Publications
180 results found
Vande Voorde J, Steven RT, Najumudeen AK, et al., 2023, Metabolic profiling stratifies colorectal cancer and reveals adenosylhomocysteinase as a therapeutic target., Nat Metab, Vol: 5, Pages: 1303-1318
The genomic landscape of colorectal cancer (CRC) is shaped by inactivating mutations in tumour suppressors such as APC, and oncogenic mutations such as mutant KRAS. Here we used genetically engineered mouse models, and multimodal mass spectrometry-based metabolomics to study the impact of common genetic drivers of CRC on the metabolic landscape of the intestine. We show that untargeted metabolic profiling can be applied to stratify intestinal tissues according to underlying genetic alterations, and use mass spectrometry imaging to identify tumour, stromal and normal adjacent tissues. By identifying ions that drive variation between normal and transformed tissues, we found dysregulation of the methionine cycle to be a hallmark of APC-deficient CRC. Loss of Apc in the mouse intestine was found to be sufficient to drive expression of one of its enzymes, adenosylhomocysteinase (AHCY), which was also found to be transcriptionally upregulated in human CRC. Targeting of AHCY function impaired growth of APC-deficient organoids in vitro, and prevented the characteristic hyperproliferative/crypt progenitor phenotype driven by acute deletion of Apc in vivo, even in the context of mutant Kras. Finally, pharmacological inhibition of AHCY reduced intestinal tumour burden in ApcMin/+ mice indicating its potential as a metabolic drug target in CRC.
Green FM, Castellani ME, Jia Y, et al., 2023, Development of High Throughput Microscope Mode Secondary Ion Mass Spectrometry Imaging., J Am Soc Mass Spectrom, Vol: 34, Pages: 1272-1282
This paper describes the development and initial results from a secondary ion mass spectrometer coupled with microscope mode detection. Stigmatic ion microscope imaging enables us to decouple the primary ion (PI) beam focus from spatial resolution and is a promising route to attaining higher throughput for mass spectrometry imaging (MSI). Using a commercial C60+ PI beam source, we can defocus the PI beam to give uniform intensity across a 2.5 mm2 area. By coupling the beam with a position-sensitive spatial detector, we can achieve mass spectral imaging of positive and negative secondary ions (SIs), which we demonstrate using samples comprising metals and dyes. Our approach involves simultaneous desorption of ions across a large field of view, enabling mass spectral images to be recorded over an area of 2.5 mm2 in a matter of seconds. Our instrument can distinguish spatial features with a resolution of better than 20 μm, and has a mass resolution of >500 at 500 u. There is considerable scope to improve this, and through simulations we estimate the future performance of the instrument.
Xiang Y, Metodiev M, Wang M, et al., 2023, Enhancement of ambient mass spectrometry imaging data by image restoration, Metabolites, Vol: 13, Pages: 1-16, ISSN: 2218-1989
Mass spectrometry imaging (MSI) has been a key driver of groundbreaking discoveries in a number of fields since its inception more than 50 years ago. Recently, MSI development trends have shifted towards ambient MSI (AMSI) as the removal of sample-preparation steps and the possibility of analysing biological specimens in their natural state have drawn the attention of multiple groups across the world. Nevertheless, the lack of spatial resolution has been cited as one of the main limitations of AMSI. While significant research effort has presented hardware solutions for improving the resolution, software solutions are often overlooked, although they can usually be applied in a cost-effective manner after image acquisition. In this vein, we present two computational methods that we have developed to directly enhance the image resolution post-acquisition. Robust and quantitative resolution improvement is demonstrated for 12 cases of openly accessible datasets across laboratories around the globe. Using the same universally applicable Fourier imaging model, we discuss the possibility of true super-resolution by software for future studies.
