progress with new outcomes.
Impact publications, press release ( see http://www.mitsubishielectric.com/news/2016/0215.h tml?cid=rss), media coverage, joint experiments
Start Year 2013
 
Description Microworks 
Organisation MicroWorks
Country United States 
Sector Private 
PI Contribution We are feeding into the design of new x-ray optics; we are suggesting new x-ray mask designs to target new application, and testing them once they have been produced
Collaborator Contribution They stretched their design capabilities to design "ad hoc" masks, and provide test structures for our experiments
Impact Joint grant "Dynamic multi-modal x-ray imaging (DM-MX)", EU ATTRACT Scheme, € 100,000 and paper (Buchanan et al J Appl Phys 2020)
Start Year 2019
 
Description Microworks 
Organisation MicroWorks
Country United States 
Sector Private 
PI Contribution We are feeding into the design of new x-ray optics; we are suggesting new x-ray mask designs to target new application, and testing them once they have been produced
Collaborator Contribution They stretched their design capabilities to design "ad hoc" masks, and provide test structures for our experiments
Impact Joint grant "Dynamic multi-modal x-ray imaging (DM-MX)", EU ATTRACT Scheme, € 100,000 and paper (Buchanan et al J Appl Phys 2020)
Start Year 2019
 
Description Oclaro equipment 
Organisation Oclaro
Country United States 
Sector Private 
PI Contribution Intellectual expertise to perform experiments using Oclaro modulators as part of UNLOC experimental work
Collaborator Contribution Provision of advanced optical modulators and sources for the UCL Optical Networks Lab and UNLOC experimental programme to guide the development of next generation components and subsystems. Most recent devices provided in December 2016. A new programme of joint experiments is planned in 2017 including the use of semiconductor optical amplifiers.
Impact Publications from joint experiments, insights on next generation system design and management of nonlinearity in advanced optical communication systems. Direct contribution to the development of digital communications infrastructure.
Start Year 2012
 
Description Perkin Elmer 
Organisation Perkin Elmer
Country United States 
Sector Private 
PI Contribution We are adapting our technology for use in pre-clinical imaging, including direct contributions to the top-level design of an pre-clinical scanner protitype
Collaborator Contribution They have trained us on the needs of the pre-clinical imaging industry and are funding research in our group.
Impact Two papers: 1) Modregger P, Meganck J, Hagen C K, Massimi L, Olivo A and Endrizzi M "Improved iterative tomographic reconstruction for x-ray imaging with edge-illumination", Phys. Med. Biol. 64 (2019) 205008 https://doi.org/10.1088/1361-6560/ab439d 2) Hagen C K, Endrizzi M, Towns R, Megank J A and Olivo A "A preliminary investigation into the use of edge illumination x-ray phase contrast micro-CT for preclinical imaging", Mol. Imaging Biol. (2019) 10.1007/s11307-019-01396-5 DOI: 10.1007/s11307-019-01396-5
Start Year 2017
 
Description Photonic Science 
Organisation Photonic Science
Country United Kingdom 
Sector Private 
PI Contribution We have modified a design of one of their cameras by introducing a structured scintillator matching the requirements of our phase-based imaging methods
Collaborator Contribution They run preliminary tests on the camera to our requests then made the camera available for testing in our labs
Impact N/A
Start Year 2018
 
Description Quantum Communications Hub 
Organisation Quantum Communications Hub
Country United Kingdom 
Sector Learned Society 
PI Contribution The ultra high resolution optical spectrum analysis capability has been used in the testing of National Dark Fibre Infrastructure Service fibre transmission paths that are used for quantum key distribution field trials.
Collaborator Contribution Quantum key distribution experiments.
Impact Quantum key distribution field trials.
Start Year 2016
 
Description Scintacor 
Organisation Scintacor
Country United Kingdom 
Sector Private 
PI Contribution We are opening new device development frontiers alongside application developments
Collaborator Contribution They are developing new scintillator technology specifically aimed at our imaging methods
Impact Further funding (2018 "Low-cost, structured scintillators for x-ray phase contrast imaging and application to the early diagnosis of osteoarticular diseases", EPSRC/UCL Impact Acceleration Account "Discovery to Use" (D2U), £97,772, see below) to which they have contributed directly. The first test structures are being produced as I write.
Start Year 2018
 
