Abstract: The invention relates to an apparatus for spectroscopically analysing a gas, said apparatus having at least one radiation source (1), at least one detection apparatus (12; 20), at least one sample chamber (13) and a system of optical elements (4; 5; 6; 7; 9; 10; 11; 18; 19) which is intended and set up to direct at least part (3b) of the radiation (3) emitted by the radiation source (1) through the sample chamber (13) onto the detection apparatus (20), wherein the sample chamber (13) is used to hold a gaseous sample which contains the gas to be analysed, and wherein the apparatus is configured in such a manner that the sample can continuously flow through the sample chamber (13), and means (16) are provided for the purpose of determining the pressure and/or the volume and/or the concentration of the sample in the sample chamber (13). The invention also relates to a corresponding method for spectroscopically analysing a gas.
APPARATUS FOR SPECTROSCOPICALLY ANALYSING A GAS
The invention relates to an apparatus for the
spectroscopic analysis of a gas according to the
preamble of claim 1, to a method for the spectroscopic
analysis of a gas according LO the preamble a claim 18
and to the use of an apparatus according to the
invention according to the preamble of claim 18.
The analysis of a gas has very main possible
applications, particular in medicle. The
concentration of CO2 is often studied, for example, in
the respiratory air of partients who have previously
been administered with 13C- labeled substance which are
converted by the body and lead to the porduction of
13CO2 (13C breath tests). Such studies are suitable for
example for the diagnosis of helicobacter cylori, for
measurements of the gastric emptying time ot for live
function tests.
In the prior art the concetration of CO2 is
determined by mass spectrometry, Fourie transform
infrared spectrometry or by direct irregulator chemical
analysis. The use of said techniques generatory requires
great outlay or. expensive instruments of equipment,
which cannot be used directly or the patients for this
reason, nondispersive isotope-selective infrared
spectroscopy (NDIRS) for example Fisher Analysen
Instrumente, Leipzig) and a method based on infrared
emission and absorption -LARA) are also used in the
prior art. Both methods, however, measure by relative
13CO2 concentration changes and do not all an, absointe
13CO2 concentration measurement. In the latter two
methods, an estimated total CO production itc of a
patient being examined is used as a has is for
calculating the relative 13CO2 concentration changes,
without it being possible to determine the a use total
CO2 production exactly.
The NDIRS method is sensitive enough to measure for
example the relative 13CO2. concerntration chrees in the
respiraratory air of patients, but in the event of
different carrier gas mixtures (for example O2 it
gives varying results which are therefore difficult to
evaluate and it therefore allows only very limited
resolution of the 13C metabolism owing of its slow
measurement method. The measurement accuracy of NDTRS
is likewise limited in this case, and in particular is
insufficient especially for directiy quantative
measurements such as determination of the quantative
liver-function capacity when other measurement effects
such as varying carrier gases are added (Pe i, F. , R.
M. Zagari, et al. 2003. "As internet andd intra-
laboratory comparison at 13CO breath analysis. Aliment.
Pharmacol. Ther. 17(10): '1291-97. Further, NDTRE
instruments cannot be used in a mobile fashed.
Furthermore, effectively only the 13CO2/ 12CO2 ratio is
determined owing to method limitations. The absolute
amount of 13CO2 expired per unit time can he calculated
from this with the aid of the patient's measured CO2
production rate per minute, in a single and vidual,
however, the CO, production rate can be measured
directly only with great difficulty. For calculation in
the prior art, an estimated standard value if the CO.
production rate is therefore used which is respectively
adapted to the body surface area cf the individual
(Schoeller, D. A., J. F. Schneider, at (1977).
"Clinical diagnosis with the stable isotope 13C'. in CO2
breath tests: methodology and fundamental
considerations." J. Lab. Clin. Med. 90: : 412-21,
Schoeller, D. A., P. C. Klein, et al. (198:). Fecal 13C
analysis for the detection and quartration of
intest:inal malabsorption. Limits of detector and
application to disorders of intestinal cho vigiycine
metabolism." J. Lab. Clin. Med. 97(3): 420-50. This
method leads to considerable Inaccuracy in many
clinical studies, in which the CO2 product or rate of
the individual is varied relative to the from state.
US 2004/0211905 Al describes a breath analyser in which
parts of exhaled respiratory air are introduced through
a gas exchange system into a spectrometer for analysis.
Only the relative ratio of two isotopes of a gas
relative to one another can be determind in the
analyzer, but. not the absoment concentration of one
isotope alone. Preferably notable of the related air,
rather oniy parts of it, are introduced into the
spectrometer by using the gas exchange system
US 6,186,958 describes a breath analyzer which is
designed for the online analysis cf continuously
exhaled respiratory air by using a popullatary of gas
discharge Lamps, which are respectively failled with
only one isotope of a gas to be analyzed, this analyzer-
can distinguish between indiviual isotopes of the gas.
Even by means of this analyser , however of this only
possible to determine one rotative rote of the
individual isotopes of the gas with respect to one
another. This is due in particular to the fast that the
concentration of the respiratory air to be analyzed to
a sample chamber of the analyzer cannot be determined.
It was an object of the present invention to provide and
apparatus which is suitable for determining the
absolute concentration of a gas in a gas mixture to
develop a method by means of which such determination
is carried out as well as to provide a suitable use for
an apparatus according to the invention.
This object is achieved by an apparatus naving the
features of claim 1, a method having tr e creatures of
claim 18 and the use of an apparatus a oring to the
invent ion having the features of claim 28.
