U.S. patent number RE31,879 [Application Number 06/403,121] was granted by the patent office on 1985-05-07 for method and arrangement for measuring the concentration of gases.
This patent grant is currently assigned to Max-Planck-Gesellschaft zur Forderung der Wissenschaften e.V.. Invention is credited to Dietrich W. Lubbers, Norbert Opitz.
United States Patent |
RE31,879 |
Lubbers , et al. |
May 7, 1985 |
Method and arrangement for measuring the concentration of gases
Abstract
A method and an arrangement for measuring the concentration of
gases in a sample includes the generation of a monochromatic light
beam having predetermined color characteristic. An indicator
generates light signals indicative of the concentration of the
gases in a sample to be measured and includes a light-transmissive
surface positioned to be impinged by the monochromatic light beam,
a diffusion membrane adapted to be placed in the proximity of a
sample and being permeable to a selected gas component thereof, and
an indicating substance positioned to be impinged by the
monochromatic light beam penetrating the light-transmissive surface
and by the gas component penetrating the diffusion membrane. The
indicating substance reacts when illuminated by the incident
monochromatic light by emitting a resultant light beam having an
emitted component which has a color characteristic different from
the predetermined color characteristic of the monochromatic light
beam. The resultant light beam is conducted away from the
indicating substance through the light-transmissive surface.
Finally, the emitted component is discriminated from the resultant
light beam so that the change in the color characteristic of the
indicating substance can be measured and correlated with the
concentration of gases in the sample.
Inventors: |
Lubbers; Dietrich W. (Dortmund,
DE), Opitz; Norbert (Dortmund, DE) |
Assignee: |
Max-Planck-Gesellschaft zur
Forderung der Wissenschaften e.V. (Munich, DE)
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Family
ID: |
5940013 |
Appl.
No.: |
06/403,121 |
Filed: |
July 29, 1982 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
Issue Date |
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2184 |
Jan 8, 1979 |
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Reissue of: |
661636 |
Feb 26, 1976 |
04003707 |
Jan 18, 1977 |
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Foreign Application Priority Data
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Feb 25, 1976 [DE] |
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2508637 |
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Current U.S.
Class: |
436/133; 422/562;
422/82.07; 422/86; 432/163; 432/172; 600/310; 600/367; 600/476 |
Current CPC
Class: |
G01N
21/643 (20130101); Y10T 436/255 (20150115); Y10T
436/204998 (20150115); G01N 2021/6434 (20130101) |
Current International
Class: |
G01N
21/64 (20060101); G01N 021/64 (); G01N 021/79 ();
G01N 033/84 () |
Field of
Search: |
;422/55-58,85-88,90,91
;356/39,40 ;128/633,636,665 ;436/133,163,172 |
References Cited
[Referenced By]
U.S. Patent Documents
Foreign Patent Documents
Other References
Fluorescence Analysis, White et al., pp. 102-115, 298-305, 1970.
.
Fluorescence Assay in Biology and Medicine, Undenfriend et al., pp.
30, 31, 58, 159, 484, 485, 488-491, 1969. .
Oxygen Quenching of Pyrenebutyric Acid Fluorescence in Water,
Vaughan et al., pp. 464-473, Biochemistry (9) (3) Feb. 3,
1970..
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Primary Examiner: Marcus; Michael S.
Attorney, Agent or Firm: Peterson; Gordon L.
Parent Case Text
.Iadd.This application is a continuation of application Ser. No.
2,184, filed Jan. 8, 1979 abandoned. .Iaddend.
Claims
We claim: .[.1. A method of measuring the concentration of gases in
a sample comprising the steps of generating a monochromatic light
beam having a predetermined color characteristic; generating light
signals indicative of the concentration of gases in a sample to be
measured by positioning an indicator having a light-transmissive
surface positioned to be impinged by said monochromatic light beam,
a diffusion membrane adapted to be placed in the proximity of a
sample and being selectively permeable to a gas component thereof,
and an indicating substance positioned to be impinged by the
monochromatic light beam penetrating said light-transmissive
surface and by said gas component penetrating said diffusion
membrane, said indicating substance reacting when illuminated by
said incident monochromatic light beam by emitting a resultant
light beam having an emitted component which has a color
characteristic different from said predetermined color
characteristic; conducting said resultant light beam away from said
indicating substance through said light-transmissive surface; and
discriminating said emitted component from said resultant light
beam so that the change in the color characteristic of said
indicating substance can be measured and correlated with the
concentration of gases in the sample..]. .[.2. In an arrangement
for measuring the concentration of gases in a sample, a combination
comprising means for generating a monochromatic light beam having a
predetermined color characteristic; indicating means for generating
light signals indicative of the concentration of gases in a sample
to be measured, including a light-transmissive surface positioned
to be impinged by said monochromatic light beam, a diffusion
membrane adapted to be placed in proximity of a sample and being
permeable to a selected gas component thereof, and an indicating
substance positioned to be impinged by said monochromatic light
beam penetrating said light-transmissive surface and by said gas
component penetrating said diffusion membrane, said indicating
substance reacting when illuminated by said incident monocrhomatic
light beam by emitting a resultant light beam having an emitted
component which has a color characteristic different from said
predetermined color characteristic; means for conducting said
resultant light beam away from said indicating substance through
said light-transmissive surface; and means for discriminating said
emitted component from said resultant light beam so that the change
in the color characteristic of said indicating substance can be
measured and correlated with the concentration of gases in the
sample..]. .[.3. The arrangement of claim 2, wherein said
indicating substance is sealingly embedded throughout said
diffusion
membrane..]. 4. The arrangement of claim .[.2.]. .Iadd.33.Iaddend.;
and further comprising means for controlling the temperature of a
sample. .[.5. The arrangement of claim 2, wherein the indicating
substance is
.beta.-methyl-umbelliferon..]. 6. The arrangement of claim .[.2.].