Kowalka AMM, Alexiadou K, Cuenco J, et al., 2023, Commentary on "The road to reliable peptide assays is paved with good guidelines", CLINICAL ENDOCRINOLOGY, ISSN: 0300-0664
Dannhorn A, Doria ML, McKenzie J, et al., 2023, Targeted Desorption Electrospray Ionization Mass Spectrometry Imaging for Drug Distribution, Toxicity, and Tissue Classification Studies, METABOLITES, Vol: 13
Patel P, Kumar S, Doria L, et al., 2022, The clinical utilisation of tissue imaging Mass Spectrometry as a diagnostic model for Oesophageal Adenocarcinoma, Publisher: OXFORD UNIV PRESS, ISSN: 0007-1323
Steven RT, Niehaus M, Taylor AJ, et al., 2022, Atmospheric-Pressure Infrared Laser-Ablation Plasma- Postionization Mass Spectrometry Imaging of Formalin-Fixed Paraffin-Embedded (FFPE) and Fresh-Frozen Tissue Sections with No Sample Preparation, ANALYTICAL CHEMISTRY, Vol: 94, Pages: 9970-9974, ISSN: 0003-2700
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- Citations: 3
Wu V, Tillner J, Jones E, et al., 2022, High resolution ambient MS imaging of biological samples by desorption electro-flow focussing ionization, Analytical Chemistry, Vol: 94, Pages: 10035-10044, ISSN: 0003-2700
In this study, we examine the suitability of desorption electro-flow focusing ionization (DEFFI) for mass spectrometry imaging (MSI) of biological tissue. We also compare the performance of desorption electrospray ionization (DESI) with and without the flow focusing setup. The main potential advantages of applying the flow focusing mechanism in DESI is its rotationally symmetric electrospray jet, higher intensity, more controllable parameters, and better portability due to the robustness of the sprayer. The parameters for DEFFI have therefore been thoroughly optimized, primarily for spatial resolution but also for intensity. Once the parameters have been optimized, DEFFI produces similar images to the existing DESI. MS images for mouse brain samples, acquired at a nominal pixel size of 50 μm, are comparable for both DESI setups, albeit the new sprayer design yields better sensitivity. Furthermore, the two methods are compared with regard to spectral intensity as well as the area of the desorbed crater on rhodamine-coated slides. Overall, the implementation of a flow focusing mechanism in DESI is shown to be highly suitable for imaging biological tissue and has potential to overcome some of the shortcomings experienced with the current geometrical design of DESI.
Paizs P, Roberts D, Danckert N, et al., 2022, Gut microbial co-metabolism influences the tumor microenvironment, Annual Meeting of the American-Association-for-Cancer-Research (AACR), Publisher: AMER ASSOC CANCER RESEARCH, ISSN: 0008-5472
Sani M, Ford L, Simon D, et al., 2022, A prospective pilot study of desorption electrospray ionisation mass spectrometry (DESI-MS) for the early detection of colorectal adenoma., Annual Meeting of the American-Association-for-Cancer-Research (AACR), Publisher: AMER ASSOC CANCER RESEARCH, ISSN: 0008-5472
Inglese P, Huang HX, Wu V, et al., 2022, Mass recalibration for desorption electrospray ionization mass spectrometry imaging using endogenous reference ions, BMC Bioinformatics, Vol: 23, Pages: 1-17, ISSN: 1471-2105
BackgroundMass spectrometry imaging (MSI) data often consist of tens of thousands of mass spectra collected from a sample surface. During the time necessary to perform a single acquisition, it is likely that uncontrollable factors alter the validity of the initial mass calibration of the instrument, resulting in mass errors of magnitude significantly larger than their theoretical values. This phenomenon has a two-fold detrimental effect: (a) it reduces the ability to interpret the results based on the observed signals, (b) it can affect the quality of the observed signal spatial distributions.ResultsWe present a post-acquisition computational method capable of reducing the observed mass drift by up to 60 ppm in biological samples, exploiting the presence of typical molecules with a known mass-to-charge ratio. The procedure, tested on time-of-flight and Orbitrap mass spectrometry analyzers interfaced to a desorption electrospray ionization (DESI) source, improves the molecular annotation quality and the spatial distributions of the detected ions.ConclusionThe presented method represents a robust and accurate tool for performing post-acquisition mass recalibration of DESI-MSI datasets and can help to increase the reliability of the molecular assignment and the data quality.
