Nano-bio enabled diagnostic devices for oral healthcare

Periodontal disease (gum disease) is a major healthcare problem which affects the tissues that surround and support the teeth (the periodontium). Patients with periodontal disease suffer gum inflammation and bleeding and also have receding gums and loss of the underlying bone (which forms the tooth socket) as the result of damaging enzymes activated as the result of inflammation. Teeth become loose and tooth function is compromised. Indeed, this condition often leads to tooth loss. The Adult Dental Health survey of 2009 revealed some 15% of the UK population aged over 55 have severe periodontal disease. Furthermore, in comparison to the findings of the 1998 survey, more people in the UK are now affected by periodontal disease and people are developing more severe disease earlier in life. In addition, smokers have a greatly increased risk of developing severe periodontal disease as do individuals with obesity and diabetes. Thus, an ageing population making poor diet and lifestyle choices presents an increasing oral healthcare burden. In economic terms, periodontal disease is time-consuming and expensive to treat and the holistic cost of periodontal disease to the UK economy was estimated as £2.78 billion in 2008.

Dentistry is traditionally a surgical discipline focussing on diagnosis and repair but has now embraced the principles of monitoring and prevention. The overall aim of this project, therefore, is to develop a device that will ultimately enable patients and dentists to diagnose and monitor periodontal disease economically, accurately and simply. A successful pilot project, also funded by the Technology Strategy Board, has shown that technology which combines microelectronics and biotechnology to produce a small sensor (a 'nano-bio sensor') can measure the activity of enzymes which cause tissue destruction in periodontal disease.We now aim to assess the value of the sensor to oral healthcare, and in particular periodontal disease. We will use saliva sampling which is acceptable to patients because collection is simple, non-invasive and involves minimal discomfort. We will conduct a clinical trial in which we will monitor patients with periodontal disease of varying degrees of severity and collect saliva samples throughout their treatment for analysis using the device. In this trial
we will examine progression of disease and the effects of treatment to model relevant clinical scenarios. Furthermore, we will compare the device's performance against more established laboratory assays.

These devices will allow for much earlier assessment of disease risk, thereby helping to prevent development of severe disease and to facilitate disease management for example by defining changes in disease activity and assessing the effects of treatment. For the clinician this device will provide an immediate and direct measure of the underlying biological processes which will accelerate clinical decision making in a cost effective and cost saving manner. For the patient, selfmonitoring will be possible as saliva sampling requires no special skills and the device is simple to use; this will increase patient awareness, encourage adjustment in oral healthcare and inform healthcare decisions. The nano-bio sensor is small and portable and therefore can be employed not only in the home but also in communities not served by healthcare facilities; in this regard these devices could contribute to epidemiological studies as well as individual healthcare. Beyond periodontal disease, oral cancer, Sjogren's disease and peri-implantitis (an undesirable inflammatory response to
dental implants) are oral healthcare problems which can be monitored by salivary analysis. Increasingly, saliva is seen as a useful diagnostic fluid for a range of systemic disorders such as cardiovascular disease and diabetes. In the laboratory these devices could straightforwardly provide immediate analytical data improving on traditional, complicated protocols.

The immediate beneficiaries of the development of the nano-biosensor for monitoring periodontal disease will be the dental profession. There are numerous examples of chair side biomarker monitoring devices in use by medical practitioners e.g. those employed for diabetes management. Our study will provide the performance data and clinical trial data which are fundamental to the further development of the device and acceptance by dentists. Treatment of periodontal disease is timeconsuming, expensive and difficult; the specialist periodontist will benefit from the use of this device which will help to monitor disease activity post-treatment, assess disease stability and help develop new treatments and interventions.
Periodontal disease is common in an ageing population and is increasingly seen by General dental practitioners (GDPs) and treatment for this complex disease is often not straightforward. GDPs will use the device to provide objective data which will help inform their clinical decision-making (particularly decisions about when to commence treatment, when a treatment target has been attained, and when to refer for specialist care).Thus the device will deliver tangible benefit in terms of clinical outcomes but will also improve economic outcomes by allowing for more efficient patient care (fewer visits,
immediate clinical management decisions, and targeted therapy for those patients who need it most).

The device is small and amenable to mass production and furthermore, it is simple to use; therefore, it is economically viable and practical for home use by the patients themselves. There are many benefits of this approach, and the great value of patient self monitoring as an integral component of disease management is exemplified by the daily measurement of glucose levels by patients with diabetes. Self monitoring means that patients will become more involved in their oral healthcare and will take more responsibility for managing their periodontitis, which is a fundamental prerequisite for
successful treatment, and which will increase awareness and compliance to treatments and interventions. Direct provision of information will allow for immediate adjustments in oral hygiene practices and, in turn, provide useful information for the dentist responsible for their care. Ultimately, use of this device will increase knowledge and understanding of this common oral inflammatory disease by the public and will help inform their healthcare decisions. Research has shown that improved oral healthcare is directly related to improved quality of life, therefore there are wider benefits from use of this device. Improvements to oral healthcare will also have a wider economic benefit.

A number of technologies have been invented with the aim of providing point of care devices for healthcare. However, many have not made it to the marketplace because of inadequate performance data and lack of substantial clinical trials; the present proposal addresses these critical issues.

The project brings together researchers and healthcare professionals from different disciplines who will derive mutual benefit from this academic association. Thus, the Research Associate will be exposed to the biotechnology industry and will gain an appreciation of how scientific knowledge and discovery can be used for economic benefit. The Dental Hygienist and Nurse will be involved in studies of fundamental science which underpins disease pathogenesis and will appreciate the opportunity of using this information in healthcare improvement. The investigators will benefit from the development of new perspectives to their established research programmes and the opportunity for further development of the technology and this app roach to patient management. New projects that could evolve from this research include NIHR i4i funding to examine attitudes toward uptake of this device in the dental clinic and the home.