.Iadd.33.Iaddend., wherein the indicating substance is
Pyrene-butyric
acid. 7. The arrangement of claim .[.2.]. .Iadd.33.Iaddend.; and
further comprising additional indicating substances intermixed with
said first-mentioned indicating substance. .[.8. The arrangement of
claim 2; and further comprising a reflecting wall located behind
said membrane..]. .[.9. The arrangement of claim 2; and further
comprising an absorption
wall located behind said membrane..]. 10. The arrangement of claim
.[.2.]. .Iadd.33.Iaddend., wherein sid discriminating means
comprises filtering means for permitting substantially only said
emitted light to pass
through. 11. The arrangement of claim .[.2.]. .Iadd.33.Iaddend.,
wherein said indicating means is comprised of a plurality of
particles, each
comprising said indicating substance and said diffusion membrane.
12. The arrangement of claim .[.2.]. .Iadd.33.Iaddend.; and further
comprising additional indicating means adjacent said
first-mentioned indicating means, said additional indicating means
having a diffusion membrane selectively permeable to another gas
component and an indicating substance
which reacts with the latter. 13. The arrangement of claim 12,
wherein the diffusion membrane of said first-mentioned indicating
means is substantially permeable to oxygen; and wherein the
diffusion membrane of said additional indicating means is
substantially permeable to
carbondioxide. 14. The arrangement of claim .[.2.].
.Iadd.33.Iaddend.; wherein said means for generating said
monochromatic light beam includes a light-conductive cable for
directing said monochromatic light beam towards said indicating
means; and wherein said conducting means comprises another
light-conductive cable for directing said resultant light beam away
from
said indicating means. 15. The arrangement of claim 14; and further
comprising additional indicating means located adjacent said
first-mentioned indicating means; and wherein said monochromatic
light beam comprises two monochromatic components, each being
directed by said
one light-conductive cable towards said respective indicating
means. 16. The arrangement of claim 15, and wherein both said
indicating means respectively emit emitted light components, each
being conducted by said other light-conductive cable towards said
discrimination means so that
each emitted light component is individually measured. 17. The
arrangement of claim .[.2.]. .Iadd.33.Iaddend.; and further
comprising a portable housing containing said means for generating
a monochromatic light beam and said discrimination means for
transporting the measuring arrangement
to a sample. 18. The arrangement of claim 17, wherein said
indicating
means is interchangeably mounted in said housing. 19. The
arrangement of claim 17; and further comprising additional
measuring electrodes mounted
in said housing. 20. The arrangement of claim .[.2.].
.Iadd.34.Iaddend., wherein said light-transmissive surface is
planar and constitutes an upper layer, and wherein said indicating
substance is generally located in a
plane intermediate said upper layer and said diffusion membrane.
21. The arrangement of claim .[.20.]. .Iadd.34.Iaddend., wherein
said indicating substance is arranged in a dichroic layer having
one side which absorbs said monochromatic light beam. .[.22. The
arrangement of claim 20, wherein said membrane has a reflective
layer on its side facing said indicating substance..]. .[.23. The
arrangement of claim 20 wherein said membrane has
an absorbing layer on its side facing said indicating substance..].
24. The arrangement of claim .[.2.]. .Iadd.33.Iaddend., wherein
said means for generating a monochromatic light beam includes means
for modifying the latter into a plurality of separate monochromatic
components, each monochromatic component being directed towards
said indicating substance.
5. The arrangement of claim 24, wherein said modifying means
comprises a plurality of monochromatic filters, each positioned to
be impinged by said
monochromatic light beam. 26. The arrangement of claim 24, wherein
said conducting means comprises a plurality of light-reflective
elements, each
positioned to be impinged by said emitted light component. 27. The
arrangement of claim 26, wherein said discriminating means
processes each
of said emitted light components. .Iadd.28. A method of measuring
at least the pH value of a sample comprising the steps of
generating a light beam having a predetermined color
characteristic; generating light signals indicative of the pH value
of a sample to be measured by positioning an indicator having a
light-transmissive surface positioned to be impinged by said light
beam, a diffusion membrane adapted to be placed in the proximity of
a sample and being selectively permeable to a component of the
sample which will allow a pH measurement of the sample to be made,
and a pH indicating substance which is capable of fluorescing
positioned to be impinged by the light beam penetrating said
light-transmissive surface and by said component penetrating said
diffusion membrane, said pH indicating substance responding when
illuminated by said incident light beam by emitting a resultant
light beam having a fluorescent emitted component which has a color
characteristic different from said predetermined color
characteristic and is related to the pH value of the sample;
conducting said resultant light beam away from said indicating
substance through said light-transmissive surface; and
discriminating said emitted component from said resultant light
beam so that the change in the color characteristic of said
indicating substance can be measured and correlated with the pH
value of the sample. .Iaddend. .Iadd.29. A method as defined in
claim 28 wherein said sample is blood. .Iaddend. .Iadd.30. A method
as defined in claim 28 wherein the pH indicating substance is
beta-methyl-umbelliferon. .Iaddend. .Iadd.31. A method of measuring
the concentration of carbon dioxide in a sample comprising the
steps of generating a light beam having a predetermined color
characteristic; generating light signals from which the
concentration of carbon dioxide in a sample to be measured can be
determined by positioning an indicator having a light-transmissive
surface positioned to be impinged by said light beam, a diffusion
membrane adapted to be placed in the proximity of a sample and
being selectively permeable to at least a carbon dioxide component
thereof, and an indicating substance which is capable of
fluorescing positioned to be impinged by the light beam penetrating
said light-transmissive surface and by said carbon dioxide
component penetrating said diffusion membrane, said indicating
substance responding when illuminated by said incident light beam
by emitting a resultant light beam having a fluorescent emitted