Strittmatter N, Richards FM, Race AM, et al., 2022, Method To Visualize the Intratumor Distribution and Impact of Gemcitabine in Pancreatic Ductal Adenocarcinoma by Multimodal Imaging, ANALYTICAL CHEMISTRY, Vol: 94, Pages: 1795-1803, ISSN: 0003-2700
Strittmatter N, Kanvatirth P, Inglese P, et al., 2021, Holistic characterization of a salmonella typhimurium infection model using integrated molecular imaging., Journal of the American Society for Mass Spectrometry, Vol: 32, Pages: 2791-2802, ISSN: 1044-0305
A more complete and holistic view on host-microbe interactions is needed to understand the physiological and cellular barriers that affect the efficacy of drug treatments and allow the discovery and development of new therapeutics. Here, we developed a multimodal imaging approach combining histopathology with mass spectrometry imaging (MSI) and same section imaging mass cytometry (IMC) to study the effects of Salmonella Typhimurium infection in the liver of a mouse model using the S. Typhimurium strains SL3261 and SL1344. This approach enables correlation of tissue morphology and specific cell phenotypes with molecular images of tissue metabolism. IMC revealed a marked increase in immune cell markers and localization in immune aggregates in infected tissues. A correlative computational method (network analysis) was deployed to find metabolic features associated with infection and revealed metabolic clusters of acetyl carnitines, as well as phosphatidylcholine and phosphatidylethanolamine plasmalogen species, which could be associated with pro-inflammatory immune cell types. By developing an IMC marker for the detection of Salmonella LPS, we were further able to identify and characterize those cell types which contained S. Typhimurium.
Metodiev MD, Steven RT, Loizeau X, et al., 2021, Modality Agnostic Model for Spatial Resolution in Mass Spectrometry Imaging: Application to MALDI MSI Data, ANALYTICAL CHEMISTRY, Vol: 93, Pages: 15295-15305, ISSN: 0003-2700
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- Citations: 1
Pruski P, Dos Santos Correia G, Lewis H, et al., 2021, Direct on-swab metabolic profiling of vaginal microbiome host interactions during pregnancy and preterm birth, Nature Communications, Vol: 12, ISSN: 2041-1723
The pregnancy vaginal microbiome contributes to risk of preterm birth, the primary cause of death in children under 5 years of age. Here we describe direct on-swab metabolic profiling by Desorption Electrospray Ionization Mass Spectrometry (DESI-MS) for sample preparation-free characterisation of the cervicovaginal metabolome in two independent pregnancy cohorts (VMET, n = 160; 455 swabs; VMET II, n = 205; 573 swabs). By integrating metataxonomics and immune profiling data from matched samples, we show that specific metabolome signatures can be used to robustly predict simultaneously both the composition of the vaginal microbiome and host inflammatory status. In these patients, vaginal microbiota instability and innate immune activation, as predicted using DESI-MS, associated with preterm birth, including in women receiving cervical cerclage for preterm birth prevention. These findings highlight direct on-swab metabolic profiling by DESI-MS as an innovative approach for preterm birth risk stratification through rapid assessment of vaginal microbiota-host dynamics.