Description 3. Incoherent x-ray phase contrast imaging methods based on intensity modulation, Direct Conversion AIC Opening Symposium, Graefeling Application and Innovation Centre, Munich, Germany, Jul 5-6 2019 
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 Present new technological capabilities to specific actors in detector industry
Year(s) Of Engagement Activity 2019
 
Description An introduction to x-ray phase contrast imaging and its applications, IMASENIC Headquarters, Barcelona, Spain, Feb 21 2020 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Industry/Business
Results and Impact Present new technological capabilities to specific actors in detector industry
Year(s) Of Engagement Activity 2020
 
Description Current state-of-the-art and applications of edge-illumination x-ray phase contrast imaging, Nikon, Yokohama Plant, Yokohama city, Kanagawa, Japan Oct 25 2019 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Industry/Business
Results and Impact Engage with Nikon HQs in Japan (so far we had an intense collaboration with the UK Branch "Nikon X-Tek Systems")
Year(s) Of Engagement Activity 2019
 
Description Detecting the undetectable - transforming the use of x-rays 124 years after their discovery, UCL Minds Lunch Hour Lectures, UCL, Oct 29 2019 
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 Public engagement - present new technological capabilities and their applications to the general public
Year(s) Of Engagement Activity 2019
 
Description Incoherent and multi-modal phase-based x-ray imaging and tomography, workshop on mask-based x-ray imaging, Technical University of Denmark (DTU), Lyngby, 7 Nov 2019 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Present new technological capabilities to students from an overseas university
Year(s) Of Engagement Activity 2019
 
Description Incoherent and non-interferometric lab-based x-ray phase contrast imaging: recent scientific developments and first pre-commercial prototypes, ESRF Seminars, Grenoble, France, Dec 18 2019 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Present new technological capabilities to key international lab with its students, technical staff and practitioners
Year(s) Of Engagement Activity 2019
URL http://www.esrf.eu/home/events/Seminars/area-events/esrf-seminars-list/incoherent-and-non-interferom...
 
Description Laboratory-based phase contrast tomography, CCPi Tomographic Imaging "Lunch & Learn" Seminar Series, held remotely (Zoom), May 12 2020 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Postgraduate students
Results and Impact Present new technological capabilities to students and CT users from across the UK
Year(s) Of Engagement Activity 2020
 
Description Multi-modal x-ray imaging, Academia-Government networking event on transport security, The Principal, Manchester, Nov 22 2018 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Policymakers/politicians
Results and Impact Present new technological capabilities to policymakers and industry
Year(s) Of Engagement Activity 2018
 
Description Opportunities for x-ray phase contrast imaging with laser-driven sources, held remotely (zoom), Community Meeting on Wakefield Acceleration, Sept 8 2020 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Postgraduate students
Results and Impact Present new technological capabilities to students and practitioners from a different community (laser plasma sources)
Year(s) Of Engagement Activity 2020
 
Description Phase contrast imaging: giving x-rays soft tissue sensitivity, Medical Imaging Convention 2019, NEC Birmingham, Mar 26-27 2019 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Present new technological capabilities to medical practitioners
Year(s) Of Engagement Activity 2019
 
Description Stand at "Made@UCL" Science Fair, Oct 5 2019 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Public engagement - present new technological capabilities and their applications to the general public
Year(s) Of Engagement Activity 2019
 
Description UCL Physics and Engineering in Medicine Podcast "How to advance x-ray imaging, seeing the unseen" (May 5), made available on Jun 19: 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Postgraduate students
Results and Impact Public engagement - discuss new technological capabilities and their applications for the benefit of students and the general public
Year(s) Of Engagement Activity 2020
URL https://soundcloud.com/user-857709813/5-how-to-advance-x-ray-imaging-seeing-the-unseen
 
Description X-Rays do not have soft tissue sensitivity? Think again. CABI Seminar Series, UCL Centre for Advanced Biomedical Imaging, London, UK, Feb 7 2020 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Postgraduate students
Results and Impact Present new technological capabilities to biomedical students
Year(s) Of Engagement Activity 2020