Search Results (19)

Phospholipids are the main building components of cell membranes and are also used for cell signaling and as energy storages. Cancer cells alter their lipid metabolism, which ultimately leads to an increase in phospholipids in cancer tissue. Surgical energy instruments use electrical or vibrational energy to heat tissues, which causes intra- and extracellular water to expand rapidly and degrade cell structures, bursting the cells, which causes the formation of a tissue aerosol or smoke depending on the amount of energy used. This gas phase analyte can then be analyzed via gas analysis methods. Differential mobility spectrometry (DMS) is a method that can be used to differentiate malignant tissue from benign tissues in real time via the analysis of surgical smoke produced by energy instruments. Previously, the DMS identification of cancer tissue was based on a ‘black box method’ by differentiating the 2D dispersion plots of samples. This study sets out to find datapoints from the DMS dispersion plots that represent relevant target molecules. We studied the ability of DMS to differentiate three subclasses of phospholipids (phosphatidylcholine, phosphatidylinositol, and phosphatidylethanolamine) from a control sample using a bovine skeletal muscle matrix with a 5 mg addition of each phospholipid subclass to the sample matrix. We trained binary classifiers using linear discriminant analysis (LDA) and support vector machines (SVM) for sample classification. We were able to identify phosphatidylcholine, -inositol, and -ethanolamine with SVM binary classification accuracies of 91%, 73%, and 66% and with LDA binary classification accuracies of 82%, 74%, and 72%, respectively. Phosphatidylcholine was detected with a reliable classification accuracy, but ion separation setups should be adjusted in future studies to reliably detect other relevant phospholipids such as phosphatidylinositol and phosphatidylethanolamine and improve DMS as a microanalysis method and identify other phospholipids relevant to cancer tissue. Full article

Cannabis has been used historically for both medicinal and recreational purposes, with the most notable cannabinoids being cannabidiol (CBD) and tetrahydrocannabinol (THC). Although their therapeutic effects have been well studied and their recreational use is highly debated, the underlying mechanisms of their biological effects remain poorly defined. In this study, we use isobaric tag-based sample multiplexed proteome profiling to investigate protein abundance differences in the human neuroblastoma SH-SY5Y cell line treated with CBD and THC. We identified significantly regulated proteins by each treatment and performed a pathway classification and associated protein–protein interaction analysis. Our findings suggest that these treatments may lead to mitochondrial dysfunction and induce endoplasmic reticulum stress. These data can potentially be interrogated further to investigate the potential role of CBD and THC in various biological and disease contexts, providing a foundation for future studies. Full article

Cardiolipin (CL) is a mitochondrial lipid with diverse roles in cellular respiration, signaling, and organelle membrane structure. CL content and composition are essential for proper mitochondrial function. Deranged mitochondrial energy production and signaling are key components of glial cell cancers and altered CL molecular species have been observed in mouse brain glial cell xenograft tumors. The objective of this study was to describe CL structural diversity trends in human astrocytoma tumors of varying grades and correlate these trends with histological regions within the heterogeneous astrocytoma microenvironment. To this aim, we applied desorption electrospray ionization coupled with high field asymmetric ion mobility mass spectrometry (DESI-FAIMS-MS) to map CL molecular species in human normal cortex (N = 29), lower-grade astrocytoma (N = 19), and glioblastoma (N = 28) tissues. With this platform, we detected 46 CL species and 12 monolysocardiolipin species from normal cortex samples. CL profiles detected from glioblastoma tissues lacked diversity and abundance of longer chain polyunsaturated fatty acid containing CL species when compared to CL detected from normal and lower-grade tumors. CL profiles correlated with trends in tumor viability and tumor infiltration. Structural characterization of the CL species by tandem MS experiments revealed differences in fatty acid and double bond isomer composition among astrocytoma tissues compared with normal cortex and glioblastoma tissues. The GlioVis platform was used to analyze astrocytoma gene expression data from the CGGA dataset. Decreased expression of several mitochondrial respiratory enzyme encoding-genes was observed for higher-grade versus lower-grade tumors, however no significant difference was observed for cardiolipin synthesis enzyme CRLS1. Full article

