Owlstone Medical has developed a microchip sensor capable of detecting biomarkers of disease on breath – a breathalyzer for disease. This sensor, along with the company’s breath sample collector (recently featured on Medgadget), allows for the development of non-invasive, early stage disease detection and precision medicine tools for cancer as well as inflammatory and infectious diseases.
We had the opportunity to talk to Billy Boyle, CEO of Owlstone Medical, about the latest technologies the company has developed, as well as the concepts underlying their use.
Conn Hastings, Medgadget: Can you give us a brief overview of where the field of breath testing is at?
Billy Boyle, Owlstone Medical: Despite modern breath testing’s origin decades ago in 1971 with the work of Nobel Prize winner Linus Pauling, there is still limited agreement in identified breath biomarkers with given diseases. Breath testing is rarely used routinely in a clinical setting, other than examples such as using fractional exhaled nitric oxide (FeNO) for certain types of asthma or the 13C test for H. pylori infection. This lack of widespread adoption is due to three main factors: first the difficulty in reproducibly collecting and storing a high quality breath sample, second the expense and limited accessibility of high-end analytical instruments for breath detection, and third the small size and lack of blinded validation in most breath studies to date.
Owlstone Medical has addressed the first of these factors with its Respiration Collector for In Vitro Analysis (ReCIVA) breath collector, and the second with its Field Asymmetric Ion Mobility Spectrometer (FAIMS) sensor platform. These in turn reliably collect and then analyse the volatile organic compounds found in a person’s breath. To address the third of these factors, Owlstone Medical is engaging in large-scale clinical trials to develop robust, validated tests for disease detection and to guide precision medicine treatment choices.
Medgadget: What are the benefits of breath as a sample medium? How does it compare to other sampling media such as blood or urine?
Boyle: The primary benefit of breath is that it is non-invasive and pain-free: patients are much more willing to consent to a test if it avoids needles or even more invasive techniques such as biopsies.
Beyond patient comfort, the volatile chemicals found on breath directly reflect the underlying activity and state of the cells and tissues that they arise from. These chemicals, or metabolites, enter the bloodstream and are exchanged through the lungs into the breath we exhale. The whole of your entire blood flow circulates through your body in about a minute, so by sampling your breath over this short time the volatile metabolites throughout your entire blood supply can be sampled. Continuously sampling breath over a short period of time allows you to concentrate these exhaled chemicals so they can be detected even at low concentrations that wouldn’t show up in a blood test.
Medgadget: Congratulations on the approval in Europe of the ReCIVA Pediatric Breath Collector. What was the motivation for the development of a specific pediatric device?
Boyle: Thank you! Obtaining samples such as blood or cell biopsies from children can be difficult and in some cases even unethical, so there is a great need for better, non-invasive options to help diagnose children.
The paediatric version of ReCIVA is first being used in EMBER (East Midlands Breathomics Pathology Node), a £2.5 million project funded by the Medical Research Council (MRC) and the Engineering and Physical Sciences Research Council (EPSRC), whose aim is to develop breath-based systems for molecular pathology of disease in order to clinically validate breathomics as a new diagnostic modality.
Medgadget: Currently, the ReCIVA breath sampler provides a standardized method to obtain breath samples for later analysis in the lab. The sampler can also be directly attached to an analytical device for real-time analysis in the clinic. Is there any scope for direct integration of miniaturized analytical components into the sampler itself, potentially allowing for point of care diagnosis of a variety of diseases?
Boyle: The ReCIVA breath sampler captures breath into small, stable sorbent tubes that are compatible with a wide variety of analytical platforms; typically in a lab but potentially at point of care as well. Also, it is possible to incorporate the thumbnail-sized microchip at the heart of Owlstone Medical’s proprietary FAIMS sensor platform into the sampler to create a low cost, portable device ideal for point of care operation, and this work is planned in our roadmap.
Medgadget: Owlstone Medical have also developed the miniaturized Field Asymmetric Ion Mobility Spectrometer (FAIMS), which is at the heart of the Lung Cancer Indicator Detection (LuCID) project. In simple terms, how does the device operate and how accurately can it detect lung cancer? Can it be used by non-specialists?
Boyle: The FAIMS sensor platform is effectively a mass spectrometer miniaturized onto a chip. Electric fields first ionize the volatile chemicals it detects, then separates them due to each individual ion’s weight and shape, then selectively steers these ions to the detector where they are counted. This design allows for high sensitivity, so that these chemicals can be detected in the parts per billion and in some cases parts per trillion levels, as well as high selectivity so that these chemicals can be seen against the high amount of chemical noise typically found in a breath sample.
For lung cancer, the LuCID project is identifying and validating a small number of volatile metabolite biomarkers that distinguish between healthy patients and those with lung cancer, even at the earliest stage of the disease when the patient is otherwise asymptomatic.
As the FAIMS sensor selects the ions by adjusting voltages, it is inherently software programmable: the same chip can be used across a wide range of indications simply by changing the software. Because of this, once a given test is developed and validated, the sensor can be set up for simple, push-button operation by a non-specialist.
Medgadget: Finally, can you tell us about the LuCID concept and the proposal for a lung cancer screening program?
Boyle: The LuCID study is the world’s largest breath-based study ever undertaken for early cancer detection. It is funded by the Small Business Research Initiative for Healthcare (SBRI Healthcare), and is a National Health service (NHS) England funded initiative. It aims to save 10,000 lives and save the NHS £245 million by 2020. By detecting metabolites on patient’s breath that are indicative of lung cancer the test will detect lung cancer earlier than current methods, allowing for less expensive treatments with better survival outcomes. If detected at stage 1, the 5-year survival rate for lung cancer is 54%, but this drops to just 4% if the cancer is not detected at stage four.
In the first instance, the test will be used in conjunction with the current screening methods such as low dose computed tomography (LDCT) and positron emission tomography (PET) screening, which has a high number of false-positives and therefore leads to unnecessary, invasive follow-up procedures on healthy patients. Following on from this, screening breath tests will be developed to further improve early detection of lung cancer for more effective treatment and better patient outcomes.
Link: Owlstone Medical…