A new non-invasive and potentially inexpensive frontier in the diagnosis of cancer relies on the detection of volatile organic compounds (VOCs) in exhaled breath samples. Breath can be sampled and analyzed in real-time, leading to fascinating and cost-effective clinical diagnostic procedures. Nevertheless, breath analysis is a very young field of research and faces challenges, mainly because the biochemical mechanisms behind the cancer-related VOCs are largely unknown. In this review, we present a list of 115 validated cancer-related VOCs published in the literature during the past decade, and classify them with respect to their “fat-to-blood” and “blood-to-air” partition coefficients. These partition coefficients provide an estimation of the relative concentrations of VOCs in alveolar breath, in blood and in the fat compartments of the human body. Additionally, we try to clarify controversial issues concerning possible experimental malpractice in the field, and propose ways to translate the basic science results as well as the mechanistic understanding to tools (sensors) that could serve as point-of-care diagnostics of cancer. We end this review with a conclusion and a future perspective.

Assessment, origin, and implementation of breath volatile cancer markers

Surface enhanced Raman scattering (SERS) is a trace detection technique that extends even to single molecule detection. Its potential application to the noninvasive recognition of lung malignancies by detecting volatile organic compounds (VOCs) that serve as biomarkers would be a breakthrough in early cancer diagnostics. This application, however, is currently limited by two main factors: (1) most VOC biomarkers exhibit only weak Raman scattering; and (2) the high mobility of gaseous molecules results in a low adsorptivity on solid substrates. To enhance the adsorption of gaseous molecules, a ZIF-8 layer is coated onto a self-assembly of gold superparticles (GSPs) in order to slow the flow rate of gaseous biomarkers and depress the exponential decay of the electromagnetic field around the GSP surfaces. Gaseous aldehydes that are released as a result of tumor-specific tissue composition and metabolism, thereby acting as indicators of lung cancer, are guided onto SERS-active GSPs substrates through a ZIF-8 channel. Through a Schiff base reaction with 4-aminothiophenol pregrafted onto gold GSPs, gaseous aldehydes are captured with a 10 ppb limit of detection, demonstrating tremendous prospects for in vitro diagnoses of early stage lung cancer.

Selective Surface Enhanced Raman Scattering for Quantitative Detection of Lung Cancer Biomarkers in Superparticle@MOF Structure.

Researchers experimentally demonstrate an upconversion system for field-deployable mid-infrared spectral imaging. The system provides a room-temperature dark noise of 0.2 photons per spatial element per second — a billion times below the dark noise level of cryogenically cooled cameras — and a quantum efficiency of 20%.

/pdf/room-temperature-mid-infrared-single-photon-spectral-imaging-2d151o7knv.pdf

Room-temperature mid-infrared single-photon spectral imaging

Upper digestive endoscopy with biopsy and histopathological evaluation of the biopsy material is the standard method for diagnosing gastric cancer (GC). However, this procedure may not be widely available for screening in the developing world, whereas in developed countries endoscopy is frequently used without major clinical gain. There is a high demand for a simple and non-invasive test for selecting the individuals at increased risk that should undergo the endoscopic examination. Here, we studied the feasibility of a nanomaterial-based breath test for identifying GC among patients with gastric complaints. Alveolar exhaled breath samples from 130 patients with gastric complaints (37 GC/32 ulcers / 61 less severe conditions) that underwent endoscopy/biopsy were analyzed using nanomaterial-based sensors. Predictive models were built employing discriminant factor analysis (DFA) pattern recognition, and their stability against possible confounding factors (alcohol/tobacco consumption; Helicobacter pylori) was tested. Classification success was determined (i) using leave-one-out cross-validation and (ii) by randomly blinding 25% of the samples as a validation set. Complementary chemical analysis of the breath samples was performed using gas chromatography coupled with mass spectrometry. Three DFA models were developed that achieved excellent discrimination between the subpopulations: (i) GC vs benign gastric conditions, among all the patients (89% sensitivity; 90% specificity); (ii) early stage GC (I and II) vs late stage (III and IV), among GC patients (89% sensitivity; 94% specificity); and (iii) ulcer vs less severe, among benign conditions (84% sensitivity; 87% specificity). The models were insensitive against the tested confounding factors. Chemical analysis found that five volatile organic compounds (2-propenenitrile, 2-butoxy-ethanol, furfural, 6-methyl-5-hepten-2-one and isoprene) were significantly elevated in patients with GC and/or peptic ulcer, as compared with less severe gastric conditions. The concentrations both in the room air and in the breath samples were in the single p.p.b.v range, except in the case of isoprene. The preliminary results of this pilot study could open a new and promising avenue to diagnose GC and distinguish it from other gastric diseases. It should be noted that the applied methods are complementary and the potential marker compounds identified by gas-chromatography/mass spectrometry are not necessarily responsible for the differences in the sensor responses. Although this pilot study does not allow drawing far-reaching conclusions, the encouraging preliminary results presented here have initiated a large multicentre clinical trial to confirm the observed patterns for GC and benign gastric conditions.

/pdf/a-nanomaterial-based-breath-test-for-distinguishing-gastric-zc3esvwjx2.pdf

A nanomaterial-based breath test for distinguishing gastric cancer from benign gastric conditions.

https://www.jto.org/article/S1556-0864(15)31770-6/pdf

Exhaled breath analysis with a colorimetric sensor array for the identification and characterization of lung cancer.

Quantitative breath analysis of volatile organic compounds of lung cancer patients.

Physicochemical characterization and hypoglycemic potential of a novel polysaccharide from Polygonatum sibiricum Red through PI3K/Akt mediated signaling pathway

Guo-Bing Xu

Papers

Quantitative breath analysis of volatile organic compounds of lung cancer patients.

Physicochemical characterization and hypoglycemic potential of a novel polysaccharide from Polygonatum sibiricum Red through PI3K/Akt mediated signaling pathway