In-situ Characterisation of the Crystal Growth of Organic Materials through Microscopic Imaging, Image Processing and Machine Learning

The crystal growth of organic materials is of significant importance within the speciality and fine chemical industries. This reflects its utility in materials purification and its use in preparing a wide range of compounds which have the well-defined crystal size, shape and polymorphic form needed for optimal product performance. The latter is important e.g. in ensuring the reproducible dissolution and stability behaviour needed to maintain the safety and efficacy of ingredients within formulated products.<br /> <br /> The inherent molecular-scale complexity of organic materials can directly impact on the physical chemical properties of crystals, notably their crystallisation in low symmetry crystallographic structures which have anisotropic external crystal morphologies and surface properties. Changes to, or variability in, these properties can affect their performance, e.g. their purity, bioavailability, powder flow, stability and manufacturability. Current crystal size measurements can be over-simplistic in terms of shape characterisation being focussed mostly on spherical particles. Such methods do not reflect the facetted (polyhedral) crystal morphologies common found within organic solids where different crystal habit faces can exhibit different surface chemistry which can expose different intermolecular binding interactions within the chemical processing environment. Currently, there is a critical capability gap in terms of being able to relate the molecular structure of a material to its performance in its crystalline particulate form. This knowledge gap has led to increasing interest in fusing in-situ experimental crystallisation studies with a knowledge of its core molecular structure and its simulated surface properties based upon crystallographic data linked to artificial intelligence (AI) and machine learning approaches. <br /> <br /> This project addresses the above need by applying digital AI-enabled technology to develop morphologically-based shape descriptors with targeted utility for the precise 3D characterisation of crystalline particulates in-situ. Overall, the project aims to enable the capability to design organic crystalline ingredients and the products resulting from their formulation to a much tighter specification notably higher quality, more consistency and less variability. The proposed project is directly associated with an EPSRC research project (https://eps.leeds.ac.uk/research-project/1/faculty-of-engineering-and-physical-sciences/4417/advanced-crystal-shape-descriptors-for-precision-particulate-design-characterisation-and-processing-shape4ppd).

<p style="margin-bottom:11px">The aim of this project is to support the production of precision crystalline particulate materials through actual characterisation of 3D crystal shape and size. To do this machine learning will be applied to map the images from in-situ microscopy to a description of 3D crystal shape and functional properties. This will help enable the design and manufacture of crystalline fine chemicals to a much tighter specification for particle size and shape than is currently feasible, resulting in more consistency, less variability in physical and chemical properties and concomitantly higher quality.</p> <p>This project will suit a self-motivated graduate student with a chemical process engineering or physical sciences background. The student will carry out interdisciplinary research at the University of Leeds which has an international reputation for excellence in teaching and research. The student will seek to integrate crystallisation technology with&nbsp;AI/machine learning approaches, under the supervision of the experts from these two areas, with a focus on the 3D crystal characterisation of crystallisation processes. The student will achieve the project aims through various research tasks including:</p> <ol> <li>Literature review including crystallisation of organic materials together with their crystallography, crystal growth kinetics and morphology.</li> <li>Development and commissioning of a novel in-situ microscopy systems for the dynamic characterisation of crystal morphology and the kinetic mechanisms of growth.</li> <li>Experimental studies of the morphological characterisation and crystal growth kinetics collecting crystal images prepared under varying process conditions</li> <li>Using molecular and crystallographic modelling to characterise in-situ microscopy data integrating &nbsp;this with AI/machine learning techniques</li> <li>Extending microscopy approach to on-line imaging tools for monitoring the dynamics of&nbsp; the growth of a population of crystals as observed during batch and continuous crystallisation processes, integrating this with process simulations notably through morphological population balance modelling</li> </ol> <p>The final deliverables will be inclusively:</p> <ol> <li>Rapid characterisation of a representative crystallisation process together with the temporal development of crystal morphology and growth kinetics as a function of solution supersaturation.</li> <li>Understanding the effect of additives, impurities and solid-solution formation upon the crystal growth process.</li> <li>Comparison of microscopy single crystal growth data with in-process crystallisation measurement during a representative crystallisation processes.</li> </ol> <p>The project is an interdisciplinary research with team science skills of particle technology (characterisation) and artificial intelligence (machine learning). The supervisory team includes experts from Schools of Chemical and Process Engineering (Prof K J Roberts, Dr R B Hammond, Dr C Y Ma), and Computing (Prof D C Hogg), and the industrial company Syngenta (Dr N George). This studentship project will be experiment-intensive using the crystallisation laboratories at the School of Chemical and Process Engineering which are exceptionally well equipped with e.g. in-situ microscopy, crystallisation systems (1ml, 7ml, 100ml, 500ml, 1L, 2L, 5L and 20L), solid-state characterisation instruments (including Keyence VHX7000 Digital Microscope, IGC/GC, DSC, TGA, DVS, FTIR, UV-vis, Morphologi G3, XRD, SEM, etc.).</p> <p>Support&nbsp;by the project&rsquo;s industrial partner, Syngenta, will provide placement opportunities for industrial case studies. In addition, there will be further opportunities for collaborative work with a number of other UK university research groups.</p>

