Flow-Xl: A New UK Facility for Analysis of Crystallisation in Flow Systems

Lead Research Organisation: University of Leeds
Department Name: Sch of Chemistry

Abstract

Crystalline materials are everywhere. They are abundant in nature (eg bones and seashells) and in the environment (eg. rocks and ice) and are found across a diverse selection of everyday products including pharmaceuticals, batteries and food. Crystallisation can also be undesirable, such as in the formation of kidney stones or scale in a kettle. The ability to control crystallisation processes - to generate particles with specific sizes, shapes and structures, and to control where and when crystallisation occurs - therefore promises huge benefits to society. Here, we need to develop strategies to prevent crystallisation. All of these goals can only be achieved by developing a robust understanding of the mechanisms that underlie crystal nucleation and growth.

This project will create a new UK, and indeed world-first research facility - Flow-Xl - that can address this challenge. Flow-Xl will be located at the University of Leeds and will enable in situ, time-resolved characterisation of crystallisation processes in highly controlled environments. This will be achieved by coupling X-ray diffraction and Raman spectroscopy to a range of fully-integrated flow platforms. These analytical techniques will be used simultaneously to study crystallisation pathways from amorphous and poorly crystalline precursor materials, through crystalline intermediates, to the ultimate crystal products. This combined capability is not currently available anywhere else in the world.

Flow-Xl is also extremely timely, where it is only possible because top-of-the-range laboratory X-ray instruments are now so good that they can replace synchrotrons for many experiments. Parallel innovative data processing and analysis methods will be developed and provided for Flow-Xl users, building on our key breakthrough methodology. These will allow the maximum information to be obtained from Flow-Xl experiments.

The use of flow systems is also critical to our technique, and Flow-Xl will offer a number of contrasting flow platforms. The simplest of all is continuous flow, which mimics many industrial manufacturing processes. Many industrial crystallisation processes also take place in stirred vessels, and these environments will be studied by withdrawing solution from a batch reactor through a flow loop for analysis. Finally, it will be possible to study crystallisation in segmented flow, where individual droplets provide highly reproducible reaction environments that are ideally suited to fundamental studies of crystallisation mechanisms. Flow-Xl will also enable us to share our expertise in the manufacture of flow-cells for X-ray measurements with the entire UK research community.

Flow-Xl will be operated as a multi-user facility that is open to all academic and industrial researchers across the UK, and will be supported by an experienced research officer. This will allow the equipment to be fully utilised for a wide range of projects spanning industrial processes through to developing fundamental understanding. In addition to providing a cutting-edge, stand-alone research facility, Flow-Xl will also support Diamond Light Source and its users by providing an alternative or precursor to synchrotron time for many experiments. This frees-up precious beam-time for experiments that really need it, and enables researchers to conduct screening/ feasibility experiments prior to their beam-time.

The facility will support a range of existing projects including the formation of organic framework compounds, biomineralisation and bio-inspired crystallisation, fouling, materials discovery, production of single enantiomer crystals, polymorph selection and the development of artificial intelligence in modelling of crystallisation. By building a strong user community from academia and industry over the course of the project, we will ensure this powerful new facility finds application across a wide range of scientific programmes.

Planned Impact

We will establish a unique, laboratory-based facility (Flow-Xl) for in situ X-ray diffraction and Raman study of crystallisation and materials assembly processes under flow conditions. Flow-Xl will provide researchers from academia and industry with a new capability, allowing them to analyse crystallisation and assembly processes in situ with excellent time resolution and definition of reaction conditions. While the need to characterise crystallisation mechanisms is central to virtually every study of crystallisation phenomena, it remains a significant challenge.

Contributions to the Knowledge Base
The state-of-art equipment will provide the community with a new experimental capability that will contribute to the fundamental knowledge base across a wide range of disciplines (chemistry, pharma, materials, food) through high impact papers, presentations at key international conferences, seminars and our focused user events.

Collaboration and Network Activities
The facility will offer support and access for a broad user-base interested in the discovery, development and application of crystallisation methods across the fine chemical, pharmaceutical and materials sectors. The research enabled by Flow-Xl will be exploited by collaboration with a range of critical mass research and community networks. These include the CMAC Manufacturing Hub, UK Catalysis Hub, Centre for Sustainable Chemical Technologies, Centre for Sustainable Chemistry, the Materials Innovation Factory, the Royce Institute, the Leeds Institute for Process Research and Development (iPRD), Diamond Light Source and the Directed Assembly Network. In particular, Flow-Xl will complement experimental opportunities at Diamond, and we will work in partnership with them to ensure opportunities are maximised.

