Note: Descriptions are shown in the official language in which they were submitted.
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S P E C I F I C A T I 0 N
This invention relates to a means and method for
monitorlng blood glucose levels and to elements employed in
the practice of same.
Referring to diabetes, as illustra-tive of the need
for rapid and frequent analysis of blood glucose levels, diabetes
is characterized by elevated blood glucose. The severity o~
this disturbance, and the extent to which diet and insulin
treatment are successful in maintaining blood glucose in the
normal range is believed to determine onset and severity of
the devastating renal, retinal and cardiovascular manifesta-
tions of the disease.
In di.abe~ic patients dependent on insulin injections,
total absence of endogenous insulin, antibody agains~ insulin,
or less understood types of "insulin resistance", control o~
glucose can be particularly difficult.
In these patients, checking for spill of glucose into
the urine and spot blood glucose determinations on an out~patient
basis may not provide sufficient information to bring blood
glucose back under control. Thus hospitalization for more
inter.se study is required.
Furthermore, determining glucose spill into the urine
can sometimes lead to an erroneous judgment abou-t the patient's
current insulin requirement~ Thi.s is because some diabetics
spill glucose into the urine from ~he effects of too much,
rather than too li~tle, insulin, The cause of this seeming
paradox is recurrent hypoglycenic insulin reactions. Each of
these reactions is ~ransient and may or may not cause symptoms,
but is ~ollowed by a massive rebound hyperglycemia, ~ediated through
adrenalin and glucagon reIease and less well understoo~ mechanism,
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To evaluate and successfully -treat ~hese patients, -the physici.an
must obtain frequent blood ylucose determinations.
Frequent blood glucose de-termination is also desirable
when a diabetic patient is acutely ill, undergoing surgery,
childbirth, or su~fering from severe ketoa~idosis~ occasionally,
non~diabetic patien-ts such as the acutely.il:L patient treated
with a pharmacoloyic dose of corticosteroid, or the patient
with recurrent fainting spe~ls who is suspect of having func-
tional hypoglycemia needs to have frequent serial blood glucose
determinations madeO
In summary~ there is a need for an instrument, pxefer-
ably a portable instrument, suitable for continuous glucose
monitoring~ Numerous attempts have been made to provide this
capability but, to the present, no instrument has emerged which
is sufficiently free from problems for acceptance into broad
clinica]. use. Problems encountered have included poor precision
of the glucose detector, clotting and drift in khe blood sampling
system, and non-linearity of the signal output. Such instruments
tend to be complicated and have required ~requent and sometimes
complex calibration.
It is an object of this invention to provide an
instrument and method for fxequent and rapid analysis of blood
glucose, which is relatively free of the problems heretof~re
encountered, which is portable to enable use for a bedside
2S instrument for continuous monitoring of blood glucose levels
in a patient, which can be automated for maintaining a pre-
determined analysis program, and which is relatively free of
clotting and/or dri~t in the system for blood sampling and
linear in the signal output, and it is a related ob~ect to
produce and to provide elements for use in the successful
operation of the blood glucose analyzer for monitoring blood
glucose levels.
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Thus, ln accordance with the present invention, -there
is provided a method for monitoring blood glucose levels
comprising the steps of equalizing the oxygen concentration in a
bloocl sample by con-tacting the sample with a:ir for a sufficient
length of time to effect oxygen equalization~ transferring the
sample after air-oxygen equalization to a sensor having an elect-
rode covered with a hydrophobic membrane hav:ing a surface on which
glucose oxidase is immohilized whereby oxygen is consumed by
reaction with glucose in the blood in the presence of the
glucose oxidase, and measuring oxygen consumption resulting from
the reaction of glucose in the blood in determining the level of
glucose in the blood.
In another aspect, the invention provides an apparatus
for monitoring blood glucose levels comprising a sensor having
an electrode, at least a portion of which is covered with a
hydrophobic membrane having glucose oxidase enzyme immobilized
to a surface portion thereof, a canula adapted to mount a
catheter for withdrawing blood from a patient, a source of IV
solution and means connecting the source of IV solution with -the
canula for draining the IV solution back through the canula to
the patient when blood is not being withdrawn, a pump having an
inlet connected to the canula and an outlet connected to waste,
a source of buffer solutionl an equalizing member for equalizing
the temperature and oxygen level of an increment of blood to be
sensed, a syringe having an inlet connected to the source of -the
buffer and an outlet connected to the canula for flushing said
increment of withdrawn blood to the equalizing member, another
syringe having an inlet connected to the sensor for withdrawing
liquid that has been sensed and an outlet connected to waste~
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and a passage communicating the equalization member with the
sensor for the -transmission of an equalized increment of blood
to the sensor for determination of the leve:L of glucose in the
blood in the presence of the sensor.
