Engineering approaches to exploiting human Cardio-spheroids in Drug discovery.

Lead Research Organisation: Heriot-Watt University
Department Name: Sch of Engineering and Physical Science

Abstract

"his is a PhD research project that integrates engineering/Physics/chemistry/biology to develop new biophysical tools to interrogate organoids in a reproducible and 'high throughput' manner. This will enable the screening of cardio relevant small compound libraries and personalised drug discovery. Cardio -spheroids (CS) are bioengineered human heart-like organoids and are emerging as powerful tools in drug discovery. These organoids are 500 'balls' of human cardiomyocytes that beat with a similar frequency to the human heart rhythm (60-70 BPM). Their electrical activity is strikingly similar to the human ECG. Drug discovery companies are producing a large number of cell lines, however, it is not clear whether these organoids will be useful in the drug discovery process, transplantation or safety testing. The size and material properties of the CSs render them unsuitable for use in conventional electrophysiological microelectrode arrays (one organoid/64 electrode array). The PhD project would involve, collaborating with Censo Technologies Ltd in standardizing the production of these organoids, developing trapping technologies that allow the flexible electrical measurement to be carried out on a large scale (custom multielectrode arrays), characterising the cell lines electrophysiologically and developing standard protocols and devices for upscaling the process.
Training will be given in cell programming, cell culture, library and compound selection, electrophysiology (multi-electrode arrays and voltage clamp), imaging and signal processing.
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Publications

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Studentship Projects

Project Reference Relationship Related To Start End Student Name
EP/R512539/1 01/10/2017 30/09/2021
1974532 Studentship EP/R512539/1 01/10/2017 30/09/2021 Mario Alvarez Martinez
 
Description Microelectrode array technology can be used to assess cell viability in a medical setting. During pancreatic islet (the cells that control blood sugar levels and are affected in diabetes) transplantation, cell viability is assessed subjectively by microscope inspection using a live/dead fluorescence assay. Donated pancreases are a scarce resource and >80% are discarded because of marginal islet yields viabilities. As transplant outcomes are associated with islet numbers and viability, quantitative assessments of islet viability would enable more pancreases to be used, better isolation protocols and more transplants.
- I have propose the islet electrical activity as an objective marker to assess islet viability and improve transplant outcomes. For this purpose, I have build a customized microelectrode array.
- My experiments suggest that islet electrical activity is comparable to other methods with some advantages such as objective, quick and real-time, label-free and economical. However, further develpment of the device is needed to confirm our results.
Exploitation Route The prototype device I have engineered needs further development to be high-throughput and to allow systematical measurements. Following my experiments, electrical activity might be used to assess cell viability in a clinical setting. It could be used also for drug screening, as it was the outcome in the initial project.
Sectors Healthcare,Pharmaceuticals and Medical Biotechnology

 
Description A fast, low cost device to assess islet quality before clinical islet transplantation in man
Amount £40,000 (GBP)
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 10/2018 
End 02/2020
 
Description Engineering a microelectrode array with microfluidics to assess cell viaiblity prior to islet transplantation in type 1 diabetes 
Organisation University of Edinburgh
Department Queen's Medical Research Institute Edinburgh
Country United Kingdom 
Sector Academic/University 
PI Contribution We collaborate with the QMRI and the Royal Infirmary of Edinburgh to improve islet transplant outcomes in type 1 diabetes. For this purpose, I engineered a MEA with integrated microfluidics in order to assess islet viability. The device still a prototype and the results are preliminary, but it could be implemented to replace the current method to assess viability due to tis lack of objectivity.
Collaborator Contribution They provided us with pancreatic islets to carry out the experiments and we were able to use their facilities to perform some tests using other techniques to assess viability such as oxygen consumption rates
Impact It is multi-disciplinary involving the clinical tea, molecular physiology and bioengineering
Start Year 2019
 
Description The Good Choice: three pilot teaching sessions in two different prisons (HMP Low Moss and HMP Shotts) and one young offender institution (HMYOI Polmont) to a varied group of inmates. 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Other audiences
Results and Impact I co-delivered three teaching sessions about health to different groups of inmates. As our PhD is related to diabetes, the topic we selected was about healthy lifestyle choices with a focus in metabolism. Our goal was to transfer these health choices to real life situations and help participants to be engaged and reinserted in society. Increasing health awareness among inmates could have positive outcomes for rehabilitating, it may motivate the pursuit of education and self-improvement during incarceration or after are release to help reinstate in society.
Instead of a formal lecture, we created a dialogue with the inmates, with a relaxed, informal but academic approach. With this approach, we lowered the perceived barriers between the teacher and students. Therefore, the participants were very involved asking questions and being part of the discussion.
After the sessions we received anonymous written feedback and all of them were very engaged and grateful.
We decided to apply for funding to develop the project more in-depth and we got economical support from the Endocrinology Society and The Physiological Society. However, as I am now doing a research placement, we could not cotinue collaborating with the prisions.
Year(s) Of Engagement Activity 2019