component which has a color characteristic different from said
predetermined color characteristic and is related to the
concentration of carbon dioxide in the sample; conducting said
resultant light beam away from said indicating substance through
said light-transmissive surface; discriminating said emitted
component from said resultant light beam so that the change in the
color characteristic of said indicating substance can be
ascertained; and correlating the changes in the color
characteristic with the concentration
of carbon dioxide in the sample. .Iaddend. .Iadd.32. A method as
defined in claim 31 wherein said indicating substance includes a pH
indicating substance. .Iaddend. .Iadd.33. In an arrangement for
measuring the concentration of gases in a sample, a combination
comprising means for generating a monochromatic light beam having a
predetermined color characteristic; indicating means for generating
light signals indicative of the concentration of gases in a sample
to be measured, including a light transmissive surface positioned
to be impinged by said monochromatic light beam, a diffusion
membrane of silicone adapted to be placed in proximity of a sample
and being permeable to a selected gas component thereof, and an
indicating substance sealingly embedded throughout said diffusion
membrane and positioned to be impinged by said monochromatic light
beam penetrating said light-transmissive surface and by said gas
component penetrating said diffusion membrane, said indicating
substance reacting when illuminated by said incident monochromatic
light beam by emitting a resultant light beam having an emitted
component which has a color characteristic different from said
predetermined color characteristic; means for conducting said
resulting light beam away from said indicating substance through
said light transmissive surface; and means for discriminating said
emitted component from said resultant light beam so that the change
in the color characteristic of said indicating substance can be
measured and correlated with the concentration of gases
in the sample. .Iaddend. .Iadd.34. In an arrangement for measuring
the concentration of carbon dioxide in a sample, a combination
comprising means for generating a light beam having a predetermined
color characteristic; indicating means for generating light signals
from which the concentration of carbon dioxide in a sample to be
measured can be determined, including a light transmissive surface
positioned to be impinged by said light beam, a diffusion membrane
adapted to be placed in proximity of a sample and being permeable
to at least a carbon dioxide component thereof, and an indicating
substance which is capable of fluorescing positioned to be impinged
by said light beam penetrating said light-transmissive surface and
by said carbon dioxide component penetrating said diffusion
membrane, said indicating substance responding when illuminated by
said incident light beam by emitting a resultant light beam having
a fluorescent emitted component which has a color characteristic
different from said predetermined color characteristic and is
related to the concentration of carbon dioxide in the sample; means
for conducting said resulting light beam away from said indicating
substance through said light transmissive surface; means for
discriminating said emitted component from said resultant light
beam so that the change in the color characteristic of said
indicating substance can be ascertained and means for correlating
the change in the color characteristic with the concentration of
carbon dioxide in the sample. .Iaddend. .Iadd.35. A method as
defined in claim 34 wherein said indicating substance includes
a
pH indicating substance. .Iaddend. .Iadd.36. In an arrangement for
measuring at least one of the characteristics of a sample wherein
the sample characteristics consist essentially of the pH value and
the concentration of gases in the sample, a combination comprising
means for generating a light beam having a predetermined color
characteristic; indicating means for generating light signals
indicative of the sample characteristic to be measured, including a
light transmissive surface positioned to be impinged by said light
beam, a selectively permeable diffusion membrane of silicone
adapted to be placed in proximity of a sample and being permeable
to a component thereof, and an indicating substance in said
diffusion membrane and positioned to be impinged by said light beam
penetrating said light-transmissive surface and by said component
penetrating said diffusion membrane, said indicating substance
being capable of fluorescing and reacting when illuminated by said
incident light beam by emitting a resultant light beam having a
fluorescent emitted component which has a color characteristic
different from said predetermined color characteristic; means for
conducting said resultant light beam away from said indicating
substance through said light transmissive surface; and means for
discriminating said emitted component from said resultant light
beam so that the change in the color characteristic of said
indicating substance can be measured and correlated
with the sample characteristic to be measured. .Iaddend. .Iadd.37.
An arrangement as defined in claim 36 wherein the indicating
substance is mixed with the membrane. .Iaddend. .Iadd.38. An
arrangement as defined in claim 36 including an absorption surface
facing said indicating substance and being between the indicating
substance and the sample. .Iaddend. .Iadd.39. An arrangement as
defined in claim 36 including a reflective surface facing said
indicating substance and being between the indicating substance and
the sample. .Iaddend. .Iadd.40. An arrangement as defined in claim
36 wherein said indicating substance is sealingly embedded
throughout said diffusion membrane. .Iaddend. .Iadd.41. An
arrangement as defined in claim 40 wherein the membrane includes a
polymer and said polymer is mixed with the indicating substance.
.Iaddend. .Iadd.42. An arrangement as defined in claim 36 wherein
said membrane is permeable to a component of the sample which will
allow a pH measurement of the blood to be made and said indicating
substance is a pH indicating substance.
.Iaddend. .Iadd.43. An arrangement as defined in claim 42 wherein
said indicating substance is sealingly embedded throughout said
diffusion membrane and said membrane includes a polymer and said
polymer is mixed with the indicating substance. .Iaddend. .Iadd.44.
An arrangement as defined in claim 36 wherein said membrane is
permeable to at least a carbon dioxide component of the sample and
said predetermined color characteristic is related to the
concentration of carbon dioxide in the sample. .Iaddend. .Iadd.45.
