CHEMICAL ANALYSIS OF EXHALED HUMAN
BREATH USING HIGH RESOLUTION
MM-WAVE ROTATIONAL SPECTRA
Tianle Guo, Jessica R. Thomas, Daniela R. Branco, Ivan R. Medvedev
Department of Physics
DAVID DOLSON, Department of Chemistry
Wright State University, Dayton, OH
HYUN-JOO NAM, Department of Bioengineering,
TX,KENNETH O, Electrical Engineering,
University of Texas at Dallas, Dallas, TX
Experimental Setup
Continuous Wave THz Spectrometer
Microwave Synthesizer
Custom Built
Diode Multipliers
Virginia Diodes Heterodyne Reciever, 210~270 GHz
Absorption Cell
2 m long by 4 inches wide (14 L), Large; 2 m long by 1 inches wide (0.875 L), Small
Preconcentrator
ENTECH 7100A; Markes Sorbent tubes
Preconcentrator
Custom Built Microwave
Synthesizer
Absorption
Cell(Small)
Absorption
Cell(Large)
Our System versus GC-MS
MM-WAVE ROTATIONAL
Gas Chromatography–
Mass Spectrometry
Do no need Calibration. Only need to
acquire a library once.
Day to Day calibration
High number of resolution elements
100,000 leads to high specificity
Much lower number of resolution
elements 200, leads to possible ‘false
positive’ and ‘false negative’
Suitable for lighter polar molecules
more accurate results for larger
molecules
Young
Sophisticated
Blood glucose Assessment based
in Breath analysis - Prior Work
•
Breath acetone(1) and methyl nitrate(2) level were reported linear related to blood-sugar level.
(1)C.N. Tassopoulos. (1969). BREATH-ACETONE AND BLOOD-SUGAR MEASUREMENTS IN
DIABETES. the lancet. 293 (7609), p1282-1286.
(2)Galassetti, P. R.. "Exhaled methyl nitrate as a noninvasive marker of hyperglycemia in type 1
diabetes." Proceedings of the National Academy of Sciences: 15613-15618.
•
•
The eventuality of metabolizing glucose and aspartame into Methanol is known from
professional literature.
A higher amount of breath CO in diabetic person was noticed, and there was a positive
correlation between exhaled CO levels and the incidence of glycemia.
(3)Paredi, P.. "Exhaled Carbon Monoxide Levels Elevated in Diabetes and Correlated With
Glucose Concentration in Blood: A New Test for Monitoring the Disease?." Chest: 1007-1011
•
Patients with diabetics may have a higher Breath Isoprene
(4)Barker M, Hengst M, Schmid J, et al. Volatile organic compounds in the exhaled breath of young patients
with cystic fibrosis. Eur Respir J 2006;27:929e36.
•
Toluene is one of the potential markers used for the diagnosis of diabetes
(5)Shin, Jungwoo. "Thin-Wall Assembled SnO2 Fibers Functionalized by Catalytic Pt Nanoparticles and their
Superior Exhaled-Breath-Sensing Properties for the Diagnosis of Diabetes." Advanced Functional
Materials 23: p2357-2367.
Analytical Chemical Detection Algorithm
1. Create the spectral libraries
•Collect overview spectra of the pure samples at well defined pressures (1 mTorr, 5 mTorr, 10
mTorr)
•These overview spectra are then overlaid in order to choose 5 of the strongest lines of each
chemical that do not overlap with other chemicals.
•The amount of pressure for each chemical used in our library is determined by matching
pressure broadening of the library spectra to the breath spectra.
2. Record spectra of the chemicals in breath
•Breath/Air samples were then collected into a Tedlar bag/Sorbent tubes
•Use preconcentrator/Sorbent tubes to remove major air constituents (O2, N2, H2O, and CO2)
•Inject preconcentrated breath into the absorption cell
•Record the snippet spectra
3. Perform spectral analysis
•Calculate partial pressures of every chemical present in the absorption cell by performing the
Least Squares Fitting (LSF) of the mixture spectrum to the library spectrum.
•Can get the volumetric dilution of each chemical in the original breath sample based on the
volume of the absorption cell and the preconcentration efficiency
Spectra – Example
Breath Collection Method
Tedlar Bag Vs Sorbent tubes
1.
By using Tedlar Bags, we collect all the exhaled
breath. However, most valuable chemicals from
metabolism are in the alveolar volume (last portion of
exhalation). Using Tedlar Bag will lower the sensitivity
and bring contamination from environment.
2.
Entech 7100A use cold trap, and high boiling
temperature chemical will be taken away.
3.
Tenax TA is a weak sorbent, cannot catch CarbonMonoxide .
Tenax TA 35/60, Carborgraph
1TD 40/60, Carboxen 1003 40/60
Entech 7100A
With Tenax TA
Bio-VOC Breath sampler
127CC Exhaled Breath
Contamination of the cell
(Old cell – Large volume)
Black—Baseline(empty)
Red—--Breath
Contamination of the cell
(New Cell – Small Volume)
Blue—Baseline(empty)
Red—--Breath
Comparison of Two Method
Black – Old system
Red – New system
Comparison of Two Method
Black – Old system
Red – New system
Comparison of Two Method
Chemicals Currently Studied
Chemicals
Normal Breath
Sensitivity(Old)
Sensitivity(New)
Ethanol
0 - 1663 ppb
24 ppb
2.4ppb
Methanol
32 - 1684 ppb
8.1 ppb
1.6ppb
Acetone
177 - 3490 ppb
68 ppb
11ppb
Acetaldehyde
0 - 104 ppb
10 ppb
1.5ppb
Chloromethane
-
33 ppb
0.12ppb
HCN
4.4 ppb
0.5 ppb
10ppt
Methyl Cyanide
4.4 ppb
12 ppb
80ppt
CO
0~100ppm
16ppb
60ppt
Formalradehyde
40ppb(breath),
100ppb(environment)
14.7ppb
2.6ppb
Methyl Nitrate*
10 - 30 ppt
3 ppb
-
Toluene
0-0.1ppb
450 ppb
-
Isoprene
50~1000ppb
1200ppb
-
Breath Chemicals & Blood Sugar
Experimental Process
•Subject I, female, healthy.