Particular embodiments of the present invention will
now be described for purposes of illustration, but not of
limitation, wi-th reference to the accompany:ing drawings, in which:
Figure 1 is a flow diagram of a blood glucose analyzer
embodying the features of this invention;
Figure 2 is a flow diagram similar to that of Figure 1
with modifications in the analyzer;
Figure 3 is a graph of the determination for blood
glucose levels derived from the example in the application; and
Figure ~ is a schema-tic sectional elevational view of
an electrode embodying the features of this invention.
In accordance with the practice of this invention, use
is made of a glucose detector embodying an immobilized enzyme
electrode which can be operated in a rate detection mode. The
high performance of the detector is based, in part, on the
development of an electrode covered with a hydrophobic membrane,
*
such as Teflon, having glucose oxidase bonded onto the surface
thereof in an immobilized state.
The invention will be described with reference to an
instrument, diagrammatically illustrated in Figure 1, for analysis
of blood glucose at frequent intervals for substantially con-
tinuous monitoring of glucose levels in patients' blood. While
description will be made for operation over 2 minute intervals,
it will be understood that the frequency of determinations for
blood glucose levels can be made on more frequent or less frequent
intervals, but on an intermittent basis, as will hereinafter be
described.
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The instrument diagrammed in Figure 1 comprises asmall bore plastic tube 10 fitted with an inLravenous single
lumen luer lock ll connected catheter 12. Connected to this tube
via line l~, fitted wl-th a pinch val.ve 16, is an intravenous
infusion bag 1.8 adapted to be filled with a s~erile pharma-
col~gical saline solution containing sufficient heparin, about
400 ~ per liter, for infusion to prevent any thrombus formation
in the catheter between cycles for drawing patient's blood.
Also connected to the tube 10 is a second line 20 leading to a
container 22 adapted to be filled with a solution containing
a calibrated amount of glucose for calibrating the instrument,
the flow of which into the tubing system is controlled by a
pinch valve 24.
A blood sample loop 26 of a measured volume is inter-
posed in the line between a blood sample pump 28 and the catheter,
preferably between the inlet from the source of calibrating solu-
tion and the pump, with pinch valves 30 and 32 on opposite sides
of the loop for closing off the loop, One end of the blood sample
loop 26 is connec~ed by line 34 to the analyzer 36 with a pinch
valve 38 to isolate the loop from the analyzer, while the other
end of the loop is connected by line 40 to the outlet of a
syringe 42, The inlet of the syringe communi.cates through line
44 to a source 46 of a buffer solution 48 such as a phosphate
buffer, with pinch valve 50 in line 40 to isolate the blood
sample loops from the syringe, Line 52 connects the outlet
from the pump 28 to waste which may be in the form o-f a waste
container 54.
In the illustrated modification, the analyzer 36 is
~ormed with an upper compartment 56 for first bringing the
blood sample to oxygen and temperature equilibrium before the
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sample is displaced from the upper compartment to a lower
electrode sensing c~vette 58 containing the enzyme electrode
glucose sensor 60, hereinafter to be described in greater detail,
and a magnetic stirring bar 62 for rapid mixing of the sample
during analysis~
~ he cllvette is provided with an out:let in the bottom
portion which is connected by line 64 to the inlet of syringe 66
while the outlet from the syringe 66 is connected by line 68
to waste, such as container 54. The cuvette is also provided
with an inlet connected by line 70 to the outlet from syringe
72 while the inlet to the syringe 72 is connected by line 74 to
a source 48 of a buffer solution, such as a phosphate buffer.
The cuvette is provided with an orifice 90 to maintain the cuvette
at atmospheric pressure.
The upper compartment 56 has an outlet 76 in the upper
portion connected by line 78 to a source of negative air pressure,
indicated by the numeral 80, and to a source of positive air
pressure, indicated by the numeral 82. The line 78 is provided
with a valve 84 for controlling communication of the negative
air pressure line and a valve 86 for controlling communication
with the positive air pressure line.
The syringes 42, 66 and 72 are preferably joined in
a syringe table 88 for conjoint actuation of the piston type
actuator in each of the three syringes.
In operation, with valves 16, 24, 38 and 50 closed,
and valves 30 and 32 open, the catheter 12 is connected into a
blood vessel of the patient and the pump 28 is operated over
a 20 second period for withdrawal of patient's blood into and
through the sample loop 26 to fill the loop. In the illustrated
modification, when use is made of a canula 10 having a diameter
of 0.03 inch and a length of 3 feet, 200 microliters of blood
is drawn over a 20 second interval to fill the sample loop 26
with the patient's blood, At the same time, the syringe table
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is raised to draw buffer into the syringes 4~ and 72 and to
empty the electrode cuvette by withdrawal of the contents
thereof into the syringe 66.
During the remainder of the blood analysis cycle,
and until the next cycle occurs, with valves 30 and 32 closed
and valve 1~ open, heparinized saline drains back through line
10 at a rate of 1/2 to 1 ml/minute -to flush the catheter to
prevent any thrombus formation in the catheter.
