Medical Device Link.

Originally Published IVD Technology May 2003

In Person

Through collaboration and multidisciplinary integration, sensor technology advances by leaps 
and bounds at one research center.

Brian MacCraith, PhD, is director of the National Centre for Sensor Research at Dublin City University (Dublin, Ireland). He can be contacted at brian.maccraith@dcu.ie.

IVD manufacturers often depend on sensor technology for the effectiveness of the devices they produce. Improvements in sensor technology promise a future of less-invasive, more-accurate, and more-informative diagnostic devices. 

To paint a vivid image of the changes to diagnostic devices likely to come from advances in sensor technology, IVD Technology editor Richard Park spoke with Brian MacCraith, PhD, director of the National Centre for Sensor Research (NCSR) at Dublin City University (Dublin, Ireland). In this interview, MacCraith talks about aspects of IVDs that are likely to be enhanced by sensor research, collaborating with industry, and bringing basic research to the marketplace.

IVD Technology: Please provide some background information about the National Centre for Sensor Research.

Brian MacCraith: Our research team is focused on developing the science and applications of biosensors and chemical sensors. We have a staff of approximately 130 full-time researchers with expertise in the disciplines of biology, biotechnology, chemistry, and physics. The multidisciplinary aspect of the center staff is integral to its ability to unite the core elements required to develop chemical sensors and biosensors.

In September 2002, we moved into a new state-of-the-art facility that houses several specialized facilities including a microfabrication suite, cleanrooms, and biohazard units, in addition to custom-built discipline-specific sensor laboratories that house the departments of physics, chemistry, and biotechnology. We have conducted sensor research at Dublin City University for about 20 years, and the center has grown dramatically in the past seven or eight years. Soon it will be one of the largest sensor research facilities in this part of the world.

The intersection of nano- and microsystems with life sciences supported by advances from other sciences, especially photonics, is the main focus of the center. Much of our expertise resides in advanced diagnostics devices and point-of-care devices. Our key philosophy is taking a multidisciplinary approach to developing sensor-driven diagnostic solutions.

Defining Research Priorities

How did NCSR identify the core competencies required by its staff and the areas of research that serve as priorities for the center?

We are always aware of global, international, and technological trends. We try to keep abreast of what the industry is doing, of what is happening in the research literature, and at international conferences.

If you look at technology trends in the major developed countries and across the world, whether in the United States, Germany, or Japan, there’s a lot of common focus. Point-of-care testing and technology is on everyone’s hit list. The concept of moving towards centralized healthcare is also very popular. We have paid attention to these trends and developed our strategy by matching our internal core competencies against them. Where our competencies meet global trends and major areas of technological growth is where we have placed our research priorities.

With all of the real-time biological detection technological advances that are occurring, we believe that will be the major growth area over the next decade. It’s a very exciting vision. We believe that we will soon move from IVDs to on-body and wearable diagnostics. As a result we are doing work in that area, developing wearable, networked sensors, and we may also develop some in vivo systems. 

We are looking at interstitial fluids and technologies that work outside of the body by using wireless technology. For example, patients can swallow a pill-sized device that uses a high-fidelity sensor and an antenna to transmit an image of the small intestine to a receiver outside of the body as the sensor moves through it. 

How did the center select point-of-care technologies and networked sensors as two areas to focus its efforts on?

We examined a global trend, in terms of commercial opportunities and societal implications for sensors. We predicted where the biggest demand will be, and matched those areas with our capabilities. For sensors in general, micro-fabrication, miniaturization, integration, and mass produceability are where we expect the biggest demand will be.

In selecting sensor networking as a research focus, we followed a similar process. At the center, we predict that biomedical diagnostics is a much bigger market opportunity than environmental monitoring. Chances are that our society will, within the next decade, incorporate millions of sensors into our environment. The sensors will provide a constant flow of information about our own personal health and the environment we live in. 
We feel that our ability to miniaturize sensors will be essential to realizing this vision of the future. Our abilities to develop technology for networking these sensors will be used for creating what we would call “autonomous sensing devices.” These devices would require low-battery operation and would be very small. They would be able to communicate with either local processing units or would exist as arrays of sensors in a particular environment, from which people could retrieve information. 