•Subject II, Diabetic type 1
•breath (500cc) was collected Randomly, (no condition
controlled), over several days,
•Breath samples consisted of approximately 2
exhalations.
•Blood Sugar level was collected right after the
breath by OneTouch® UltraMini® blood glucose
meter.
•Breath spectra was recorded for each sample.
Breath Results – Subject I (non diabetic)
Chloromethane
Acetaldehyde
5E-08
2.50E-08
Acetone
2.50E-07
4.5E-08
4E-08
2.00E-08
2.00E-07
3.5E-08
3E-08
1.50E-08
1.50E-07
2.5E-08
2E-08
1.00E-08
1.00E-07
1.5E-08
5.00E-09
5.00E-08
1E-08
5E-09
0.00E+00
60
80
100
120
140
160
0.00E+00
0
60
110
HCN
60
160
Methanol
1.60E-07
7.00E-09
1.40E-07
6.00E-09
1.20E-07
5.00E-09
1.00E-07
4.00E-09
8.00E-08
1.5E-07
3.00E-09
6.00E-08
0.0000001
2.00E-09
4.00E-08
60
80
100
120
140
160
140
160
0.0000002
5E-08
0.00E+00
0.00E+00
120
2.5E-07
2.00E-08
1.00E-09
100
Ethanol
0.0000003
8.00E-09
80
0
60
80
100
120
140
160
60
80
100
120
140
160
Breath Results – Subject II (Type 1)
Chloromethane
Acetaldehyde
1.80E-07
Acetone
2.50E-07
2.50E-06
2.00E-07
2.00E-06
PP in breath
PP in breath
1.40E-07
1.20E-07
1.00E-07
8.00E-08
6.00E-08
4.00E-08
PP in breath
1.60E-07
1.50E-07
1.00E-07
5.00E-08
1.50E-06
1.00E-06
5.00E-07
2.00E-08
0.00E+00
0.00E+00
110
130
150
170
190
Glucose Level (mg/dL)
0.00E+00
110
210
130
150
170
190
Glucose Level (mg/dL)
HCN
Methanol
4.00E-08
3.50E-08
PP in breath
PP in breath
3.00E-08
2.50E-08
2.00E-08
1.50E-08
1.00E-08
5.00E-09
0.00E+00
110
160
210
Glucose Level (mg/mL)
110
210
5.00E-07
4.50E-07
4.00E-07
3.50E-07
3.00E-07
2.50E-07
2.00E-07
1.50E-07
1.00E-07
5.00E-08
0.00E+00
110
130
150
170
190
Glucose Level (mg/dL)
210
160
Glucose Level (mg/dL)
210
Breath Results – Subject II at high levels
Acetone
8.00E-07
• at the high blood glucose level, we
found a possible negative linear
relationship in Acetone, Acetaldehyde,
and Methanol.
7.00E-07
6.00E-07
5.00E-07
4.00E-07
Acetone
3.00E-07
Linear (Acetone)
2.00E-07
y = -1E-08x + 2E-06
R² = 0.8045
1.00E-07
0.00E+00
130 150 170 190 210 230
Acetaldehyde
9.00E-08
8.00E-08
7.00E-08
6.00E-08
5.00E-08
4.00E-08
3.00E-08
2.00E-08
1.00E-08
0.00E+00
Methanol
3.50E-07
3.00E-07
Acetaldehye
2.50E-07
2.00E-07
Linear
(Acetaldehye)
R² = 0.7229
130
150
170
190
210
230
Methanol
1.50E-07
Linear (Methanol)
1.00E-07
R² = 0.9471
5.00E-08
0.00E+00
130 150 170 190 210 230
Type 2 Diabetic
with New Cell, Strong Sorbent tube
NAME
AMOUNT IN BREATH/ppb
Methyl Cynaide
9.86±0.08
Chloromethane
0.83±0.01
Acetaldehyde
33.6±1.5
Acetone
46.7±8.2
HCN
6.99±0.02
Ethanol
33.8±2.4
Methanol
61.5±2.6
CO
13.5±0.1
Formaldehyde
71.8±0.3
Conclusion & Path Forward
Conclusion
•
We now can see 9 chemicals which are potentially related to diabetes and
blood glucose level. We successfully detected CO and Formaldehyde and
improved the sensitivity of our system by a factor of 10.
•
The blood glucose experiment is still in progress. Our preliminary results show
that there may exist a relationship between blood glucose level and
concentrations of acetone, acetaldehyde and methanol.
Path forward
•
Improve Sensitivity and extend the current chemical list.
•
•
Collect more data with the new system
Conduct a more controlled experiment on blood glucose level. (overnight fasting,
food)