Cyranose 320 Select QA/QC Applications

Medical Applications
of
Nanocomposite Sensor
Arrays
eNose® - Medical Applications
Cyranose® 320
• Handheld Chemical Vapor Detector
• Designed for Industrial / Commercial Use
• Evaluated as an exempt Research Tool to
determine efficacy of sensor arrays for a
variety of medical applications
eNose® - Medical Applications
Vapor passes over the
polymer matrix and
produces a change
in dc resistance for
each sensor
32 chemical sensors in
standard array
Using pattern matching
algorithms, the data
is converted into a
unique response pattern
(PCA, CDA, ANN, SVM)
eNose® - Medical Applications
Premise –
Routine Diagnosis
and
Health Monitoring
through Breath Analysis
Low cost and low power
nanotechnology sensors
will enable affordable
and reliable devices
for home health and
point of care products
eNose® - Medical Applications
product analogy:
spirometer on a PC card
Hippocrates - treatise on breath aroma and disease
Lavoisier and Laplace (1784) - showed that respiration consumes
oxygen and eliminates carbon dioxide
Nebelthau (mid 1800s) - showed that diabetics emit breath acetone
Anstie (1874) - isolated ethanol from breath
Pauling (1971) - used GC to detect 250 compounds in breath
Phillips (1999) - used GC/MS to detect 3000 compounds in breath
2000 - present - new advances in breath analysis each year through laser
spectroscopy, mass spectrometry and eNose analysis
eNose® - Medical Applications
University of Pennsylvania uses handheld eNose for pneumonia, CSF and sinusitis
research in the ER and outpatient clinic
Lai, S. et al. Identification of upper respiratory bacterial pathogens with the electronic nose. Laryngoscope. 112(6) 975-9 (2002);
Aronzon, A. et al. Differentiation between cerebrospinal fluid and serum with electronic nose. Otolaryngol Head Neck Surg 133(1) 916 (2005); Thaler, ER, Hanson, CW. Use of an electronic nose to diagnose bacterial sinusitis. American Journal of Rhinology, 20(2)
170-172 (2006)
Cleveland Clinic uses handheld eNose for lung cancer research
Machado, R. et al Detection of Lung Cancer by Sensor Array Analyses of Exhaled Breath. Am. J. Respir. Crit. Care Med. 171(11)
1286-1291 (2005)
University of Amsterdam uses handheld eNose for COPD, asthma and cancer
Dragonieri, S. et al. An electronic nose in the discrimination of patients with asthma and controls. J Allergy Clin Immunol. 120(4):
856-62 (2007); Dragonieri, S. et al. An electronic nose in the discrimination of patients with non-small cell lung cancer and COPD.
Lung Cancer 64(2) 166-70 (2009); Lazar, Z. et al. Electronic nose breathprints are independent of acute changes in airway caliber in
asthma. Sensors 10(10) 9127-38 (2010); Fens, N. et al. Exhaled air molecular profiling in relation to inflammatory subtype and
activity in COPD. Eur Respir. J. 38 1301-1309 (2011).
Research teams around the world use the handheld eNose: Australia, New
Zealand, Germany, Hungary, Italy …
Dent, A. et al. Electronic nose distinguishes lung cancer from healthy smoking controls. Supplement to Journal of Thoracic
Oncology: (2010); Hattesohl AD, et al. Discrimination between COPD patients with and without alpha 1-antitrypsin deficiency using
an electronic nose. Respiratory Disease Diagnosis 16(8) 1258-64 (2011); Chapman, EA et al. A breath test for malignant
mesothelioma using an electronic nose. Eur Respir J. December 2011. Timms, C. et al. Detection of gastro-oesophageal reflux
disease (GORD) in patients with obstructive lung disease using exhaled breath profiling. J Breath Res. January 2012.
eNose® - Medical Applications
Com pound as a
A n a ly s is
D is e a s e
d is e a s e m a r k e r
In s t r u m e n t
A c u te c a r d ia c a llo g r a ft r e je c tio n
P e n ta n e
G C /F ID
M y o c a r d ia l in fa r c tio n ( M I)
H y d ro c a rb o n s
G C /F ID
A s th m a
N itr ic O x id e
C L a n a ly z e r
COPD / ARDS
NO, CO
C L a n a ly z e r
B re a s t C a n c e r
P e n ta n e
G C /F ID
D ia b e te s
A c e to n e
G C /F ID
H e m o ly s is
C a r b o n m o n o x id e
E C C O a n a ly z e r
G C /T C D
H . p y lo r i in fe c tio n
13
CO 2 or
14
CO2
Is o to p e R a tio M S
Is o to p e R a tio IR
A lc o h o lic liv e r d is e a s e
P e n ta n e
G C /F ID
L iv e r c ir r h o s is
D im e th y l s u lfid e
G C /F P D
V o la tile fa tty a c id
G C /F ID
A c e to n e
G C /F ID
W e ig h t R e d u c tio n
VOCs from bacterial infection
acids, alcohols, aldehydes, amines, ketones,
hydrocarbons, sulfur compounds
eNose® - Medical Applications
semivolatiles in
breath condensate
volatiles excreted
in breath
eNose® - Medical Applications
acetone
RT: 0.00 - 56.99
3.06
7.43 8.60
23.28
NL:
4.19E5
30.95
TIC MS
test216
4.5
4.0
3.5
CO2
phenol
Relative Abundance
3.47
3.0
isoprene
2.5
29.36
2.0
1.5
11.75
24.95
18.08
1.0
28.87
16.15
14.61
4.65
20.43
11.52
2.58
54.42
35.38
13.33
0.5
33.45
27.67
36.16
36.41
21.43
5.04
56.77
38.94
40.20
46.85
42.96 44.81
54.06
53.89
51.80
0.0
0
5
10
15
20
25
30
Time (min)
35
40
45
50
55
GC/MS can identify many but not all breath constituents
eNose® - Medical Applications
CO2 sensor
NRBV
P
CO2
air
supply
1L sample can
Elaborate means for collection of breath constituents for analysis
eNose® - Medical Applications
Measure the entire breath profile
Simplicity of sample measurement
An eNose received FDA approval in 2002 for
Urinary Tract Infection (UTI)
Bacterial Vaginosis (BV)
eNose® - Medical Applications