User Engagement and Training
Flow-Xl will be operated with a user-focused model; our goal is to create a vibrant academic and industrial user community. Extensive support will be provided by an experienced research officer, and researcher training will include the use of flow platforms, diffraction and Raman techniques and analysis of multi-variate data. Flow-Xl will therefore offer valuable training for the next generation of chemists, physicists, engineers and materials scientists who need to control crystallisation or materials assembly for functional materials, supramolecular chemistry, crystal and particle engineering and sustainable manufacturing. Engagement via access visits, applications support and user meetings will ensure that users are able to benefit from developments in experimental approaches, to carry out new experiments and adapt flow systems to meet their research needs. This ambitious and varied project also provides an exceptional training opportunity for a postdoctoral researcher.

Economic and Societal Benefit
Flow-Xl provides excellent opportunities for economic benefit via engagement with industry. It will support existing industries and open up new opportunities for growth in areas including food, fine chemicals and pharmaceuticals by enabling characterisation and optimisation of crystallisation processes. Continuous processing is attracting increasing attention, but is hindered through a lack of in situ XRD characterisation. Flow-Xl will therefore contribute to the economy by delivering manufacturing-related research, increasing the competitiveness of advanced process manufacturing by developing new, agile, cost-effective processes and creating innovative products through new technologies. Our network of industry users includes leading pharmaceutical manufacturers AZ, Bayer, GSK, Lilly, Novartis, Pfizer, Roche, Takeda and agrichemical manufacturer Syngenta; we will grow this network over the award.

We will deliver public engagement via a dedicated website and articles, various events such as Science cafes and through the STEM Ambassador programme, using examples and demonstrators to inspire the next generation of researchers

Publications

10 25 50
publication icon
Nahi O (2022) Polyamines Promote Aragonite Nucleation and Generate Biomimetic Structures. in Advanced science (Weinheim, Baden-Wurttemberg, Germany)

publication icon
Nahi O (2022) Positively Charged Additives Facilitate Incorporation in Inorganic Single Crystals. in Chemistry of materials : a publication of the American Chemical Society

 
Description Flow-Xl is a new facility designed for the analysis of crystallisation processes that will enable researchers to conduct in situ studies of crystallisation mechanisms and pathways with unprecedented reproducibility and time resolution. It allows researchers to study crystallisation pathways from amorphous and poorly crystalline precursor materials, through crystalline intermediates, to the ultimate crystal products. This will ultimately enable strategies to be developed that will allow us to control crystallisation processes in applications as diverse as the production of pharmaceuticals and nanoparticles or the prevention of scale formation.

Flow-Xl combines X-ray diffraction (XRD) and Raman spectrometry to study crystallisation processes in highly controlled environments. It comprises a high performance X-ray diffractometer, a Raman spectrometer and a range of crystallisation environments including temperature-regulated segmented flow and continuous flow platforms, and
batch reactors. This capability has only just become possible, where state-of-the-art X-ray diffractometers are now so good that they can replace synchrotrons for many experiments.

This is a world-first instrumental platform that combines state-of-the-art flow environments with in situ diffraction and spectroscopic measurements in a laboratory situation and opens up this capability to all UK researchers.
Exploitation Route The facility is now fully available for access by users within the University of Leeds and external (from academic and industry)
Sectors Agriculture

Food and Drink

Chemicals

Energy

Environment

Healthcare

Manufacturing

including Industrial Biotechology

Pharmaceuticals and Medical Biotechnology

URL https://eps.leeds.ac.uk/dir-record/facilities/4391/flow-xl-a-new-uk-facility-for-analysis-of-crystallisation-in-flow-systems
 
Description We have now established a new facility (Flow-Xl) for the in situ study of crystallisation processes under highly controlled reaction conditions, where state-of-the-art XRD and Raman spectroscopy are coupled with a wide range of crystallisation platforms. This facility is open to all UK researchers, and we have had users from academia and industry.
First Year Of Impact 2023
Sector Agriculture, Food and Drink,Chemicals,Manufacturing, including Industrial Biotechology
Impact Types Societal

 
Title Establishment of Flow-Xl facility 
Description We have built a new UK facility, named Flow-Xl, for studying crystallisation processes in flow systems. The facility comprises a state-of-the-art single crystal X-ray diffractometers and Raman spectrometer, and enables experiments that would have previously required access to a synchrotron source. 
Type Of Material Improvements to research infrastructure 
Year Produced 2022 
Provided To Others? No  
Impact The instrument is in its commissioning phase and will then be made openly available to UK researchers. 
 
