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      Diagnosis and Classification of 17 Diseases from 1404 Subjects via Pattern Analysis of Exhaled Molecules

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      ACS Nano
      American Chemical Society
      sensor, nanoparticle, carbon nanotube, noninvasive, diagnosis, disease, breath, volatile organic compound

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          Abstract

          We report on an artificially intelligent nanoarray based on molecularly modified gold nanoparticles and a random network of single-walled carbon nanotubes for noninvasive diagnosis and classification of a number of diseases from exhaled breath. The performance of this artificially intelligent nanoarray was clinically assessed on breath samples collected from 1404 subjects having one of 17 different disease conditions included in the study or having no evidence of any disease (healthy controls). Blind experiments showed that 86% accuracy could be achieved with the artificially intelligent nanoarray, allowing both detection and discrimination between the different disease conditions examined. Analysis of the artificially intelligent nanoarray also showed that each disease has its own unique breathprint, and that the presence of one disease would not screen out others. Cluster analysis showed a reasonable classification power of diseases from the same categories. The effect of confounding clinical and environmental factors on the performance of the nanoarray did not significantly alter the obtained results. The diagnosis and classification power of the nanoarray was also validated by an independent analytical technique, i.e., gas chromatography linked with mass spectrometry. This analysis found that 13 exhaled chemical species, called volatile organic compounds, are associated with certain diseases, and the composition of this assembly of volatile organic compounds differs from one disease to another. Overall, these findings could contribute to one of the most important criteria for successful health intervention in the modern era, viz. easy-to-use, inexpensive (affordable), and miniaturized tools that could also be used for personalized screening, diagnosis, and follow-up of a number of diseases, which can clearly be extended by further development.

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          Most cited references63

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          Diagnosing lung cancer in exhaled breath using gold nanoparticles.

          Conventional diagnostic methods for lung cancer are unsuitable for widespread screening because they are expensive and occasionally miss tumours. Gas chromatography/mass spectrometry studies have shown that several volatile organic compounds, which normally appear at levels of 1-20 ppb in healthy human breath, are elevated to levels between 10 and 100 ppb in lung cancer patients. Here we show that an array of sensors based on gold nanoparticles can rapidly distinguish the breath of lung cancer patients from the breath of healthy individuals in an atmosphere of high humidity. In combination with solid-phase microextraction, gas chromatography/mass spectrometry was used to identify 42 volatile organic compounds that represent lung cancer biomarkers. Four of these were used to train and optimize the sensors, demonstrating good agreement between patient and simulated breath samples. Our results show that sensors based on gold nanoparticles could form the basis of an inexpensive and non-invasive diagnostic tool for lung cancer.
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            A review of the volatiles from the healthy human body.

            A compendium of all the volatile organic compounds (VOCs) emanating from the human body (the volatolome) is for the first time reported. 1840 VOCs have been assigned from breath (872), saliva (359), blood (154), milk (256), skin secretions (532) urine (279), and faeces (381) in apparently healthy individuals. Compounds were assigned CAS registry numbers and named according to a common convention where possible. The compounds have been grouped into tables according to their chemical class or functionality to permit easy comparison. Some clear differences are observed, for instance, a lack of esters in urine with a high number in faeces. Careful use of the database is needed. The numbers may not be a true reflection of the actual VOCs present from each bodily excretion. The lack of a compound could be due to the techniques used or reflect the intensity of effort e.g. there are few publications on VOCs from blood compared to a large number on VOCs in breath. The large number of volatiles reported from skin is partly due to the methodologies used, e.g. collecting excretions on glass beads and then heating to desorb VOCs. All compounds have been included as reported (unless there was a clear discrepancy between name and chemical structure), but there may be some mistaken assignations arising from the original publications, particularly for isomers. It is the authors' intention that this database will not only be a useful database of VOCs listed in the literature, but will stimulate further study of VOCs from healthy individuals. Establishing a list of volatiles emanating from healthy individuals and increased understanding of VOC metabolic pathways is an important step for differentiating between diseases using VOCs.
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              Volatile organic compounds of lung cancer and possible biochemical pathways.