Background: Volatile organic compound (VOC) profiles as biomarkers for hepatocellular carcinoma (HCC) are understudied. We aimed to identify VOCs from the exhaled breath for HCC diagnosis and compare the performance of VOCs to alpha-fetoprotein (AFP). The performance of VOCs for predicting treatment response and the association between VOCs level and survival of HCC patients were also determined. Methods: VOCs from 124 HCC patients and 219 controls were identified using the XGBoost algorithm. ROC analysis was used to determine VOCs performance in differentiating HCC patients from controls and in discriminating treatment responders from non-responders. The association between VOCs and the survival of HCC patients was analyzed using Cox proportional hazard analysis. Results: The combination of 9 VOCs yielded 70.0% sensitivity, 88.6% specificity, and 75.0% accuracy for HCC diagnosis. When differentiating early HCC from cirrhotic patients, acetone dimer had a significantly higher AUC than AFP, i.e., 0.775 vs. 0.714, respectively, p = 0.001. Acetone dimer classified HCC patients into treatment responders and non-responders, with 95.7% sensitivity, 73.3% specificity, and 86.8% accuracy. Isopropyl alcohol was independently associated with the survival of HCC patients, with an adjusted hazard ratio of 7.23 (95%CI: 1.36–38.54), p = 0.020. Conclusions: Analysis of VOCs is a feasible noninvasive test for diagnosing and monitoring HCC treatment response. Full article

Tomato sauce is a world famous food product. Despite standards regulating the production of tomato derivatives, the market suffers frpm fraud such as product adulteration, origin mislabelling and counterfeiting. Methods suitable to discriminate the geographical origin of food samples and identify counterfeits are required. Chemometric approaches offer valuable information: data on tomato sauce is usually obtained through chromatography (HPLC and GC) coupled to mass spectrometry, which requires chemical pretreatment and the use of organic solvents. In this paper, a faster, cheaper, and greener analytical procedure has been developed for the analysis of volatile organic compounds (VOCs) and the colloidal fraction via multivariate statistical analysis. Tomato sauce VOCs were analysed by GC coupled to flame ionisation (GC-FID) and to ion mobility spectrometry (GC-IMS). Instead of using HPLC, the colloidal fraction was analysed by asymmetric flow field-fractionation (AF4), which was applied to this kind of sample for the first time. The GC and AF4 data showed promising perspectives in food-quality control: the AF4 method yielded comparable or better results than GC-IMS and offered complementary information. The ability to work in saline conditions with easy pretreatment and no chemical waste is a significant advantage compared to environmentally heavy techniques. The method presented here should therefore be taken into consideration when designing chemometric approaches which encompass a large number of samples. Full article

Colorectal symptoms are common but only infrequently represent serious pathology, including colorectal cancer (CRC). A large number of invasive tests are presently performed for reassurance. We investigated the feasibility of urinary volatile organic compound (VOC) testing as a potential triage tool in patients fast-tracked for assessment for possible CRC. A prospective, multi-center, observational feasibility study was performed across three sites. Patients referred to NHS fast-track pathways for potential CRC provided a urine sample that underwent Gas Chromatography-Mass Spectrometry (GC-MS), Field Asymmetric Ion Mobility Spectrometry (FAIMS), and Selected Ion Flow Tube Mass Spectrometry (SIFT-MS) analysis. Patients underwent colonoscopy and/or CT colonography and were grouped as either CRC, adenomatous polyp(s), or controls to explore the diagnostic accuracy of VOC output data supported by an artificial neural network (ANN) model. 558 patients participated with 23 (4%) CRC diagnosed. 59% of colonoscopies and 86% of CT colonographies showed no abnormalities. Urinary VOC testing was feasible, acceptable to patients, and applicable within the clinical fast track pathway. GC-MS showed the highest clinical utility for CRC and polyp detection vs. controls (sensitivity = 0.878, specificity = 0.882, AUROC = 0.896) but it is labour intensive. Urinary VOC testing and analysis are feasible within NHS fast-track CRC pathways. Clinically meaningful differences between patients with cancer, polyps, or no pathology were identified suggesting VOC analysis may have future utility as a triage tool. Full article

