Development of assays for a new dielectrophoresis system applicable to stem cell development, cancer research and the early detection of cancer
Lead Research Organisation:
University of Surrey
Department Name: Mechanical Medical and Aerospace Eng
Abstract
In numerous medical and research applications, it is important to discriminate between differentkinds of cells as early as possible e.g. cancer/non-cancer, differentiated/undifferentiated,healthy from unhealthy and so on. Often, conventional assays are too slow, expensive orinaccurate. DEP-well technology can use a cells unique electrical fingerprint to distinguish acancer cell from a normal cell, detect the differentiation pathway of a stem cell two weeks beforeother techniques can identify it, more reliably and less extensively. This project will develop newassays for this technology for cancer diagnostics and drug research.
Publications
Broche LM
(2011)
Rapid, automated measurement of dielectrophoretic forces using DEP-activated microwells.
in Electrophoresis
Fry CH
(2012)
Cytoplasm resistivity of mammalian atrial myocardium determined by dielectrophoresis and impedance methods.
in Biophysical journal
Ismail A
(2015)
Characterization of human skeletal stem and bone cell populations using dielectrophoresis.
in Journal of tissue engineering and regenerative medicine
Labeed FH
(2011)
Biophysical characteristics reveal neural stem cell differentiation potential.
in PloS one
Liang X
(2014)
Human oral cancer cells with increasing tumorigenic abilities exhibit higher effective membrane capacitance.
in Integrative biology : quantitative biosciences from nano to macro
Mulhall HJ
(2015)
Apoptosis progression studied using parallel dielectrophoresis electrophysiological analysis and flow cytometry.
in Integrative biology : quantitative biosciences from nano to macro
Mulhall HJ
(2011)
Cancer, pre-cancer and normal oral cells distinguished by dielectrophoresis.
in Analytical and bioanalytical chemistry
Mulhall HJ
(2013)
Epithelial cancer cells exhibit different electrical properties when cultured in 2D and 3D environments.
in Biochimica et biophysica acta
| Description | The Collaboration fund aimed to boost innovation by linking University-led research to definable commercial outcomes. This project aimed to develop new biological assays to further exploit a novel item of equipment developed at the University of Surrey and being prepared for commercial release in 2012. The equipment, known as the DEP-well, uses electric fields to determine the electrical properties of cells, and has potential applications in cell biology and cancer diagnosis. The Collaboration Fund grant was awarded in order to develop assays for the DEP-Well equipment. The first of these is the diagnosis of oral cancer. Our preliminary work had indicated that there are differences between normal oral tissue and cancerous cells. As a result of this study we have substantially increased our data set to nearly 100 samples, gathered from two hospitals in London and another in Bradford. These data show a statistically-significant difference between healthy and cancerous tissue can be detected using our device. Further work is now being conducted to optimise the system in order to construct a point-of-care device for detecting oral cancer at the doctor's or dentist's surgery; we have since secured a further £178k for a stage one clinical trial, funded by the NHS with potential for significant further funded following a successful first trial. Analysis by NHS statisticians has shown that if the system continues to perform at the levels indicated by the trial to date, it has the potential to save approximately 1000 lives and £20M a year in the UK alone. The work with the three collaborating institutions on stem cell work (Southampton; Bergen in Norway, UCI in America) has been fruitful, producing a number of publications. The first, with UCI showing that our system can predict neural stem cell differentiation, was published in the journal PLoS ONE. Papers on the work with Southampton (showing differences in the stem cells in bone marrow) and Bergen (showing that differences in the electrical properties of stem cell membranes can predict whether they will become cancerous) are in press and submitted, respectively. The final line of work was in the use of the system for drug discovery and laboratory use. This included studying apoptosis (cell death) induction, ion channel activity, cell life cycle activity and measurements from cardiac cells to understand the physiological basis of heart function. This activity largely took place at Surrey but also involved industrial collaboration with a major pharmaceutical research company. This has also led to publications on cardiac physiology (Biophysical Journal), with the life cycle and apoptosis work (which has demonstrated that the electrical properties of cancer cells are directly related to drug dosage) are in preparation and will be submitted in the next three months; the short duration of the grant has meant that there has been insufficient time to publish all of the work from this work, and it is anticipated that it will all be published by Spring 2012. The work also had many side-benefits, including the optimisation of the chemical composition of DEP-well suspending medium. |
