Inner Space

Nanotechnology is a phenomenon poised to change our lives. One of the largest fields for nanotechnology use is the medical device market. Over the next five to six years, technologies are set to become available that will have a massive impact across the whole market, changing it forever.

But forget preconceived notions born of a misspent youth reading science fiction, as the truth about nanotechnology is not all miniature robots rebuilding and restructuring a patient from the inside out. The truth is that nanotechnology will allow diseases to be detected earlier – at the level of one or two cells – and thus enable earlier treatment and a much improved prognosis for the patient.

To accomplish this, along with even greater possibilities, a deeper understanding of how the human body works is still required, as a sensor or a nanoscale device cannot be used to detect or treat a condition if you don’t know what you are looking for. So, although nanotechnology in medicine is developing rapidly, the quantum leap whereby nanoscale devices take over vital functions of the body may still be a long way off.

Currently, nanotechnology in medicine is all about the detection and treatment of disease at a microscopic level and not about enhancement of the function of the human body, although this may be on the agenda in the future.

DEFINING NANOTECHNOLOGY

It is important to understand exactly what nanotechnology is and what it is possible to achieve through its application. Ottilia Saxl, CEO at the Institute of Nanotechnology, based at the University of Stirling in Scotland, says: "When people talk about nanotechnology they always try and define it in terms that are sometimes quite hard to relate to; but what is easier to relate to is the fact that we are creatures whose characteristics are defined at the nanoscale – and likewise the characteristics of disease are defined at the nanoscale.

"So, as time goes on, if we have better tools to enable us to understand more about the molecular basis of diseases and how they manifest themselves, the more we will understand. We can work at the nanoscale to manipulate atoms and molecules – [discovering] how to cure diseases earlier... and we can create new devices and therapies that are more body friendly and compatible and give a better solution to disease.

"It has always been a kind of Holy Grail to detect disease as early as possible – the later disease is detected the more difficult it is to cure, the more painful for the patient and the more long-term and expensive it is. If you can detect disease at the level of a cell or two, you can treat it much more effectively, so one of the techniques for nanotechnology is in imaging, which is critical to all of this. Imaging companies are looking at not only imaging the body but also how accurately and how early conditions can be detected."

A disease site has a different chemistry to other tissues and a chemical marker (functionalised molecule) can be tailored to interact with a specific disease chemistry and cause an actuator or reaction to indicate the disease, such as fluorescence. The contrast marker can also be designed to carry a therapeutic drug at the same time as the diagnosis and be triggered by various means (such as ultrasonics, magnetic field) to release the drug at the disease site as treatment – this is called theranostics (identification/diagnosis and treatment).

"Another approach to diagnostics is to have a diagnostic tool, which would consist of an array of sensors able to carry out over 100 different tests incorporated in a single nanoscale device, inside or outside the body, which could monitor the levels of enzymes and hormones and other physiological and biochemical parameters to detect a disease condition," adds Saxl.

"We have established that nanoscale devices can be used to target disease and deliver drugs but another active area of research is in organ regeneration where a nanotechnology scaffold structure, containing artificial capillaries and ducts (also nanodevices) can be used to grow a new organ from a piece of the patient’s own tissue. Obviously this would mean no problems with rejection."

Finally, there is the development of artificial retinas (highly sophisticated sensor arrays) and cochlear implants using micro electro mechanical (MEMs) devices. "These will be some of the most sophisticated devices to integrate with the human body ever produced and will have the power to change people’s lives immeasurably," says Saxl. These are exciting times and over the next ten to 15 years nanotechnology will develop, mature and be a major driving force in the area of medical devices.

MEDICAL DEVICE MARKET

What is the current state of the market? Are there any devices incorporating nanotechnology? Abhishek Dutta, a research analyst with Frost and Sullivan, puts the market into perspective: "At present, nanotechnology for medical devices has not yet evolved to an extent that there are many on the market. The major influx of nanotechnology-based devices in the marketplace is expected within five to six years. It will be huge and will be a major force in many medical fields, indeed, there are so many companies researching imaging technology and MEMs that the magnitude of nanotechnology will surpass anything seen previously.

"Of course there are silver (antimicrobial), barium sulphate and titanium oxide nanoparticles incorporated into artificial joint and implant surfaces, which have been used because of their excellent antibacterial properties and their ability to act as a key for bone cement," adds Dutta. When the technology has evolved for use inside the human body there will be biocompatibility issues to be addressed and this will lead to regulatory considerations – another hurdle for nanotechnology to overcome.