Such an apparatus for the spectroscop of analysis of a
gas comprises at least, one raotation source, at least
one detection apparatus, at least one sample chamber
and a system of optical, elements, which is intended and
adapted to direct at least a part of the radiation
emitted by the radiation source through the sample
chamber onto the derection apparatus, the sample
chamber being use a to receive a gase sample which
contains the gas to be analyzed. This apparatus is
distinguished in that it is configured so that the
sample can flow continuously through the sample
chamber, and so that means are provided for determining
the pressure and/or the volume and/or the concentration
of the sample in the sample chamber.
Such means may for example to a pressure meter or a
volume meter, optionally in conjunction with a
temperature sensor.
The system of optical elemcents consists of lenses,
mirrors, filters and bean splitter no comparable
elements, their number and sequence in the beatn path of
the apparatus being freely selectable along as the
desired guiding effect is achieved. In general only as
many optical elements are used as are required for best
possible performance of the apparatus.
In a preferred configuretion of the invention, the
apparatus for the spectroscopic analysis of a gas is
configured so that essentially only absorption of a
single isotope of the gas is excited by the emitted
radiation and/or recorded by the detection apparatus.
In order to achieve this, the emittel radiation
preferably passes through a fitter which only transmits
radiation in the desired wavelengh range a narrowband
detection apparatus is futhermore, preferably used
which is particularly sensitive in the wavelength range
to be analyzed and the detection power of which is
essentially unaffected by radiation possitivly incident
with a different, wavelength. A radiation source which
only emits radiation, in a narrow wavelength range may
also preferably be used, so that essentiallyally so
absorption other than the desired absorption is
excited. The aforementioned fanctional elements may be
used individually or in any desired combination in an
apparatus according to the invention, in order to
achieve the essentially isotope-selective excitation.
In order to allow a high intermation density of the gas
analyses carried out by means of the a apparatus, the
apparatus is preferably configured so that the
spectroscopic analysis is carried of with time
resolution. To this end a radiation source which emits
pulsed light is preferably used, or a chopper which can
convert continuous radiation by interrupting the light
beam into radiation with a defined repetition rate is
positioned in the beam path.
The time resolution is preferably better than the second
and particularly preferably between 0.2 and 0.4 second
(for example 0.3 second or better). More that 3
measurements can thus be carried out per second with a
preferred alternative embodiment of the invention,
which results in fine graduation of a the profile of
the analysis being carried out.
Since} in particular molecular vibrations are intended
to be studied, the radiation source preferably emits
light, with a wavelength in the infrared range, medium
infrared being particular prefered. Medeium infrared
has a wavelength of about, 2.5 to 50 micrometer
(corresponding to 4000 to 200 cm-1).
So that pulsed radial ion with a high energy density and
brilliance is directly emitted by the radiation source,
a quantum cascade laser is preferably used.
For an application of the apparatus according to the
invention to study 13CO2 absorptions, which represents a
preferred use of the invention, a quantum cascade do laser
which emits light in a wavenumber range of about 2280
to 2230 cm2 is preferably suitable. The P branch of
13CO2 in the gas phase absorbs in this wavonumber range,
while essentially no other interfering absortions for
example by 12CO2, H2O or O2, can, be observed.
For the sensitive and specific absorption of the 13CO2
bands preferably being studied, it is preferable to use
a photovoltaic mercury cadimum telluride detector (MCT
detector) which does not require cooling with liquid
nitrogen. A detection maximum of the no detector around
2270 cm-1 is advantageous.
Since 13CO2 has only a small absorption, albeit without
interference, in the spectral range preferably being
studied, the sample chamber preferably contains a
multiplicity of mirrors which reflect the light beam
input, into the sample chamber repeatedly to and fro
inside the sample chamber. In this way, the beam path
travelled by the light beam is increased by a multiple
and the amount of gas studied is virtually increased
This method may also be applied to other substances
which only have a low extinction coefficient in the
range respectively studied.
The mirrors are preferably arranged so that the beam
path tc be traveled by the light beam inside be sample
chamber is longer than 1.5 m and up to 2.5 m or more.
The sample chamber per se, on the other hand is only a
few centimeters or decimeters large.
The sample to be studied is preferably respiratory air,
which contains the gas to be analyzed. The inspiratory
air is preferably exhaled directly into the apparatus
by an individual, so that the respiratory air is
exhaled air.
In a preferred configuration of the inventin one gas
to be analyzed is 13CO2.
The exhaled respiratory air or another sample is
preferably transferred by means of a tube, which in a
preferred configuration is heated in order to prevent
water from accumulating in the tube, and in order to
guarantee that the gas temparature remains constants. To
ensure reliable functional integrity of the apparatus,
it is preferably configured so that only specially
developed
tubes can be connected to the apparatus. Optionally, a
first adapter is to be used for the connection. If
respiratory air is to be analyzed as the sample, then
it is expedient, to provide the tube with a second
adapter in the form of a mouthpiece in order to allow
respiratory air to be blown easily into the tube.
So that the sample flowing into the sample chamber can
also leave the sample chamber again, it is preferably
provided with a gas outlet means which makes it
possible for the sample no flow out of the sample
chamber. The gas outlet means is configurer to that it
allows the sample or another substance to flow out of
the sample chamber, but does not allow the sample or
substance to flow into the sample chamber the gas
outlet means may for example be configured so that when
there is a particular pressure in the sample chamber,
it opens and allows the sample to flow out of the
sample chamber. This pressure may be only a little
higher than the normal ambient air pressure.