High-field asymmetric ion mobility spectrometry (FAIMS) spectra of single chemicals are easy to interpret but identifying specific chemicals within complex mixtures is difficult. This paper demonstrates that the FAIMS system can detect specific chemicals in complex mixtures. A homemade FAIMS system is used to analyze pure ethanol, ethyl acetate, acetone, 4-methyl-2-pentanone, butanone, and their mixtures in order to create datasets. An EfficientNetV2 discriminant model was constructed, and a blind test set was used to verify whether the deep-learning model is capable of the required task. The results show that the pre-trained EfficientNetV2 model completed convergence at a learning rate of 0.1 as well as 200 iterations. Specific substances in complex mixtures can be effectively identified using the trained model and the homemade FAIMS system. Accuracies of 100%, 96.7%, and 86.7% are obtained for ethanol, ethyl acetate, and acetone in the blind test set, which are much higher than conventional methods. The deep learning network provides higher accuracy than traditional FAIMS spectral analysis methods. This simplifies the FAIMS spectral analysis process and contributes to further development of FAIMS systems. Full article

The study evaluates the suitability of a field asymmetric ion mobility spectrometry (FAIMS) system for early detection of the Pythium leak disease in potato tubers simulating bulk storage conditions. Tubers of Ranger Russet (RR) and Russet Burbank (RB) cultivars were inoculated with Pythium ultimum, the causal agent of Pythium leak (with negative control samples as well) and placed in glass jars. The headspace in sampling jars was scanned using the FAIMS system at regular intervals (in days up to 14 and 31 days for the tubers stored at 25 °C and 4 °C, respectively) to acquire ion mobility current profiles representing the volatile organic compounds (VOCs). Principal component analysis plots revealed that VOCs ion peak profiles specific to Pythium ultimum were detected for the cultivars as early as one day after inoculation (DAI) at room temperature storage condition, while delayed detection was observed for tubers stored at 4 °C (RR: 5th DAI and RB: 10th DAI), possibly due to a slower disease progression at a lower temperature. There was also some overlap between control and inoculated samples at a lower temperature, which could be because of the limited volatile release. Additionally, data suggested that the RB cultivar might be less susceptible to Pythium ultimum under reduced temperature storage conditions. Disease symptom-specific critical compensation voltage (CV) and dispersion field (DF) from FAIMS responses were in the ranges of −0.58 to −2.97 V and 30–84% for the tubers stored at room temperature, and −0.31 to −2.97 V and 28–90% for reduced temperature, respectively. The ion current intensities at −1.31 V CV and 74% DF showed distinctive temporal progression associated with healthy control and infected tuber samples. Full article

Current available methods for the clinical diagnosis of urinary tract infection (UTI) rely on a urine dipstick test or culturing of pathogens. The dipstick test is rapid (available in 1–2 min), but has a low positive predictive value, while culturing is time-consuming and delays diagnosis (24–72 h between sample collection and pathogen identification). Due to this delay, broad-spectrum antibiotics are often prescribed immediately. The over-prescription of antibiotics should be limited, in order to prevent the development of antimicrobial resistance. As a result, there is a growing need for alternative diagnostic tools. This paper reviews applications of chemical-analysis instruments, such as gas chromatography–mass spectrometry (GC-MS), selected ion flow tube mass spectrometry (SIFT-MS), ion mobility spectrometry (IMS), field asymmetric ion mobility spectrometry (FAIMS) and electronic noses (eNoses) used for the diagnosis of UTI. These methods analyse volatile organic compounds (VOCs) that emanate from the headspace of collected urine samples to identify the bacterial pathogen and even determine the causative agent’s resistance to different antibiotics. There is great potential for these technologies to gain wide-spread and routine use in clinical settings, since the analysis can be automated, and test results can be available within minutes after sample collection. This could significantly reduce the necessity to prescribe broad-spectrum antibiotics and allow the faster and more effective use of narrow-spectrum antibiotics. Full article

