Knowledge is power


SCIENCE FOUNDATION IRELAND:Early diagnosis can mean the difference between life and death in a range of illnesses including cancer, cardiovascular disease and meningitis. DCU’s BDI is working to shorten the odds

EARLY DIAGNOSIS facilitating appropriate intervention followed by ongoing monitoring is central to the successful treatment of serious illnesses such as cancer, meningitis and cardiovascular disease. For the past five years the Science Foundation Ireland-funded Biomedical Diagnostics Institute (BDI) based in Dublin City University (DCU) has been working on the development of technologies which will enable cost-effective early diagnosis of many conditions. It is now moving on to translate such novel diagnostic devices into a clinical and commercial reality.

“We have just received our second tranche of funding from Science Foundation Ireland,” explains BDI director Professor Michael Berndt. “For the past five years the institute has been focused on the development of platform technologies. This funding will enable us to focus our collective expertise in innovative diagnostic research to address some of the biggest challenges in human disease. Our partnership of five Irish universities and six industrial [stakeholders] will focus on significant diagnostic challenges facing society. Specifically, we will address unmet diagnostic need in the key disease areas of oncology, cardiovascular and infectious disease. Over the next five years we will be engaged in the development of prototype diagnostic devices.”

The BDI’s main area of activity lies in creating miniaturised systems in which low concentrations of target biomarkers can be reliably detected in small volumes of biological samples. The integration of a range of scientific and engineering disciplines required for the development of these diagnostic devices, combined with the integration of clinical, industrial and academic expertise, is a unique feature of the institute.

“We have a very good mix of physicists, chemists, biologists, engineers and others working in the institute,” says Prof Berndt. “We are working on a wide range of technologies including bio-recognition, micro-fluidics, photonics and nanotechnology in the development of these diagnostic devices.”

In essence, the BDI is seeking to develop smart one-stop-diagnostic-shops for use at, or near, point-of-care by healthcare professionals. The concept is of a single, easy-to-use device that will take the sample, perform the test and deliver the result in a single action. “Our devices will be able to take fluids such as blood in very small quantities, process them and produce a result. For example, we might be interested in just one cell in that sample and we might have to analyse the DNA of that one cell. Our devices will be capable of doing this,” says Berndt.

At present there are six clinical strands to the institute’s research. Three of them are concerned with cancer, two with cardiovascular disease and one with bacterial meningitis.

The first strand in the cancer area is the development of a diagnostic platform for circulating tumour cells. Disseminated malignancy, or metastasis, is responsible for the vast majority of cancer-related deaths worldwide and circulating tumour cells play a central role in this. “This device will detect tumour cells circulating in a patient’s bloodstream which may be prognostic for metastatic cancer,” Berndt explains. “This will be the most challenging area of our research. We are trying to identify very rare cells in the blood, capture and analyse them.”

The diagnosis and prognosis of breast cancer is the subject of the second strand. Breast cancer is the commonest malignancy among women in the developed world, with 1.3 million new cases diagnosed and 465,000 deaths annually worldwide. Early diagnosis remains a challenge but dramatically reduces morbidity and mortality. Correlation of molecular subtypes of malignant breast cancer with circulating micro-RNAs suggests there may be specific circulating micro-RNA signatures of breast cancer.

“We believe these micro-RNAs change with breast cancer so the detection of changes could be suggestive of either the presence of the disease, a relapse or of how well a patient is responding to treatment,” says Berndt.

The third strand of research is in colorectal cancer. Every year approximately 600,000 people are diagnosed and over 250,000 die of the disease in the USA and Europe alone, making it the second leading cause of death from cancer among adults. The BDI project is looking at the immune response of patients to establish if certain antibodies are markers for colon cancer.

The cardiovascular disease research is focused on identifying patients who are at risk of developing the disease as well as potentially fatal blood clotting conditions such as deep vein thrombosis.

The final strand of research is concerned with designing a device to detect the three target organisms of bacterial meningitis.

These projects were selected following a rigorous review process, as Berndt outlines. “In January, we brought together a long list of challenges and needs which could be addressed following consultation with the clinicians we work with. We came up with a shortlist of the areas we were most interested in and this was reviewed by our external advisory board and our external partners.”

The main academic partners of the BDI are DCU, National University of Ireland, Galway, Royal College of Surgeons in Ireland, Trinity College Dublin, and the Tyndall National Institute, Cork. The six companies involved are Analog Devices Inc, Becton Dickinson and Co, Biosurfit SA, Inverness Medical Innovations Inc, JJ Ortho-Clinical Diagnostics and Millipore.

In order to achieve its objective of translating research outputs into clinical application, the institute has established a comprehensive commercialisation process. This begins with the definition of the clinical and commercial relevance and strategy for each diagnostic technology or platform. This process was carried out earlier in the year and resulted in the current six strands of research. It encompasses intellectual property protection, the establishment of effective governance, the management of links with key stakeholders, and fostering an entrepreneurial ethos within the institute.

“We work closely with members of the commercial community to maximize the practical utility of our diagnostic platforms”, says Berndt. “Through licensing, agency-sponsored partnerships, and industry-focused collaborations, we are able to ensure that the expertise and infrastructure of the BDI is making a real impact on transforming the face of biomedical diagnostics.”

Prototype devices are expected within the next three years, with commercialisation set to follow quickly afterwards.

Diagnostics in action Printed electronics

An example of the work being carried out at the BDI is the development of a cholesterol test using the emerging technology of printed electronics. The project is the result of a European collaboration spearheaded by BDI researcher Dr Tony Killard and could revolutionise the way blood tests, such as cholesterol tests, are performed.

“Printed electronics will completely change the way we use technology” says Killard. Also called flexible or plastic electronics, it is already creeping into everyday life. The latest flat-panel televisions are now manufactured using printed conducting plastics, which are gradually replacing costly silicon electronics in many applications.

Killard’s team has been developing printed biosensors and diagnostics for some years and sees the potential of this technology to change the way blood tests are performed. Currently, to perform a blood test “they need a little sensor strip and a meter to read the measurement. Now, all this will be combined onto a single piece of plastic”.

Irish and other European experts are combining the BDI’s printed cholesterol sensor with printed batteries and printed digital displays. The device will also be able to communicate with a mobile phone to send the result to a doctor.

Such devices have significant potential for people living in isolated areas, or those who do not have easy access to healthcare, particularly in the developing world.

“These strips don’t need their batteries to be changed or their meters serviced. You simply use the strip, get your result and dispose, or recycle,” says Killard. Production costs are also low, as test strips can be printed in extremely large volumes.