An arrangement as defined in claim 44 wherein said indicating
substance is sealingly embedded throughout said diffusion membrane
and said membrane includes a polymer and said polymer is mixed
with the indicating substance. .Iaddend. .Iadd.46. In an
arrangement for measuring the concentration of gases in a sample, a
combination comprising means for generating a monochromatic light
beam having a predetermined color characteristic; indicating means
for generating light signals indicative of the concentration of
gases in a sample to be measured, including a light transmissive
surface positioned to be impinged by said monochromatic light beam,
a diffusion membrane adapted to be placed in proximity of a sample
and being permeable to a selected gas component thereof, and an
indicating substance sealingly embedded throughout said diffusion
membrane and positioned to be impinged by said monochromatic light
beam penetrating said light-transmissive surface and by said gas
component penetrating said diffusion membrane, said indicating
substance reacting when illuminated by said incident monochromatic
light beam by emitting a resultant light beam having an emitted
component which has a color characteristic different from said
predetermined color characteristic; means for conducting said
resulting light beam away from said indicating substance through
said light transmissive surface; and means for discriminating said
emitted component from said resultant light beam so that the change
in the color characteristic of said indicating substance can be
measured and correlated with the concentration of gases in the
sample, said indicating substance being
betamethyl-umbelliferone.
.Iaddend. .Iadd.47. In an apparatus for measuring at least one of
the characteristics of blood within a body wherein the sample
characteristics consist essentially of the pH value and the
concentration of gases in the blood, a combination comprising:
means for generating a light beam having a predetermined color
characteristic;
a catheter receivable in a vein or artery and having a distal end,
said catheter including indicating means for generating light
signals indicative of the sample characteristic to be measured and
a light-conductive cable means having an input end for conducting
the light beam from the input end to the indicating means;
said indicating means including a light-transmissive surface
positioned to be impinged by said light beam, a diffusion membrane
permeable to a selected component of the blood, and an indicating
substance which fluoresces positioned to be impinged by said light
beam penetrating said light-transmissive surface and by said
component penetrating said diffusion membrane, each of said
light-transmissive surface, diffusion membrane and indicating
substance being near said distal end of said catheter, said
indicating substance being in said diffusion membrane and
responding when illuminated by said incident light beam by emitting
a resultant light beam having a fluorescent emitted component which
has a predetermined color characteristic different from said
predetermined color characteristic, said catheter including light
conductive cable means for conducting said resulting light beam
away from said indicating substance; and
means for discriminating said emitted component from said resultant
light beam received from said last-mentioned light conductive cable
means so that the change in the predetermined color characteristic
of said indicating substance can be measured and correlated with
the sample characteristic to be measured. .Iaddend. .Iadd.48. An
apparatus as defined in claim 47 wherein the membrane includes a
polymer and said polymer is
mixed with the indicating substance. .Iaddend. .Iadd.49. An
apparatus as defined in claim 47 wherein the membrane includes
silicone. .Iaddend. .Iadd.50. In an apparatus for measuring at
least one of the characteristics of blood within a body wherein the
sample characteristics consist essentially of the pH value and the
concentration of gases in the blood, a combination comprising:
means for generating a light beam having a predetermined color
characteristic;
a catheter receivable in a vein or artery and having a distal end,
said catheter including indicating means for generating light
signals indicative of the sample characteristic to be measured and
a light-conductive cable means having an input end for conducting
the light beam from the input end to the indicating means;
said indicating means including a light-transmissive surface
positioned to be impinged by said light beam, a diffusion membrane
permeable to a selected component of the blood, and an indicating
substance which fluoresces positioned to be impinged by said light
beam penetrating said light-transmissive surface and by said
component penetrating said diffusion membrane, each of said
light-transmissive surface, diffusion membrane and indicating
substance being near said distal end of said catheter, said
indicating substance responding when illuminated by said incident
light beam by emitting a resultant light beam having a fluorescent
emitted component which has a predetermined color characteristic
different from said predetermined color characteristic, said
catheter including light conductive cable means for conducting said
resulting light beam away from said indicating substance; and
means for discriminating said emitted component from said resultant
light beam received from said last-mentioned light conductive cable
means so that the change in the predetermined color characteristic
of said indicating substance can be measured and correlated with
the sample characteristic to be measured. .Iaddend. .Iadd.51. An
apparatus for measuring at least one of the characteristics of
blood within a body wherein the sample characteristics consist
essentially of the pH value and the concentration of gases in the
blood, the apparatus is adapted to receive a light beam having a
predetermined color characteristic and is coupled to provide an
optical signal to discriminating means, said apparatus
comprising:
indicating means for generating light signals indicative of the
sample characteristic to be measured;
a light-conductive cable means having an input end for receiving
the light beam and conducting the light beam to the indicating
means;
said indicating means including a light-transmissive surface
positioned to be impinged by said light beam, a diffusion membrane
permeable to a selected component of the blood, an indicating
substance which fluoresces positioned to be impinged by said light
beam penetrating said light-transmissive surface and by said
component penetrating said diffusion membrane, said apparatus being
receivable in a vein or artery and having a distal end, each of
said light-transmissive surface, diffusion membrane and indicating
substance being near said distal end of said apparatus, said
indicating substance responding when illuminated by said incident
light beam by emitting a resultant light beam having a fluorescent
emitted component which has a color characteristic different from
said predetermined color characteristic; and
1ight conductive cable means for conducting said resulting light
beam away from said indicating substance to the light
discriminating means whereby the light discriminating means can
discriminate said emitted component from said resultant light beam
so that the change in the color characteristic of said indicating
substance can be measured and correlated with the sample
characteristic to be measured. .Iaddend. .Iadd.52. An apparatus as
defined in claim 51 wherein said membrane is permeable to a
component of the blood which will allow a pH measurement of the
blood to be made and said indicating substance is a pH indicating
substance. .Iaddend. .Iadd.53. An apparatus as defined in claim 51
wherein said membrane is permeable to at least a carbon dioxide
component of the blood and said predetermined color characteristic
is related to the concentration of carbon dioxide in the blood.