In the home, doctor’s office, hospital, and operating room, advances in sensor communication will be required. These advances will allow the patient to be unencumbered by the burden of being linked to machines or walking around with a device. 

We look at chemical and biosensors as molecular information gatherers. And the information they gather must be transmitted as efficiently as possible. Therefore networking sensors and incorporating more communications technology is an obvious and necessary requirement.

What specific strategic plans has NCSR made for developing networking technology?

We will invest in important elements of infrastructure in terms of equipment and specialist laboratories, and develop key teams in the center to address the central issues. 

As we put together project teams, we find that people are not only driven by the science, but also by the satisfaction of enhancing society by providing technologies that allow for earlier detection.

Developing Sensors for IVDs

What portion of the center’s work is devoted toward developing sensors and what portion is devoted toward researching detection technology for IVDs? 

Much of the center’s work is directed toward the development of generic sensors, the application of which is transferable to a range of disciplines. Approximately 50% of our work has a direct application in the development of IVDs. Much of the work that can be applied to IVDs has applications for other areas that have use for similar detection technologies. Over the past few years, we have focused on developing intellectual property in the area of fundamental detection technologies. Many of those technologies have applications in the IVD arena. 

For example, we have made some significant breakthroughs in the enhancement of fluorescence detection. This technology can be applied to IVDs in either low- or medium-density arrays of antibodies in fluorescence-based assays or biochips. The technology is also of use when developing coatings for the bottoms of smart microwells.

We have focused on looking at where light goes when fluorescence-based detection technologies are used. This research involves looking at the fundamental emission properties of light emitted at an interface. We established that the light travels in a very specific direction. From that knowledge, we have been able to establish two significant international patent applications, one of which describes how to increase, by at least one order of magnitude, the fluorescence we can detect. That is one example of a project that has major significance for diagnostics, but that can be used in other applications as well.

What other research does NCSR conduct for the development of detection technologies for laboratory tests?

We have a strong development team that includes experts in the areas of antibody production and antibody engineering. These scientists are developing more-specific and more-sensitive assays based on the quality of both the antibodies and the labels used.

Other teams are working on an emerging technology that employs metallic nanoparticles to enhance the emission properties of fluorescence. 
We are constantly working to enhance the efficiency of a system, and thereby lowering the cost at which we can get comparable performance. One of our goals is to develop diagnostic systems based on arrays of fluorescent spots using low-cost, battery-operated CMOS (complementary metal oxide semiconductor) camera technology and disposable, low-cost plastic biochips. 

Is NCSR developing detection technologies of use specifically for IVDs?

We develop both optical and electrochemical detection technologies. Most of our discoveries in the optical arena have focused on fluorescence. We also have developed platforms that enhance the efficiency of detecting color changes on thin films by close to an order of magnitude. Many simple sensor systems can be based on such colorimetric devices.

Similarly, on the electrochemical side, we have developed electrochemical immunosensor devices based on a low-cost, disposable, conducting polymer electrode platform. We have used this technology to analyze environmental and clinical analytes such as pesticides and vitamins. We are currently investigating its potential to monitor warfarin therapy and menstrual hormones in urine. We are also investigating ways of packaging the system as an IVD device, and have made significant methodological developments that have allowed us to perform rapid, real-time, calibrated immunoassays in a one-step throwaway package.

Based on your experience, what elements are required for developing effective detection technologies for IVDs?

Number one, an understanding of the full picture is important. Researchers should have an understanding of the device’s operation and its operational constraints. They must also have an understanding of the key elements of sample presentation, preparation, and biorecognition.
Understanding the detection technology’s strengths and limitations and possessing an awareness of the integration and mass produceability of available technologies are also very useful. To date, there has been a strong emphasis on empirical approaches and too small a focus on the underlying fundamental science of detection devices.

Collaboration

How does NCSR approach research projects brought to the center by outside institutions, in terms of assembling a team and designing a research plan?

We begin by defining the key enabling components of the project assigned to us, and then we assemble a multidisciplinary team containing all of the elements necessary to complete the task. Our broad range of core competencies, that range from synthesis and antibody engineering to transduction technologies and microsystems fabrication, is very important to creating a well-rounded team.