A method for the spectroscopic analysis of a gas
comprises the following steps introducing a sample
which contains the gas to be analyzed, into a sample
chamber by the sample flowing into the sample chamber,
the sample chamber allowing subsequent flow of the
sample out of the sample chamber direction at least a
part of radiation emitted by a radiation source through
the sample chamber onto a detection apparatus by means
of a system of optical elements for analysis of the gas
and detecting absorption of the radiation by the gas to
be analyzed by means of the defection apparatus. Such a
method is distinguished in that a variation of the
pressure and/or volume and/or concentration of the
sample in the sample chamber during the analysis is
determined by suitable means.
Preferably, essentially only absorption of a single
isotope of the gas is excited by the emitted radiation
and detected by the detection apparatus, in conjunction
with determining the pressure, volume or concentration
change of the sample in the sample chamber during the
analysis, it is thus possible to determine the absolute
concentration of an isotope of the gas.
In a preferred application of the method, the
spectroscopic analysis is carried out with time
resolution in order to obtain analytical measurement
values as a function of time, in this way, for example,
it is possible to determine concentration changes of
the gas to be analyzed over the time duration of the
analysis.
The time resolution is preferably better than 1 second
and particularly preferably between 0.2 ard 0.4 second
(for example 0.3 second or better. With such a time
resolution, even rapid metabolic processes can still be
studied accurately without entailing the risk of a
significant information loss due to averaging or non-
detection of various states owing to excessively long
measurement intervals.
Absorption of the gas to be analyzesd s preferably
detected in the medium infrared range, detection in the
wavenumber range of from 2230 to 2280 cm-1 being
particularly preferred.
In a preferred configuration of the invention, the
sample to be analyzed is exhaled respiratory air, the
gas to be analyzed preferably being 13CO2.
The respiratory air is preferably introduced into the
sample chamber using a tute, which is heated in order
to avoid condensation of gaseous constituents of the
sample on the inner wall of the tube of a accumulation
liquid constituents of the sample there, and to ensure
thermal regulation of the sample.
In a preferred configuration of the invention, the
sample flows our, of the sample chamber through an
outlet means, which prevents substances from being able
to enter the sample chamber. The outlet means thus
allows exclusive sample transport out of the sample
chamber.
The apparatus according to the invention is suitable
for the determination of a biological parameter of an
individual, a spectroscopic analysis of a gaseous
sample originating from an individual being carried out
for this determination. In particular exhaled
respiratory air may be envisaged as a gaseous sample.
The sample is analyzed outside the individuals body.
The biological parameter is preferably the functional of
an organ of the individual, function and capacity
determinations of the liver and the pancreas being
particularly preferred.
In a variant of the invention, the apparatus may also
be used to determine the concentration of an enzyme,
for example lactase, by means of analyzing the
individual's respiratory air and thus being able to
draw conclusions about enzyme deficiency states of the
individual.
In another variant of the invention, the apparatus may
also be used to determine the concentration of a
microbial species, for example a particular bacterium,
a virus or a fungus in an organ or a tissue of the
individual. This may preferably involve determining the
Helicobacter pylori concentration in the individuals
stomach.
Other advantages and details of the invention will be
explained in more detail with the aid of drawings, in
which:
Fig. 1 shows a schematic representation of the
structure of an apparatus according to the
invention for the spectroscopic analysis of the
gas,
Fig. 2 shows a diagram for the calculation of a
difference signal, based on signals which are
detected by an apparatus according to Fig. 1,
and
Fig. 3 shows a schematic representation of possible
profiles of the 13CO2 concentration in exhaled
respiratory air.
Figure 1 shows a schematic representation (not true to
scale) of an infrared spectrometer as an exemplary
embodiment of an apparatus according to the invention
for the spectroscopic analysis of a gas.
The infrared spectrometer comprises a radiation source
1 in the form of a laser or a globar and a driver 2 for
the radiation source 1, which is electronically
connected to the radation source 1. Radiation is
emitted by the radiation source 1 in the form of a
light beam 3, which has a wavelength in the medium
infrared. After in leaves the radiation source 1, the
light beam 3 initially strikes a cylindrical lens 5
which ensures parallel propagation of the light beam 3.
After a variable distance, it strikes a first lens 5
which is arranged on the same optical axis as the
cylindrical lens 4 and focuses the light beam 3 onto a
second lens 6, which is likewise arranged on the same
optical axis as the cylindrical lens 4 and the first
lens 5. The second lens 6 ensures highly collimated,
essentially parallel propagation of the ligt beam 3.
In the futher course of its propagation, the light
beam strikes a filter 7 which transmits only that part
of the light beam 3 which is intended to be used tor
the detection of a sample. In this exemplary
embodiment, the filter 7 is a narrowband infrared
filter which only transmits light, with a wavelength
corresponding to a wavenumber of about 2260 ± 20 cm-1.
A chopper 8, which is employed in particular whenever a
globar is used as the radiation source 1, is arranged
between the second lens 6 and the filter 7. While a
laser can directly emit pulsed radiation, the radiation
which is emitted by a globar is continious unpulses
radiation. Owing to the chopper 8, which is
electronically connected to the driver 2 of the
radiation source 1, the radiation emitted by a globar
can also be pulsed.
The radiation emitted by a preferably used quantum.
cascade laser has a repetition rate of 10 kHz. If a
globar is used instead or the laser, then a repetition
rate of about 10 kHz is set up bγ means of the chopper
8.
After the light beam 3 has passed through the filter 7,
it strikes a beam splitter 9 which splits the light
beam 3 into a first sub-beam 3a and a second, sub-beam
3b. The first sub-beam 3a is deviated through 90º by
the beam splitter, while the second sub-beam beam 3b
passes through the beam spliter in continution on of the
original propagation direction of the light beam 3. The
first sub-beam 3a is directed by means of a deviating
mirror 10 and a third lens 11 onto a first detetor 12,
which detects the intensity of the first sub-beam 3a.