.Iaddend. .Iadd.54. An apparatus as defined in claim 51 including
an absorption surface facing said indicating substance and being
between the indicating substance and the blood. .Iaddend. .Iadd.55.
An apparatus as defined in claim 51 including a reflective surface
facing said indicating substance and being between the indicating
substance and the blood. .Iaddend.
Description
BACKGROUND OF THE INVENTION
The present invention relates generally to a method and an
arrangement for measuring the concentration of gases in a sample
and, more particularly, to a method and an arrangement which
optically measures the concentration of oxygen and carbon dioxide
dissolved in blood.
It is known in the prior art to provide test cells filled with an
indicating substance which reacts with a gas component to be
measured in a sample by emitting a fluorescent-type light beam when
the indicating substance is illuminated by monochromatic light.
When the concentration or distribution of the gas component
changes, the indicating substance changes its color characteristic
and intensity. In turn this difference in intensity is measured by
a light-measuring device. Fluorescent-type indicators are popular
because it is relatively simple to filter the fluorescent-type
component, thus making possible a high signal-to-noise ratio.
However, fluroescent-type indicators have not been successfully
used to measure gases dissolved in the blood stream, because, for
example, albumin in the blood interferes with the reaction of the
indictor substance.
Thus, the prior art proposed various electrode techniques to
measure the concentration of gases. However, such
electrode-measuring techniques are possessed of many disadvantages.
For example, in the measurement of the partial pressure of oxygen,
the polarization-type electrodes must be constituted of very pure
material which requires a great deal of costly and frequent
maintenance. Moreover, the concentration distribution can only be
determined on a point-by-point basis. Even if the prior art
electrodes are inserted transcutaneously through the skin, then
still only very slight gas quantities ever reach the electrodes.
Furthermore, the measurement is strongly influenced by the inherent
properties of the electrodes themselves. Since the electrodes
require a large amount of gas to flow towards them so as to
generate a detectable electrical current, electrode arrangements
having large surface areas are impractical. Thus, oxygen
concentration distributions are not readily attainable in the prior
art.
With respect to the partial pressure measurement of gases other
than oxygen, Stow and Randall Amer. J. Physiol. 179/678p-1954
disclose the measurement of carbondioxide with glass electrodes.
However, such electrodes require measuring times of over 30 seconds
which are undesirably long in most applications. Moreover, the
accuracy of the measurement is substantially reduced by the
presence of the required reference electrode.
SUMMARY OF THE INVENTION
Accordingly, it is a general object of the present invention to
overcome the drawbacks of the prior art.
Another object of the present invention is to provide a method and
an arrangement for measuring the concentration of gases in a sample
which eliminates the use of electrode-measuring techniques.
Still another object of the present invention is to provide a
method and an arrangement for measuring gas concentrations which is
relatively maintenance-free.
Yet another object of the present invention is to provide a method
and an arrangement for measuring gas concentrations which is
fast-acting and universally usable.
A further object of the present invention is to provide a method
and an arrangement for measuring gas concentrations which optically
shows the entire distribution of the gas in the blood at any one
time.
In keeping with these objects and others which will become apparent
hereinafter, one feature of the invention resides, briefly stated,
in a method and arrangement for measuring the concentration of
gases in a sample which comprises means for generating a
monochromatic light beam having a predetermined color
characteristic. Indicating means are further provided for
generating light signals indicative of the concentration of gases
in a sample to be measured. The indicating means includes a
light-transmissive surface positioned to be impinged by the
monochromatic light beam, a diffusion membrane which is adapted to
be placed in the proximity of a sample and which is selectively
permeable to a gas component thereof, and an indicating substance
positioned to be impinged by the monochromatic light beam
penetrating the light-transmissive surface and by the gas component
penetrating the diffusion membrane. The indicating substance reacts
when illuminated by the incident monochromatic light by emitting a
resultant light beam having an emitted component which has a color
characteristic different from the predetermined color
characteristic of the monochromatic light beam. The resultant light
beam is conducted away from the indicating substance through the
light-transmissive surface, and means for discriminating the
emitted component from the resultant light beam is provided so that
change in the color characteristic of the indicating substance can
be measured and correlated with the concentration of gases in the
sample.
In accordance with this feature, the indicating substance reacts
very quickly towards an equilibrium condition even with very small
quantities of gas being diffused from the sample through the
diffusion membrane. This is especially true if the
light-transmissive surface is juxtaposed over the diffusion
membrane so as to bound a flat, planar space which is ony a few
microns thick. The relatively large surface area of the indicating
substance permits average measuring values of the gas concentration
to be obtained in a relatively short time. A plurality of such thin
so-called optodes distributed over an area can be used to measure
the distribution of concentration over that area.
Another feature of the invention is that all of the various parts
of the arrangement are mounted in a portable housing which can be
easily moved towards the place where the sample is to be measured.
The housing may also contain additional electrode elements for
conducting the resultant electrical signal which is indicative of
the gas concentration towards an indicating device.
Still another feature is that one optode can be interchanged in the
same arrangement with other optodes which have a different
diffusion membrane which is selectively permeable to another gas
component to be measured. The interchangeability of the optodes in
the portable housing provides for greater versatility.
In accordance with yet another feature, the optode may be
constituted not of the aforementioned multilayered-type
construction, but of a supporting foil in which the indicating
substance is randomly interspersed and sealingly embedded. The foil
itself simultaneously serves as the gas-permeable membrane as well
as the light-transmissive surface. The design of the optode insures
an especially simple and sturdy construction. The embedding of the
indicating substance throughout the foil is obtained by
conventional chemical and physio-chemical techniques, preferably by
polymerization of a solution of .[.silicon.]. .Iadd.silicone
.Iaddend.or any synthetic plastic material such as
polyvinylchloride mixed with the indicating substance.