Capece D, D'Andrea D, Begalli F, et al., 2021, Enhanced triacylglycerol catabolism by Carboxylesterase 1 promotes aggressive colorectal carcinoma., Journal of Clinical Investigation, ISSN: 0021-9738
The ability to adapt to low-nutrient microenvironments is essential for tumor-cell survival and progression in solid cancers, such as colorectal carcinoma (CRC). Signaling by the NF-κB transcription-factor pathway associates with advanced disease stages and shorter survival in CRC patients. NF-κB has been shown to drive tumor-promoting inflammation, cancer-cell survival and intestinal epithelial cell (IEC) dedifferentiation in mouse models of CRC. However, whether NF-κB affects the metabolic adaptations that fuel aggressive disease in CRC patients is unknown. Here, we identified carboxylesterase 1 (CES1) as an essential NF-κB-regulated lipase linking obesity-associated inflammation with fat metabolism and adaptation to energy stress in aggressive CRC. CES1 promoted CRC-cell survival via cell-autonomous mechanisms that fuel fatty-acid oxidation (FAO) and prevent the toxic build-up of triacylglycerols. We found that elevated CES1 expression correlated with worse outcomes in overweight CRC patients. Accordingly, NF-κB drove CES1 expression in CRC consensus molecular subtype (CMS)4, associated with obesity, stemness and inflammation. CES1 was also upregulated by gene amplifications of its transcriptional regulator, HNF4A, in CMS2 tumors, reinforcing its clinical relevance as a driver of CRC. This subtype-based distribution and unfavourable prognostic correlation distinguished CES1 from other intracellular triacylglycerol lipases and suggest CES1 could provide a route to treat aggressive CRC.
Manoli E, Mason S, Ford L, et al., 2021, Validation of ultrasonic harmonic scalpel for real-time tissue identification using rapid evaporative ionization mass spectrometry, Analytical Chemistry, Vol: 93, Pages: 5906-5916, ISSN: 0003-2700
In this study, we integrate rapid evaporative ionization mass spectrometry (REIMS) with the Harmonic scalpel, an advanced laparoscopic surgical instrument that utilizes ultrasound energy to dissect and coagulate tissues. It provides unparalleled manipulation capability to surgeons and has superseded traditional electrosurgical tools particularly in abdominal surgery, but is yet to be validated with REIMS. The REIMS platform coupled with the Harmonic device was shown to produce tissue-specific lipid profiles through the analysis of porcine tissues in both negative and positive ionization modes. Comparison with other methods of electrosurgical dissection, such as monopolar electrosurgery and CO2 laser, showed spectral differences in the profile dependent on the energy device used. The Harmonic device demonstrated major spectral differences in the phospholipid region of m/z 600–1000 compared with the monopolar electrosurgical and CO2 laser-generated spectra. Within the Harmonic REIMS spectra, high intensities of diglycerides and triglycerides were observed. In contrast, monopolar electrosurgical and laser spectra demonstrated high abundances of glycerophospholipids. The Harmonic scalpel was able to differentiate between the liver, muscle, colon, and small intestine, demonstrating 100% diagnostic accuracy. The validation of the Harmonic device–mass spectrometry combination will allow the platform to be used safely and robustly for real-time in vivo surgical tissue identification in a variety of clinical applications.
Dannhorn A, Ling S, Powell S, et al., 2021, Evaluation of UV-C Decontamination of Clinical Tissue Sections for Spatially Resolved Analysis by Mass Spectrometry Imaging (MSI), ANALYTICAL CHEMISTRY, Vol: 93, Pages: 2767-2775, ISSN: 0003-2700
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- Citations: 2
Sands CJ, Gómez-Romero M, Correia G, et al., 2021, Representing the metabolome with high fidelity: range and response as quality control factors in LC-MS-based global profiling., Analytical Chemistry, Vol: 93, Pages: 1924-1933, ISSN: 0003-2700
Liquid chromatography-mass spectrometry (LC-MS) is a powerful and widely used technique for measuring the abundance of chemical species in living systems. Its sensitivity, analytical specificity, and direct applicability to biofluids and tissue extracts impart great promise for the discovery and mechanistic characterization of biomarker panels for disease detection, health monitoring, patient stratification, and treatment personalization. Global metabolic profiling applications yield complex data sets consisting of multiple feature measurements for each chemical species observed. While this multiplicity can be useful in deriving enhanced analytical specificity and chemical identities from LC-MS data, data set inflation and quantitative imprecision among related features is problematic for statistical analyses and interpretation. This Perspective provides a critical evaluation of global profiling data fidelity with respect to measurement linearity and the quantitative response variation observed among components of the spectra. These elements of data quality are widely overlooked in untargeted metabolomics yet essential for the generation of data that accurately reflect the metabolome. Advanced feature filtering informed by linear range estimation and analyte response factor assessment is advocated as an attainable means of controlling LC-MS data quality in global profiling studies and exemplified herein at both the feature and data set level.
