Optical measurement of concentration

The concentration of a substance of interest is measured by exposing a peable-membrane face of an indicator chamber containing an indicator to the substance, monochromator radiation being incident upon the indicator through a transparent wall of the indicator chamber, the exiting radiation being received by a light-metering unit for ascertainment of the effect upon the indicator's absorbence of fluorescence of the substance of interest. The indicator substance is additionally exposed to a reference substance of known concentration which is permitted to engage the indicator substance by diffusion through such permeable membrane, in order that the indicator be calibrated.

BACKGROUND OF THE INVENTION 
The present invention concerns methods and arrangements for the optical 
measurement of the concentration of a substance of interest by resort to 
light measurement utilizing a monochromator and a light-metering unit. 
With methods and arrangements of this type, an indicator is contained in 
an indicator chamber at least a part of which is bounded by a membrane 
permeable to the substance of interest, with at least a part of the 
indicator chamber furthermore being transmissive for radiation entering 
and exiting the indicator chamber. The permeable membrane is placed in 
contact with the substance of interest, and molecules or particles of the 
substance of interest diffuse into the indicator chamber. Radiation from 
the monochromator is directed into the indicator chamber, and the spectral 
response of the indicator therein to the monochromator radiation (i.e., a 
change of color or a fluorescent response) depends upon the concentration 
of the substance of interest. 
Using arrangements and methods of the type in question, it is necessary to 
calibrate the indicators employed, when high-precision concentration 
measurements are called for. This may be quite difficult, especially 
inasmuch as the indicator within the indicator chamber is generally not 
accessible but instead blocked from access by the aforementioned permeable 
membrane. 
The indicator-chamber structure, containing an indicator and bounded by the 
aforementioned permeable membrane and radiation-transmissive wall is 
referred to herein as an optode, a term used in previous patents involving 
such type of indicator-chamber structure, e.g., U.S. Pat. No. 4,003,707. 
One way to calibrate such an optode is by performing a concentration 
measurement with respect to a comparison substance whose concentration is 
known in advance, e.g., using a comparison sample containing the substance 
of interest in a known concentration. However, there exist applications in 
which this would be problematic due to the remoteness of the optode from 
the sample of interest, for example as in the case of blood gas 
concentration measurements performed using a catheter inserted into a 
blood vessel. 
SUMMARY OF THE INVENTION 
Accordingly, it is a general object of the invention to greatly facilitate 
the calibration of such optodes. 
In accordance with one embodiment of the invention, the optode is provided 
with a comparison or reference chamber which can accommodate a reference 
sample of known concentration, with both the reference substance of known 
concentration and the substance of interest whose concentration is to be 
measured both permeating into the indicator compartment of the optode, so 
that the signals or signal components respectively attributable to the 
reference sample and the sample of interest can be compared, in one or 
another way, for calibration purposes. 
The advantage of such an approach is that it becomes possible to perform 
calibrations in a very short time, with little or no manipulative work, 
and even concurrently with actual measurement of the concentration of the 
substance of interest. 
In one embodiment of the invention, the optode has, as usual, a 
permeable-membrane face through which the substance of interest diffuses 
into the indicator compartment. However, the opposite face of the optode, 
through which the monochromator radiation enters the indicator compartment 
and through which the fluorescent radiation emitted by the indicator or 
merely the radiation reflected by the indicator exits the indicator 
compartment, is likewise a permeable membrane exposed to a reference 
sample, the reference sample being optically transmissive for the 
radiation which enters through it into the indicator compartment and exits 
through it from the indicator compartment. 
In another embodiment of the invention, the optode comprises two component 
optodes. One of the component optodes is provided with means exposing its 
permeable membrane to a reference or comparison sample. Monochromatic 
radiation is incident upon both component optodes, and the radiation 
emitted from both component optodes is measured to generate a signal 
dependent upon the difference in the spectral response of the indicator 
contained in the two component optodes. 
