Using a chemiresistor-based alkane sensor to distinguish exhaled breaths of lung cancer patients from subjects with no lung cancer

Abstract

Background: Breath alkanes are reported to be able to discriminate lung cancer patients from healthy people. A simple chemiresistor-based sensor was designed to respond to alkanes by a change in resistance measured by a digital multimeter connected to the sensor. In preclinical experiments, the sensor response was found to have a strong positive linear relationship with alkane compounds and not responsive to water.This study aimed to determine the ability of the alkane sensor to distinguish the exhaled breaths of lung cancer patients from that of chronic obstructive pulmonary disease (COPD) patients and control subjects without lung cancer. Methods: In this cross-sectional study, 12 treatment-naive patients with lung cancer, 12 ex-or current smokers with COPD and 13 never-smokers without lung disease were asked to exhale through a drinking straw into a prototype breath-in apparatus made from an empty 125 mL Vitagen ® bottle with the chemiresistor sensor attached at its inside bottom to measure the sensor peak output (percentage change of baseline resistance measured before exhalation to peak resistance) and the time taken for the baseline resistance to reach peak resistance. In recent years, there has been an increasing interest in finding a diagnostic method for lung cancer that is minimally invasive, free of radiation and accurate in detecting lung cancer at its early stage. This is because the National Lung Screening Trial (NLST) (3) conducted on 53,454 study subjects demonstrated that the chest tomography (CT) scan and chest X-ray imaging are associated with very high false-positive results in detecting lung cancer in early stages (96.4% for low-dose CT scan; 94.5% for chest X-ray). Furthermore, one person out of 2,500 people screened by chest imaging will die of radiationinduced cancer (4). To address this issue, previous studies show that using the pattern of endogenous volatile organic compounds (VOCs) in the exhaled breath for the detection of lung cancer is one of the promising solutions. Cellular metabolisms produce VOCs, such as alcohols, alkanes, etc., that will be carried in the bloodstream. Subsequently, the VOCs diffuse into the alveolar air in the blood-gas interface quickly in the lung because of their low solubility in the blood, and they are exhaled out of the lung (5). Therefore, analysing the composition of VOCs in exhaled breath can provide a window into the biochemical process of the body and detect altered metabolism, particularly in cancer cells. This method has a few advantages: it is non-invasive, potentially inexpensive and it is very easy to obtain exhaled breath (6,7). Compared to biomarkers in serum, the breath contains a less complicated mixture of VOCs. Moreover, breath testing provides direct and real-time monitoring, and has the potential of detecting lung cancer when it is still localised as VOCs markers are transmitted to the alveoli to be exhaled at the onset of the disease. Another important advantage is the presence of lung cancer tumour is not masked by other diseases sin...

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“…In previous studies, 16,33,34 we have found that the sensor array output is not affected by current smoking. Tan et al 26 have made a similar finding. To the best of our knowledge, this is the first publication of breath print analysis that distinguishes between LC in heavy smokers from that in light-to-minimal smokers, suggesting a possible metabolic difference between LCs in these two groups.…”

“…We also compared LC with benign nodules, with results similar to those from previous studies. 13,14,19,20,26,27 In our previous pilot study of patients from Colorado, we showed that benign pulmonary nodules could be well discriminated from LC by a unique breath print. 25 The nanoarray sensors could also discriminate between adenocarcinomas and SCCs and between early-stage and advanced disease.…”

“…23 A recent cross-sectional study that included use of a chemiresistor-based alkane sensor demonstrated that the peak output and the time to peak values for patients with LC were statistically different from those for chronic obstructive pulmonary disease and healthy controls. 26 LC was diagnosed with sensitivity of 83.3% and a specificity of 88%. In another interesting study performed by Peralbo-Molina et al, five different metabolites (monopalmitin, benzyl alcohol, monostearin, 2,4-diphenyl-4-methyl-2-E-pentene, and p-cresol) were used to form three panels.…”

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“…The most common types of hybrid sensing layers are those composed of a conductive inorganic material, surrounded by an organic functional film where the gaseous analytes are adsorbed therefore changing the conductivity of the device [ 15 ]. CNTs, MNPs (e.g., Au) [ 15 ], or carbon black [ 15 , 108 ] can be used as the conductive part while non-conducting molecular ligands (MCNPs) [ 51 , 108 , 109 ] or polymers [ 110 ] as the organic one. Such sensors offer the prospect of cross-reactive sensor-array development since the organic part is selected based on the chemical and physical properties of the VOCs [ 16 ].…”

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“…There has also been interest in the biofuels industry in biosensors for detecting the intracellular concentrations of biosynthesized alkanes ( Wu et al, 2015 ). Finally, there are potential medical applications for alkane biosensors in analysis of breath samples for lung cancer diagnosis ( Tan et al, 2016 ).…”