IEEE SENSORS JOURNAL, VOL. 10, NO. 1, JANUARY 2010 159 DNA-Coated Nanosensors for Breath Analysis A. T. Charlie Johnson, Samuel M. Khamis, George Preti, Jae Kwak, and Alan Gelperin Abstract—The analysis of breath and body odors can provide valuable information relevant to disease detection, diagnosis and treatment. A variety of technical developments are being pursued to develop electronic devices intended to analyze volatile compo- nents of breath and body odors with the sensitivity, selectivity, and learning ability of high-end mammalian olfactory systems. Here, we describe a new sensor technology that has the potential to supply a large set of diverse and sensitive odorant sensors with electronic readout to provide information-rich odorant-elicited signals for analysis by pattern recognition algorithms. In addition, we demonstrate that these sensors can provide discrimination of odorant homologues consisting of aldehydes and organic acids commonly found in human breath and other body emanations over a range of concentrations. Index Terms—Breath diagnosis, carbon nanotubes, field effect transistors, human odortypes, odor sensors, pattern recognition, pi-pi stacking. I. INTRODUCTION T HE mammalian olfactory system has no equal in its ability to detect small differences in the patterns of mul- tiple molecular signatures, for example, differences in the trace odorants associated with single-gene differences in genetic loci controlling the immune system [1], trace odorants signaling buried land mines [2], and odorant signatures of cancer and other human disease states [3], [4]. Breath analysis is receiving increased attention from analytical chemists, clinicians and technologists as breath-derived volatile compounds provide a potentially rich source of chemical cues directly relevant to disease detection, diagnosis, and long-term monitoring [5]. The design principles revealed in recent work on biological olfactory systems [6] provide guidelines for designing an elec- tronic olfactory system. A critical part of any engineered system aiming to mimic mammalian olfaction is a large and diverse array of sensors able to provide an information-rich set of uncor- related signals for analysis by a smart [7] adaptive pattern recog- nition system. Ideally the sensor array would be large enough to Manuscript received June 01, 2009; accepted August 06, 2009. Current ver- sion published December 16, 2009. This work was supported in part by Army Research Office Grant W911NF-07-1-0399 (AG, ATCJ), in part by the Depart- ment of Homeland Security (AG, GP, ATCJ), in part by JSTO, in part by DTRA, and in part by Army Research Office Grant W911NF-06-1-0462 (ATCJ). The associate editor coordinating the review of this manuscript and approving it for publication was Prof. Cristina Davis. A. T. Johnson and S. M. Khamis are with the Department of Physics and Astronomy, University of Pennsylvania, Philadelphia, PA 19104 USA. G. Preti is with Monell Chemical Senses Center, Philadelphia, PA 19104 USA, and also with the Department of Dermatology, School of Medicine, Uni- versity of Pennsylvania, Philadelphia, PA 19104 USA. J. Kwak is with Monell Chemical Senses Center, Philadelphia, PA 10954 USA. A. Gelperin is with Monell Chemical Senses Center, Philadelphia, PA 19104 USA, and also with the Princteon Neuroscience Institute, Department of Molecular Biology, Princteon University, Princeton, NJ 08544 USA (e-mail: agelperin@princeton.edu). Digital Object Identifier 10.1109/JSEN.2009.2035670 obtain the sensitivity boost available when hundreds or thou- sands of identical receptors converge their inputs onto a small number of integrating units, as occurs in the glomeruli of bio- logical olfactory systems [8]. If engineered correctly, the artifi- cial olfactory system may provide a test-bed for exploring new properties of the biological olfactory system [9]. A variety of selective chemosensing methods have been applied to breath analysis since the report by Linus Pauling in 1971 indicating that exhaled breath contained more than 250 compounds [10]. The sensing methods applied to breath anal- ysis are extremely diverse, including metalloporphyrin-based colorimetric sensors [11], [12], polymer-carbon black com- posite films [13], [14], metallophthalocyanine-carbon black composites [15], infrared cavity leak-out spectroscopy [16], quantum cascade lasers [17], organic semiconductor-based thin-film transistors [18]–[20], nanowires [21], [22], micro- cantilevers [23], biological olfactory receptors [24]–[26], conductive polymer gate FETs [27], dye-labeled DNA films [28], and MEMS-based chemiresistive microsensor arrays [29], to name a few. These issues have recently been reviewed [30]–[33]. We have recently developed a new sensor technology for odorant detection, combining the selective odorant interactions of single-stranded DNA oligomers [28] with the sensitivity of single-walled semiconducting carbon nanotubes to pertur- bations of their surface electronic environment [34]. We have tested the responses of sensor devices to a variety of odorants, including several volatile organic compounds found in human breath. The responses obtained to date encourage the view that the new sensor technology comprised of single-stranded DNA-coated semiconducting carbon nanotubes arrayed as semiconductor elements in field effect transistors can make a useful contribution to the clinical analysis of volatile organic compounds in human breath. The goal of our research is to contribute to the development of a new generation of devices for electronic olfaction, capable of matching or exceeding the demonstrated sensitivity and se- lectivity of trained biological olfactory systems [35]–[41]. The short-term goal is to develop a sensory technology that lends itself to fabrication of sensor chips containing hundreds of sen- sors providing patterns of uncorrelated input to a pattern recog- nition component that implements both sensor pattern recogni- tion and a highly developed learning ability [42]–[44]. With a sufficiently large, diverse and sensitive sensor array [45] the de- vice can learn to recognize known weak odorant signals present in a background of strong, unknown and time varying odorant signals, as demonstrated in biological olfaction during breath or body odor analysis [3], [46], [47]. II. DNA-COATED NANOTUBES AS ODOR SENSORS Single-walled carbon nanotube FETs are fabricated by de- positing an array of gold electrodes onto a field of CNTs syn- 1530-437X/$26.00 © 2009 IEEE Authorized licensed use limited to: University of Pennsylvania. Downloaded on January 8, 2010 at 13:21 from IEEE Xplore. Restrictions apply.