Note : Les descriptions sont présentées dans la langue officielle dans laquelle elles ont été soumises.
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Case 850114
Description
Ion Concentration Measurement System that Employs
Measuring and Reference ~ield Effect Transistor
Electrodes Sensitive to the Same Ion
Backqround and DescriPtion of the Invention
The present invention generally relate~ to an ion
concentration measurement system~ more particularly to a
system that is capable of being incorporated into a catheter
for in vivo measuring and monitoring of the concentration of
an ion within the human body. The system includes a
measuring electrode and a reference electrode, both of which
are ion-sensitive ield effect transistor ~IS~ET)
transducers that are both sensitive to the ~ame ion~ A
differentlal circuit connects the measuring ISFET and the
reference ISFET so that changes in one ISFET will be
measured as a real output signal and so that changes in both
ISF~TIs will not result in an output signal. The reference
ISFET is structured so that it is in contact with a rinsing
liquid having a known composition and a known ion
concentration.
Systems for monitoring and mea~uring ion
concentrations have been devised and used in order to
measure ~nd monitor ion activity within liquids such as
human blood. Some su~h sy~tems incorporate an electrode
2n that employs an ISFET component. ISFET components are field
effect transistors for the selective measurement of the
concentration, or pI, of an ion within a liquid. Ofte~,
these systems are used in order to mea~ure and monitor the
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hydrogen ion concentration, or pH, of a liquid suc.h as
blood. A variety of reference electrodes have been proposed
for use in conjunc~ion with measuring ISFET electrode
components. United States Letters Patent No. 4,G20,830
describes reference electrodes in this regard, while other
systems employ an ion-selective electrode such as an Ag/AgCl
electrode as the reference electrode which is in contact
with a liquid of constant concentration. One difficulty
with using an ion-selective electrode as the reference
electrode is that such electrodes mea~ure ionic
concentrations7 and when these concentrations change, such
electrodes change their reference potential, which results
in undesirable inconsistency and inaccuracy with respect to
the entire measuring system. Ideally, a reerence electrode
should provide a steady referen~e potentlal within the
electrochemical circuit of this type of device, particularly
when the device is used for ln ivo measurement and
monitoring of physiologically importan pI parameters.
Preerably, these types of device~ are sized and
structured so a~ ~o be capable of being placed ln VlVO
within the bloodstream or the like, typically by means of a
catheter structureO Such structures are superioL ~o devices
having electrodes that are adhered to the patient's skin,
which is a less desirable approach in view of the unstable
skin-electrode lnterface and their characteristic o~
requiring a relatively long dlstance between the actiY2
electrode and the reference electrode. Such device~ are
also dif~icult to apply in connection with continuous ~lood
analysis in extra-corporal blood circuits such as tho3e
utilized during hemodialysis and open-heart ~urgical
procedures. Accordingly, it is advantageous to carry out in
_~ivo ion concentration measurements with a system that
incorporates a catheter structure in order to achieve in
vivo measurements within the bloodstream or the like.
Other electrical measuring ~ystems for measuring
ion concentrations include a pH-F~T ~nd a reference F~T
component. In some such systems both FET components are
contacted with the liquid to be measured, such as the blood,
one such FET component being coated with a pH-sensitive
layer and the other FET component being coated with a
membrane that is intended to be insensitive to any and all
ions. This latter feature is not readily achieved inasmuch
as it is exceedingly difficul~ to manufacture a membrane
that is truly ion-insPnsitive.
The present invention provides a system for ln
_vo ion concentration measurement and monitoring, such as
that carried out within the bloodstream of a patientl which
system does not experience substantial drit, and which
system i5 designed so that both the measuring component and
the reference component are sensitive to one and tha same
ion so that the measuring component and the reference
comp~nent will exhibit substantially identical
sensitivities. In an important aspect of this inventivn,
the measuring ISFET transducer component and the reference
ISFET transducer component are connected together by mean~
o a differential circuit so that corresponding change~ in
the behavior of both ISFET'~ will be compensated by the
diferential circuit, typical changes in behavior b~ing the
result o variatîons such a~ drift, temperature changes,
aging and the like Aclditionally, the reerence ISF~T
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component includes a structure so tha~ the referenc~ ISFET
can be contacted with a rinsing liquid of known, and
typically sonstant, composition and ion concentration. ~ost
advantageously, the system is inçorporated in o a catheter
structure suitable for direct incorporation illtO the
bloodstream or the like of the patient.
It is accordingly a general object of the present
invention to provide an improved ion concentration
measurement system that is particularly well-suited for in
vivo usage.
