Lung Cancer (LC) is the most lethal cancer, accounting for 28% of cancer deaths globally. In Europe, there are 383,900 incident cases every year, resulting in 341,800 fatal casualties. The average lifetime cost of treating LC patients in Europe is €46,000 - €61,000 per patient. Detecting LC in its early stages, while still localized, can be expected to increase the 5-year-survival rate by 3-4 times. Unfortunately, LC diagnostic tests currently available, e.g. bronchoscope biopsy, pulmonary puncture and computer tomography (CT) are unsatisfactory, since they often identify tumors at an intolerably late stage of the disease, occasionally miss tumors and sometimes provide high rates of false positives, a fact that leads to over-utilization of the medical system and to unnecessary medical procedures. Indeed, these methods are not suited for widespread screening as they are not efficient in terms of time and costs and more importantly are unpleasant for the patient and not free of complications.

The LCAOS project is an EU funded collaborative under the 7th Framework Program whose aim is to enable the earliest possible detection of lung cancer (LC) using volatile biomarkers present in exhaled breath and/or headspace of LC tissues/cells by applying a novel, non-invasive, easy-to-use tool. This tool will be based on a Nano Artificial NOSE (NA-NOSE) concept, which makes use of cross-selective and sensitive sensor arrays that are trained in their ensemble to detect LC biomarkers. In LCAOS we uniquely modify this artificial nose concept by using a 3D silicon nanowire (Si NW) based field effect transistors (FETs) that show increased sensitivity to LC biomarkers. This ‘NA-NOSE’ will be used to screen and identify high risk groups for LC, and monitor the therapy provided to people affected by LC to establish point-of-care diagnostics and less invasive treatments. Specifically, the LCAOS partners propose to:

  1. develop arrays of chemically-sensitive FETs of molecule-terminated Si NWs;
  2. test the feasibility of the developed devices for sensing volatile biomarkers of LC from in-vitro tissues and from exhaled breath;
  3. develop an improved understanding of the signal transduction of the various volatile biomarkers, aided by sophisticated pattern recognition methods;
  4. develop improved systems that will enable the ‘NA-NOSE’ to clearly distinguish the targeted biomarkers from environmental clutter and to correlate the LC’s metabolite signature with genetic aberrations in the related pathways; and to
  5. perform clinical-related studies to assess LC conditions in actual patients and tissues and in the presence of real-world confounding signals.

A true breakthrough in early detection of LC will only be achieved by establishing non-invasive screening using biomarker detection in the human breath or headspace of LC tissue using LCAOS’s reliable, easy-to-use ‘NA-NOSE’ concept, which will be ready to be deployed after the development of:

  1. proto-type of novel, cross-sensitive nanowire-based sensors to be integrated in the ‘NA-NOSE’ trained to detect LC related mixtures of biomarkers;
  2. novel algorithms to reduce the dimensionality of the ‘NA-NOSE’ information to safely distinguish between healthy and LC individuals, as well as between different sub-types of LC and different types of cancer;
  3. novel, company-manufactured, ready-to-use integrated ‘NA-NOSE’ devices, to be tested in clinical studies/environments for large-scale screening and cancer research;
  4. a method based ‘NA-NOSE’ to detect and improve the outcome of therapies;
  5. a method based ‘NA-NOSE’ to guide surgeons during surgery based on LC tissue analysis; and
  6. a method for identification of new biomarkers that are related to different stages of LC.

The testing of the novel ‘NA-NOSE’ for the early detection of LC, essentially from breath and tissue headspace samples will be carried out in two parallel tracks:

  1. Lab-track evaluation - will be carried out using simulated compositions of clinical samples and, also, real clinical samples, which will be provided by the clinical partner.
  2. Clinical-track evaluation of an integrated, professionalized, easy-to-use ‘NA-NOSE’ tool - will be carried out at two clinical institutes.

This four-year initiative started at April, 01 2011 and is implemented by eight world-renowned expert groups representing a wide range of expertise ranging from engineering to medical centers from six countries, including Israel, Germany, United Kingdom, Spain, the Netherlands, and Austria. The anticipated LCAOS achievements have the potential to reduce cancer mortality, by enabling widespread, trustworthy screening, especially suitable for high-risk populations. The ‘NA-NOSE’ would be suitable for use outside of specialist settings and would significantly reduce costs in health budgets. In addition, the ‘NA-NOSE’ could be used for immediate diagnosis of fresh LC tissues in operating rooms, where a dichotomic diagnosis is crucial to guide surgeons. The easy-to-use (no medical specialists required) ‘NA-NOSE’ technology detects cancer based on a change in the blood chemistry and/or metabolic activity (which is reflected in the chemical composition of the exhaled breath and cell/tissue headspace) rather than by tumor imaging, thus permitting earliest cancer detection i.e. before a tumor of detectable size has formed.  The effectiveness of the ‘NA-NOSE’ in detecting LC volatile biomarkers specifically and selectively will provide a launch pad for identifying other types of cancer from simple analysis of clinical samples, including breast, colon, and prostate cancers. Biomarkers that are indicative of other disease (e.g., heart failure, kidney disease, liver disease, etc.) can be also tested with the same easy-to-use ‘NA-NOSE’ approach.