NEW YORK (360Dx) – As more research is directed into the use of patients' breath as a basis for medical diagnoses, a consortium of nine European and Middle East partners have joined the fray by developing a nanosensor attached to a smartphone for screening gastric cancer at the point of care.
The platform, called the SniffPhone, was developed as part of a four-year, €5.8 million ($6.6 million) European Union Horizon 2020 Funding Programme, by the consortium, which comprises Technion - Israel Institute of Technology, the coordinator of the effort; NanoVation in Israel; Cellix in Ireland; Microfluidic ChipShop in Germany; the University of Latvia; the University of Innsbruck in Austria; Siemens in Germany; JLM Innovation in Germany; and VTT Technical Research Centre of Finland.
The prototype is made up of nanomaterials-based chemical sensor that uses a smartphone to send measurements wirelessly to a dedicated cloud platform where the results are analyzed by medical specialists.
The group has developed and validated its SniffPhone prototypes through clinical studies and it expects to commercialize the sensor via an undisclosed spin-off company, according to Kari Antila, a senior scientist at VTT who managed his firm's component of the project.
In practice, the nanosensors developed by the consortium measure volatile organic compounds from a breath sample. The device is being developed to be comfortable and painless to use, and to provide a cost-effective alternative for screening gastric cancers, Antila said. Â
VTT has worked with project partners to implement a platform for transferring data from the smartphone to a cloud-based storage space, and to build analysis tools and methods for recognizing high-risk patients.
Antila noted that it has also developed a mobile application that guides users in providing a breath sample. The app shares a preliminary analysis with them and alerts them if they need to see a physician. For physicians, VTT has developed a separate cloud-based analysis tool connected with the same platform, he said.
To date, no breath cancer diagnostic test has been cleared by regulators or are even commercially available for clinical use. However, breath-based diagnostic tests could become important in enabling broader screening for gastric cancers, Agne Krilaviciute, a researcher in the Division of Clinical Epidemiology and Aging Research at the German Cancer Research Center, said in an interview.
With colleagues, Krilaviciute evaluated the potential for using breath testing for early detection of gastric cancers in making screening more efficient, and they published the results of their study last year in the Journal of Breath Research.
She is not involved in the development of the SniffPhone. Although Krilaviciute is familiar with the SniffPhone project, she declined to speak specifically about it.
In her own work based on literature searches, she and her colleagues found that conducting gastric cancer screening using breath tests reduced the number of endoscopies that would be needed by between nine and 10 times.
"That would be a significant improvement and could making it worth it for countries, including those with low prevalence, to introduced broad screening programs," Krilaviciute said.
The SniffPhone leverages technology developed by Hossam Haick, a professor in the Technion - Israel Institute of Technology. The developers are getting ready to release the results of a new study in an undisclosed peer-reviewed publication that shows promising results for validation of the device that they've developed and clinically tested thus far, Antila said.
The current prototype is an automated version of technology that was previously described in peer-reviewed journals, he said. In 2015, in the journal Gut, the test developers described the use of nanoarray analysis as a noninvasive screening tool for gastric cancer and related precancerous lesions and for surveillance of the precancerous lesions. They collected 968 breath samples from 484 patients, including 99 with gastric cancer. The nanoarray analysis made it possible to discriminate between the patients with gastric cancer and the control group with 73 percent sensitivity, 98 percent specificity, and 92 percent accuracy.
In 2017 in the journal ACSNano, they described the use of pattern analysis of exhaled molecules in the diagnosis and classification of a range of diseases, including cancers, inflammatory conditions, and neurological conditions.
The platform used a nanoarray with chemiresistive layers of molecularly modified gold nanoparticles and a random network of single-wall carbon nanotubes. The gold nanoparticles and single-wall carbon nanotubes provide electrical conductivity, and an organic layer functions as a sensing recognition element for adsorbed volatile organic compounds.
During exposure to breath samples, interaction between the VOCs and the organic sensing layer changes the electrical resistance of the sensors.
In conjunction with artificial intelligence methods, the researchers used the nanoarray for a meta-analysis of several groups of subjects under real-world circumstances during the study published in ACSNano. In blind experiments with 1,404 subjects, the researchers reported that the device had 86 percent accuracy and enabled detection of disease conditions and discrimination between them.Â
The population included 591 healthy controls and 813 patients diagnosed with one of 17 different diseases — lung cancer, colorectal cancer, head and neck cancer, ovarian cancer, bladder cancer, prostate cancer, kidney cancer, gastric cancer, Crohn’s disease, ulcerative colitis, irritable bowel syndrome, idiopathic Parkinson’s, atypical Parkinsonism, multiple sclerosis, pulmonary arterial hypertension, pre-eclampsia, and chronic kidney disease.
One breath sample obtained from each subject was analyzed with the artificially intelligent nanoarray for disease diagnosis and classification, and a second was analyzed with GC-MS for exploring its chemical composition. Analysis using the artificially intelligent nanoarray showed that each disease has its own unique signatures.
Gastric cancer screening
The device under development at Technion has potential for application in a number of indications, but screening of gastric cancers could provide an opportunity for its adoption and for the use of breath tests generally.
At present, country-level screening for gastric cancers only occurs in South Korea and Japan, Krilaviciute said. The prevalence of cancers is higher there than in the US and many countries in Western Europe.  Â
"In countries with very low prevalence, it becomes extremely costly to screen the broad population using gastrointestinal endoscopy," Krilaviciute said. However, gastric cancer is deadly when diagnosed at a late stage and its mortality rate is driving the need for overall broader screening, she noted.
Five-year survival rates are about 5 percent for distant gastric cancer that has spread to other parts of the body such as the liver, according to the American Cancer Society. By comparison, the five-year survival rate is about 68 percent when the cancer is localized and there is no sign that it has spread outside the stomach.
Effective and accurate detection is important because the disease tends to be asymptomatic, and people often don't know that they have pre-cancer or cancer unless they seek testing or other clinical screening specific to the condition, Krilaviciute said.
Along with Krilaviciute and the SniffPhone developers, others working on breath-based diagnostic tests include Cambridge, UK-based Owlstone Medicine. Clinical trials for its technology are being conducted for several indications, including gastric cancer.
Additionally, a team led by Washington University in St. Louis is developing a breath-based test for malaria. And Avisa Pharma is developing breath-based technology for detecting bacterial infections.
According to Antila, the SniffPhone could provide advantages over other breath tests in development because it is being designed to deliver results within minutes and directly at the point of care.
But before that test, or any other breath-based diagnostic, is ready for clinical use, more research will be needed, Krilaviciute said.
"More studies are needed in various populations and at different age groups for all of the breath tests that are in development," she said.