Title Dataset for 'Serial Small- and Wide-Angle X-ray Scattering with Laboratory Sources' 
Description This dataset contains measurements used in the paper, 'Serial Small- and Wide-Angle X-ray Scattering with Laboratory Sources' from the journal, IUCrJ (doi: 10.1107/S2052252522007631). Included are the raw SAXS, WAXS, and XRD patterns used in the evaluation of different samples, sample environments, and X-ray scattering instruments. From these data, the authors determined that it is feasible to perform serial SAXS/WAXS analysis of materials using laboratory X-ray sources with the aid of micro- and milli-fluidic sample environments. 
Type Of Material Database/Collection of data 
Year Produced 2022 
Provided To Others? Yes  
URL https://archive.researchdata.leeds.ac.uk/1010/
 
Description Batch cooling crystallisation of Iron Heptahydrate 
Organisation University of Leeds
Department School and Chemical and Process Engineering
Country United Kingdom 
Sector Academic/University 
PI Contribution Run facility used to study the cooling crystallisation of Iron Heptahydrate in a batch process vessel using Raman spectroscopy
Collaborator Contribution developed the project
Impact Project still on-going
Start Year 2023
 
Description Batch cooling crystallisation of Iron Heptahydrate (process vessel) 
Organisation University of Leeds
Department School and Chemical and Process Engineering
Country United Kingdom 
Sector Academic/University 
PI Contribution Assistance with running experiment on Flow-XL
Collaborator Contribution Test new experimental system
Impact None yet
Start Year 2022
 
Description Batch cooling crystallisation of L-glutamic acid 
Organisation University of Leeds
Department School and Chemical and Process Engineering
Country United Kingdom 
Sector Academic/University 
PI Contribution Run facility where study of the batch cooling crystallisation of L-glutamic acid was carried out in a process vessel, using XRD and Raman spectroscopy
Collaborator Contribution developed the project
Impact project still on-going
Start Year 2023
 
Description Batch cooling crystallisation of L-glutamic acid (process vessel) 
Organisation University of Leeds
Department School and Chemical and Process Engineering
Country United Kingdom 
Sector Academic/University 
PI Contribution Assistance with running experiment
Collaborator Contribution Test experiment for Flow-Xl facility
Impact None yet
Start Year 2022
 
Description Crystallization of mucin in sodium chloride solutions 
Organisation University of Leeds
Department School and Chemical and Process Engineering
Country United Kingdom 
Sector Academic/University 
PI Contribution Offered facility and support for studying the crystallization of mucin in sodium chloride solutions in droplet environments using an acoustic levitator and in situ XRD
Collaborator Contribution They developed the experiment
Impact Project still underway
Start Year 2023
 
Description Droplet crystallisation of Alpha Olefin Sulfonate 
Organisation University of Leeds
Department School and Chemical and Process Engineering
Country United Kingdom 
Sector Academic/University 
PI Contribution Provided flow-Xl facility to study the crystallisation of Alpha Olefin Sulfonate in droplets using an acoustic levitator, coupled with XRD and Raman
Collaborator Contribution They developed the experiment
Impact project still underway
Start Year 2023
 
Description Droplet crystallisation of Alpha Olefin Sulfonate (acoustic levitator) 
Organisation University of Leeds
Department School and Chemical and Process Engineering
Country United Kingdom 
Sector Academic/University 
PI Contribution Help with running experiment/ use of facility
Collaborator Contribution Use of facility
Impact School of Chemical and Process Engineering, University of Leeds - Prof. David Harbottle; Student: Robin Winder - Droplet crystallisation of Alpha Olefin Sulfonate (acoustic levitator)
Start Year 2023
 
Description Monitoring of the phase transformation of pharmaceutical hydrates 
Organisation GlaxoSmithKline (GSK)
Country Global 
Sector Private 
PI Contribution Run the facility and offer assistance with experiments looking at the solution mediated phase transformation of pharmaceutical hydrates (XRD). GSK will be paying for access to the equipment (costs under negotiation)
Collaborator Contribution Developed the experiment
Impact Project still underway
Start Year 2024
 
Description Nik Kapur microfluidics 
Organisation University of Leeds
Department Institute of Transport Studies
Country United Kingdom 
Sector Academic/University 
PI Contribution Our research team has identified the problem that needs to be solved - characterisation of inorganic materials by XRD on-chip. We contribute expertise in materials chemistry and XRD analysis.
Collaborator Contribution Nik Kapur has assisted in the design of microfluidic devices that can be used for synchrotron XRD analysis of crystallisation within droplets. His expertise in fluid dynamics and the design and manufacture of devices has been invaluable.
Impact 1 paper to date. Multi-disciplinary collaboration between chemistry and engineering.
Start Year 2014
 
Description Polarised Raman of paracetamol single crystals 
Organisation University of Leeds
Department School and Chemical and Process Engineering
Country United Kingdom 
Sector Academic/University 
PI Contribution Assistance with making measurements
Collaborator Contribution Trial capabilities of Flow-Xl
Impact None yet
Start Year 2022
 
