Article

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

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
ACS Nano, 2017, 11 (1), pp 112–125
DOI: 10.1021/acsnano.6b04930
Publication Date (Web): December 21, 2016
Copyright © 2016 American Chemical Society
ACS Editors' Choice - 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.

Abstract

Abstract Image

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.

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acsnano.6b04930.

  • Detailed methods section, additional results and figures, and an appendix on the inclusion and exclusion criteria of the study population (PDF)

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Article Views: 53,178 Times
Received 24 July 2016
Date accepted 2 December 2016
Published online 21 December 2016
Published in print 24 January 2017
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