The second sub-beam 3b is directed into a sample
chamber 13. The chamber 13 is filed with a
gaseous sample, which is supplied to the sample chamber
13 through a gas inlet 14 in the direction of the arrow
and can leave the sample chamber 13 through a gas
outlet 15 in the direction of the arrow. The gas outlet
15 is configured so that no gas can enter the sample
chamber 13 through the gas outlet. By means of a gas
flow meter 16, the volume of gas supplied to the sample
chamber 13 through the gas inlet 14 is measured so that
the quantity of gas contained in the sample chamber 13
is always accurrately know. The gas flow meter 16 is
electronically connected to a computer 17 and can
transfer the data which it acquires to the computer 17.
The sample chamber 13 contains ,a system of a plurality
of mirrors 18, which direct the second sub-beam 3b to
and fro inside the sample chamber 13 so the the
beam path of the second sub-beam 3b in the sample
chamber is lenghthened relative to the actual length
dimension of the sample chamber 13. Lastly, one, of the
mirrors 18 directs the second sub-beam 3c back out of
the sample chamber. After passing through a fourth lens
19, the second sub-beam 3b strikes a second selector 20
by which the intensity of the second sub-beam 3b is
detected.
Because the intensity ot the first sub-beam 3a, which
does not experience any at attenuation by an absorbing
substance, is always measured in parallel with the
intensity of the second sub-beam 3b which is attenuated
by the absorption oil the sample 13 in the sample
chamber, it is possible to compensate for minor
intensity differences of the radiation 3 emitted by the
radiation source 1. Measurement errors, which could
occur owing to such a minor intensity differences, can
be avoided in this way.
The first detector 12 is electronically connected to a
first lock-in amplifier 21 and to a second lock-in
amplifier 22. The second defector 20 is connected to
the second lock-in amplifier 22. The two lock-in
amplifiers 21 and 22 are used to amplify the relatively
weak intensity signals of the two suo-beams 3a and 3b
as detected by the two detectors 12 and 20. Both lock-
in amplifiers are part of an electronic component
module of the infrared spectrometer, which also
includes the driver 2 of the radiation source 1, the
chopper 8, the gas flow meter 16, the first detector
12, the second detector 20 and the computer 17.
Inside the electronic component, module, the chopper 8
is electronically connected directly to the drive 2 of
the radiation source 1, the first detector 12, the
first lock-in amplifier 21 and the second lock-in
amplifier 22. Futhermore, the first lock-in amplifier
21 and the second lock-in amplifier 22 are connected
directly to one another and to the computer 17. The
respective electronic connections are used for data
interchange and synchronization of the individual
components with one another. The computer 17 is used to
display and evaluate the acquired data.
By using pulsed light with a repetition rate of about
10 kHz, it is possible to detect lock-in-amplified
signals with a time resolution of about 0.3 second. The
advantages of such a time resolution with the explained
in more detail in the description of Figure 8.
As a filter 7 in order to determine the 13CO2 content in
a sample, a narrowband infrared filter is used which
limits the infrared component right that can pass
through the filter
to those wavelengths in which 13CO2 exhibits
characteristic absorption bands. This is preferabley the
wavelength range which corresponds in wave numbers of
from 2280 to 2230 cm-. It is also possible to use a
filter which only transmits light in a wavelength range
that corresponds to wavenumbers of from 2282 to
2250 cm-1.
The first detector 12 and the second detector 13CO2 are
both photovoltaic mercury cadmium telluride detectors
(MCT detectors) with a peak response sensitivity of 1.6
A/W. In contrast, to conventional MCT detectors, these
MCT detectors do not have to be cooled with liquid
nitrogen. Instead, the cooling is carried out by means
of a Peltier element. An average power of about N3 mW
distributed over 40 cm- for a laser as the adiation
source 1 gives a measurement signal of a few hundred
μA. The noise of each of the two lock-in amplifiers 21
and 22 lies in the pA range, and therefore an away
from the signal range. The signal can thus still be
attenuated strongly - without, entering the no range.
Assuming 13CO2 absorption with an absorption coefficient
ε = 30 m2/mol and a 13CO2 concentration of about 1.4.10-4
mol/m3 in normal ambient: air, an absorption of about
0.0042 per meter by the 13CO2 may he estimated. The beam
path in the sample chamber 13, which contains the gas,
is therefore several meters, (for example 1.5 to 2.5 m)
in order to ensure sufficient absorption of the
incident second sub-beam 3b by the 13CO2.
Compared with the prior art, the following advantages
and improvements are achieved by an apparatus according
to the invention as described in Figure 1:
It is possible to carry out measurements of the
absolute concentration of a gas per time, interval.
The concentration measurerment takes place more
rapidiy, so that faster evalution of the data is
also possible.
The data reliability is greater owing to a lower
susceptibility to fluctuations.
Concentration changes can be tracked in real-time.
The flow measurement technique allows continuous
measurement of the gas samples.
The 13CO2 concentration is measured independently of
the 13CO2 concentration.
The measurement results are independernt of most
carrier gases. Thus, carrier gases which are
employed in anesthesia may also be used as carrier
gases.
The apparatus can be used directly on a patient.
A compact design allows mobile user.
Precisely measuring the 13CO2 concentration and
obviating an estimate of the CO2 production rate
permit more accurate quantitative infecerces for
example quantitative inferences about the liver-
function capacity)
In conjunction and with reference to the infrared
spectrometer represented in Figure 1, Fiqure 2 shows a
diagram for the calculation of a difference signal SD
based on two individual signals D1 and D2, union are
detected by the first detector 12 and the second
detector 20. Numerical references refer to Fiqure 1,
while letters as references refer to Figure 2.
