Noninvasive Disease Diagnosis through Breath Analysis Using DNA-Functionalized SWNT Sensor Array

Noninvasive diagnostics of diseases via breath
analysis has attracted considerable scientific and clinical interest for
many years and become more and more promising with the rapid
advancements in nanotechnology and biotechnology. The volatile
organic compounds (VOCs) in exhaled breath, which are mainly
blood borne, particularly provide highly valuable information about
individuals’ physiological and pathophysiological conditions.
Additionally, breath analysis is noninvasive, real-time, painless, and
agreeable to patients. We have developed a wireless sensor array
based on single-stranded DNA (ssDNA)-functionalized single-walled
carbon nanotubes (SWNT) for the detection of a number of
physiological indicators in breath. Seven DNA sequences were used
to functionalize SWNT sensors to detect trace amount of methanol,
benzene, dimethyl sulfide, hydrogen sulfide, acetone, and ethanol,
which are indicators of heavy smoking, excessive drinking, and
diseases such as lung cancer, breast cancer, and diabetes. Our test
results indicated that DNA functionalized SWNT sensors exhibit
great selectivity, sensitivity, and repeatability; and different
molecules can be distinguished through pattern recognition enabled
by this sensor array. Furthermore, the experimental sensing results
are consistent with the Molecular Dynamics simulated ssDNAmolecular
target interaction rankings. Thus, the DNA-SWNT sensor
array has great potential to be applied in chemical or biomolecular
detection for the noninvasive diagnostics of diseases and personal
health monitoring.





References:
[1] Owen, O. E., et al., "Acetone Metabolism during Diabetic-
Ketoacidosis", Diabetes. vol. 31, no. 3, pp. 242-248, 1982.
[2] Cao, W. Q., Duan, Y. X., "Breath analysis: Potential for clinical
diagnosis and exposure assessment", Clin Chem. vol. 52, no. 5, pp. 800-
811, 2006.
[3] PR, G., et al., "Breath ethanol and acetone as indicators of serum glucose
levels: an initial report", Diabetes Technol Ther. vol. 7, no. 1, pp. 115-
23, 2005.
[4] Manolis, A., "The Diagnostic Potential of Breath Analysis", Clin Chem.
vol. 29, no. 1, pp. 5-15, 1983.
[5] Amann, A., Spanel, P., Smith, D., "Breath analysis: the approach
towards clinical applications", Mini reviews in medicinal chemistry. vol.
7, no. 2, pp. 115-29, 2007.
[6] Ligor, T., et al., "The analysis of healthy volunteers' exhaled breath by
the use of solid-phase microextraction and GC-MS", J Breath Res. vol.
2, no. 4, pp., 2008.
[7] Buszewski, B., Kesy, M., Ligor, T., Amann, A., "Human exhaled air
analytics: Biomarkers of diseases", Biomed Chromatogr. vol. 21, no. 6,
pp. 553-566, 2007.
[8] Kim, S. N., Rusling, J. F., Papadimitrakopoulos, F., "Carbon nanotubes
for electronic and electrochemical detection of biomolecules", Advanced
Materials. vol. 19, no. 20, pp. 3214-3228, 2007. [9] Liu, Z., Winters, M., Holodniy, M., Dai, H. J., "siRNA delivery into
human T cells and primary cells with carbon-nanotube transporters",
Angewandte Chemie-International Edition. vol. 46, no. 12, pp. 2023-
2027, 2007.
[10] Prato, M., Kostarelos, K., Bianco, A., "Functionalized carbon nanotubes
in drug design and discovery", Accounts Chem Res. vol. 41, no. 1, pp.
60-68, 2008.
[11] Snow, E. S., Perkins, F. K., Houser, E. J., Badescu, S. C., Reinecke, T.
L., "Chemical detection with a single-walled carbon nanotube
capacitor", Science. vol. 307, no. 5717, pp. 1942-1945, 2005.
[12] Novak, J. P., et al., "Nerve agent detection using networks of singlewalled
carbon nanotubes", Appl Phys Lett. vol. 83, no. 19, pp. 4026-
4028, 2003.
[13] Bradley, K., Gabriel, J. C. P., Star, A., Gruner, G., "Short-channel
effects in contact-passivated nanotube chemical sensors", Applied
Physics Letters. vol. 83, no. 18, pp. 3821-3823, 2003.
