NATURE NANOTECHNOLOGY | VOL 4 | OCTOBER 2009 | www.nature.com/naturenanotechnology 621
news & views
B
reath analysis — which links
the patterns of volatile organic
compounds (VOCs) in exhaled
breath to medical conditions — is a new
frontier in medical diagnostics because it is
non-invasive and potentially inexpensive.
Various analytical and spectroscopic
methods exist to measure these compounds
in exhaled breath, but none of these
techniques have proved to be ideal. Current
technologies are expensive, slow, insensitive
and cumbersome to use, or require the
disease bio-markers to be concentrated
before measurements. For breath testing to
become a clinical reality, several advances
in our knowledge of disease-specic
breath biomarkers, sensor development
and breath collection techniques need to
occur. Furthermore, large studies of diverse
groups of people are required to better
assess the accuracy of the tests.
On page 669 of this issue, Hossam Haick
and colleagues
1
from Technion-Israel
Institute of Technology and the Rambam
Health Care Campus — building on work
done in collaboration with researchers at the
University of Colorado Cancer Center
2
—
report a chemical sensor matrix composed
of gold nanoparticles that can rapidly and
accurately distinguish the exhaled breath
of lung cancer patients from the breath
of healthy individuals without needing to
pre-treat or dehumidify the breath samples
in any way. e sensor is expected to be
an inexpensive and non-invasive portable
diagnostic tool for lung cancers that is
suitable for widespread use in clinics.
Lung cancer, which is the world’s leading
cause of cancer-related mortality, is the
most studied disease for breath analysis. At
present, lung cancer is diagnosed by taking
a sample of lung tissue (known as a biopsy)
for examination by a pathologist, and the
nature of the cancer is assessed using a
host of imaging techniques. ese methods
are invasive and expensive, so a sensitive
and specic breath-testing tool would
be welcomed.
Exhaled breath is composed primarily
of nitrogen, oxygen, and carbon dioxide.
Trace amounts of VOCs are also found in
the breath (typically with concentrations in
the range of parts per billion to parts per
trillion). Exogenous VOCs inhaled from
environmental sources or absorbed through
skin, and endogenous VOCs generated
by our body’s metabolic processes aect
the types of compounds present in breath.
Many lines of evidence suggest that the
cellular metabolic processes of diseased
tissue, such as those found in lung tumours,
are dierent from the metabolic processes
of normal cells
3–5
. If the dierences in
VOCs of diseased and normal breath can
be accurately and consistently identied,
a disease-specic breath test could
be developed.
Standard gas chromatography and
mass spectrometry, and advanced lab-
based analytics (such as single-ion ow
tube mass spectrometry and ion-mobility
spectroscopy) have been used to identify the
compounds and/or quantify the components
in the breath. In addition, various chemical
sensor matrix platforms — such as
colorimetric sensor arrays, carbon polymer
arrays, single-walled carbon nanotubes,
coated quartz crystals and surface acoustic
wave sensors
6,7
— have been used to detect
VOC biomarkers specic to lung cancer.
e output from these sensors may be a
change in colour, conductivity, vibration
or sound that occurs when the compounds
interact with the sensor. Accuracies of
70–85% have been reported for lung cancer
detection, but none have been developed
and validated for clinical use. e chemical
sensor matrices are more likely to become
a clinical and laboratory diagnostic tool
because they are potentially easier to use and
less expensive.
An ideal chemical sensor for breath
analysis should be sensitive at very low
analyte concentrations in the presence of
water vapour, because exhaled breath is fully
humidied. Furthermore, it should respond
rapidly and dierently to small changes in
concentration, and provide a consistent
output that is specic to a given exposure.
When not in contact with the analyte, the
sensor should return to its baseline state
rapidly, or be simple and inexpensive
enough to manufacture large numbers of
disposable units.
e Israeli team created an array of
nine cross-reactive chemiresistors, each of
which contained assemblies of 5-nm gold
nanoparticles that were functionalized with
dierent organic groups. When exposed
to VOCs, the resistance of the sensors
changes, and because of their chemical
diversity, the responses of the array are
unique (Fig. 1). Using gas chromatography
and pattern-recognition methods, Haick
and co-workers identied 42 VOCs in
patient breaths that represent lung cancer
biomarkers, and used four of these to
optimize the sensor by simulating diseased
breaths. When exposed to breath samples
from real patients, the sensors were able
to discriminate cancerous breath from
healthy ones with good accuracy. e
sensors were sensitive to between one
NANOMEDICINE
Sning out lung cancer
A sensor consisting of an array of gold nanoparticles can distinguish the breath of lung cancer patients from the
breath of healthy individuals without the need to pre-treat or dehumidify the samples.
Peter Mazzone
Normal Abnormal
Figure 1 | Chemical sensors tell the dierence between the breaths of lung cancer patients
(right; coloured bubbles) and the breaths of healthy ones (blue and grey bubbles). Output from the
sensors will vary based on the pattern of volatile organic compounds in the breath and the type of sensors
used. Solid colours in the array represent compounds detected in lung cancer patients whereas pastel
colours represent compounds found in normal breath.
?

2
0
0
9

C
C
F
nnano_N&V_OCT09.indd 621 25/9/09 10:54:02
© 2009 Macmillan Publishers Limited. All rights reserved