| Exploitation Route | The system developed in previous work, and exploited in this project, is aimed primarily at providing a new tool for cell biologists in both academic and industrial environments; indeed, it is anticipated that the majority of units will be shipped to pharmaceutical companies. However, even where the use is within an academic environment; it is through the sale of a unit of technology being sold commercially to an academic lab by a company. The key development areas in this project - those of drug discovery, stem cell sorting and cancer detection - are of particular interest for those developing cancer therapies and other medical interventions. The applicants are already in receipt of a grant to take the oral cancer detection use of the system forward. If, as a result of this second grant the system receives NHS approval, it could be rolled out to every dentist's surgery in the UK. In several countries, oral cancer is the number 1 cancer killer and the potential to save 1000 lives per year in the UK and many more worldwide. This grant was awarded under the Collaborative Fund scheme for encouraging interaction between University labs and SMEs, with the aim of developing new assay target for a technology platform developed at the University of Surrey and licensed to DEPtech ltd. As such, the results of this project have a direct bearing on the commercialisation of that platform, due to begin sales in January 2012. |
| Sectors | Healthcare,Pharmaceuticals and Medical Biotechnology |
| Description | BBSRC Responsive mode |
| Amount | £299,663 (GBP) |
| Funding ID | BB/M021556/1 |
| Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 06/2015 |
| End | 06/2017 |
| Description | EPSRC-MILES Scheme |
| Amount | £9,984 (GBP) |
| Funding ID | EP/I000992/1 |
| Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 03/2013 |
| End | 01/2014 |
| Description | NIHR |
| Amount | £199,390 (GBP) |
| Funding ID | II-ES-1010-10163 |
| Organisation | National Institute for Health Research |
| Sector | Public |
| Country | United Kingdom |
| Start | 07/2012 |
| End | 08/2014 |
| Title | Minimal samples |
| Description | The system developed has provided the means of analysing human and animal blood samples from finger/tail pricks. For humans, this means that human blood sample collection is less invasive. For animal studies, this is signficant as the amount of sample required will mean less animals would be sacrificed . This sort of sampling would be ideal for animal ultradian studies, as the same animal could be looked at for the entire study without being sacrificed at the end. Further funding will be sought from NC3Rs as a result of this. |
| Type Of Material | Biological samples |
| Provided To Others? | No |
| Impact | The most notable impact is that of animal studies. The tail prick sampling has proved to be sufficient to provide sufficient electrophysiological data. This will mean that animals would need to be sacrificed to achieve complete sets of data, especially for ultradian studies. |
| Description | Collaboration with University of California at Irvine |
| Organisation | University of California, Irvine |
| Country | United States |
| Sector | Academic/University |
| PI Contribution | We brought expertise and equipment for the development of dielectrophoresis for the analysis of neural stem cells |
| Collaborator Contribution | The US group brought skills and knowledge relating to neural stem cells, as well as providing the cells themselves |
| Impact | This work was highly multi-disciplinary, involving engineers and cell biologists to explore the applicaiton of electric fields for the analysis and sorting of neural stem cells. As a result of this work we have produced a well-cited paper. Our colleagues in the US have used this work to secure research funding from a California funding organisation (CIRM), which they have used to further this collaboration through the purchase of equipment. |
| Start Year | 2009 |
| Description | Collaboration with the University of York |
| Organisation | University of York |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | The work has raised awareness of the technology developed and its various applications. Of particular note, its non-invasiveness, label-free and very fast data acquisition. We are currently working at generating preliminary data for a subsequent grant application to Cancer Research UK (CRUK). CRUK had responded positively to our initial application and we have been invited to put a full grant at the next stage. |
| Collaborator Contribution | The partner is providing cells and related media and consumables for data collection. This would provide the necessary preliminary data for our subsequent full grant application to CRUK. |
| Impact | The collaboration is multi-disciplinary and will result in a publication (that is still in preparation) to demonstrate the physical background in obtaining membrane potential using dielectrophoresis. Usually this parameter is obtained by patch clamping or membrane potential sensitive dyes (which can be substrates hence provide artefactual results). The data will also be used to apply for a full grant from CRUK. |
| Start Year | 2015 |
| Description | MILES: Looking for electrical signatures in red blood cells |
| Organisation | University College London |
| Department | MRC Laboratory for Molecular Cell Biology |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | We found that there are significant electrophysiological changes in red blood cells at different times of the day. The results demonstrated that circadian electrophysiological activity does take place in red blood cells. |