An additional feature of the invention resides in controlling the
temperature at which the gas is measured. Heating and/or cooling
coils, heat exchangers, or Peltier-type elements, or the like, can
be employed to control the temperature of the gas. If the heat
input necessary for effecting a temperature change in the sample is
measured, the perfusion rate of the sample can also be
determined.
The means for generating light signals indicative of the
concentration of gases may comprise one or more adjacent optodes,
each containing a different indicating substance; or a single
optode having separate sections, each of which contains its own
respective indicating substance; or a single supporting foil having
separate indicating substances embedded therein. It is especially
desirable if a pair of optodes are used transcutaneously to measure
the partial pressure of oxygen and/or carbondioxide being diffused
from a blood vessel through the surrounding skin. The optodes may,
in accordance with the invention, be arranged in the free end of a
catheter having light-conductive fibers which convey light beams
toward and away from the optodes. The catheter can be arranged then
directly in a vein or artery. If two optodes are employed, then the
incident light beam contains two monochromatic components which are
subsequently separately processed. The use of two simultaneously
acting optodes overcomes the prior art disadvantage of having to
separately measure the oxygen and carbondioxide gas concentrations
at separate times at one location on the skin.
Still another feature of the arrangement is to arrange the
indicating substance in dichroic layers so as to absorb the
incoming monochromatic light beam and reduce scattered radiation
effects.
Also, it is desirable to provide a reflective surface on the inner
side of the diffusion membrane, or on the inner side of a wall
placed behind the diffusion membrane, in order to direct the
monochromatic light beam twice through the indicating substance.
This is especially desirable if the monochromatic light beam does
not have sufficient strength or purity to illuminate the indicating
substance.
On the other hand, if sufficient energy and purity is provided in
the incoming monochromatic light beam, the diffusion membrane or
the wall placed behind the same can be darkened or provided with a
light-absorbing layer so as to reduce scatter.
If the optode is formed with a large light-impinging surface area,
cross-diffusion is substantially reduced by providing for fine,
subdivided groups of optodes.
Still another feature of the invention resides in using very small
optodes in particle form, each containing indicator substance.
These particles can then be introduced into the sample. Such a
measuring method is extremely fast-acting since the combined outer
surface areas of all the particles is quite high.
The novel features which are considered as characteristic for the
invention are set forth in particular in the appended claims. The
invention itself, however, both as to its construction and its
method of operation, together with additional objects and
advantages thereof, will be best understood from the following
description of specific embodiments when read in connection with
the accompanying drawings.
BRIEF DESCRIPTION OF THE DRAWING
FIG. 1 is a diagrammatic view of a first embodiment in accordance
with the present invention;
FIG. 2 is a diagrammatic view of still another embodiment in
accordance with the present invention;
FIG. 2a is an enlarged view of a detail of FIG. 2
FIG. 3 is still another diagrammatic view of an additional
embodiment according to the present invention;
FIG. 4 is an enlarged, partial diagrammatic view of a detail of the
arrangement;
FIG. 5 is a diagrammatic of still another embodiment in accordance
with the present invention which uses the modification illustrated
in FIG. 4; and
FIG. 6 is a bottom view of the catheter illustrated in FIG. 5.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
Referring firstly to the FIG. 1 of the drawing, this illustrated
embodiment for measuring gases in a sample comprise means 2 for
generating a monochromatic light beam. Light emanating from a light
source 230 is focussed by lens element 232 onto a light-dispersion
prism 231. The resulting beam is split up into its spectral
components and focussed by another lens element 232 towards the
exit opening or aperture 233.
In order to select one of the spectral components to serve as a
source of monochromatic light, i.e. a light beam having
substantially a single frequency and wavelength, an adjusting
arrangement comprising an adjusting screw 234 is provided. By
turning screw 234, the entire monochromatic light arrangement is
moved and thereby the desired wavelength can be obtained through
the aperture 233.
The monochromatic light beam generally identified by reference
numeral 20 is directed towards a so-called "optode 1". The optode
generates the light signal which is indicative of the concentration
of the gases in a sample. Optode 1 is composed of an upper layer 60
having a light-transmissive surface positioned to be impinged by
the monochromatic beam 20, and a juxtaposed lower diffusion
membrane 105. The layer 60 and the membrane 105 together bound a
space for an indicating substance 100. The membrane 105 is chosen
so that it is permeable to a selected gas component of the sample
being measured. If the indicating substance 100 is a liquid, it is
preferable if the membrane 105 and the layer 60 are fluid-tightly
sealed relative to each other.
The indicating substance 100 is positioned in the optode 1 so that
it is impinged by a major portion of the monochromatic light beam
20 which penetrates the light-transmissive layer 60. Moreover, when
illuminated by the beam 20, the substance 100 reacts with the gas
component which penetrates the diffusion membrane 105 and changes
its color characteristic. Specifically, the substance 100 emits a
fluorescent-type beam whose color and intensity is different from
the color characteristic of the monochromatic light beam.
The resultant light beam emanating from the optode is comprised of
two components 20 and 22. Component 20 is essentially composed of
the monochromatic light beam being reflected from the indicating
substance and/or the light-transmissive layer 60. COmponent 22 is
the fluorescent light signal emitted by the substance 100
itself.
The resultant beam is then conducted away from the indicating
substance 100 through the light-transmissive layer 60 so that
information contained in component 22 can be discriminated from
component 20 and used to yield the desired information as to the
concentration of the gas currently being measured in the
sample.