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                Author and article information

                Journal
                ACS Nano
                ACS Nano
                nn
                ancac3
                ACS Nano
                American Chemical Society
                1936-0851
                1936-086X
                21 December 2016
                24 January 2017
                : 11
                : 1
                : 112-125
                Affiliations
                []Department of Chemical Engineering and Russell Berrie Nanotechnology Institute, Technion−Israel Institute of Technology , Haifa 3200003, Israel
                []Division of Neuroimmunology and Multiple Sclerosis Center, Carmel Medical Center and Rappaport Family Faculty of Medicine, Technion−Israel Institute of Technology , Haifa 31096, Israel
                [§ ]Movement Disorders Clinic, Department of Neurology, Carmel Medical Center, and Rappaport Family Faculty of Medicine, Technion−Israel Institute of Technology , Haifa 31096, Israel
                []Department of Molecular Pharmacology, Rappaport Family Faculty of Medicine, Technion−Israel Institute of Technology , Haifa 31096, Israel
                []Univ. Paris-Sud, Faculté de Médecine, Université Paris-Saclay, AP-HP, Centre National de Référence de l′Hypertension Pulmonaire Sévère, Département Hospitalo-Universitaire (DHU) Thorax Innovation, Service de Pneumologie, Hôpital de Bicêtre, UMRS _999, INSERM and Univ. Paris−Sud, Laboratoire d’Excellence (LabEx) en Recherche sur le Médicament et l′Innovation Thérapeutique (LERMIT), Centre Chirurgical Marie Lannelongue, Le Plessis Robinson 92350, France
                [# ]Department of Nephrology and Hypertension Baruch Padeh Medical Center , Poriya 15208, Israel
                []Department of Obstetrics and Gynecology, Emek Medical Center, Afula 18101, and Rappaport Family Faculty of Medicine, Technion−Israel Institute of Technology , Haifa 31096, Israel
                []Department of Obstetrics and Gynecology, Nazareth Hospital EMMS, Nazareth, and Faculty of Medicine in the Galilee, Bar Ilan University , Ramat Gan, Israel
                []The Department of Otolaryngology Head and Neck Surgery, Carmel Medical Center , Haifa 3436212, Israel
                []Department of Urology, Bnai Zion Medical Center , Haifa 31048, Israel
                []Department of Oncology, The First Affiliated Hospital of Anhui Medical University , Hefei 230032, China
                []Internal Medicine C and Gastroenterology Departments, Rambam Medical Center, Rappaport Family Faculty of Medicine, Technion−Israel Institute of Technology , Haifa 3525408, Israel
                []Department of Gastroenterology, Bnai Zion Hospital and Rappaport Family Faculty of Medicine, Technion−Israel Institute of Technology , Haifa 31096, Israel
                []Faculty of Medicine, University of Latvia , Digestive Diseases, Riga East University Hospital, 19 Rainisboulv, LV1586 Riga, Latvia
                []Digestive Diseases Centre, GASTRO , 6 Linezeraiela, LV1006 Riga, Latvia
                []Department of Radiation Oncology, Baptist Cancer Institute (BCI) , 1235 San Marco Boulevard, Suite100, Jacksonville, Florida 32207, United States
                []Pulmonary and Critical Care Associates, Orange Park, Florida 32073, United States
                [†† ]Pulmonary Diseases, Baptist Medical Center , Jacksonville, Florida 32217, United States
                [‡‡ ]Oncologic Imaging Division, Florida Radiation Oncology Group , Jacksonville, Florida 32217, United States
                [§§ ]Thoracic Cancer Unit, Davidoff Cancer Center , RMC, Kaplan Street, Petach Tiqwa 49100, Israel
                Author notes
                Article
                10.1021/acsnano.6b04930
                5269643
                28000444
                64ee0c1b-ecac-4dd9-a64e-802a8454924c
                Copyright © 2016 American Chemical Society

                This is an open access article published under an ACS AuthorChoice License, which permits copying and redistribution of the article or any adaptations for non-commercial purposes.

                History
                : 24 July 2016
                : 02 December 2016
                Categories
                Article
                Custom metadata
                nn6b04930
                nn-2016-04930j

                Nanotechnology
                sensor,nanoparticle,carbon nanotube,noninvasive,diagnosis,disease,breath,volatile organic compound

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