Gas mixture quantification is essential for the recording and reproducing odors, because an odor consists of multiple chemical compounds. Gas mixture quantification using field asymmetric ion mobility spectrometry (FAIMS) was studied. Acetone, ethanol, and diethyl ether were selected as components of a ternary gas mixture sample as representatives of the ketone, alcohol, and ether chemical classes, respectively. One hundred and twenty-five points with different concentrations were measured. The results were evaluated by error hypersurface, variance, and the coefficient of variation. The error hypersurface showed that it is possible to reach the target composition by following the error-hypersurface gradient. Successful convergence was achieved with the gradient descent method in a simulation based on the measurement data. This result verified the feasibility of the quantification of a gas mixture using FAIMS. Full article

The reliable online analysis of volatile compounds in exhaled breath remains a challenge, as a plethora of molecules occur in different concentration ranges (i.e., ppt to %) and need to be detected against an extremely complex background matrix. Although this complexity is commonly addressed by hyphenating a specific analytical technique with appropriate preconcentration and/or preseparation strategies prior to detection, we herein propose the combination of three different detector types based on truly orthogonal measurement principles as an alternative solution: Field-asymmetric ion mobility spectrometry (FAIMS), Fourier-transform infrared (FTIR) spectroscopy-based sensors utilizing substrate-integrated hollow waveguides (iHWG), and luminescence sensing (LS). By carefully aligning the experimental needs and measurement protocols of all three methods, they were successfully integrated into a single compact analytical platform suitable for online measurements. The analytical performance of this prototype system was tested via artificial breath samples containing nitrogen (N₂), oxygen (O₂), carbon dioxide (CO₂), and acetone as a model volatile organic compound (VOC) commonly present in breath. All three target analytes could be detected within their respectively breath-relevant concentration range, i.e., CO₂ and O₂ at 3-5 % and at ~19.6 %, respectively, while acetone could be detected with LOQs as low as 165-405 ppt. Orthogonality of the three methods operating in concert was clearly proven, which is essential to cover a possibly wide range of detectable analytes. Finally, the remaining challenges toward the implementation of the developed hybrid FAIMS-FTIR-LS system for exhaled breath analysis for metabolic studies in small animal intensive care units are discussed. Full article

A needle-to-cylinder electrode, adopted as an ion source for high-field asymmetric ion mobility spectrometry (FAIMS), is designed and fabricated by lithographie, galvanoformung and abformung (LIGA) technology. The needle, with a tip diameter of 20 μm and thickness of 20 μm, and a cylinder, with a diameter of 400 μm, were connected to the negative high voltage and ground, respectively. A negative corona and glow discharge were realized. For acetone with a density of 99.7 ppm, ethanol with a density of 300 ppm, and acetic ether with a density of 99.3 ppm, the sample gas was ionized by the needle-to-cylinder chip and the ions were detected by an LTQ XL™ (Thermo Scientific Corp.) mass spectrometer. The mass spectra show that the ions are mainly the protonated monomer, the proton bound dimer, and an ion-H₂O molecule cluster. In tandem with a FAIMS system, the FAIMS spectra show that the resolving power increases with an increase in the RF voltage. The obtained experimental results showed that the micro needle-to-cylinder chip may serve as a miniature, low cost and non-radioactive ion source for FAIMS. Full article