Bacteria Identification
• ENT bacteria, infant Otitis Media, adult Urinary Tract Infection
Univ. Pennsylvania Hospital (HUP)
• Ventilator Associated Pneumonia
• Sinusitis
• Cerebrospinal fluid in the ER
Cleveland Clinic Foundation (CCF)
• Lung Cancer
• ARDS, COPD, asthma
• CF, PPH
Univ. of Amsterdam (AMC)
• Asthma
• Small cell cancer and COPD
eNose® - Medical Applications
Canonical Discriminant Analysis
2 Week Prediction Success
tests
ID
66
e
5
H. influenzae
4
e
3
Function 2
e
e
2
1
0
0
-1
-2
a a
a
ca c
ab
c
ac
cb a
b
bb
c bc
b
-3
ee
f
f
f
f
f
e
e e
f
f
f
d
Staph.
aureus
Strept. pneumoniae
Strept. pyogenes
c
-4
strep A+B
Staph
H. flu
B. catarrh.
B. catarrhalis
f
-4
-10
20
eNose® - Medical Applications
0
0
10
Function 1
PC 1
10
d
d
d
d
d
d d
20
28/28
13/13
15/15
15/15
100%
100%
100%
100%
Lai SY et al, Identification of Upper Respiratory
Bacterial Pathogens with the Electronic Nose.
Laryngoscope 112, 975-9 (2002).
eNose® - Medical Applications
Bacteria classification using Cyranose 320 electronic nose. Biomed Eng Online. 2002; 1 (1): 4
Ritaban Dutta, 1 Evor L. Hines,1 Julian W. Gardner,1 and Pascal Boilot1
eNose® - Medical Applications
VOCs from bacterial
metabolism
alcohols
ketones
aldehydes
eNose® - Medical Applications
organic acids
hydrocarbons
sulfides, thiols
amines
Compounds from immune system
response to infection
Inflammation:
NOx CO VOCs
Enterotoxin stimulus: VOCs ?
Bacteria
Metabolites
S. aureus
2-methylbutanol
3-methylbutanol
Strept.
pneumoniae
2-butanol
lactic acid
H. influenzae
acetic acid
indole
Sample
taken from
exhaled
gases.
Cyranose
320
eNose® - Medical Applications
70
infected
60
William Hanson, MD
Erica Thaler, MD
P r e d ic te d S c o r e
50
40
R O C based on C D A
30
1 .0
0 .9
20
0 .8
normal
10
0 .7
0
20
40
60
80
100
TP
0 .6
0
0 .5
0 .4
A c tu a l S c o re
0 .3
eNose measurements on exhaled breath
compare favorably to the combined
pulmonary infection score (CPIS) used to confirm
ventilator associated pneumonia in the ICU
0 .2
ROC 86%
0 .1
0 .0
0 .0
Amer. Thoracic Society 2002
eNose® - Medical Applications
0 .1
0 .2
0 .3
0 .4
0 .5
FP
0 .6
0 .7
0 .8
0 .9
1 .0
c = 1 0 0 , w = 0 .5
M odel
% c o rre c t
# c o rre c t
% c o rre c t
SVM
1 2 3 /1 2 3
100
1 1 8 /1 2 3
9 5 .9
S V M + P C A (2 )
1 2 3 /1 2 3
100
1 1 3 /1 2 3
9 1 .9
S V M + P C A (3 )
1 2 3 /1 2 3
100
1 2 1 /1 2 3
9 8 .4
Methods

Nasal swabs
- sampling of infection hotspot with calgiswab

Nasal breathing cup
eNose® - Medical Applications
# c o rre c t
c=10, w=5
Serpil Erzurum, MD
Raed Dweik, MD
Roberto Machado, MD
eNose® - Medical Applications
10
5
• Detection of lung cancer in
non-smokers is feasible
Control
Lung Cancer
• Discrimination from several
disease controls: COPD,
ARDS, PPH, asthma,a-1, CBE
PC2
0
-5
-10
• Goal: early detection of
small tumors
-15
-20
-20
-10
0 PC1
10
20
Machado RF et al (CCF) Detection of Lung Cancer by Sensor
Array Analyses of Exhaled Breath. Amer. Jour. Respiratory &
Critical Care Medicine v171 1286-1291 (2005).
eNose® - Medical Applications
30
DiNatale, et al (Univ Rome) Lung cancer identification
by the analysis of breath by means of an array of nonselective gas sensors. Biosensors & Bioelectronics v18
1209-1218 (2003)
eNose® - Medical Applications

Many diseases produce a measurable pattern of
volatile chemicals in breath, urine and blood

Non-invasive breath measurement will provide rapid
diagnosis and treatment monitoring capability for
physicians in emergency and point-of-care
applications

Low cost and low power intelligent
sensor array devices will enable
home health diagnosis and monitoring
capability for many individuals
eNose® - Medical Applications
For application or product information,
please contact:
Sensigent
[email protected]
626-768-2626
www.sensigent.com
eNose® - Medical Applications