Only about 1% of the infrared light shore into the
sample chamber 13 as the second sub-beam 3b is absorbed
at the absorption wavelengths of 13CO2 in this signal,
an absorption change of less than 1% is intended to be
measured. This is done by measuring the signal D2 of
the first detector 12 and the signal D2 of the second
detector 20, with subsequent differencing L. Since the
two detector signals D1 and D2, are much greater than
their difference SD, only a first sub-signal S1 or S2
which covers a few percent (preferably about 2%) of the
signal D1 or D2, respectively, is used for the direct
measurement. This splitting of the signals D1, and D2
into a first sub-signal S1 aNd S2 respectively, and a
second sub-signal S3 and S4 respectively, is carried out
by using two voltage dividers ST1 and ST2.
The difference signal SD is measured usind the sub-
signals S3 and S4, which respectively cover the main
components of the detector signals D1 and D2. The two
signals S1 and SD are amplified by the first and second
lock-in amplifiers 21 and 22 respectively (or
alternatively in a one-shot measurement with integrated
preamplifiers) and converted into digital signals by an
analog-digital converter in the computer 17. The
desired measurement signal of the absoprtion the
sample chamber A = -log(D2/D1) is determined by
recording -log (11-SD/S1)= εcd-φ.
Here ε is the extinction coefficient of 13CO2, c is the
concentration and d is the beam path or the second sub-
beam 3b in the sample chamber 13. The constant
parameter φ contains structural parameters for example
the splitting ratio of the beam splitter 9 and the base
13CO2 concentration in the infrared spectrometer. The
measurement signal thus directly delivers the desired
13CO2 concentration c of the sample for known (and
constant) values ε, d and φ. For installation and
maintenance, standardization of the infrared
spectrometer may
readily be carried out with known 13CO2 concentrations.
The absorption data are correlated with the gas flow-
meter 16, so that adaptation to the concentration
differences of the sample in the sample chamber 13 can
be carried out.
This manner of data acquisition makes it possible to
utilize the high sensitivity of the first and second
detectors 12 and 20, the two lock-in amplifiers 2l and
22 and the analog-digital converter. The overall
equipment structure of the infrared spectrometer with
the sample chamber ]3 and said electronic elements as
compact, transportable and insensitive to external
effects. This further increases the range of use.
Figure 3 schematically shows two profiles of the 13CO2
concentration in exhaled respiratory air, plotted over
a time frame of a few seconds. Such profilies can be
determined by means of an apparatus according to the
invention, as represented in Figure 1.
While the 13CO2 concentration in the respiratory air of
an individual with a healthy liver, after application
of a 13C-labelled substance metabolizable to 13CO2 in the
individual's liver, rises very rapid1y after-
application of the substance and then returns to a low
level (solid curve), the 13CO2 concentration in the
respiratory air of an individual with a diseased liver-
reaches only very low vaiuos after application of the
substance, before subsequently approaching a level
which is comparable with or lower than that of the
individual with a healthy liver (dashed curve).
Depending on the nature and severity of the liver
disease, it is possible to find various curved profiles
which inter alia may be very similar to that of a
healthy liver. Only by measurement with a high time
resolution - preferably in the subsecond ange, as is
possible with an apparatus according to the invention -
can the curves represented in Figure 3 be determined
accurately enough, as represented by specifying
exemplary measurement instants A to F. If a comparable
study were to be carried out with a device which can
measure only at the measurement instants C and F, for
example owing to an inferior time resolution, then the
results integrated over the periods 0 to C and C to F
would respectively be obtained.
This would mean that discrimination between individuals
with healthy and diseased livers could only be carried
out insufficiently. This would be
the case in particular when, instead of the linear
profile of the two curves beyond the measurement
instant E as represented in Figure 3, level differences
still occur which could quite feasibly remain
undiscovered by mutual cancellation in the event of an
integrated measurement due to inferior time resolution.
The use of an apparatus according to the invention -
for example as represented in Figure 1 - will be
explained in more detail below with the aid of
application examples.
Example 1 - Use as a Breath Analyzer for Liver-Function
Determination
Although application of an apparatus according to the
invention is not restricted to breath test alone, but
instead may generally be used for the analysis of any
gas mixtures, use in breath analysis is suitable.
Thus, the liver funtion of an individual may be
determined quantitatively which an appratus according
to Figure 1. Such determination is of great importance
in many fields of medicine. Chronic liver diseases are
widespread in Europe, 8.9 million people being infected
with hepatitis C alone. These patients with progressive
disease are usually in constant medical care. In the
therapy and management of patients with chronic liver
diseases, significantly improved therapy can be carried
out by quantification of the liver function. Estimating
the liver function is crucial for making suitable
therapy decisions.
Partial liver resection is a conventional method in
modern surgery. It is carried out as a segment
resection or hemihepatectomy along the anatomical
boundaries. Extended interventions in the
parenchymatous organ have been made possible by the
development of a wide variety of operation techniques.
The postoperative morbidity and mortality due to liver
failure owing to deficient, liver-function capacity in
the event of predamaged or insufficient remaining liver
tissue is however a significant problem. A large number
of operative interventions must however be carried out
in a predamaged liver tissue, usually a ciirrhotically
altered liver.
