"Gold Plated" Breath Test Accurately Diagnoses Lung Cancer

Roxanne Nelson

September 04, 2009

September 4, 2009 — A sensor made from gold nanoparticles is able to distinguish the breath of lung cancer patients from that of healthy individuals, report researchers from Israel. The results of a new study show that this technology has the potential to form the basis of an inexpensive and noninvasive diagnostic tool for lung cancer.

Reporting in the August 30 online issue of Nature Nanotechnology, the researchers were able to identify 42 lung cancer biomarkers using solid-phase microextraction and gas chromatography/mass spectrometry. "We selected 5 volatile biomarkers, which can be used to train and optimize the array of sensors, to simulate healthy breath and lung cancer breath," said lead author Hossam Haick, PhD, senior lecturer at the Russell Berrie Nanotechnology Institute, Technion–Israel Institute of Technology, Haifa.

"We demonstrated that our device has a potential not only to distinguish lung cancer patients from healthy controls but also to identify different types of primary lung cancer," Dr. Haick told Medscape Oncology.

These findings show great promise for fast, easy, and cost-effective early diagnosis and screening of lung cancer, Dr. Haick explained. "The developed devices are expected to be relatively inexpensive, portable, and amenable to use in widespread screening, making them potentially valuable in saving millions of lives every year."

Increasing Interest in "Breath Tests"

There has been increasing interest in the use of breath tests as a diagnostic tool for lung cancer, and results have been promising, as previously reported by Medscape Oncology . Studies using gas chromatography/mass spectrometry have shown that a number of volatile organic compounds (VOCs) are elevated in lung cancer patients. In healthy human breath, levels of VOCs range between 1 and 20 parts per billion, but these levels are elevated to between 10 and 100 parts per billion in patients with lung cancer, according to the researchers.

At this time, there are methods of measuring VOCs, but these techniques are expensive, slow, and require complex instruments. In addition, they require preconcentration of the biomarkers to improve detection. Conversely, Dr. Haick explained that the sensing technology developed by his team is simple, inexpensive, and portable and does not require the exhaled breath to be pretreated in any way.

4-Phase Study

The study consisted of 4 phases, beginning with the collection of breath samples obtained from 56 healthy control participants and 40 lung cancer patients who had already been diagnosed with the disease but had not yet begun treatment.

During the second phase, the researchers identified the VOCs that would serve as biomarkers for lung cancer in the breath samples and determined their relative compositions. They identified 33 biomarker VOCs that were elevated in lung cancer patients but not in healthy control participants.

In the third phase, they designed 9 cross-reactive chemiresistors, which were assembled from gold nanoparticles (5 nm in diameter) with different organic functionalities. Before testing the sensors with the collected breath samples, the researchers evaluated sensor response to several representative lung cancer biomarkers and found that the sensors responded "rapidly and fully reversibly to a wide variety of concentrations." They observed similar characteristics when the sensors were exposed to the actual breath samples of both healthy individuals and lung cancer patients.

When the response of the 9 sensors to both healthy and lung cancer breath samples was analyzed, the researchers noted that there was "no overlap of the lung cancer and healthy patterns."

Finally, in the fourth and final phase, they prepared simulated breath patterns that were based on the analysis of the breath samples. The simulation experiments demonstrated satisfactory accuracy (>86%) and good reproducibility (>90%), even when conducted on different days.

Potential Exists for Other Applications

"Given the impact of the rising incidence of cancer on health budgets worldwide, the proposed technology will be a significant savings for both private and public health expenditures," said Dr. Haick. "The potential exists for using the proposed technology to diagnose other conditions and diseases, which could mean additional cost reductions and enhanced possibilities to save lives."

Although clinical trials are generally the preferred option for validating the efficiency of sensor arrays, the researchers point out that clinical trials are time-consuming and expensive and that simpler strategies can be used. One approach would be to use "artificial" mixtures of VOCs that simulate both cancerous and healthy breath.

The researchers add that they have been getting "promising results" for diagnosing other diseases using this approach. "In addition, such a tool might be used for immediate diagnosis of fresh tissues of lung cancer in operating rooms, where a dichotomic diagnosis is crucial to guide surgeons," said Dr. Haick.

The study was supported by the Marie Curie Excellence Grant of the European Commission's FP6 program, the Alfred Mann Institute, the Israel Cancer Association, and the Technion's Russell Berrie Nanotechnology Institute. The authors have disclosed no relevant financial relationships.

Nat Nanotechnol. Published online August 30, 2009.

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