Paraskevaidi M, Cameron SJS, Whelan E, et al., 2020, Laser-assisted rapid evaporative ionisation mass spectrometry (LA-REIMS) as a metabolomics platform in cervical cancer screening, EBioMedicine, Vol: 60, ISSN: 2352-3964
BackgroundThe introduction of high-risk human papillomavirus (hrHPV) testing as part of primary cervical screening is anticipated to improve sensitivity, but also the number of women who will screen positive. Reflex cytology is the preferred triage test in most settings but has limitations including moderate diagnostic accuracy, lack of automation, inter-observer variability and the need for clinician-collected sample. Novel, objective and cost-effective approaches are needed.MethodsIn this study, we assessed the potential use of an automated metabolomic robotic platform, employing the principle of laser-assisted Rapid Evaporative Ionisation Mass Spectrometry (LA-REIMS) in cervical cancer screening.FindingsIn a population of 130 women, LA-REIMS achieved 94% sensitivity and 83% specificity (AUC: 91.6%) in distinguishing women testing positive (n = 65) or negative (n = 65) for hrHPV. We performed further analysis according to disease severity with LA-REIMS achieving sensitivity and specificity of 91% and 73% respectively (AUC: 86.7%) in discriminating normal from high-grade pre-invasive disease.InterpretationThis automated high-throughput technology holds promise as a low-cost and rapid test for cervical cancer screening and triage. The use of platforms like LA-REIMS has the potential to further improve the accuracy and efficiency of the current national screening programme.
Van Meulebroek L, Cameron S, Plekhova V, et al., 2020, Rapid LA-REIMS and comprehensive UHPLC-HRMS for metabolic phenotyping of feces, TALANTA, Vol: 217, ISSN: 0039-9140
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- Citations: 9
Dannhorn A, Kazanc E, Ling S, et al., 2020, Universal Sample Preparation Unlocking Multimodal Molecular Tissue Imaging, ANALYTICAL CHEMISTRY, Vol: 92, Pages: 11080-11088, ISSN: 0003-2700
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- Citations: 29
Tzafetas M, Mitra A, Paraskevaidi M, et al., 2020, The intelligent knife (iKnife) and its intraoperative diagnostic advantage for the treatment of cervical disease (vol 117, pg 7338, 2020), PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol: 117, Pages: 18892-18892, ISSN: 0027-8424
Koundouros N, Karali E, Tripp A, et al., 2020, Metabolic fingerprinting links oncogenic PIK3CA with enhanced arachidonic acid-derived eicosanoids, Cell, Vol: 181, Pages: 1596-1611.e27, ISSN: 0092-8674
Oncogenic transformation is associated with profound changes in cellular metabolism, but whether tracking these can improve disease stratification or influence therapy decision-making is largely unknown. Using the iKnife to sample the aerosol of cauterized specimens, we demonstrate a new mode of real-time diagnosis, coupling metabolic phenotype to mutant PIK3CA genotype. Oncogenic PIK3CA results in an increase in arachidonic acid and a concomitant overproduction of eicosanoids, acting to promote cell proliferation beyond a cell-autonomous manner. Mechanistically, mutant PIK3CA drives a multimodal signaling network involving mTORC2-PKCζ-mediated activation of the calcium-dependent phospholipase A2 (cPLA2). Notably, inhibiting cPLA2 synergizes with fatty acid-free diet to restore immunogenicity and selectively reduce mutant PIK3CA-induced tumorigenicity. Besides highlighting the potential for metabolic phenotyping in stratified medicine, this study reveals an important role for activated PI3K signaling in regulating arachidonic acid metabolism, uncovering a targetable metabolic vulnerability that largely depends on dietary fat restriction.
