Note: Descriptions are shown in the official language in which they were submitted.
1 This invention relates to a method and
apparatus for measuring the concentration of various
kinds of gases existing in biological tissue and
biological fluid, especially, blood, the method being
one of measures adapted ~or quantitatively gathering
biological conditions in the field of medical science.
In particular, the present invention relates to a
method and apparatus for measuring a partial pressure
in a living body on the basis of the polarography.
Two major methods have hitherto been
available for the gas concentration or partial pres-
sure measurements.
A first method is based on the so-called
spot measurement wherein blood is extracted from a
living body and thereafter the gas concentration is
measured through a chemical analysis process.
A second method is such that a small sensor
is inserted into a living body and the gas concentration
in terms of an electrical signal is measured.
Disadvantageously, the ~irst method
consumes much time until a result is obtained and
besides, blood being in process of extraction from
the living bod~ tends to come into contact with ambient
air, and gas exchan~e will be caused between the
extracted blood and the ambient aix with the result
l that a measured value representative of a gas
concentration in the llving body tends to be
inaccurate.
The second method, on the other hand, is
excellent which can provide instantaneous results,
thus facilitating on-line monitoring of a living body
condition. This method has therefore been proposed in
various ways mainly on the basis of polarographic
process. This method utilizing an electrode reaction,
however, faces a problem of temperature dependency in
which current or voltage values obtained greatly
depend on temperatures and accurate values can not
be obtained unless the living body is kept at a
constant temperature.
For example, a sensor for measuring the
oxygen concentration in liquid usually has a cathode
made of a noble metal such as gold, platinum, silver
or the like and an anode, such as an Ag/AgCl electrode.
Oxygen is reduced at the surface of the cathode and
a polarographic current which has a small current
value due to the reducing reaction is measured.
Since the current value varies with an oxygen
concentration in the liquid and temperature of the
liquid as well, it can not be concluded that a
varying current value directly indicates a variation
in the oxygen concentration in the liquid. According-
ly, in order to determine the variation in the
oxygen concentration in the liquid, the liquid
1 must be kept at a constant temperature or the oxygen
concentration must be corrected by measuring temper-
ature changes so as to be converted into a value
at a reference temperature.
With an object to be examined in the form
of a living body, however, it is practically difficult
to maintain the living body at a constant temperature
and such a maintenance is contradictory to the
very purpose of on-line monitoring of the living
body. For these reasons, appropriate temperature
correction is required.
Further, in measuring a partial pressure
of gas prevailing in blood with an electrode made
of noble metal alone, measured values vary on account
of pulsation or lowered reaction ra~e by blood
component deposition on the electrode surface. To
cope with such problems, it has been proposed to
apply various coverings or coatin~s on the electrode
surface. Since in this case the covering or coating
by itself increases the temperature dependency,
the need for temperature correction becomes imminent
more and more.
It is an object of the present invention
to provide a method and apparatus which provide
accurate and rapid measurements o~ a gas partial
pressure in a living body on the basis of the
polarography principle by compensating for ~emperature
changes in the living body.
`:
1 According to the invention, a gas partial
pressure sensor having a biomedical electrode
disposed in the living body and a separate temperature
sensor are disposed in or on the living body, an
output value produced from the gas partial pressure
sensor is sequentially corrected to a value at a
reference temperature by a body temperature information
signal produced from the temperature sensor in accord-
ance with a predetermined temperature correction
formula, and the gas par-tial pressure value is
sequentially calculated from a predetermined working
curve which represents a relationship between the
gas partial pressure value and the corrected output
value from the gas partial pressure sensor, both values
being at the reference temperature.