Particularly for certain contexts of use, it is advantageous that the 
optode be exposed to the reference sample by provision of a reference 
compartment bounded by a permeable membrane of the optode, with the 
reference sample being passed through the reference compartment. For 
example, if the optode is at the end of a catheter inserted into a blood 
vessel, the reference sample can be transmitted to and from the remote end 
of the catheter, so that calibration of the indicator can be performed 
with the catheter in place. The use of such a technique also makes it 
possible to employ the optode to measure the concentration of the 
substance of interest on a null-method basis. Using that technique, the 
concentration of the reference sample is initially zero and the optode 
exposed only to the sample to be measured. Then the concentration of the 
reference sample is progressively increased, until the spectral response 
of the indicator becomes identical to that which it exhibited in response 
to the reference sample alone. 
It is especially advantageous to use for the reference sample a carrier 
substance containing the substance of interest, i.e., containing a 
component the same as the substance whose concentration is to be measured 
but of known concentration. In that event the measurement signal derived 
from the radiation emitted from the optode is indicative of the relative 
values of the known concentration of the substance of interest and the 
unknown concentration of the substance of interest. 
When the measurement signal is, as just stated, indicative of the relative 
values of the known and unknown concentrations of the substance of 
interest, the measurement signal can also be used as an actuating signal 
for a servo adjuster operative for automatically varying the value of the 
known concentration until it equals that of the unknown concentration. 
Using such an approach it becomes possible to measure the concentration of 
the substance of interest by resort to familiar relationships applying to 
the mixing ratio of two substances. 
When the reference substance is a gas, this can greatly simplify the work 
performed in practical respects, because then the substances employed are 
easily mixed and also readily removed from the reference compartment. 
However, the use of calibrating liquids can also be advantageous in some 
respects, e.g., by introducing the possibility of temperature control via 
the calibrating liquid itself, and by virtue of the ease with which a 
calibrating liquid can be transmitted, e.g., along the length of a 
catheter to the optode at the end of the catheter. 
In another embodiment of the invention, in which use is made of two 
component optodes as referred to earlier, use is made of a fiber-optic 
structure having two branches at its remote end and three branches at its 
proximate end. One of the three proximate-end branches receives light from 
the monochromator employed, and the constituent fibers of this 
proximate-end branch extend through the fiber-optic structure towards the 
remote end, half of them going to one remote-end branch and the other half 
of them going to the other remote-end branch. The two component optodes 
are each located at one of the remote-end branches and receive 
monochromator radiation in this way. The other two proximate-end branches 
of the fiber-optic structure each emits light onto a respective one of two 
light-metering units, all the fibers of one of these two proximate-end 
branches extending to only a respective one of the two remote-end 
branches, and all the fibers of the other of these two proximate-end 
branches extending to only the other one of the two remote-end branches; 
in this way, the light emitted from each of the two component optodes 
finds its way only to a respective one of the two light-metering units 
employed. 
With that arrangement, it becomes possible to locate one remote-end branch 
at the sample of interest, e.g., inserted into a blood vessel by means of 
a catheter, but with the other remote-end branch located outside or remote 
from the sample, e.g., so as to minimize the number of components which 
need be introduced by such catheter. 
Alternatively, however, it is also contemplated that the reference chamber 
be provided as the head of a light-conductive catheter, with the conduits 
for transmission of the reference sample to and from the reference chamber 
running alongside and being fixed to the light-conductive structure of the 
catheter. This makes for a very simple structure particularly easy to 
handle when working in low-access contexts. This structure can be made 
particularly simple when the conduits for the reference sample are made of 
polymerized polyvinylchloride, with the reference conduits being of one 
piece with the chamber containing the indicator. 
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 drawing.