This discrimination process can occur in many ways. For example, in
FIG. 1, if an especially pure monochromatic signal is desired (i.e.
a monochromatic signal having predominantly a single frequency)
then a very slight apertural width is provided for the exit opening
233. In addition, it is advantageous if a modulator 4 having a
movable shutter is positioned in the path of the incident
monochromatic light beam 20 so as to repeatedly interrupt beam 20
and vary its itensity at a predetermined frequency. (At the same
time the modulator 4 generates an electrical signal which has the
frequency of interruption of the light to be used in the
amplifier-demodulator unit 3 for phase sensitive demodulation of
the light signal.) The monochromatic light beam then receives the
intelligence at the optode so that, when the resultant light beam
is passed through the filter 221, only the component 22 remains.
Component 22 is thereupon focussed by lens 222 onto the photocell
or receiver 223, whereupon the receiver conveys the information to
be processed in known manner to the relatively stable and
preferably noiseless electronic amplifier-demodulator unit 3, which
is preferably phase-sensitive. The resulting information signal is
then conducted to a display instrument 31.
In use, the optode 1 is placed so that the membrane 105 is in
direct contact with the sample. For example, if the sample is
blood, then the blood B can be passed through a flow-through
chamber 6. An upper side of the chamber 6 is constituted by the
optode 1; a bottom opposite side of the chamber is generally
identified by reference numeral 61. If the concentration of the gas
in the blood to be measured changes, then the amount of gas being
diffused through membrane 105 will correspondingly change. This, of
course, means that the strength or intensity of the
fluorescent-type emitted light component 22 will also change. This
change in color characteristic will then be sensed and displayed on
the display instrument 31 which can serve either as a direct or
differential read-out device.
If it is desired to employ a plurality of monochromatic light beam
components, then each monochromatic component can be provided with
its own modulator that is operative at different respective
frequencies. Each frequency after being received by the photocell
can be processed in the same electronic unit and be individually
separated and displayed by using the respective electrical signals
for phase sensitive demodulation.
In case it is desired to control the temperature of the sample
during the measurement, the temperature-control means 1000 is
placed in the proximity of the sample for cooling and/or heating
the latter. In FIG. 1, the temperature-controlling means 1000 is
configurated as an annular coil surrounding the optode and is in
heat-exchange relationship with the blood B. If the temperature
information is processed with the gas-concentration information,
then the perfusion rate is determinable.
In order to increase the strength and intensity of the emitted
light component 22, it is very desirable to provide a reflective
surface at the inner side of the bottom wall 61 of the flow-through
chamber 6 so that the incident monochromatic light beam will pass
twice through the indicating substance 100. In this case it is
advantageous if small apertural widths are provided at the
monochromatic arrangement 2, or if the indicating substance 100 is
arranged in dichroic layers.
If, on the other hand, the purity and strength of the monochromatic
light component is adaquate for exciting the indicating substance
100 to produce an emitted light component of sufficient strength,
then it is desirable to provide an absorbing layer on the inner
side of the bottom wall 61. Thus, instead of providing a
mirror-like surface as in the above-mentioned case, the bottom wall
is blackened. This is advantageous in reducing scatter radiation
caused by the incoming monochromatic beam so that the outgoing
resultant beam is essentially comprised of relatively more emitted
light component 22 and less of the reflected light component
20.
Turning now to the embodiment of FIG. 2, the means for generating
monochromatic light is simplified from the arrangement shown in
FIG. 1 and is provided with a light source 230 which projects at
its light onto a lens which, in turn, directs the light through a
monochromatic filter 3210. Filter 2310 is operative for allowing
substantially only the desired monochromatic light beam 20 to pass
therethrough towards the optode 103.
Optode 103 is analogous to optode 1 as discussed in FIG. 1 and is
similarly provided with light-transmissive surface 1060, indicating
substance 100 and gas-permeable membrane 1050. One essential
difference, however, relates to the placement of the optode and the
size thereof with respect to the sample. In FIG. 1, a flow-through
chamber 6 was used; in the present case, the membrane 1050 is
positioned a very slight distance from a tissue or skin or like
object O so that gas diffusing therefrom penetrates the membrane
1050 and reacts with the indicating substance 100. Optode 103 is
preferably annular and clamped in position by clamping ring 1030
which is provided in housing bracket arm 400. It is advantageous if
the ring 1030 is removable so that different optrodes, each adapted
to measure a different gas component, can be interchanged as
desired. In order to insure that the diffused gas is directed
towards membrane 1050, sealing means 1001 is provided intermediate
optode 103 and the object O.
The resultant light beam again has two components, and the emitted
fluorescent-type light component 22 is discriminated from the
reflected component 20 by passing the resultant beam through a
filter 221 which serves to pass substantially only the light
component 22. Lens 2210 focusses the light component 22 onto an
image area i. Thereupon, the image-amplifier arrangement 7 with the
high voltage source 7' electronically produces an electrono-optic
image on the display screen 70.
Thus, this device can display a stationary or static concentration
distribution of a gas being measured. Of course, the display must
be previously calibrated to account for the particular indicating
substance being used, the particular gas being measured, the
distance of the optode from the object, the size of the optode,
etc. If the indicating substance is subdivided into layers to
reduce cross-diffusion, this fact must also be taken into
consideration. The display of the image on a screen can be
permanently recorded by using a camera or like image-recording
device.
Instead of forming the optode as a sealed multi-layered
construction, i.e. upper light-transmissive layer (60 or 1060), a
lower diffusion membrane (105 or 1050), and a middle layer of
indicating substance 100, the optodes for all of the previously
disclosed embodiments may be constituted of a supporting foil in
which the indicator substance is sealingly embedded. The foil is
generally constituted of any gas-diffusable material, such as a
solution of .[.silicon.]. .Iadd.silicone .Iaddend.or any synthetic
plastic material such as polyvinylchloride randomly mixed with the
indicating substance preferably in a polymerization-type reaction.