Abbassi-Ghadi N, Antonowicz S, McKenzie J, et al., 2020, De novo lipogenesis alters the phospholipidome of esophageal adenocarcinoma, Cancer Research, Vol: 80, Pages: 2764-2774, ISSN: 0008-5472
The incidence of esophageal adenocarcinoma is rising, survival remains poor, and new tools to improve early diagnosis and precise treatment are needed. Cancer phospholipidomes quantified with mass spectrometry imaging can support objective diagnosis in minutes using a routine frozen tissue section. However, whether mass spectrometry imaging can objectively identify primary esophageal adenocarcinoma is currently unknown and represents a significant challenge, as this microenvironment is complex with phenotypically similar tissue-types. Here we used desorption electrospray ionisation mass spectrometry imaging (DESI-MSI) and bespoke chemometrics to assess the phospholipidomes of esophageal adenocarcinoma and relevant control tissues. Multivariable models derived from phospholipid profiles of 117 patients were highly discriminant for esophageal adenocarcinoma both in discovery (area-under-curve = 0.97) and validation cohorts (AUC = 1). Among many other changes, esophageal adenocarcinoma samples were markedly enriched for polyunsaturated phosphatidylglycerols with longer acyl chains, with stepwise enrichment in pre-malignant tissues. Expression of fatty acid and glycerophospholipid synthesis genes was significantly upregulated, and characteristics of fatty acid acyls matched glycerophospholipid acyls. Mechanistically, silencing the carbon switch ACLY in esophageal adenocarcinoma cells shortened GPL chains, linking de novo lipogenesis to the phospholipidome. Thus, DESI-MSI can objectively identify invasive esophageal adenocarcinoma from a number of pre-malignant tissues and unveils mechanisms of phospholipidomic reprogramming. These results call for accelerated diagnosis studies using DESI-MSI in the upper gastrointestinal endoscopy suite as well as functional studies to determine how polyunsaturated phosphatidylglycerols contribute to esophageal carcinogenesis.
Tzafetas M, Mitra A, Paraskevaidi M, et al., 2020, The intelligent-Knife (i-Knife) and its intraoperative diagnostic advantage for the treatment of cervical disease, Proceedings of the National Academy of Sciences of USA, Vol: 117, Pages: 7338-7346, ISSN: 0027-8424
Clearance of surgical margins in cervical cancer prevents the need for adjuvant chemoradiation and allows fertility preservation. In this study, we determined the capacity of the rapid evaporative ionization mass spectrometry (REIMS), also known as intelligent knife (iKnife), to discriminate between healthy, preinvasive, and invasive cervical tissue. Cervical tissue samples were collected from women with healthy, human papilloma virus (HPV) ± cervical intraepithelial neoplasia (CIN), or cervical cancer. A handheld diathermy device generated surgical aerosol, which was transferred into a mass spectrometer for subsequent chemical analysis. Combination of principal component and linear discriminant analysis and least absolute shrinkage and selection operator was employed to study the spectral differences between groups. Significance of discriminatory m/z features was tested using univariate statistics and tandem MS performed to elucidate the structure of the significant peaks allowing separation of the two classes. We analyzed 87 samples (normal = 16, HPV ± CIN = 50, cancer = 21 patients). The iKnife discriminated with 100% accuracy normal (100%) vs. HPV ± CIN (100%) vs. cancer (100%) when compared to histology as the gold standard. When comparing normal vs. cancer samples, the accuracy was 100% with a sensitivity of 100% (95% CI 83.9 to 100) and specificity 100% (79.4 to 100). Univariate analysis revealed significant MS peaks in the cancer-to-normal separation belonging to various classes of complex lipids. The iKnife discriminates healthy from premalignant and invasive cervical lesions with high accuracy and can improve oncological outcomes and fertility preservation of women treated surgically for cervical cancer. Larger in vivo research cohorts are required to validate these findings.