DESCRIPTION OF THE PREFERRED EMBODIMENTS 
In FIG. 1, a sample of interest 1, containing a substance of interest whose 
concentration is to be ascertained, is passed into and out of a measuring 
compartment 10. The right face of measuring compartment 10 is constituted 
by an optode 30. The use of optodes is disclosed, for example, in U.S. 
Pat. No. 4,003,707 granted Jan. 18, 1977. An optode is a compartment which 
contains an indicator substance. At least one wall of the optode is a 
membrane permeable to a substance of interest whose concentration in a 
sample of interest is to be measured. At least one wall of the optode, 
e.g., in the case of a planar optode the wall opposite to the 
permeable-membrane wall, is optically transmissive for monochromator 
radiation entering the indicator chamber of the optode, and likewise is 
optically transmissive for radiation exiting the optode; the exiting 
radiation may be fluorescent radiation emitted by an indicator which is 
excited by the monochromator radiation to an extent dependent upon the 
concentration of the molecules or particles of the substance of interest 
diffusing in through the permeable membrane, or the exiting radiation may 
be the reflected version of the monochromator radiation as reflected by an 
indicator whose spectral absorbance depends upon such concentration. As 
explained, for example, in the U.S. patent identified above, a planar 
optode may be essentially comprised of two layers, one being the permeable 
membrane, the other being the radiation-transmissive layer, with a layer 
of indicator confined therebetween. However, a planar optode may, for 
example, be so designed that both its opposite walls are permeable 
membranes themselves transmissive to the radiation in question. 
In FIG. 1, the right face of optode 30 bounds a reference or comparison 
chamber 20 through which a reference sample is passed. The substance of 
interest in the sample of interest 1 diffuses through the left 
permeable-membrane wall of the optode 30 into the indicator space within 
the optode, and likewise, a reference substance passed through reference 
chamber 20 diffuses through the right permeable-membrane wall of optode 30 
for interaction with the indicator within the optode. The reference 
substance in the reference sample 2 is of known concentration. The light 
401 exiting from within the optode 30 passes through transparent reference 
compartment 20 and is received by a light-metering unit 50 provided with a 
numerical display 60. Initially the light measurement is performed with no 
reference sample present in reference chamber 20, so that the spectral 
(i.e., absorbance and/or fluorescence) response of the indicator within 
optode 30 be determined only by the concentration of the substance of 
interest in the sample of interest 1. Equivalently, if the reference 
sample 2 consists of an optically transparent carrier containing a 
substance which diffuses into optode 30, the concentration of the 
reference substance within the reference sample 2 can initially be kept at 
zero. The numerical value indicated by numerical display 60 is noted. 
Then, the concentration of the reference substance 2 transmitted through 
reference compartment 20 is progressively increased, until the numerical 
indication provided by display 60 is the same as before, i.e., the same as 
with no reference substance present. It is particularly advantageous that 
the reference substance 2, which diffuses into the right 
permeable-membrane wall of the optode 30 be identical, except in 
concentration, to the substance of interest in the sample of interest 1. 
In that case, when the reference concentration has been brought to a value 
resulting in a numerical read-out the same as before, there is simple 
correspondence between the known concentration of the reference substance 
and the now known concentration of the substance of interest in the sample 
of interest 1. 
FIG. 2 depicts another embodiment, in which the optode 30 employed consists 
of two component optodes 31, 32, for example formed by sealing-together 
the walls of optode 30 intermediate its upper and lower edges to form two 
separate internal indicator spaces. Monochromatic radiation 400 is 
incident as before, preferably from a single monochromator illuminating 
both component optodes 31, 32. In this embodiment, one component optode 31 
is provided with the measuring chamber 10, and the other component optode 
32 is provided with the reference chamber 20. The radiation 401 which 
exits from the two component optodes 31, 32 is preferably incident upon 
two light-metering units, each provided with a respective numerical 
display, such as 50, 60 in FIG. 1. When the concentration of the reference 
substance 2 has been brought to a value such that the metered radiation 
401 exiting from both component optodes 31, 32 is the same, then the 
concentration of the substance of interest in the sample of interest 1 is 
now known to be equal to the reference concentration. 