The gas partial pressure in the living body
is usually represented by a value at a reference
temperature of about 37C. But, sometimes the bodily
temperature decreases by scores of cen~igrade degrees
during a surgical operation. Especially, during
an operation for heart disease, the body is sometimes
cooled to below 10C. After the operation, the
patient often becomes feverish with his temperature
rising to over 40C. Thus, the body temperature
deviates from the reference temperature by over 10C
during the operation and by 5 to 6C after the
operation. Even with the dropping mercury electrode
described previously, the electrolytic current varies
-- 4 --
1 by 2% as the temperature varies by 1C and with the
electrode used in the present invention, the elec-
trolytic current varies by about 3%. For example,
when the temperature of the living body deviates
from the reference temperature by 20C, the electroly-
tic current deviates from the actual value by 40 to
60%. Accordingly, without the correction according to
the present invention, the measured value of the
partial pressure in the living body greatly dif~ers
from an actual partial pressure. Conversely, the
method of the present invention can reduce the error
to a large extent to assure accurate measurement of
actual gas partial pressure and can constantly apprize
physicians and nurses of an accurate partial pressure
in blood or tissue of the patient.
The invention will now be described by
way of example with reference to the accompanying
drawings.
Fig. 1 is a diagram useful ln explaining
the principle of polarography.
Fig. 2 is ano~her diagram similar to Fig. 1
in which a platinum electrode has a porous membrane
as a covering.
Fig. 3 is a circuit block diagram of the
apparatus according to the present invention.
Fig. 4 is a detailed block diagram of
the apparatus according to the present invention.
Referring to Fig. 1, when a voltage is
1 applied across a cathod, or platin~m electrode 1
which constitutes a biomedical electrode) and an anode,
or c~unter electrode 2 in a solu~ion 5 in a container
4 from a power supply 3, a polarographic current I
due to electrolytic reaction flows and indicat~d
by a meter 6. With a dropping mercury electrode,
for example, the current I varies under ~he influence
of a temperature dep0ndency because of the gas
diffusion by about 2% at l~G. In other words, the
amount of the tempexature dependency is about 2%/C.
It has been proposed as shown in Fig. 2
to use a biomedical electrode 1' whose tip end
surface is covered with ~ membrane which has an outer
thin, dense layer having fine pores of an average
diameter of 20 A to 0.7 ~m and an inner porous layer,
contiguous to and integral with the outer layer,
having fine pores of an average diameter of 0.7 ~m
or more, in European patent application No. 122,952
published on October 31st, 1984
assigned to the same assignee as the present applica-
tion. When the electrode 1' having its tip end
covered with such a porou.s membrane 7 is used, the
temperature dependency is larger than that of the
dropping mercury elec~rode since many fac~ors such as
pore size, surface affinity and thickness of the
porous membrane 7 affect the gas diffusion to increase
the temperature dependency, there~y adversely
a~fecting the gas partial pressure mea~urement.
-- 6 --
1 Through various experiments, the present inventors
found that the polarographic current I was in
a certain relationship with temperatures of an
object to be examined, and that temperature correction
for the polarographic current can be accomplished
by using this relationship.
Fig. 3 is a block diagram for implementation
of the present invention. In this embodiment, in
order to eliminate the problems described previously,
an operation unit 12 comprise a microcomputer board
so that a value of a polarographic current I from
a gas partial pre~sure sensor 8 is digitized by an
interface unit 9 and inputted to the operation unit
12 and a biomedical temperature information signal
from a temperature sensor 10 is digitized by the
interface unit 9 and inputted to the operation unit
12, and the polarographic current value is temper-
ature corrected and calculated from a predetermined
value and a programmed formula to provide a gas
partial pressure value. The same results may be
obtained by an operation unit 12 of a mini-computer
or of a dedicated logical circuit which substitutes
~or the microcomputer operation unit 12. A subsidiary
advantage of the present invention resides in
that in addition to the input data for a working
curve preparation which is programmed in advance of
measurement, a new value can be readily inputted at
a desired time.
1 More particularly, in accordance with the
principle of polarography, the output signal of the
partial pressure sensor developing in the course
of time lapse varies with not only temperatures but
also, for example, amounts of substance in blood
component deposited to the platinum electrode, or
biomedical electrode as described previously, and
variations in the sensor output signal can not be
eliminated completely even when the porous membrane
7 is applied to the platinum electrode 1'. Accord-
ingly, it is very advantageous that a new value ~or
the working curve preparation can be inputted in
an advanced phase of the measurement.
