Early detection of lung cancer is a key factor for increasing the survival rates of lung cancer patients. The analysis of exhaled breath is promising as a noninvasive diagnostic tool for diagnosis of lung cancer. We demonstrate the quantitative analysis of carbonyl volatile organic compounds (VOCs) and identification of lung cancer VOC markers in exhaled breath using unique silicon microreactor technology. The microreactor consists of thousands of micropillars coated with an ammonium aminooxy salt for capture of carbonyl VOCs in exhaled breath by means of oximation reactions. Captured aminooxy-VOC adducts are analyzed by nanoelectrospray Fourier transform-ion cyclotron resonance (FT-ICR) mass spectrometry (MS). The concentrations of 2-butanone, 2-hydroxyacetaldehyde, 3-hydroxy-2-butanone, and 4-hydroxyhexenal (4-HHE) in the exhaled breath of lung cancer patients (n = 97) were significantly higher than in the exhaled breath of healthy smoker and nonsmoker controls (n = 88) and patients with benign pulmonary nodules (n = 32). The concentration of 2-butanone in exhaled breath of patients (n = 51) with stages II though IV non–small cell lung cancer (NSCLC) was significantly higher than in exhaled breath of patients with stage I (n = 34). The carbonyl VOC profile in exhaled breath determined using this new silicon microreactor technology provides for the noninvasive detection of lung cancer.

Analysis of specific exhaled carbonyls can differentiate early lung cancer from benign pulmonary disease. Breath analysis was more specific than PET for a lung cancer diagnosis. Judicious use of these data may expedite the care of patients with lung cancer.

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The manipulation of cationic lipid structure to increase polynucleotide binding and delivery properties while also minimizing associated cytotoxicity has been a principal strategy for developing next-generation transfection agents. The polar (DNA-binding) and hydrophobic domains of transfection lipids have been extensively studied; however, the linking domain comprising the substructure used to tether the polar and hydrophobic domains has attracted considerably less attention as an optimization variable. Here, we examine the use of an oxime ether as the linking domain. Hydrophobic oxime ethers were readily assembled via click chemistry by oximation of hydrophobic aldehydes using an aminooxy salt. The facile ligation reaction delivered the title compounds with hydrophobic domain asymmetry. Using the MCF-7 breast cancer, H1792 lung cancer and PAR C10 salivary epithelial cell lines, our findings show that lipoplexes derived from the oxime ether lipids transfect in the presence of serum at higher levels than commonly used liposome formulations, based on both luciferase and GFP assays. Given the biological compatibility of oxime ethers and their ease of formation, this functional group should find much application as a linking domain in future designs of transfection vectors.

We describe an aminooxy reagent for the capture of trace aldehyde and ketone volatile organic compounds (VOCs) in exhaled breath.