The configuration of FIG. 2 has the advantage that, by using component 
optodes 31, 32 of identical characteristics, the measurements become 
independent of fluctuations in the spectral composition of the radiation 
400 employed. 
FIG. 3 depicts a modification of FIG. 2, in which the two component 
optodes, the monochromator and the two light-metering units are optically 
intercoupled by means of a multi-branch fiber-optics structure 100. At its 
remote end, fiber-optics structure 100 has two branches 101, 102, and at 
its proximate end three branches 103, 104, 105. A monochromator 41 or 
other light source delivers light into branch 103. First and second 
component optodes 30, 31 are respectively located adjacent branches 101 
and 102, and the two light-metering units 51, 52, with their respective 
numerical displays 61, 62 receive light from branches 104, 105. In 
particular, the constituent fibers of branch 103 extend, half of them, to 
branch 101, and the other half of them extend to branch 102. All the 
constituent fibers of branch 104 extend through to branch 101, and all the 
constituent fibers of branch 105 extend through to branch 102. 
Accordingly, the constituent fibers of branch 101 consist of fibers which 
discharge light from light source 41 and fibers which transmit light back 
to light-metering unit 51. Likewise, the constituent fibers of branch 102 
consist of fibers which discharge light from light source 41 and fibers 
which transmit light back to light-metering unit 52. At the end face of 
each remote-end-branch 101 or 102, the light-emitting and light-receiving 
fibers can be randomly arranged or arranged in accordance with a 
predetermined spatial scheme. 
The first component optode 30 is provided at the end of branch 101 and, 
here by way of illustration, is directly exposed to the sample of interest 
1; alternatively, first component optode 30 could be provided with a 
respective measuring compartment as at 10 in FIG. 2. The second component 
optode 31 is provided at the end of branch 102 and is here provided with a 
respective reference compartment 20, i.e., as in FIG. 2. 
With the configuration of FIG. 3, it becomes a simple matter to 
simultaneously irradiate both optodes 30, 31 and to simultaneously meter 
the light emitted from both. In FIG. 3, the various branches of 
fiber-optics structure 100 are shown quite spread apart, especially for 
the sake of clarity. The two branches 101, 102 can indeed be maintained 
spaced from each other, where the context of use makes this advantageous, 
for example where a low-access sample of interest 1 would make immediately 
adjoining location of the reference chamber 20 undesirable. Alternatively, 
however, the two branches 101, 102 can be understood to run directly 
alongside each other, with the two component optodes 30, 31 likewise 
located adjacent, e.g., with the two branches 101, 102 housed in a single 
tubular housing. Likewise, the three branches 103, 104, 105 might run 
alongside each other into a single housing containing the light source and 
the two metering units, or may be discrete branches such as shown. As 
before, when the numerical read-outs provided by the two displays 61, 62 
are the same, then the reference concentration has been adjusted to equal 
the concentration to be ascertained. 
In FIG. 3, as in all embodiments, it is not necessary to proceed on the 
basis of two measured-radiation signals and to bring them, in the manner 
explained above, into simple equality. For example, instead of two 
numerical displays, use may be made of a single numerical display 
operative for indicating the difference as between the two radiation 
measurements, with the operator then adjusting the reference concentration 
until the difference is reduced to zero. Alternatively, such difference 
signal may be used as the actuating signal for a servo regulator operative 
for automatically adjusting the reference concentration, so as to 
automatically bring the reference concentration into equality with the 
unknown concentration. In the case of the configuration disclosed in FIG. 
1, the radiation-measurement signal produced by metering unit 50, 
accompanied by a signal indicating the concentration of the reference 
substance, could be applied to a computer, for determination of the 
unknown concentration by means of computation. These alternatives to 
progressive increase or decrease of the reference-substance concentration, 
having been stated, will be understood by persons skilled in the art. 