The electronic nose (eNose) is an instrument designed to mimic the human olfactory system. Usage of eNose in medical applications is more popular than ever, due to its low costs and non-invasive nature. The eNose sniffs the gases and vapours that emanate from human waste (urine, breath, and stool) for the diagnosis of variety of diseases. Diabetes mellitus type 2 (DM2) affects 8.3% of adults in the world, with 43% being underdiagnosed, resulting in 4.9 million deaths per year. In this study, we investigated the potential of urinary volatile organic compounds (VOCs) as novel non-invasive diagnostic biomarker for diabetes. In addition, we investigated the influence of sample age on the diagnostic accuracy of urinary VOCs. We analysed 140 urine samples (73 DM2, 67 healthy) with Field-Asymmetric Ion Mobility Spectrometry (FAIMS); a type of eNose; and FOX 4000 (AlphaM.O.S, Toulouse, France). Urine samples were collected at UHCW NHS Trust clinics over 4 years and stored at −80 °C within two hours of collection. Four different classifiers were used for classification, specifically Sparse Logistic Regression, Random Forest, Gaussian Process, and Support Vector on both FAIMS and FOX4000. Both eNoses showed their capability of diagnosing DM2 from controls and the effect of sample age on the discrimination. FAIMS samples were analysed for all samples aged 0–4 years (AUC: 88%, sensitivity: 87%, specificity: 82%) and then sub group samples aged less than a year (AUC (Area Under the Curve): 94%, Sensitivity: 92%, specificity: 100%). FOX4000 samples were analysed for all samples aged 0–4 years (AUC: 85%, sensitivity: 77%, specificity: 85%) and a sub group samples aged less than 18 months: (AUC: 94%, sensitivity: 90%, specificity: 89%). We demonstrated that FAIMS and FOX 4000 eNoses can discriminate DM2 from controls using urinary VOCs. In addition, we showed that urine sample age affects discriminative accuracy. Full article

Conventional methods for diagnosing gastrointestinal (GI) diseases have involved analysis of headspace volatile organic compounds (VOCs) present in the breath, urine, or fecal samples of patients. Most previous diagnostic testing methods have utilized purely metabolomic-type approaches to analyze VOCs with analytical instruments such as gas chromatography-mass spectroscopy (GC-MS), nuclear magnetic resonance (NMR) metabolomics, selected ion flow tube-mass spectrometry (SIFT-MS), proton transfer reaction-mass spectrometry (PTR-MS), and field asymmetric ion mobility spectroscopy (FAIMS). These sophisticated and expensive methods usually involve the use of large immobile (non-portable) benchtop instruments, requiring extensive data manipulations and analyses along with advanced modeling procedures to achieve diagnostic interpretations of complex chemical data. Colonoscopies and biopsies are more invasive and discourage patient-participation in prophylactic GI-disease screenings. The more recent availability of portable electronic nose gas-sensing devices, developed with the aim of simplifying disease diagnoses by analysis of headspace VOC mixtures collectively using multi-sensor arrays, allow the production of disease-specific aroma signatures (VOC profiles) based on detection of precise complex mixtures of disease biomarker metabolites. Electronic-nose (e-nose) devices provide very fast results, are easy to operate, and are more readily applicable to clinical practice. This paper summarizes some very recent e-nose technologies being developed and tested for GI-disease diagnostic applications, including ones with dual-technology and multi-technology sensor arrays for both pattern recognition and identification of key-metabolite chemical species. In addition, novel portable electronic devices, developed with new operational mechanisms and sensor types, are described which offer possibilities of providing new means of diagnosing GI-tract diseases. Full article

The injection and ionization of volatile organic compounds (VOA) by an integrated chip is experimentally analyzed in this paper. The integrated chip consists of a needle-to-cylinder electrode mounting on the Polymethyl Methacrylate (PMMA) substrate. The needle-to-cylinder electrode is designed and fabricated by Lithographie, Galvanoformung and Abformung (LIGA) technology. In this paper, the needle is connected to a negative power supply of −5 kV and used as the cathode; the cylinder electrodes are composed of two arrays of cylinders and serve as the anode. The ionic wind is produced based on corona and glow discharges of needle-to-cylinder electrodes. The experimental setup is designed to observe the properties of the needle-to-cylinder discharge and prove its functions as an ion source and air pump. In summary, the main results are as follows: (1) the ionic wind velocity produced by the chip is about 0.79 m/s at an applied voltage of −3300 V; (2) acetic acid and ammonia water can be injected through the chip, which is proved by pH test paper; and (3) the current measured by a Faraday cup is about 10 pA for acetic acid and ammonia with an applied voltage of −3185 V. The integrated chip is promising for portable analytical instruments, such as ion mobility spectrometry (IMS), field asymmetric ion mobility spectrometry (FAIMS), and mass spectrometry (MS). Full article