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Microfluidic Deformation for Intracellular Delivery

PGR-P-1094

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Key facts

Type of research degree
PhD
Application deadline
Monday 31 January 2022
Project start date
Saturday 1 October 2022
Country eligibility
International (open to all nationalities, including the UK)
Funding
Competition funded
Source of funding
University of Leeds
Supervisors
Dr Kevin Critchley and Dr Aleks Ponjavic
Additional supervisors
Prof Steve Evans
Schools
School of Physics and Astronomy
Research groups/institutes
Molecular and Nanoscale Physics
<h2 class="heading hide-accessible">Summary</h2>

The aim of this PhD to study a high-throughput microfluidic platform to facilitate the controlled uptake of nanoparticles into live cells for intracellular probes (for reporting on cancer cells), respectively, using experimental methods. We will explore the non endocytotic uptake of optical intracellular nano-reporters for live cells. Endocytosis limits the ability of probes to report on the cytoplasm. Intracellular nano-reporters improve the ability to assess the physiochemical properties of cancer cells, e.g., ion concentration, redox potential, and pH. We will study their fate of NPs when taken into cells to determine whether these allow better reporting of the redox environment. During this PhD you will develop a deeper understanding of the biophysics of cells, under shear flow, in relation to the factors that control the disruption of membranes, and their repair. This includes, but is not limited to, membrane pore size, pore lifetimes, and pore density as a function of the shear stress applied and the cell type. To do this we will be using advanced fluorescence microscopy techniques as well as electron microscopy. You will be trained in how to work with cells and perform the biological assays.

<h2 class="heading hide-accessible">Full description</h2>

<p>Mechanical deformation using microfluidics can be used to allow the uptake of nanoparticles into cells.&nbsp; However, much is left to understand about this process and this is what will define the PhD.&nbsp; For example, the pore density (in the cell membrane), diameter, and lifetime as a function of cell type and deformation conditions will need to be determined. The pore size will be analyzed by comparing the uptake of a range polymer based dyes. The uptake can be characterized by flow cytometry and complimented by fluorescence microscopy. The pore lifetime is likely to be dependent on cell type, the pore size, and factors such presence of Ca<sup>2+</sup> (increase in Ca<sup>2+</sup> signals for healing response).&nbsp; The lifetime of the pores will be addressed by uptake and release experiments.&nbsp; Measuring the fluorescence from a dye after the deformation will establish the healing time. In another method, dye-loaded live cells will be prepared before deformation.&nbsp; The loss of fluorescence signal can be monitored &lsquo;post&rsquo; deformation time.&nbsp; By measuring the fluorescence signal, on chip, as a function of channel position downstream of the deformation, the first 30 ms can be assessed by fast fluorescence microscopy. For longer times (seconds to minutes), the release kinetics can be assessed off chip by conventional fluorescence microscopy.&nbsp; Fluorescence microscopy can therefore reveal when and where the healing has taken place for the cells.</p> <p>&nbsp;</p>

<h2 class="heading">How to apply</h2>

<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 that you are applying for <em><strong>PHD Physics &amp; Astronomy FT</strong></em> and&nbsp;in the research information section&nbsp;that the research degree you wish to be considered for is <em><strong>Microfluidic Deformation for Intracellular Delivery</strong></em> as well as Dr&nbsp;Kevin Critchley 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>

<h2 class="heading heading--sm">Entry requirements</h2>

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.

<h2 class="heading heading--sm">English language requirements</h2>

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.

<h2 class="heading">Funding on offer</h2>

<p><strong>Self-Funded or externally sponsored students are welcome to apply.</strong></p> <p><strong>UK&nbsp;</strong>&ndash;&nbsp;The&nbsp;<a href="https://phd.leeds.ac.uk/funding/209-leeds-doctoral-scholarships-2022">Leeds Doctoral Scholarships</a>, <a href="https://phd.leeds.ac.uk/funding/198-akroyd-and-brown-scholarship-2022">Akroyd &amp; Brown</a>, <a href="https://phd.leeds.ac.uk/funding/199-frank-parkinson-scholarship-2022">Frank Parkinson</a> and <a href="https://phd.leeds.ac.uk/funding/204-boothman-reynolds-and-smithells-scholarship-2022">Boothman, Reynolds &amp; Smithells</a> are available to UK applicants. The&nbsp;<a href="https://phd.leeds.ac.uk/funding/102-bell-burnell-scholarship-award-awarded-by-the-iop">Bell Burnell Scholarship Award</a>&nbsp;is available to support applicants who are from groups that are currently under-represented in physics (awarded by the IOP).&nbsp; <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/63-school-of-physics-astronomy-partial-fee-only-scholarship">School of Physics &amp; Astronomy Partial Fee Scholarship&nbsp;</a>is available to support the additional academic fees of Non-UK applicants. The&nbsp;<a href="https://phd.leeds.ac.uk/funding/102-bell-burnell-scholarship-award-awarded-by-the-iop">Bell Burnell Scholarship Award</a>&nbsp;is available to support applicants who are from groups that are currently under-represented in physics (awarded by the IOP).&nbsp; &nbsp;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>

<h2 class="heading">Contact details</h2>

<p>For further information regarding the project, please contact Dr Kevin Critchley<br /> e: <a href="mailto:EMAIL@leeds.ac.uk">k.critchley@leeds.ac.uk</a></p> <p>For further information regarding your application, please contact Doctoral College Admissions<br /> e:&nbsp;<a href="mailto:maps.pgr.admissions@leeds.ac.uk">maps.pgr.admissions@leeds.ac.uk</a></p>


<h3 class="heading heading--sm">Linked funding opportunities</h3>