FIG. 4 depicts a configuration contemplated for, but by no means limited 
to, a catheter-type use. Numeral 100 denotes a fiber-optics structure, 
only the end of which is shown, whose constituent fibers serve, some of 
them, for transmitting monochromator radiation to the optode 30 and, 
others of them, for transmitting reflected or fluorescent radiation back 
towards the light-metering unit employed. The proximate face of the optode 
30 bounds a reference chamber 20 and the remote face of the optode is 
exposed to the sample of interest. Conduits 201, 202 transmit the 
reference sample to and from the reference compartment 20. For the sake of 
illustration, the conduits 201, 202 are shown spaced from the central 
fiber-optics structure 100, but these conduits would in practice be 
fastened to the fiber-optics structure along the length thereof. 
FIG. 5 depicts a modification of the configuration depicted in FIG. 4. The 
optode and the reference chamber here are consolidated into a single unit, 
along with the conduits for the reference sample. Tubular structure 2000 
comprises two conduit portions, corresponding to 201, 202 in FIG. 4. The 
remote end 2001 of this bent-around tubular structure is of enlarged size 
and constitutes the reference compartment for the reference substance. The 
tubular structure 2000 is made of polyvinylchloride, and the indicator 
substance employed is incorporated and sealed within the material of the 
wall of tubular structure 2000 at the region of the reference compartment 
2001. Other materials suitable for the tubular structure 2000 would 
include, for example, agar or silicon. In this way, the interior surface 
of the reference compartment 2001 constitutes one face of the optode, 
exposed to the reference sample, whereas the exterior surface of reference 
compartment 2001 constitutes the opposite face of the optode, exposed to 
the sample of interest. The reference sample, at varied concentration, can 
be passed through reference compartment 2001, and alternately reference 
compartment 2001 can be emptied of the reference sample so as to obtain a 
measured-radiation signal dependent only upon the concentration of the 
substance of interest in the sample of interest, to which the exterior 
surface of reference compartment 2001 is exposed. 
Configurations such as depicted in FIG. 5 can, it should be emphasized, 
also be used in cooperation with polarographic probes, and the like. For 
example, U.S. Pat. Nos. 3,918,434 and 3,985,633, both to Lubbers, et al., 
disclose a polarographic probe whose face is covered over by a permeable 
membrane, the membrane confining a layer of electrolyte between itself and 
the probe face across which it is stretched. In accordance with the 
present invention, a further membrane can be provided, covering over the 
electrolyte-bounding membrane of such probes, with the space internal to 
this double-membrane structure then constituting the reference 
compartment. Thus, the substance of interest whose concentration is to be 
polarographically ascertained diffuses into the electrolyte of the 
polarographic probe only after diffusing through the two membrane walls 
which define the reference compartment. Using the technique of FIG. 5, the 
membranes employed can be portions of the tubular structure used in FIG. 
5, the reference compartment 2001 thereof being, however, pressed flatter 
for the sake of the configuration of such polarographic probes. If, then 
the polarographic probe is to be calibrated, a reference substance can be 
transmitted through the reference compartment, so that the reference 
substance diffuse through the permeable-membrane wall of the reference 
compartment into the electrolyte of the probe and cooperate with the 
polarographic electrodes of the probe. Of course, in such a context, the 
indicator substance incorporated and sealed within the material of the 
wall of the reference compartment 2001 of the tubular structure 2000 of 
FIG. 5 need not be provided for polarography purposes, and the substance 
whose concentration is to be polarographically ascertained merely enters 
from the sample of interest through the double-membrane reference 
compartment into the probe's electrolyte. 
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 
set-ups and configurations differing from the types described above. 
While the invention has been illustrated and described as embodied in 
conjunction with optodes and polarographic probes, 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 prior art, fairly constitute essential 
characteristics of the generic or specific aspects of this invention.