Another object of the present invention is to
provide a device for ion concentration measurement that is
especially stable with respect to inaccuracies that can
develop due to drift, temperature changes, aging and the
like~ while also providing a device that i8 especially
precise and sensitive to changes in the ion concentration
being measured or monitored~ Another objeGt of this
invention is to provide an improved ion concen~ration and
measurement system which may be calibrated during ln viv~o
measurements.
These and other objects, features and advantages
of this invention will be clearly understood through a
consideration of the following detailed deacription.
Brief Description_of the Drawin~s
In the course of this description, reference will
be made to the attached drawings, wherein:
Figure 1 is an elevational view of a typical
catheter structure suitable for incorporating the ion
concentration measurement system in accordance with this
invention;
Figure 2 is a generally schematic longitudinal
sectional view of Figure l;
Figure 3 is a ~chematic diagram of the
differential circuit by which the measurin~ and reference
FET components are connected; and
Figure 4 is a schematic illustration of the
voltage drops that occur within the ion concentration
measuring system according to this invention.
_scri~tion of the Particular Embodiments
Figure 1 shows a catheter 6 adapted for insertion
into a human bloodstream, which cathetsr 6 has a top por~ion
7~ within which a measuring ISFET electrode component 1
(Figure 2) is mounted. This measuring ISFET electrode
component 1 i5 positioned such that same will contact blood
A at an opening 11 through the wall of the catheter top 7.
A pair of elec~rical condu~ors 12 connect the electrical
compon2nts of the measuring ISFET transducer electrode 1 to
suitable known FET structures and circuitry, such connection
being to the so-called drain and source location.~ associated
with the measuring ISFET electrode component 1. Electrical
conductors 12 pass through a lumen ~ that is longitudinally
posltioned throughout the catheter 6 in the direction of
arrow ~ ~Figure 2~ such being facilitated by suitahle
electrical contacts 14 (Figure 1).
An annular metal electrode 5 connects the catheter
top 7 to the main body portion of the catheter 6. This
annular metal elec~rode is connected wi~hin ~he elec~rica~
measur.ing ~ystem to function a~ a ~round for the ~,ys'cem in
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accordance with known principles. This metal electrode 5 is
desirable inasmuch as it provides stability as a ground
within the system, but it is not necessarily essential to
the operation of the measuring circuitu
A reference ISFET transducer electrode 2 is
mounted within another lumen 8 of the catheter 6. The wires
of electrode 2 pass throuyh lumen 9~ ~umen 8 and lumPn 9
are ~eparate from each other within the catheter 6 and are
~ubstantially longitudinally parallel with each other
throughout the catheter 6 until a bifurcation 3 at a
proximal location along the catheter 6. The electrical
contacts 14 pass out of one branch of the bifurcation 3,
while a tuhe 4 extends beyond the other branch of the
bifurcation 3 for receiving a length tubing 15 or the like
for communication to a source of rinsing liquid ~not shown).
The reference ISFET electrode component 2 preferably
includes a chip-mounted pH-FET and an AgJAgcl ion-selective
electrode. An openin~ 13 i~ provided through the wall of
the lumen 8 in the vicinity of, and preferably somewhat
distally of~ the reference ISF~T electrode component 2. By
this structure, the rinsing liquid can flow rom its 30urce,
through the tube 4 and out the opening 13 in accordance with
the flow B illustrated in Figure 2. This rinsing liquld is
of a constant p~ and pC1.
It is to be understood that the principles of thi~
invention will also work when the reference FET is sensitive
to other ions, "K.~ In such a ~ituation, the rinsing fluid
has a constant WK" concentration or for a Na~-FE~ and
constant Na" concentration in the rinsing fluid, and so
forth.
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In u~e for actual measurement of the param~ters of
the blood A, the catheter 6 is inserted into the bloodstream
such that the measuring ISFET electrode component 1 is in
contact with the blood A and adjust~ itself to the ion
concentration, typically the pEI~ of the blood. At this
time, the reference ISFET electrode component 2 is in
contact with the rinsing li~uid B and has a constant gate
potential VG2, provided the ion concentrationl typically the
pH of the rinsing liquid, and the liquid-junction potential
are kept constant.
With the measuring I~FET electrode component 1 and
the reference ISFET electrode component 2 of the measuring
system being connected by a differential circuit as shown in
Figure 2, typically a bridge circuit, corresponding changes
in the behavior of the measuring XSFET electrode component 1
Gr the reference ISFET electrode 2 will result in a
corresponding change in the output of the diferential
circuit E~ual changes in ISFET electrode 1 and reference
electro~e 2 will not give a change in output signal because
~0 of the differential nature of ~he circui-~. Those equal
changes may be due, for example, to drift, temperature
changes, aging, and the like. Components included in the
ion concentration mea3urement system of generally known
construction include an electrical voltage source for
~5 applying the drain ~ource voltage VDs within each FEq~
component 1 and 2, a voltage source for applying the gate
voltage VGs between the source and gate by way o the fluid
and the annular metal electrode band 5 r an amplifier ~ystem,
and appropriate current conductive wiring for electrically
3a interconnecting the various components. Detail~ regarding
~ ~2~
these particular component& will be known to those skilled
in the art.
