optimized sampling conditions for fecal volatile organic compounds

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OPTIMIZED SAMPLING CONDITIONS FOR FECAL VOLATILE ORGANIC COMPOUNDS ANALYSIS BY MEANS OF FIELD ASYMMETRIC ION MOBILITY SPECTROMETRY Sofie Bosch, Sofia el Manouni el Hassani, James A. Covington, Alfian N Wicaksono, Marije K Bomers, Marc A Benninga, Chris JJ Mulder, Nanne KH de Boer, and Tim GJ de Meij Anal. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.analchem.8b00688 • Publication Date (Web): 03 Jun 2018 Downloaded from http://pubs.acs.org on June 4, 2018

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Analytical Chemistry

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OPTIMIZED SAMPLING CONDITIONS FOR FECAL VOLATILE ORGANIC COMPOUNDS ANALYSIS

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BY MEANS OF FIELD ASYMMETRIC ION MOBILITY SPECTROMETRY.

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Sofie Bosch1, MD*, Sofia el Manouni el Hassani4, MD*, James A Covington2, Phd, Alfian N. Wicaksono2, SSi, Marije K Bomers3, MD, PhD, Marc A Benninga4, MD, PhD, Chris JJ Mulder, MD, PhD1, Nanne KH de Boer1, MD, PhD**, Tim GJ de Meij4, MD, PhD**

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* Shared first, listed alphabetically

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** Shared last, listed alphabetically

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Department of Gastroenterology and Hepatology, VU University Medical Center, Amsterdam, The Netherlands

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Amsterdam, The Netherlands

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School of Engineering, University of Warwick, Coventry, United Kingdom Department of Internal Medicine, VU University Medical Center, Amsterdam, The Netherlands Department Pediatric Gastroenterology, Emma Children’s Hospital/Academic Medical Center,

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Department Pediatric Gastroenterology, VU University Medical Center, Amsterdam, The

Netherlands

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Conflicts of interest

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The department of Gastroenterology and Hepatology of the VU University Medical Center

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has no conflicts of interest to disclose

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Financial disclosures

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S Bosch has nothing to declare.

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S el Manouni el Hassani has nothing to declare.

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JA Covington has nothing to declare.

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AN Wicaksono has nothing to declare.

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MK Bomers has nothing to declare.

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CJJ Mulder has served as a principal investigator for TEVA Pharma BV. He has received a

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research grant from TEVA Pharma BV.

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MA Benninga has served as speaker for Abbott and FrieslandCampina. He has served as

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consultant for Shire, Takeda, Norgine, AstraZeneca, Danone, Friesland Campina, Novalac and

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Mead Johnson

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NKH de Boer has served as a speaker for AbbVie and MSD. He has served as consultant and

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principal investigator for TEVA Pharma BV and Takeda. He has received a (unrestricted)

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research grant from Dr. Falk and Takeda.

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TGJ de Meij has served as a speaker for Mead Johnson. He has received a (unrestricted)

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research grant from Danone

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Analytical Chemistry

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Author contributions

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TGJ de Meij and NKH de Boer were the guarantors of this article.

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S el Manouni el Hassani and S Bosch collected the fecal samples and performed VOC

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analysis.

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JA Covington and AN Wicaksono analyzed the results.

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S Bosch drafted the first version of the manuscript.

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S el Manouni el Hassani, JA Covington, AN Wicoksono, MK Bomers, CJ Mulder, MA Benninga,

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KHN de Boer, TGJ de Meij reviewed the manuscript for important intellectual content.

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S Bosch finalized the manuscript.

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All authors agreed to the final version of the manuscript.

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Running title Optimized sampling conditions for fecal volatile organic compounds by means

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of field asymmetric ion mobility spectrometry.

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Word count 4423

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Version 3.0

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Key words Volatile organic compounds, VOC, Lonestar, FAIMS, Field Asymmetric Ion

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Mobility Spectrometry, Inflammatory bowel disease,

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Corresponding author

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Sofie Bosch, MD

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Department of Gastroenterology and Hepatology

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VU University Medical Center

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Room PK 2X 136

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De Boelelaan 1117

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1081 HV Amsterdam

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T: +31 (0)20 444 07 99

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F: +31 (0)20 444 05 54.

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E: [email protected]

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Analytical Chemistry

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Abstract (259 words)

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Background Fecal volatile organic compounds (VOCs) are increasingly considered as

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potential non-invasive, diagnostic biomarkers for various gastrointestinal diseases.

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Knowledge of influence of sampling conditions on VOC outcomes is limited. We aimed to

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evaluate effects of sampling conditions on fecal VOC profiles and to assess under which

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conditions an optimal diagnostic accuracy in the discrimination between pediatric

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inflammatory bowel disease (IBD) and controls could be obtained.

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Methods Fecal samples from de novo treatment-naïve pediatric IBD patients and healthy

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controls (HC) were used to assess effects of sampling conditions compared to the standard

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operating procedure (reference standard), defined as 500mg of sample mass, diluted with

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10mL tap water, using field asymmetric ion mobility spectrometry (FAIMS).

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Results A total of 17 IBD (15CD and 2 UC) and 25 HC were included. IBD and HC could be

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discriminated with high accuracy (accuracy=0.93, AUC=0.99, p