<p>Formal applications for research degree study should be made online through the&nbsp;<a href="https://www.leeds.ac.uk/research-applying/doc/applying-research-degrees">University&#39;s website</a>. Please state clearly in the Planned Course of Study section that you are applying for <em><strong>PHD Chemical &amp; Process Engineering FT</strong></em> and in the research information section&nbsp;that the research degree you wish to be considered for is <em><strong><span style="font-size:11.0pt"><span style="line-height:107%"><span style="font-family:&quot;Calibri&quot;,sans-serif">In-situ Characterisation of the Crystal Growth of Organic Materials through Microscopic Imaging, Image Processing and Machine Learning</span></span></span></strong></em>&nbsp;as well as&nbsp;<a href="https://eps.leeds.ac.uk/chemical-engineering/staff/228/professor-kevin-roberts">Professor Kevin Roberts</a> as your proposed supervisor.</p> <p>If English is not your first language, you must provide evidence that you meet the University&#39;s minimum English language requirements (below).</p> <p><em>As an international research-intensive university, we welcome students from all walks of life and from across the world. We foster an inclusive environment where all can flourish and prosper, and we are proud of our strong commitment to student education. Across all Faculties we are dedicated to diversifying our community and we welcome the unique contributions that individuals can bring, and particularly encourage applications from, but not limited to Black, Asian, people who belong to a minority ethnic community, people who identify as LGBT+ and people with disabilities. Applicants will always be selected based on merit and ability.</em></p> <p class="MsoNoSpacing">Applications will be considered on an ongoing basis. &nbsp;Potential applicants are strongly encouraged to contact the supervisors for an informal discussion before making a formal application. &nbsp;We also advise that you apply at the earliest opportunity as the application and selection process may close early, should we receive a sufficient number of applications or that a suitable candidate is appointed.</p> <p>Please note that you must provide the following documents at the point you submit your application:</p> <ul> <li>Full Transcripts of all degree study or if in final year of study, full transcripts to date</li> <li>Personal Statement outlining your interest in the project</li> <li>CV</li> <li>Funding information including any alternative sources of funding that you are applying for or if you are able to pay your own fees and maintenance</li> </ul>

Applicants to research degree programmes should normally have at least a first class or an upper second class British Bachelors Honours degree (or equivalent) in an appropriate discipline. The criteria for entry for some research degrees may be higher, for example, several faculties, also require a Masters degree. Applicants are advised to check with the relevant School prior to making an application. Applicants who are uncertain about the requirements for a particular research degree are advised to contact the School or Graduate School prior to making an application.

The minimum English language entry requirement for research postgraduate research study is an IELTS of 6.0 overall with at least 5.5 in each component (reading, writing, listening and speaking) or equivalent. The test must be dated within two years of the start date of the course in order to be valid. Some schools and faculties have a higher requirement.

<p style="margin-bottom:12px"><strong>Self-Funded or externally sponsored students are welcome to apply.</strong></p> <p><strong>UK</strong>&nbsp;&ndash;&nbsp;The&nbsp;<a href="https://phd.leeds.ac.uk/funding/209-leeds-doctoral-scholarships-2022">Leeds Doctoral Scholarships</a> and <a href="https://phd.leeds.ac.uk/funding/234-leeds-opportunity-research-scholarship-2022">Leeds Opportunity Research Scholarship</a> are available to UK applicants. <a href="https://phd.leeds.ac.uk/funding/60-alumni-bursary">Alumni Bursary</a> is available to graduates of the University of Leeds.</p> <p><strong>Non-UK</strong> &ndash;The&nbsp;<a href="https://phd.leeds.ac.uk/funding/48-china-scholarship-council-university-of-leeds-scholarships-2021">China Scholarship Council - University of Leeds Scholarship</a>&nbsp;is available to nationals of China. The&nbsp;<a href="https://phd.leeds.ac.uk/funding/73-leeds-marshall-scholarship">Leeds Marshall Scholarship</a>&nbsp;is available to support US citizens. <a href="https://phd.leeds.ac.uk/funding/60-alumni-bursary">Alumni Bursary</a> is available to graduates of the University of Leeds.</p> <p><strong>Important:</strong>&nbsp; Any costs associated with your arrival at the University of Leeds to start your PhD including flights, immigration health surcharge/medical insurance and Visa costs are <strong>not</strong> covered under this studentship.</p> <p>Please refer to the <a href="https://www.ukcisa.org.uk/">UKCISA</a> website for information regarding Fee Status for Non-UK Nationals.</p>

<p>For further information about this project, please contact Professor Kevin Roberts: e:&nbsp;<a href="mailto:a.e.bayly@leeds.ac.uk">k.j.roberts@leeds.ac.uk</a></p> <p>For further information about your application, please contact Doctoral College Admissions: e:&nbsp;<a href="mailto:phd@engineering.leeds.ac.uk">phd@engineering.leeds.ac.uk</a></p>