Correction procedures will now be described
specifically.
As far as the principle of polarography is
concerned, the linear relation, as represented by
P = aI ~ b ............ (1)
where P is the gas partial pressure, I is the
polarographic current value and a and b are constants,
is held between the polarographic current value I
and the gas partial pressure P. Accordingly, the gas
partial pressure can be detexmined by measuring the
polarographic cuxrent value whenever constants a and
b are determined in advance. In this manner, a
working current which represents the equation ~1)
-- 8 --
1 can be prepared.
The polarographic current I has a temperature
dependency as described previously. The present
inventors have studied the temperature dependency
in various ~anners to find that the following
equation holds approximately between the current
value and the temperature:
T-t
It = ISTk ................... ~23
where It is the polarographic current value at a
temperature t, IST is the polarographic value at a
reference temperature T, and k is the temperature co-
efficient. The temperature coefficient k is specific
to the gas partial pressure sensor but sensors
produced under the same condition have substantially
the same temperature coefficient. For precise
measurement, however, several kinds of solutions
having known gas partial pressure values are prepared,
and currents and temperatures are measured for the
respective kinas of solutions at different temper~
atures so that a temperature coefficient specific
to a sensor participating in the measurement can be
obtained through a method of least squares. For
example, gas partial pressure sensors with platinum
electrodes covered with the aforementioned porous
membrane which were produced in the same lot under a
certain condition had an average temperature
_ 9 _
l coefficien-t k of 0.97 with a variation of +0.01.
It follows therefore that if the manufacture condition
is monitored and controlled properly, the temper-
ature coefficient will satisfactorily be regarded
as being constant for the purpose of the measurement.
Next, the relationship between gas partial
pressure and current value, i.e., the working curve
can be determined in various manners as itemized
below.
(i) A biomedical electrode of a gas partial
pressure sensor is placed in an object to be measured
and a temperature sensor is placed in or on the
object to be measured. The working curve is then
determined from a current value I and a temperature
t at this time, and a gas partial pressure value PST
in the object measured by using a separate instrument
such as for example a commercially available batch
type oxygen partial pressure measuring instrument,
and a residual current value Io ~current value for
a gas partial pressure of zero) of the gas partial
press~re sensor as well. More particularly, a current
value I5T at a reference temperature TC is
determined from a current value It measured at a
temperature tC in accordance with equation (2).
The corrected current value IST thus
determined is related to the gas partial pressure PST
in accordance with the equation (l). The constant a
in the equation (1) representative of a gradient of
-- 10 _
1 the current value relative to the gas partial
PST/(IsT- Io)~ and the constant b
which is P -aI is determined by substituting PST
PST/(IST- Io)~ and IST for P, a and I, respectively,
in equation (1).
(ii~ A gas partial pressure sensor and a temper-
ature measuring sensor are placed in one kind of
solution having a known gas partial pressure value PST.
The working curve is then determined from current
value I, temperature t, gas partial pressure value
P and residual current Io of the gas partial pressure
sensor at this condition. Subsequently, constants a
and b are determined as in item (i).
(iii) A gas partial pressure sensor and a
temperature sensor are placed in two kinds of solutions
having kno~n gas partial pressure values, and the
working curve is determined from current values I
and I2, temperatures t1 and t2, and gas partia].
pressure values Pl and P2 for the different kinds
of solutions in those conditions. In particular,
the current value I1 for one solution and the current
value I2 for the other solution are respectively
converted into current values at the reference temper-
ature TC as in items (i) and (ii) and the constants
_ and b in the equation (1) are determined in a similar
manner.
The gas partial pressure P can be determined
from the polarographic current value I in accordance
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1 with the equation (1), by using the constants a and
b obtained through any one of methods itemized in
(i), (iil and (iii) as above.
