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Screening of Gastric Cancer via Breath volatile organic compounds by Hybrid Sensing Approach

Periodic Reporting for period 1 - VOGAS (Screening of Gastric Cancer via Breath volatile organic compounds by Hybrid Sensing Approach)

Reporting period: 2019-01-01 to 2020-06-30

"Screening for different diseases is required to reveal groups of individuals in whom the likelihood of a specific disease is increased and who could benefit from further medical evaluation. These benefits are compounded when considering available treatment upon early detection. The ideal screening test is low-cost, high-accuracy, non-invasive, easily repeatable, effortlessly operated and has minimal impact on daily activities. In the VOGAS project, we aim to tackle these requirements by integrating two very different nanotechnologies into a single device to detect disease markers from exhaled breath. This approach relies on convergence of three different sensing technologies, which are presumably orthogonal in nature. A breath sample is analyzed by a unique Gold Nanoparticles sensor array, a well optimized MOS sensor array and a Hollow Waveguide IR spectrometer all in parallel in a matter of minutes. This device will be placed in different point-of-care locations and the analysis will be done on site. The sensor response will be recorded, stored and pre-processed via the internal software of the device. Subsequently, it will be sent to an external server for elaborated statistical pattern recognition analysis. In general, the different statistical programs compare the responsive pattern of the sensor array as well as the spectral chromatograms to previously known samples. These have been a-priori fed to the program as a training set. This analysis is then translated to a screening result harboring a level of certainty of the particular breath sample, originating from a ""Sick"" or ""Healthy"" individual. We develop the VOGAS project with the aim of early detection of Gastric Cancer. However, we believe that the VOGAS concept represents a new approach for addressing major societal challenges in health and well-being of the general population. We envision the VOGAS concept to serve as a novel platform from which more innovative ideas and projects may immerge. In this regard the VOGAS project has its own sustainable growth prospect.
In addition to pre-screening, the new VOGAS instrument has the potential to be utilized as an on-going treatment diagnostic tool. The fact that a patient is able to take countless diagnostic measurements at different time points, in a practically effortless manner is a great advantage. Moreover, the wealth of data generated by the VOGAS device may be automatically processed to generate a continues surveillance report to be evaluated periodically by the treating doctor. Indeed, capabilities and ease of use described above, may lead to a very sophisticated monitoring environment, circumventing the need for long post-treatment hospitalization periods accompanied by painful and expensive monitoring activities."
The first 18 months evolved according to the plan with only minor delays due to the covide 19 pandemic.
Briefly:
• Sensors array fabrication - A large number of synthesis and deposition parameters were manipulated and optimized giving rise to the optimal conditions, for each chemistry. Exposure to various VOC's yielded valuable insights on the variability of sensor-to-sensor as well as on the sensor(s) drift. In addition, a complete redesign of the sensor uptake was implemented allowing redundant sensors to be included into the device. This approach was adopted from a research group in Rome who demonstrated a significant noise reduction and drift compensation due to sensor redundancy.
• Device manufacturing - Due to the need to test the VOGAS device by clinical trial including a large number of subjects and a limited time to recruit a sufficient number of Gastric Cancer (GC) patients, it was decided to build six device of the final format. This decision changes the previous plan of building only three devices of the final format and three devices which only harbor the sensor technology without the IR module. This decision was discovered to be of great importance due to the outbreak of covid-19 which delayed some of the activities, further limiting the actual time to recruit GC patients.
• VOC analysis - UOL collected samples of gastric cancer tissue and stomach content form GC patients as well as from heathy volunteers. These were shipped to UIBK for Volatile Organic Compound (VOC) analysis. The analysis by GC and PTR-MS was done along with a tissue culture study comparing VOC emission from normal and gastric cancer cell lines. This study comprising most of the work of work package 1, led to the finding of several unique and novel VOC’s whose levels are altered in malignant tissue relative to normal ones.
• Device planning - JLM has designed and manufactured the PCB boards for the VOGAS devices. The firmware and software generated by JLM was demonstrated to communicate and activate all functional parts of the prototype. In addition, the initial design has been largely modified and improved. The three sensing modules have been integrated to populate one box and additional valves have been introduced. The university of ULM has redesigned and manufactured the hallow waveguide module to be integrated to the JLM design. This was done with the aim of achieving a robust adjustment free device which can be shipped around the world with no need for additional calibration.
• Statistical analysis - Breath samples of healthy volunteers and gastric cancer patients obtained in previous projects were analyzed by VTT according to the neural adaptive statistical method. A project data base has been designed and formed and the flow of data storage and analysis was constructed. VTT also provided a safe ICT platform for data transfer and analysis which would maintain the privacy of the users.
• Clinical study – All five clinical centers, obtained the necessary permits and authorizations to conduct the clinical trials. All Standard Operating Procedures (SOPs) have been thoroughly discussed and agreed upon by all consortium member.
• Ethics – An external ethical board (EEB) was formed and all informed consent forms were evaluated. Finally, a responsible research and innovation (RRI) study and a few filed exercises were performed.
The existing screening methods for cancer suffer from a multitude of disadvantages. Some, such as colonoscopy and sigmoidoscopy are invasive and hence, pose actual risks of medical complications to the screened subjects. Others, such as TEM or mammography for example, require special facilities are expensive and subject the examined individual to risks of radiation. These caveats are compounded by the discomfort and inconvenience, time and money involved with the screening method imposes on the patient. These are all good explanations for the low number of screening methods implemented today. Despite the above, it is widely agreed that one of the most curtail obstacles in screening programs is that a very limited number of diseases currently have an effective screening approach available, e.g. screening for only four cancer types is currently recommended in the EU. The VOGAS project is based on two different and most likely orthogonal analytical methods. Therefore, while maintaining the ease of operation and invasiveness, VOGAS has a very good chance for improving signal to noise ration and hence it’s predictive value.