It is therefore of great importance that a patient's
functional liver capacity can already be determined
before partial liver resection, so that patients who no
longer have a sufficient functional reserve of their
liver tissue are not exposed to the operation risk
which is too great for them, so that other therapy
methods can be carried out. Estimating the liver
function is of great, importance in liver
transplantation,
since here the organ function must be estimated
promptly and a rapid therapy decision must be made.
Here, furthermore, in many clinical situations it is
very difficult to estimate whether there is
parenchymatous function impairment or whether other
causes are responsible for the patients clinical
symptoms. To summarize, there as therefore a great need
to provide a truly quantitative liver function test for
wide application in medicine. By a breath test with for
example 13C-labeled methacetin, this is posible when
the quantity of 13CO2 exhaled per time interval in the
exhaled air can be measured absolutely ans precisely.
Previous tests could only achieve semiquantitative
results owing to unfavorable administration (orally)
and insufficient, measurement methodology (Matsumoto,
K., M. Suehiro, et al. (1987). "[l3C] methacetin breath
test for evaluation of liver damage." Dig Dis. Sci.
32(4): 344-8; Klatt, S., C. Taut, et. al. (1997 .
"Evaluation of the 13C-methacetin breth test for
quantitative liver, function testing. " Z. Gastroenterol
35(8): 609-14). With corresponding application
(intravenously), new calculation and accurate absolute
concentration measurement by means of an apparatus
according to the invention, widespreade progress in this
field is possible.
Example 2 - Use as a Breath analyzer for Determininq
other Parameters
A further application of. an apparatus according to the-
invention is to measure the gastric emptying time. The
gastric emptying time is affected by many
gastrointestinal diseases (gastroparesis). This may be
the case for example with diabetic gastropathy,
dyspepsia or other diseases. In order to measure the
gastric emptying time, a 13C-labeled test substance (for
example octanoic acid) is administered by a test meal
and the exhalation of 13CO2 is also measured. Here,
continuous measurement by means of an apparatus
according to the invention likewise offers much better-
accuracy in the analysis of the data.
13CO2 measurements have further applications in the-
diagnosis of pancreatic diseases, in the diagnosis of
Helicobacter pylori and in the diagnosis of enzyme
deficiency states (lactase deficiency etc.) (Swart, G
R. and J. W. van der, Berg (1998). 13CO2 breath test in
gastroenterological, practice. "Scand. J. Gastroenterol.
Suppl. 225: 13-8).
List of References
1 radiation source
2 driver of the radiation source
3 light beam
3a first sub-beam
3b second sub-beam
4 cylindrical lens
5 tirst lens
6 second lens
7 filter
8 chopper
9 beam splitter
10 deviating mirrcr
11 third lens
12 first detector
13 sample chamber
14 gas inlet
15 gas outlet.
16 gas flow meter
17 computer
18 mirror
19 fourth lens
2 0 second detector
21 first lock-in amplifier
22 second lock-in amplifier
D1 signal of the first detector
D2 signal of the second detector
S1 first sub-signal of the signal of the first
detector
S2 first sub-signal of the signal of the second
detector
S3 second sub-signal of the signal cf the first
detector
S4 second sub-signal of the signal of the second
detector
SD difference signal
ST1 first voltage divider
ST2 second voltage divider
New Patent Claims
A method for the spectroscopic analysis of a
flowing gas, comprising the following steps:
continuously introducing a sample, which contains
the gas to be analyzed, into a sample chamber (13)
and continuously releasing the sample from the
sample chamber (13), the gas flow through the
sample chamber (13) being measured by any means
(16) for measuring the gas flow,
directing at least a part of radiation emitted by
a radiation source (1) through the sample chamber
(13) onto a detection apparatus (12, 2) by means
of a system of optical elements for analysis of
the gas, the sample being exposed to radiation
which a wavelength in the range of from 4000 to 200
cm-1, and
detecting absorption of the radiation by the
flowing gas to be analyzed by means of the
detection apparatus (12, 20),
the time resolution of the analysis being less
than 0.3 sec.
2. The method for the spectroscopic analusis of a
gas as claimed in claim 1, characterized in that
essentially only absorption of a single isotope of the
gas is excited by the emitted radiation (3) and
recorded by the detection apparatus (12; 20).
3. The method for the spectroscopic analysis of a
gas as claimed in claim 1 or 2, characterized in that
the sample which contains the gas to be analyzed is
respiratory air.
4. The method for the spectroscopic analysis of a
gas as claimed in one of claims 1 to 3, chracterized
in that the gas to be analyzed is 13CO2.
5. The method for the spectroscopic analysis of a
gas as claimed in one of claims 1 to 4, characterized
in that, the sample is introduced into the sample
chamber (13) by means of a tube.
6. The method for the spectroscopic analysis of a
gas as claimed in one of claims 1 to 5, characterized
in that the sample is released through an outlet means
(15) which only allows substance transport out of the
sample chamber (13).
7. The method for the spectroscopic analysis of a
gas as claimed in one of claims 1 to 6, characterized
in that the radiation source (1) and/or at least one of
the optical elements are configured for isotope-
selective excitation cf the absorption of the gas.
8. The method for the spectroscopic analysis of a
gas as claimed in one of claims 1 to 7, characterized
in that the detection apparatus (12, 20) and/or at
least one of the optical elements are configured for
isotope-selective detection of the absorption of the
gas.
9. The method for the spectroscopic analysis of a
gas as claimed in one of claims 1 to 8, characterized
in that the radiation source (1) is a quantum cascade
laser, in particular with a repetition rate of 10 kHz.
10. The method for the spectroscopic analysis of a
gas as claimed in one of claims 1 to 9, characterized
in that the detection apparatus (12, 20) is a
photovoltaic MCT detector.