[14] Wong, S. S., Joselevich, E., Woolley, A. T., Cheung, C. L., Lieber, C.
M., "Covalently functionalized nanotubes as nanometre-sized probes in
chemistry and biology", Nature. vol. 394, no. 6688, pp. 52-55, 1998.
[15] Staii, C., Johnson, A. T., "DNA-decorated carbon nanotubes for
chemical sensing", Nano Lett. vol. 5, no. 9, pp. 1774-1778, 2005.
[16] Zhang, Y. B., et al., "Functionalized carbon nanotubes for detecting viral
proteins", Nano Lett. vol. 7, no. 10, pp. 3086-3091, 2007.
[17] Zheng, M., et al., "DNA-assisted dispersion and separation of carbon
nanotubes", Nat Mater. vol. 2, no. 5, pp. 338-342, 2003.
[18] White, J., Truesdell, K., Williams, L. B., AtKisson, M. S., Kauer, J. S.,
"Solid-state, dye-labeled DNA detects volatile compounds in the vapor
phase", Plos Biol. vol. 6, no. 1, pp. 30-36, 2008.
[19] Johnson, R. R., Johnson, A. T. C., Klein, M. L., "Probing the structure of
DNA-carbon nanotube hybrids with molecular dynamics", Nano Lett.
vol. 8, no. 1, pp. 69-75, 2008.
[20] Daniel, S., et al., "A review of DNA functionalized/grafted carbon
nanotubes and their characterization", Sensors and Actuators BChemical.
vol. 122, no. 2, pp. 672-682, 2007.
[21] Meng, S., Maragakis, P., Papaloukas, C., Kaxiras, E., "DNA nucleoside
interaction and identification with carbon nanotubes", Nano Letters. vol.
7, no. 1, pp. 45-50, 2007.
[22] Yang, R. H., et al., "Noncovalent assembly of carbon nanotubes and
single-stranded DNA: An effective sensing platform for probing
biomolecular interactions", Analytical Chemistry. vol. 80, no. 19, pp.
7408-7413, 2008.
[23] Zhang, W. J., Liu, Y., Wang, M. L., "DNA-functionalized single-walled
carbon nanotube-based sensor array for gas monitoring", Smart Struct
Syst. vol. 12, no. 1, pp. 73-95, 2013.
[24] Zhang, W. J., Wang, M. L., "DNA-functionalized single-walled carbon
nanotube-based sensor array for breath analysis", International Journal
of Electronics and Electronical Engineering. vol. 4, no. 2, pp. 177-180,
2016.
[25] Liu, Y., Chen, C. L., Zhang, Y., Sonkusale, S. R., Wang, M. L., "SWNT
Based Nanosensors for Wireless Detection of Explosives and Chemical
Warfare Agents", Ieee Sens J. vol. 13, no. 1, pp. 202-210, 2013.
[26] Roine, R. P., Eriksson, C. J. P., Ylikahri, R., Penttila, A., Salaspuro, M.,
"Methanol as a Marker of Alcohol-Abuse", Alcohol Clin Exp Res. vol.
13, no. 2, pp. 172-175, 1989.
[27] Jones, A. W., "Abnormally High-Concentrations of Methanol in Breath -
a Useful Biochemical Marker of Recent Heavy Drinking", Clin Chem.
vol. 32, no. 6, pp. 1241-1242, 1986.
[28] Wester, R. C., Maibach, H. I., Gruenke, L. D., Craig, J. C., "Benzene
Levels in Ambient Air and Breath of Smokers and Nonsmokers in Urban
and Pristine Environments", J Toxicol Env Health. vol. 18, no. 4, pp.
567-573, 1986.
[29] Dent, A. G., Sutedja, T. G., Zimmerman, P. V., "Exhaled breath analysis
for lung cancer", J Thorac Dis. vol. 5, no., pp. S540-S550, 2013.
[30] Liu, Y., et al. "Single chip Nanotube sensors for chemical agent
monitoring", 16th International Solid-State Sensors, Actuators and
Microsystems Conference (TRANSDUCERS), Beijing, China, 5-9 June
2011; Beijing, China, 2011; pp. 795-798.
[31] Zhang, W. J., Wang, M. L., Cranford, S. W., "Ranking of Molecular
Biomarker Interaction with Targeted DNA Nucleobases via Full
Atomistic Molecular Dynamics", Sci Rep-Uk. vol. to be published, no.,
pp., 2015.