With particular re~erence to the voltage drop
diagram of Figure 4, the voltage VO to be measured i~ given
by the following equation:
VO - (~1 ~ 02 ~ ~L~) x a I d x R
~ VGs
where:
a Id
= transconductance of the FET
~ V~s
0LJ - liquid-junction ~otential - constan~
~1 ~2 ~ ~ pH = pH _ p~
blood rinsing liquid
Consequently: VO ~ a p~,
The ~ctual p~ value of the blood measured in
accordance with this invention is obtained by addin~ the p~
valu~ of the rinsing liquid to the p~ that is actually
measured by the dîfferential circuit.
If desired or neces~ary, an in vivo calibration of
the ion concentration measurement system according to this
invention can ~e performed in a relatively simple manne~.
First, the reference ISFET electrode component 2, with its
Ag/AgCl electrode, is exposed to the rinsing liquid, and the
in~trument is set to the ion concentLation, typlcally the p~
value, of the cinsing liquid, In a ~ubsequ~nt/ se~ond step,
blood is admitted into the lumen 8 and into contact with the
reference IS~ET electro~e component 2~ and the output signal
VO of the differential circuit is noted~ If the VO has a
value of other than zero mVolts, then the settiny of the
measuring IS~ET electrode component 1 is adjusted until the
magnitude of the output ~ignal VO of the differential
circuit is zero mVolts, Before employing ~he ion
concentration measurement system to accomplish actual
measurement or monitoring, the blood within the lumen 8 can
be expellea from the lumen 8 by means of the rinsing liquid,
after which the ion concentration measurement system is
suitably calibrated and ready for use. By the first
calibrating step, in which the reference ISFET electrode
component is exposed to the rinsing liquid, a possible
mis-setting of the reference ISFET electrode component 2 is
cvrrected, while in the second calibrating skep, a possible
mis-setting of the measuring ISFET electrode component 1 i~
corrected.
It is also po~sible to perform an in vivo
calibration of the ion concentration measurement sy~tem
accordiny to this invention when the reference FET electrode
is not provided with an "on-chip~ Ag/AgCl electrode in
following manner~ First~ blood i~ admitted into the lumen 8
and into contact with the reference ISFET electrode
component 2, which for example i~ a pH-FET, and the output
signal VO of the differential circuit is noted. If the VO
has a value of other than zero mVolts, then the setting of
the differential circuit is adju~ted until the magnitude of
the output signal VO of the differential cir~uit i~ zero
mVolts. In a subsequent or second step, a rinsing fluid
with a p~ different from that of the original rin~ing fluid
is admitted into the lumen 8 and in contact with the
re~erence ISFET electrode component 2, and the output signal
VO of the differential circuit is noted.
The output voltage VO now should be in accordance
with the pH difference between the pH value of this rinsing
solution and that of the originally used rinsing solution.
If the VO displays another value, the setting of the circuit
is adjusted until the magnitude of the output voltage shows
the proper value. Before employing the ion concentration
measurement system to accomplish actual measurement or
monitoring, the calibration rinsing solu~ion in lumen ~ can
be expelled from the lumen 8 by means of the original
rinsing solution, after which the ion concentration
measurement is suitably calibratecl and ready for use.
By virtue of the irst calibratin~ step in which
the refeence ISFET electrode is exposed to blood, a
possible off-set or mis-setting between the ISFET electrodes
1 and 2 is corrected, while in the second step a possible
change in pH-sensitivity o the system is corrected~
If the chip of the reference ISFET electrode
componellt also includes a temperature sen~or, in vivo
calibration is possible as discussed above. A~ditionally,
such is accomplished without requiring special catheter
construction and without the necessity of having to take
2S blood samples by which the calibr~tion must be performed~
Although it is desirable to have the reerence
ISFET electrode component 2 mounted at a locatiQn that is
generally close to that of the measuring ISFET elec~rode
component 1, such as the construction shown in Figures 1 and
2, it is possible to mount the reference ISFET electrode
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component 2 at a more remote location, such as within the
bifurcation 3, within the liquid connector or tube 4, or
even within the external rinsing liquid system to which the
tubing 15 is attached.
It will be understood that the embodiments of the
present invention which have been described are illustrative
of some of the applications of the principles of the present
invention. Numerous modifications may be made by those
skilled in the art without departing from the true spirit
and scope of the invention.