11. The method for the spectroscopic analysis of a
gas as claimed in one of claims 1 to 10, characterized
in that, the gas is analyzed in real time.
12. The method for the spectroscopic analysis of a
gas as claimed in one of claims 1 to 11, characterized
in that the sample is exposed to radiation in the
wavelength range of from 2280 to 2230 cm-1.
13. The method for the spectroscopic analysis of a
gas as claimed in one of claims 1 to 12, chracterized
in that the absolute concentration and total amount of
an isotope or a gas is determined per time interval by
rhe means (16) for measuring the gas flow.
14. The method as claimed claim 13, chracterized
in that the 13CO2 concentration or total 13CO2.
concentration and 13CO2 concentration or total amount of
13CO2 are determined independently of one another.
15. The method as claimed in one of the preceding
claims, usable for the determination of a biogical
parameter of an individual, the gaseous sample to be
analyzed originating from the individual and the
biological parameter being the function of an organ of
the individual, the concentration of an enzyme in an
organ and/or tissue of the individual, or the
concentration of at least, and microbial species in an
organ and/or tissue of the individual.
The invention relates to an apparatus for spectroscopically analyzing a gas, said apparatus having at least one radiation source (1), at least one detection apparatus (12; 20), at least one sample chamber (13) and a system of optical elements (4; 5; 6; 7; 9; 10; 11; 18; 19) which is intended an set up to direct at least part (3b) of the radiation (3) emitted by the radiation source (1) through the sample chamber (13) onto the detection apparatus (20), wherein the sample chamber (13) is used to hold a gaseous sample which contains the gas to be analysed, and wherein the apparatus is configured in such a manner that the sample can continuously flow through the sample chamber (13), and means (16) are provided for the purpose of determining the pressure and/or the volume and/or the concentration of the sample in the sample chamber (13). The invention also relates to a corresponding method for spectroscopically analyzing a gas.
| Section | Controller | Decision Date |
|---|---|---|
| # | Name | Date |
|---|---|---|
| 1 | abstract-4222-kolnp-2008.jpg | 2011-10-08 |
| 1 | Other Document [05-09-2016(online)].pdf | 2016-09-05 |
| 2 | 4222-kolnp-2008-specification.pdf | 2011-10-08 |
| 2 | Petition Under Rule 137 [05-09-2016(online)].pdf | 2016-09-05 |
| 3 | 4222-KOLNP-2008_EXAMREPORT.pdf | 2016-06-30 |
| 3 | 4222-kolnp-2008-pct request form.pdf | 2011-10-08 |
| 4 | 4222-KOLNP-2008-PA.pdf | 2011-10-08 |
| 4 | 4222-KOLNP-2008-(22-04-2016)-CORRESPONDENCE.pdf | 2016-04-22 |
| 5 | 4222-KOLNP-2008-PA 1.1.pdf | 2011-10-08 |
| 5 | 4222-KOLNP-2008-(22-04-2016)-FORM-1.pdf | 2016-04-22 |
| 6 | 4222-KOLNP-2008-INTERNATIONAL SEARCH REPORT.pdf | 2011-10-08 |
| 6 | 4222-KOLNP-2008-(22-04-2016)-FORM-13.pdf | 2016-04-22 |
| 7 | 4222-kolnp-2008-international publication.pdf | 2011-10-08 |
| 7 | 4222-KOLNP-2008-(22-04-2016)-FORM-5.pdf | 2016-04-22 |
| 8 | 4222-KOLNP-2008-INTERNATIONAL EXM REPORT.pdf | 2011-10-08 |
| 8 | 4222-KOLNP-2008-(22-04-2016)-OTHERS.pdf | 2016-04-22 |
| 9 | 4222-KOLNP-2008-(18-04-2016)-CORRESPONDENCE.pdf | 2016-04-18 |
| 9 | 4222-kolnp-2008-form 5.pdf | 2011-10-08 |
| 10 | 4222-KOLNP-2008-(16-03-2016)-CORRESPONDENCE.pdf | 2016-03-16 |
| 10 | 4222-kolnp-2008-form 3.pdf | 2011-10-08 |
| 11 | 4222-KOLNP-2008-(01-06-2015)-CORRESPONDENCE.pdf | 2015-06-01 |
| 11 | 4222-kolnp-2008-form 2.pdf | 2011-10-08 |
| 12 | 4222-KOLNP-2008-(01-06-2015)-OTHERS.pdf | 2015-06-01 |
| 12 | 4222-KOLNP-2008-FORM 18.pdf | 2011-10-08 |