"This may well be very important for quantum dot devices used inside the body as sensors, contrast agents and test arrays, as they must be used with a suitable coating," says Dutta. Some of the materials they contain (such as cadmium and tellurium) may be toxic if they are used as "naked" quantum dots; therefore, the integrity of the coating is an important regulatory issue.

"Nanotechnology will have a huge impact on many medical markets, particularly the pharmaceutical market. In pharmaceuticals, nanotechnology will be able to provide new drug delivery technology (nano spheres or nano capsules). Much research is being carried out at the moment on nano coatings; this type of technology could well be used for applications such as insulin delivery or even gene therapy."

Nanotechnology is going to make a lot of things possible, but we must be realistic if we want nanotechnology to do something for us. We have to understand what we are trying to achieve and how we want to achieve it – so rather than a "magic bullet", nanotechnology is an extremely exciting new technology, the limits of which have not yet been established.

FUTURE OPPORTUNITIES

Nanotechnology is a fascinating subject area, and when considered in conjunction with medical devices the potential for future applications appears very exciting indeed. But what is the future potential in this area? Where will nanotechnology propel the medical device market in ten to 15 years?

An expert in the field of nanotechnology, Dr Leonard Fass, director of academic relations, GE Healthcare, is perfectly placed to answer these questions. ‘If we can examine the field of drug delivery first (with devices such as liposomes, nano spheres and nano capsules), these can be used to deliver cocktails of drugs to specific areas and also contrast agents so that the effects of the drugs can be seen in real time.

Drug delivery systems can also be controlled very specifically and accurately by external forces such as magnetic fields or ultrasound or combined with nano particles to treat small areas of tissue.

"One example of this would be in a patient with deep vein thrombosis coming from Australia on a plane. There may be systems in place in the future where treatment will be provided in situ. In this case, there would be ultrasound transducers (capacitor micro machine ultrasound transducers) so small they could be placed on the patient’s skin and operated remotely by a doctor using satellite communication. A thrombolytic agent consisting of nano particles could already be in place throughout the body, and just a specific area would be activated (without risk of haemorrhage in other areas) to treat (dissolve) the thrombosis."

Miniaturisation is one of the key areas for nanotechnology in medical devices, where sensor devices can be made small enough to go into the body to measure functions such as heart rate or glucose levels.

"Remote sensing will be a very important area," adds Fass, especially as most patients won’t need to be in hospital – 80% of patients do not need to be there and could be monitored by physicians from their own homes. Sensors are being made so small that patients can wear them on clothes and the data can be transmitted by a mobile phone ...This is an area where nanotechnology will be very important. The power requirements of future nanotechnology medical devices inside the body may also be satisfied by the incorporation of glucose fuel cells.

"Microfluidics is another important area in medical devices and this involves miniature polymer or glass "slides" with channels of only a few microns thick that could contain as little as 1,000pl of solution. These devices can be used for analysis and separation of components (proteins, DNA) in liquids, and the preparation of micro quantities of contrast/ tracer agents in situ for new imaging techniques such as positron emission tomography (PET) to examine, for instance, the Amyloid ß plaque in the brain in Alzheimer’s disease.

"Microfluidics can also be used in phase zero microdosing (recently approved by the FDA) to test the kinetics and physical effects of new drugs at a very early stage in a human model, thereby making animal testing less necessary. Microfluidic devices may also be attached to DNA aptamers and can act as antibodies to DNA or proteins; these systems are being developed so they can act at concentrations as low as 10-18 [the atom/molecular level for very high sensitivity detection]."

Nanotechnology in medical devices is a rapidly expanding area. For the first time, devices and sensors will be small enough to go into the body to diagnose and treat disease conditions at a cellular level and even through the blood-brain barrier to examine neurological conditions. As ever there are warnings that nanotechnology could be risky and may harm the environment but these seem unfounded, as validation systems are being put into place in a similar way to those used for pharmaceuticals.

The benefits of nanotechnology in medicine far outweigh the risks. Recent studies by Qinetiq have shown that in nanotechnology manufacturing cleanroom areas the air has 25 nano particles per cubic centimetre while in a busy London street there are one million particles per cubic centimetre.

Humans have been constantly exposed to nano particles for a long time without any harmful effects, and the public is excited about the opportunities nanotechnology will offer in the years to come. A recent study by Rice University in Texas, University College London and the London Business School concluded that "US consumers are willing to use specific nano-containing products, even if there are health and safety risks, when the potential benefits are high".

Nanotechnology is set to shape the future of medical devices and the medical industry in general.