The indicating substance is so strongly embedded in the supporting
foil that, even if it were placed in direct contact with the blood
in flow-through chamber 6 of FIG. 1, the indicating substance would
not be washed away.
Besides the planar configurations of the optodes or supporting
foil, each can be adapted to conform to the particular
configuration of the object being measured. Thus, the optodes may
comprise a plurality of very small carrier particles having the
indicating substance embedded therein and which are added to a
carrier fluid containing the gas to be measured for instance to the
blood.
Turning to FIG. 3, this embodiment is essentially analogous to the
one described in connection with FIG. 2 except that the
discrimination process is different. The resultant beam is again
passed through a filter 221 which serves to screen out the
reflected light component 20. The fluorescent light component 20 is
then scanned by a first swinging mirror 200 in one direction, and
then directed by lens 222 towards a second swinging mirror 201
whereupon another scan is taken in a mutually normal direction.
Thus an areal scan is furnished. The information contained in the
scanning of the optode is then conveyed to a photoelectric element
223, whereupon the information is conducted towards an amplifier
202 and coverted into an electrono-optic image or raster which can
be viewed at the display screen 70 of the viewing apparatus
203.
In FIG. 4, the incident monochromatic light beam and the outgoing
resultant beam are respectively directed towards and away from one
or more optodes by means of light-conductive fibers 2001 and 2002
of a light-conductive cable 2000. Light-conductive fiber 2001 has
its input end 2022 connected to a source of monochromatic light so
that the latter is thereby brought to the optode whereupon it
impinges on the indicating substance. The free end of
light-conductive cable 2000 is sealingly covered with the
gas-permeable membrane 8 so that the gas being measured can
penetrate the membrane and react with the indicating substance. The
emitted light is conducted by light-conductive cable 2003 towards
its output end 2023 to a discrimination arrangement.
The light fibers may be connected to either one or more optodes
and, as shown in FIG. 4, fiber 2001 is used to illuminate a pair of
adjacent optodes 101 and 102 which lie behind each other as viewed
in direction into the plane of FIG. 4. Moreover, each optode may be
used to measure the same gas component, or preferably different gas
components when their respective gas-permeable membranes are
selected accordingly.
The inner surface of the gas-permeable membrane 8 can be provided
with a reflective coating in case an increase in the illumination
of the indicating substance by the monochromatic light is required;
alternatively, the inner surface may be provided with a blackened
coating in order to reduce scatter radiation. Of course,
light-scattering not eliminated thereby can also be reduced and
substantially eliminated by electrical means in the amplifier
circuitry.
FIG. 5 shows an embodiment of a multiple analysis-type measuring
device using the concept disclosed in FIG. 4. The light-conductive
cable 2080 is housed in a catheter whose free end is provided with
optodes 101 and 102 and covered by membrane 8. The measurement is
advantageous since obtaining a plurality of separate readings, each
of which is later processed to produce a final result, is more
accurate as compared with a single measurement device according to
Pflugers Archiv 342/41-60/1973. With this method it is possible to
account for optical interferences, white light effects, single
measurement errors, etc.
In accordance with the invention, light source 230 directs a light
beam 202 towards the input end of cable 2080. Beam 202 is modulated
by a rotating assembly wheel which comprises a drive 2501 which
turns shaft 2500. A first set of five monochromatic filters
2502-2506 are mounted on the shaft 2500 so as to intercept beam 202
in normal direction; a second set of single frequency light
filtering elements 2507-2511 is mounted on the shaft 2500 so as to
subsequently intercept beam 202 at angles of approximately
45.degree.. The second set of light elements 2507-2511 is partially
mirrored and so positioned that the resultant beams returning from
the optodes 101, 102 are sequentially reflected towards photocells
90-94. Each photocell converts the respective light signals into a
corresponding electrical signal which is then respectively
amplified in amplifiers 130-134. The plurality of electrical
signals are processed together in an analyzer unit 135 which
combines the separate signals in a manner disclosed by Pflugers,
Archiv 342/41-60/1973. The display instruments 1361 and 1362
respectively indicate the gas concentrations detected by the
optodes 101, 102. Thus, optical interference caused by the optodes
or by the blood itself, white light, and additive color effects
from the indicating substance are substantially eliminated.
By placing the optodes 101, 102 directly behind each other, it is
possible to make the free end of the catheter-type cable very thin
so that the latter can be used to measure gas components directly
even in very small blood vessels.
FIG. 6 illustrates an embodiment especially useful when the optode
is directly applied against the skin. Optode 1031 is comprised of
two adjacent membranes 110 and 111. Membrane 110 is selected to be
permeable to oxygen; and membrane 111 is selected to be permeable
to carbondioxide. Then, these two gas components can be
simultaneously measured.
As examples of typical indicating substances,
.beta.-methyl-umbelliferon can be used to directly measure the pH
value of the blood being measured from which the carbon-dioxide
value can be determined by the use of a nomograph; in addition,
pyrene butyric acid can be directly used to measure the oxygen
concentration of the sample.
It will be understood that each of the elements described above, or
two or more together, may also find a useful application in other
types of constructions differing from the types described
above.
While the invention has been illustrated and described as embodied
in a method and arrangement for measuring the concentration of
gases, it is not intended to be limited to the details shown, since
various modifications and structural changes may be made without
departing in any way from the spirit of the present invention.
Without further analysis, the foregoing will so fully reveal the
gist of the present invention that others can, by applying current
knowledge, readily adapt it for various applications without
omitting features that, from the standpoint of the prior art,
fairly constitute essential characteristics of the generic and
specific aspects of this invention.
What is claimed as new and desired to be protected by Letters
Patent is set forth in the appended claims.
* * * * *