| 13 | 4222-KOLNP-2008-(10-02-2014)-ANNEXURE TO FORM 3.pdf | 2014-02-10 |
| 13 | 4222-kolnp-2008-form 13.pdf | 2011-10-08 |
| 14 | 4222-KOLNP-2008-(10-02-2014)-CLAIMS.pdf | 2014-02-10 |
| 14 | 4222-kolnp-2008-form 1.pdf | 2011-10-08 |
| 15 | 4222-KOLNP-2008-(10-02-2014)-CORRESPONDENCE-1.pdf | 2014-02-10 |
| 15 | 4222-kolnp-2008-drawings.pdf | 2011-10-08 |
| 16 | 4222-KOLNP-2008-(10-02-2014)-CORRESPONDENCE.pdf | 2014-02-10 |
| 16 | 4222-kolnp-2008-description (complete).pdf | 2011-10-08 |
| 17 | 4222-kolnp-2008-correspondence.pdf | 2011-10-08 |
| 17 | 4222-KOLNP-2008-(10-02-2014)-FORM-1.pdf | 2014-02-10 |
| 18 | 4222-KOLNP-2008-(10-02-2014)-FORM-5.pdf | 2014-02-10 |
| 18 | 4222-KOLNP-2008-CORRESPONDENCE 1.1.pdf | 2011-10-08 |
| 19 | 4222-KOLNP-2008-(10-02-2014)-OTHERS-1.pdf | 2014-02-10 |
| 19 | 4222-kolnp-2008-claims.pdf | 2011-10-08 |
| 20 | 4222-KOLNP-2008-(10-02-2014)-OTHERS.pdf | 2014-02-10 |
| 20 | 4222-kolnp-2008-abstract.pdf | 2011-10-08 |
| 21 | 4222-KOLNP-2008-(10-02-2014)-PETITION UNDER RULE 137.pdf | 2014-02-10 |
| 21 | 4222-KOLNP-2008-(27-11-2013)-ENGLISH TRANSLATION.pdf | 2013-11-27 |
| 22 | 4222-KOLNP-2008-(27-11-2013)-CORRESPONDENCE.pdf | 2013-11-27 |
| 23 | 4222-KOLNP-2008-(10-02-2014)-PETITION UNDER RULE 137.pdf | 2014-02-10 |
| 23 | 4222-KOLNP-2008-(27-11-2013)-ENGLISH TRANSLATION.pdf | 2013-11-27 |
| 24 | 4222-kolnp-2008-abstract.pdf | 2011-10-08 |
| 24 | 4222-KOLNP-2008-(10-02-2014)-OTHERS.pdf | 2014-02-10 |
| 25 | 4222-kolnp-2008-claims.pdf | 2011-10-08 |
| 25 | 4222-KOLNP-2008-(10-02-2014)-OTHERS-1.pdf | 2014-02-10 |
| 26 | 4222-KOLNP-2008-(10-02-2014)-FORM-5.pdf | 2014-02-10 |
| 26 | 4222-KOLNP-2008-CORRESPONDENCE 1.1.pdf | 2011-10-08 |
| 27 | 4222-KOLNP-2008-(10-02-2014)-FORM-1.pdf | 2014-02-10 |
| 27 | 4222-kolnp-2008-correspondence.pdf | 2011-10-08 |
| 28 | 4222-KOLNP-2008-(10-02-2014)-CORRESPONDENCE.pdf | 2014-02-10 |
| 28 | 4222-kolnp-2008-description (complete).pdf | 2011-10-08 |
| 29 | 4222-KOLNP-2008-(10-02-2014)-CORRESPONDENCE-1.pdf | 2014-02-10 |
| 29 | 4222-kolnp-2008-drawings.pdf | 2011-10-08 |
| 30 | 4222-KOLNP-2008-(10-02-2014)-CLAIMS.pdf | 2014-02-10 |
| 30 | 4222-kolnp-2008-form 1.pdf | 2011-10-08 |
| 31 | 4222-KOLNP-2008-(10-02-2014)-ANNEXURE TO FORM 3.pdf | 2014-02-10 |
| 31 | 4222-kolnp-2008-form 13.pdf | 2011-10-08 |
| 32 | 4222-KOLNP-2008-(01-06-2015)-OTHERS.pdf | 2015-06-01 |
| 32 | 4222-KOLNP-2008-FORM 18.pdf | 2011-10-08 |
| 33 | 4222-KOLNP-2008-(01-06-2015)-CORRESPONDENCE.pdf | 2015-06-01 |
| 33 | 4222-kolnp-2008-form 2.pdf | 2011-10-08 |
| 34 | 4222-KOLNP-2008-(16-03-2016)-CORRESPONDENCE.pdf | 2016-03-16 |
| 34 | 4222-kolnp-2008-form 3.pdf | 2011-10-08 |
| 35 | 4222-KOLNP-2008-(18-04-2016)-CORRESPONDENCE.pdf | 2016-04-18 |
| 35 | 4222-kolnp-2008-form 5.pdf | 2011-10-08 |
| 36 | 4222-KOLNP-2008-INTERNATIONAL EXM REPORT.pdf | 2011-10-08 |
| 36 | 4222-KOLNP-2008-(22-04-2016)-OTHERS.pdf | 2016-04-22 |
| 37 | 4222-kolnp-2008-international publication.pdf | 2011-10-08 |
| 37 | 4222-KOLNP-2008-(22-04-2016)-FORM-5.pdf | 2016-04-22 |
| 38 | 4222-KOLNP-2008-INTERNATIONAL SEARCH REPORT.pdf | 2011-10-08 |
| 38 | 4222-KOLNP-2008-(22-04-2016)-FORM-13.pdf | 2016-04-22 |
| 39 | 4222-KOLNP-2008-PA 1.1.pdf | 2011-10-08 |
| 39 | 4222-KOLNP-2008-(22-04-2016)-FORM-1.pdf | 2016-04-22 |
| 40 | 4222-KOLNP-2008-PA.pdf | 2011-10-08 |
| 40 | 4222-KOLNP-2008-(22-04-2016)-CORRESPONDENCE.pdf | 2016-04-22 |
| 41 | 4222-KOLNP-2008_EXAMREPORT.pdf | 2016-06-30 |
| 41 | 4222-kolnp-2008-pct request form.pdf | 2011-10-08 |
| 42 | 4222-kolnp-2008-specification.pdf | 2011-10-08 |
| 42 | Petition Under Rule 137 [05-09-2016(online)].pdf | 2016-09-05 |
| 43 | abstract-4222-kolnp-2008.jpg | 2011-10-08 |
| 43 | Other Document [05-09-2016(online)].pdf | 2016-09-05 |