| Collaborator Contribution | The partners have provided valuable contributions into the potential underlying cellular mechanisms that are responsible for the changes in electrophysiological activity. The collaboration has resulted in a BBSRC bid that we have submitted in September 2014 |
| Impact | The team comprises a team of scientists from the areas of biophysics (Surrey), cell biology (Surrey, MRC LMB and cambridge), molecular biology (Surrey, MRC LMB and Camridge) and neurosciences (Cambridge). This multi-disciplinary collaboration resulted in a BBSRC bid that was submitted in September 2014, with a BBSRC reference number is BB/M021556/1. The results of this work is currently being prepared for submission to the journal: Cell. |
| Start Year | 2014 |
| Description | MILES: Looking for electrical signatures in red blood cells |
| Organisation | University of Cambridge |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | We found that there are significant electrophysiological changes in red blood cells at different times of the day. The results demonstrated that circadian electrophysiological activity does take place in red blood cells. |
| Collaborator Contribution | The partners have provided valuable contributions into the potential underlying cellular mechanisms that are responsible for the changes in electrophysiological activity. The collaboration has resulted in a BBSRC bid that we have submitted in September 2014 |
| Impact | The team comprises a team of scientists from the areas of biophysics (Surrey), cell biology (Surrey, MRC LMB and cambridge), molecular biology (Surrey, MRC LMB and Camridge) and neurosciences (Cambridge). This multi-disciplinary collaboration resulted in a BBSRC bid that was submitted in September 2014, with a BBSRC reference number is BB/M021556/1. The results of this work is currently being prepared for submission to the journal: Cell. |
| Start Year | 2014 |
| Title | 3DEP CLINICAL |
| Description | The 3DEP system uses electric fields to analyse cell samples using multi-frequency analysis. Working with collesgues in the NHS, we have found that brush samples collected from patients presenting with oral cancer can be discriminated from those with benign lesions or normal samples. Where the sample is not contaminated with blood, system efficacy reaches as high as 100% sensitivity and 94% specificity. We are now working on improved sample preparation to eliminate blood contamination ahead of a wider clinical trial. |
| Type | Diagnostic Tool - Non-Imaging |
| Current Stage Of Development | Early clinical assessment |
| Year Development Stage Completed | 2014 |
| Development Status | Under active development/distribution |
| Impact | Once the sample preparation stage is improved, this technology will save up to 1000 lives in the UK per year, and £30M in treatment costs to the NHS. Worldwide the technology stands to make an even bigger impact; in India for example there are 45,000 deaths per year from oral cancer, which could be dramatically reduced by the introduction of a low-cost early detection method. |
| URL | http://www.dielectrophoresis.net |
| Title | 3DEP-Research |
| Description | The 3DEP instrument is the culmination of many years' work to develop a device capable of assessing the electrical properties of up to 20,000 cells in 10 seconds. This has been shown to be effecting in many applications, including the discrimination between stem cells with different differentiation fates; detection of drug-induced changes in cancer cells as a new mechanism for drug discovery; and the study of circadian rhythms in cells with no gene expression, such as red blood cells. |
| Type | Therapeutic Intervention - Medical Devices |
| Current Stage Of Development | Refinement. Non-clinical |
| Year Development Stage Completed | 2014 |
| Development Status | Under active development/distribution |
| Impact | 3DEP devices have been sold to labs in the UK, USA and France, and are starting to make inroads into research areas across the cell biology spectrum. |
| URL | http://www.deptech.com |
| Title | Enhanced dielectrophoretic analysis assays |
| Description | As a result of this project, several new streams of applications have deen developed for dielectrophoretic cell analysis, including drug ction detection and cancer screening. |
| Type Of Technology | New/Improved Technique/Technology |
| Year Produced | 2013 |
| Impact | At the moment systems have been sold to 3 countries (US, UK and France) within the first year of production |
| Description | AES conference Salt Lake City |
| Form Of Engagement Activity | A formal working group, expert panel or dialogue |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | The session sparked questions and discussion around problems encountered in the research area. The outcomes included troubleshooting, workshops and awareness. |
| Year(s) Of Engagement Activity | 2015 |
| Description | Clock Club |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Professional Practitioners |
| Results and Impact | The presentation sparked interesting questions and exciting new ideas as feedback. |
| Year(s) Of Engagement Activity | 2015 |
| Description | Invited AES 2015 |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | An invited presentation that sparked a number of questions and interest in the field. |
| Year(s) Of Engagement Activity | 2015 |