The residual current Io in (i) and (ii)
5 methods is specific to the gas partial pressure
sensor. However, the present inventors have found
that sensors produced under the same condition have
substantially the same value of residual current
in terms of a converted gas partial pressure, as
well as the temperature coefficient k. For example,
gas partial pressure sensors with platinum electrodes
~biomedical electrodes) co~ered with the aforementioned
prorous membrane have a residual current which
corresponds to an oxygen gas partial pressure of
about 2 mmHg. As a result, the value of 2 mmHg may
be used as the value of b instead of measuring
the residual current Io~ The solution having a known
gas partial pressure is required to contain electrolytic
ions and preferably, it is physiological saline
solution or blood.
The operator can select at will one of
the above three methods. A fixed value of the
temperature coefficient k is inputted in advance but
for precise measurement, the operator may input a
value of the temperature coef~icient k specified to
a sensor used.
An arrangement for implementing the present
invention will now be described with reference to
- 12 -
l Fig. 4.
In Fig. ~, an output signal from a gas
partial pressure sensor 8 is arnplified suitably by
a partial pressure amplifier 25 and transferred to
a CPU bus line 34 ~ia a remote switch 21 and an
A/D converter 20. Connected to the CPU bus line
34 are a CPU 13, a ROM 14, a RAM 15, a timer 16 and
various I/O and O/P boards 17, 22, 23 and 24.
The output signal from the gas partial
pressure sensor 8 transferred to the CPU bus 34 is
stored in a pertinent area of the RAM 15 in accordance
with a program which has been stored in the ROM 14
and by the action of the CPU 13. On the other hand,
the output signal from the temperature sensor 10
is transferred to the CPU 13 via a temperature
amplifier 26, the remote switch 21, the A/D converter
20 and CPU bus 34. The remote switch 21 is changed
over at a suitable interval by a command via an O/P 22
in accordance with the program, for example, an
interval of 200 to 1000 msec in a measurement of a
partial pressure of oxygen in blood, and an interval
of 5 to 10 sec in a measurement of a partial pres-
sure in tissue in a living body, since in these
cases generally, there is no need to recognize
extremely rapid changes in the partial pressure and
temperature. As a result, the output signals from
the gas partial pressure sensor 8 and temperature
sensor 10 are alternately and intermittently
- 13 -
1 transferred to the CPU 13 depending on the int2rval
of the change over of the remote switch 21.
In the CPU 13, a polarographic current
value It represented by the output signal of the gas
partial pressure sensor 8 is corrected to a current
value IsT at a reference temperature T as described
in the foregoing, and then a gas partial pressure P
at the reference temperature T is calculated on the
basis of the corrected current value IST and the
working curve. The resultant gas partial pressure P
calculated sequentially, or rather practically
almost continuously, is displayed on a display 27
numerically and is recorded graphically and numerical-
ly on a graphic printer 18, together with the temper-
ature value or the gas partial pressure alone.
An extension line may also be provided fordelivery of the data to an ordinary analog recorder
30 where the recorder 30 is additionally used.
A console panel 28 includes a plurality
of console panel switches adapted to input data for
preparing the working curve before or during the
calculation of the gas partial pressure and to input
~he operator instructions in order to effect an
accurate and updated correction. The console panel
28 further includes pilot lamps (not shown) adapted
to confirm or monitor the operations in progress.
The one series of data input system
illustrated herein may be modified by doubling blocks
1 marked with a symbol * in Fig. 4 (gas partial pressure
sensor 8, temperature measuring sensor 10, remote
switch 21, A/D converter, etc.). With this modifica-
tion, oxygen partial pressure in arterial blood and
that in a biological tissue inside the myocardium
can be measured simultaneously. Results of the
simultaneous measurements may be recorded on a single
recorder 30 or graphic printer 18. If the results of
the measurements exceed a predetermined control limit,
audible or visual alarm unit 29 may be energized.
For protection of the living body, especially,
in the measurement of a human body, the amplifiers 25
and 26 may respectively include isolation amplifier
circuits employing a transformer coupling. Further,
other lines may also be isolated electrically.
As has been described, the method of the
present invention permits accurate and continuous
monitoring of gas partial pressure in the living
body and can be applied advantageously to clinical
and experimental medical treatment.
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