Description Polarised Raman of paracetamol single crystals 
Organisation University of Leeds
Department School and Chemical and Process Engineering
Country United Kingdom 
Sector Academic/University 
PI Contribution Run facility where experimental study of paracetamol single crystals using polarised Raman spectroscopy and single crystals XRD was carried out
Collaborator Contribution Developed project
Impact Project still on-going
Start Year 2024
 
Description Prof Chick Wilson 
Organisation University of Bath
Department School of Health Bath
Country United Kingdom 
Sector Academic/University 
PI Contribution We helped them carry out in situ XRD analysis of crystallisation in millifluidic segmented flow reactors at Diamond light source and analyse their data
Collaborator Contribution They participated in a number of joint beam-times
Impact We are currently writing a number of joint publications and grant proposal
Start Year 2016
 
Description ZIF-8 crystallisation as a function of processing conditions 
Organisation University of Birmingham
Department School of Chemistry
Country United Kingdom 
Sector Academic/University 
PI Contribution Assistance with running experiment
Collaborator Contribution Supply test experiment for Flow-Xl system
Impact None yet
Start Year 2022
 
Description Poster presentation 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Postgraduate students
Results and Impact Poster: Stone, R.J., Turner, T.D., Bourne, R.A., Meldrum, F.C., Kapur, N. Monitoring the influence of Mg2+ concentration on the crystal growth kinetics of Calcium Sulphate using in-line powder XRD. CDT in Molecules to Product annual conference, July 2022.
Year(s) Of Engagement Activity 2022
 
Description Presentation to IPRD group 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Industry/Business
Results and Impact Presentation about Flow-Xl facility to the industrial club of the Institute of Process Research and Development (IPRD) at Leeds University. There was significant interest in the facility from the attending industrialists.
Year(s) Of Engagement Activity 2021
 
Description Rigaku European Single-Crystal User Meeting 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact Flow-Xl: A New UK Facility for the Analysis of Crystallisation in Flow Systems, Rigaku European Single-Crystal User Meeting
Year(s) Of Engagement Activity 2023
 
Description Rigaku Webinar on Flow-Xl 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Invited Webinar: TOPIQ: Flow-Xl: A New UK Facility for the Analysis of Crystallisation in Flow Systems, Rigaku Online Resources
Year(s) Of Engagement Activity 2023
URL https://www.youtube.com/watch?v=4UDdAkdEHVw
 
Description Syngenta Newsletter 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Industry/Business
Results and Impact T. D. Turner, Flow-Xl: A New UK Facility for the Analysis of Crystallisation in Flow Systems, Syngenta Newsletter, Jan 2022
Year(s) Of Engagement Activity 2022
 
Description Syngenta Technology Transfer Workshop 
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 Presentation on "Droplet and Flow Based XRD studies" given by Dr Tom Turner, given to disseminate the capabilities of the Flow-Xl facility to the audience of academic and industrial researchers.
Year(s) Of Engagement Activity 2023
 
Description Talk - iPRD Industrial Club Meeting, University of Leeds 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Industry/Business
Results and Impact Invited Talk: Flow-Xl: A New UK Facility for the Analysis of Crystallisation in Flow Systems, iPRD Industrial Club Meeting, University of Leeds, November 4th 2021
Year(s) Of Engagement Activity 2021
 
Description Talk - Astrazeneca Group Meeting 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Industry/Business
Results and Impact Talk: Flow-Xl: A New UK Facility for the Analysis of Crystallisation in Flow Systems, Astrazeneca Group Meeting, Online, May 13th 2022
Year(s) Of Engagement Activity 2022
 
Description Talk - CDT in Molecules to Product annual conference 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Postgraduate students
Results and Impact Stone, R.J. Monitoring the influence of Mg2+ concentration on the crystal growth kinetics of Calcium Sulphate using in-line powder XRD. CDT in Molecules to Product annual conference, July 2022.
Year(s) Of Engagement Activity 2022
 
Description Talk - Crystallisation Day, University of Leeds 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Industry/Business
Results and Impact Talk: Flow-Xl: A New UK Facility for the Analysis of Crystallisation in Flow Systems, Crystallisation Day, University of Leeds, May 12th 2022
Year(s) Of Engagement Activity 2022
 
Description Talk - Syngenta Group Meeting 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Industry/Business
Results and Impact Invited Talk: Flow-Xl: A New UK Facility for the Analysis of Crystallisation in Flow Systems, Syngenta Group Meeting, Online, February 21st 2022
Year(s) Of Engagement Activity 2022
 
Description talk - Advanced Materials Research Group Seminar, University of Nottingham 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Postgraduate students
Results and Impact Talk: In-Situ Characterisation of Crystallisation Systems; Nucleation, Growth and Phase Transformations, Advanced Materials Research Group Seminar, University of Nottingham, Online, June 6th 2022
Year(s) Of Engagement Activity 2022