Another instance of how the center works is when we commercialized sensors with industrial partners in the past. Our partners would present us with very tight specifications, in terms of performance, size, costs, etc. We would then respond with a prediction of what we could achieve within a particular time frame and what elements of the project would be high risk. We like to build a feasibility phase into such projects so that our partners can evaluate outcomes at an early stage.

Do you establish strategic alliances around specific projects or goals, or are alliances established as a means for bringing ideas together and brainstorming technologies that should be developed? 

Every alliance is somewhat different. They can be developed as a means to completing a project or simply to brainstorm on a certain issue. The value of an alliance is in the richness of its research synergy. A key objective of the center is creating and maintaining a rich synergy with partners in industry.

We are not, generally, interested in short-term product development. Market-driven research is carried out here, but we tend to engage in projects that involve a longer-term plan and will have long-term applications.

What strategic alliances is NCSR planning to set up in the future?

One other area of interest for us is in combining sensing with communications to create smart autonomous devices and sensor networks. These devices will be used in on-body or in-body systems, such as smart clothing, where diagnostic information is transmitted to a remote processing unit.
We have been keen on developing partnerships with players in the area of wireless communications. We are talking to one or two industry players at the moment. We are also interested in collaborating on the development of miniaturized, biocompatible chips that could either be used in on-body or in-body implantable devices.

Bringing Technology to Market

What fundamental technologies are being developed by NCSR for commercial use?

NCSR has done a lot of work in this area. The university manages the commercialization of intellectual property generated within its research centers. 

We identify the best candidate projects for commercial development on a case-by-case basis. We evaluate each technology and determine which offers the most promise in terms of partnering, joint ventures, the generation of intellectual property, or of spin-offs. 

We’re working on a number of technologies for commercial use including enhanced biochips and smart packaging that monitors the headspace or package integrity. We are also developing detection technologies in areas outside of the biomedical arena, including technologies for food safety and environmental monitoring. We have developed sensors for food testing and water quality assessment. One of our future spin-off companies will produce intelligent sensor films for food safety and food quality monitoring. However, it is likely that our major focus will be on biomedical diagnostics.

Would an entire spin-off company ever be created for one technology, because it offers long-term capabilities?

Yes. In addition, if there’s a niche application that is not already being addressed by a major player in the market, a start-up company could be created to take advantage of filling that niche. 

However, if there is an incremental intellectual property breakthrough in an area of industry where there are major players, it’s generally better to consider potential for market penetration and distribution through one of the established companies. Developing a name out of nowhere sometimes takes too much time, effort, and money.

What detection technologies for IVDs does NCSR plan to commercialize in the next few years?

We are focusing on platform enhancements for biochips. 

We see many opportunities in the area of personal health monitoring, breath-by-breath analysis, and metabolic rate monitoring. We have been talking to some external partners about significant possibilities for developing these technologies.

Does the center have prototype manufacturing facilities, or does it rely on strategic alliances for that process? 

The center can bring a concept through to the development of a laboratory prototype. We have both fabrication and engineering capabilities. For example, we can produce a complete biochip system, including the microfluidics, embossed chips, patterned arrays, readout systems, electronics, and software, right through to a full laboratory prototype demonstrator. 

Future Developments

What trends do you anticipate will emerge in the area of detection technologies for IVDs?

I expect that there will be huge developments emerging from the area of nanobiotechnologies. I think we’re only beginning to tickle the surface of that one.

Nanobiotechnology research is already addressing some very exciting possibilities, including the ability to manipulate individual molecules and cells. Applications in photonics, in terms of trapping and manipulating molecules and cells, will also have a large impact. A sustained investment in high-quality fundamental science will lead to more-reliable and more-sensitive transduction technologies.

What research projects in the area of detection technologies for IVDs does NCSR plan to get involved with in the distant future?

The projects would come mainly out of nanotechnology research areas, such as employing nanoparticles, functionalized nanoparticles, nanoprobes, nanoelectrodes, and nanofluidic systems. In terms of detection technologies for diagnostics, we will still focus on optical and electrochemical technologies.

The complete text of this interview can be accessed on-line via the IVD Technology Web site at http://www.devicelink.com/ivdt.  

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