Pioneering noninvasive colorectal cancer detection with an AI-enhanced breath volatilomics platform.

Background: The sensitivity and specificity of current breath biomarkers are often inadequate for effective cancer screening, particularly in colorectal cancer (CRC). While a few exhaled biomarkers in CRC exhibit high specificity, they lack the requisite sensitivity for early-stage detection, thereby limiting improvements in patient survival rates. Methods: In this study, we developed an advanced Mass Spectrometry-based volatilomics platform, complemented by an enhanced breath sampler. The platform integrates artificial intelligence (AI)-assisted algorithms to detect multiple volatile organic compounds (VOCs) biomarkers in human breath. Subsequently, we applied this platform to analyze 364 clinical CRC and normal exhaled samples. Results: The diagnostic signatures, including 2-methyl, octane, and butyric acid, generated by the platform effectively discriminated CRC patients from normal controls with high sensitivity (89.7%), specificity (86.8%), and accuracy (AUC = 0.91). Furthermore, the metastatic signature correctly identified over 50% of metastatic patients who tested negative for carcinoembryonic antigen (CEA). Fecal validation indicated that elevated breath biomarkers correlated with an inflammatory response guided by Bacteroides fragilis in CRC. Conclusion: This study introduces a sophisticated AI-aided Mass Spectrometry-based platform capable of identifying novel and feasible breath biomarkers for early-stage CRC detection. The promising results position the platform as an efficient noninvasive screening test for clinical applications, offering potential advancements in early detection and improved survival rates for CRC patients.

Exhaled volatolomics profiling facilitates personalized screening for gastric cancer.

Gastric cancer (GC) is one of the most fatal cancers, characterized by non-specific early symptoms and difficulty in detection. However, there are no valid non-invasive screening tools available for GC. Here we establish a non-invasive method that employs exhaled volatolomics and ensemble learning to detect GC. We developed a comprehensive mass spectrometry-based procedure and determined of a wide range of volatolomics from 314 breath samples. The discovery, identification and verification research screened a biomarker panel to distinguish GC from controls. This panel has achieved 0.90 (0.87-0.94, 95%CI) accuracy, with an area under curve (AUC) of 0.92 (0.89-0.94, 95%CI) in discovery cohort and 0.88 (0.83-0.91, 95%CI) accuracy with an AUC of 0.91 (0.87-0.93, 95%CI) in replication cohort, which outperformed traditional serum markers. Single-cell sequencing and gene set enrichment analysis revealed that these exhaled markers originated from aldehyde oxidation and pyruvate metabolism. Our approach advances the design of exhaled analysis for GC detection and holds promise as a non-invasive method to the clinic.

On-line trace monitoring of volatile halogenated compounds in air by improved thermal desorption-gas chromatography-mass spectrometry.

Volatile halogenated compounds (VHCs) are important industrial chemicals and play a crucial role in potential stratospheric ozone-depletion and global warming. Profiling of VHCs is of great significance but replete with challenges due to the species' richness and diversity. In this study, we developed a novel method employing water removal mode combined with thermal desorption-gas chromatography-mass spectrometry (TD-GC-MS) for on-line measurement of VHCs at the ultratrace level. By removing water with Nafion dryer tandem cold trap device, VHCs could achieve better separation and identification, and detection precision of VHCs lower than 10%. The proposed method exhibited limits of detection for VHCs ranging from 0.1 to 6.2 pptv. Benefiting from the improved trapping efficiency due to water removal, we successfully quantified 34 VHCs at the Shangdianzi background station and achieved a comprehensive assessment of VHCs in ambient air.

Simultaneous determination of seven perfluoroalkyl carboxylic acids in water samples by 2,3,4,5,6-pentafluorobenzyl bromide derivatization and gas chromatography-mass spectrometry.

A new derivatization reagent, 2,3,4,5,6-pentafluorobenzyl bromide (PFBBr), was employed to determine seven perfluoroalkyl carboxylic acids (PFCAs) simultaneously in tap water with gas chromatography-mass spectrometry (GC-MS) technique in this study. Firstly, seven PFCAs were derivatized to their corresponding esters under alkaline condition. The derivatization conditions including the amount of PFBBr and K2CO3, derivatization temperature and time were optimized to increase the derivatization efficiency. The 14 tap water samples collected from different places of China were enriched and purified through solid phase extraction pretreatment. The limits of detection (LODs) and the limits of quantitation (LOQs) ranged from 0.1 ng/L to 0.28 ng/L and from 0.3 ng/L to 0.84 ng/L, respectively. The new method offers a linear relationship in the range from 2 ng/L to 2000 ng/L, and the correlation coefficients ranged from 0.9938 to 0.9994. The results showed that GC-MS combined with pre-column derivatization is a reliable method for the analysis of PFCAs in the aqueous environment.

Simultaneous determination of nine perfluoroalkyl carboxylic acids by a series of amide acetals derivatization and gas chromatography tandem mass spectrometry.

A novel and simple derivatization method using a series of amide acetals as derivatization reagents, along with gas chromatography tandem mass spectrometry (GC-MS/MS) analysis, were developed and validated for simultaneous determination of 9 perfluoroalkyl carboxylic acids (PFCAs) in this study. The structures and fragmentation pathway of PFCAs derivatives were deduced and verified. The derivatization method developed in this study improved the sensitivity of the detection of PFCAs by GC. The applicability of 6 amide acetals for the derivatization of PFCAs was demonstrated. Derivatization conditions for 9 PFCAs were optimized with addition of 20 µL of derivatization reagent and reaction at 35 °C for 30 min. 9 PFCAs derivatives were confirmed to be stable over 15 days. The instrument detection limits (IDLs) were lower than 0.01 pg/µL. The intra and inter-day precisions were below 4.06% and 5.48%, respectively. To demonstrate the utility of the derivatization method, the level of PFCAs in the marine products were detected. The alkaline digestion followed by solid-phase extraction (SPE) cleanup method was used for pretreatment. The method detection limits (MDLs) ranged from 0.04 to 0.10 ng/g, and the spiked recoveries ranged between 54.72% and 107.29%, with relative standard deviation (RSD) of 1.53%-11.89%. Five PFCAs were detected in the range of 0.66 to 499.03 ng/g dry weight.