Gowers G-OF, Cameron SJS, Perdones-Montero A, et al., 2019, Off-colony screening of biosynthetic libraries by rapid laser-enabled mass spectrometry, ACS Synthetic Biology, Vol: 8, Pages: 2566-2575, ISSN: 2161-5063
Leveraging advances in DNA synthesis and molecular cloning techniques, synthetic biology increasingly makes use of large construct libraries to explore large design spaces. For biosynthetic pathway engineering the ability to screen these libraries for a variety of metabolites of interest is essential. If the metabolite of interest or the metabolic phenotype is not easily measurable, screening soon becomes a major bottleneck involving time-consuming culturing, sample preparation, and extraction. To address this, we demonstrate the use of automated Laser-Assisted Rapid Evaporative Ionisation Mass Spectrometry (LA-REIMS) - a form of ambient laser desorption ionisation mass spectrometry - to perform rapid mass spectrometry analysis direct from agar plate yeast colonies without sample preparation or extraction. We use LA-REIMS to assess production levels of violacein and betulinic acid directly from yeast colonies at a rate of 6 colonies per minute. We then demonstrate the throughput enabled by LA-REIMS by screening over 450 yeast colonies in under 4 hours, while simultaneously generating recoverable glycerol stocks of each colony in real-time. This showcases LA-REIMS as a pre-screening tool to complement downstream quantification methods such as LCMS. Through pre-screening several hundred colonies with LA-REIMS, we successfully isolate and verify a strain with a 2.5-fold improvement in betulinic acid production. Finally, we show that LA-REIMS can detect 20 out of a panel of 27 diverse biological molecules, demonstrating the broad applicability of LA-REIMS to metabolite detection. The rapid and automated nature of LA-REIMS makes this a valuable new technology to complement existing screening technologies currently employed in academic and industrial workflows.
Cameron SJS, Alexander JL, Bolt F, et al., 2019, Evaluation of direct from sample metabolomics of human feces using rapid evaporative ionization mass spectrometry, Analytical Chemistry, Vol: 91, Pages: 13448-13457, ISSN: 0003-2700
Mass spectrometry is a powerful tool in the investigation of the human fecal metabolome. However, current approaches require time-consuming sample preparation, chromatographic separations, and consequently long analytical run times. Rapid evaporative ionization mass spectrometry (REIMS) is a method of ambient ionization mass spectrometry and has been utilized in the metabolic profiling of a diverse range of biological materials, including human tissue, cell culture lines, and microorganisms. Here, we describe the use of an automated, high-throughput REIMS robotic platform for direct analysis of human feces. Through the analysis of fecal samples from five healthy male participants, REIMS analytical parameters were optimized and used to assess the chemical information obtainable using REIMS. Within the fecal samples analyzed, bile acids, including primary, secondary, and conjugate species, were identified, and phospholipids of possible bacterial origin were detected. In addition, the effect of storage conditions and consecutive freeze/thaw cycles was determined. Within the REIMS mass spectra, the lower molecular weight metabolites, such as fatty acids, were shown to be significantly affected by storage conditions for prolonged periods at temperatures above −80 °C and consecutive freeze/thaw cycles. However, the complex lipid region was shown to be unaffected by these conditions. A further cohort of 50 fecal samples, collected from patients undergoing bariatric surgery, were analyzed using the optimized REIMS parameters and the complex lipid region mass spectra used for multivariate modeling. This analysis showed a predicted separation between pre- and post-surgery specimens, suggesting that REIMS analysis can detect biological differences, such as microbiome-level differences, which have traditionally been reliant upon methods utilizing extensive sample preparations and chromatographic separations and/or DNA sequencing.
Ogrinc N, Saudemont P, Balog J, et al., 2019, Water-assisted laser desorption/ionization mass spectrometry for minimally invasive in vivo and real-time surface analysis using SpiderMass, NATURE PROTOCOLS, Vol: 14, Pages: 3162-3182, ISSN: 1754-2189
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- Citations: 22
Tzafetas M, Mitra A, Kalliala I, et al., 2019, THE IKNIFE AND ITS APPLICATION FOR THE TREATMENT OF CERVICAL ABNORMALITIES, Publisher: BMJ PUBLISHING GROUP, Pages: A589-A589, ISSN: 1048-891X
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