Meanwhile, with valves 38 and 50 open and valves 30,
32, and 86 closed and valve 84 switched to negative air pressure,
the syringe table is operated to displace fluids Erom the syringes
to (1) deliver waste from syringe 66 to the waste container 54,
(2) deliver buffer from ~he syringe 72 through line 70 to the
electrode cuvette 58, and (3) to flush the sample from the sample
loop 26 through line 34 into the equilibration chamber 56. The
blood sample trapped in the sample loop, in a measured amount
of 40 microliters, is thus washed into the chamber 56 wi~h 200
microliters of buffer, such as a 0,2 M phosphate buffer at pH 6Ø
After the blood sample has been delivered to the
equllibration chamber 56, equilibration of the whole blood sample
to 37C and ~he oxygen tension to that of ambient air is
achieved by opening valve 84 to activate the negative air pres-
sure system which draws room air which has been equilibrated to
36C upwardly through orifice 90 through a distributor a~ the
base of chamber 56 whereby the air rises through the whole blood
sample as bubbles. Equilibration can be achieved by ~ubbling
air through the sample and buffer solu~ion in the chamber for
40 seconds to equi~ibrate the sample ~o room air P02,
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Ahout 2 seconds a:E-ter equilibration has been
achieved, valve 84 isclosed and valve 86 is opened to activate
the positive pressure system (under about 5 psi) which causes
rapid transfer (in about 0.5 second) of the equilibrated whole
blood sample from the eq~lilibration cham~er 56 to the electrode
sensing cuvette 58 which contains bufer solution, such as 2 ml.
of pH 6.0 phosphate buffer delivered from the syringe 72~ The
enzyme electrode sensor then makes a rate determination of the
glucose concentration.
In the presence of glucose, oxygen tension rapidly
falls as oxygen is consumed at the electrode -ti.p. The maximal
rate of fall in oxyten tension is recorded and detected in less
than 3 seconds. This rate is proportional to glucose concentra-
tion because of the stoichiometric relationship between oxygen
and glucose that is apparent from the following equation:
Glucose + 2 glucose gluconic acid + ~22
oxidase
Following each analysis the system is adapted auto-
matically to wash the sample loop 26, the equilibration chamber
56 and the reaction cuvette 58 be~ore another cycle.
In the illustrated modification, a cycle is carried
out over a period of 150 seconds, makiny it~possible to monitor
the blood by separate analysis every 2-1/2 minutes.
In operation, patient's blood is drawn in an amount
to ~lush the heparnized solution from the tu~ing and to fill
the loop, with the interim fluids being pumped to waste
~he apparatus is periodicall~ standardized by opening
valve 24 before r after the catheter 12 is inserted so that, upon
operation of the .pump 28, standard solution with a known
amount of glucose can be drawn into the loop 26, after ~hich
the described normal sequence of operations are csrried out
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to flush the calibrating sol.ution from the loop 26 into the
equilibration chamber 56 ~or equal.ization of temperature and
oxyyen and then from the chamber 56 into the enzyme electrode
glucose sensor 60 ~or analysis.
The.described sequence o-E operations of the valve,
pump and svringe table can obviously be connected with suitable
electrical controls for automatic seguencing of the operations
on a controlled time basis for testing for blood glucose levels
on repeated cycles of uniform duration whereby reliable compari-
sons can be made ~or following the course of medical procedure
and/or the patient's well being.
The reliability o~ the test results depends somewhat
on the eguil.ibration of the blood samples and calibrating solu-
tions for temperature and oxygen levels before the rate determina-
tion is madeO Use can be ~ade of other means for temperature
and oxygen equilibration of the fluids subiected to the test.
For example, instead of making use of an equilibration chamber
56 of the type illustrated in Figure l, use can be made o~ a.n
oxygen equilibration coil of'the type illustrated in the port-
able glucose monitor illustrated in Fiyure 2 of the drawingO
Brie~ly described, in t'he illustrated porta'ble unit,
blood is drawn by pump 100 from the patient 102 throuyh the
canula 10 inan amount to fill the blood sample loop 106.
The outlet from the pump lO0 i5 connected by line 108 to a
waste bag llO. A standard solution for calibrating the-unit
is provided in container 112 connected to a portion of the
canula 104 in advance of the loop, as in the apparatus illus-
tra-ted in Figure 1, and a bag 114 of IV solution is also
provided as in the apparatus illustrated in Figure 1, for Elow
of IV solution to the patient while the removal of whole blood
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is stopped Suitable valve members 116 and llS are provided
for controlling ~he flow from the calibration container and the
IV bottle respectively.
A compact motorized syringe table L20 :is provided ~or
operating syringes 122, 124 and 126, The inLet to syringe 122
is connected to one end of the blood sample loop for drawing
the measured amount (40 microliters) of blood from the loop
plus buffer wash solution from buf~er bag 132~ The outlet
is connected to an oxygen equilibration coil 128 of the type
well known to the skilled in the art and made of a gas pervious -
fluid imprevious fabric which allows oxygen from the environment
to penetrat~ into the coil for equilibrating the oxyyen concen-
trat~on in the blood sample. The oxygenated blood sample is
drawn by syringe 124 from the coil 128 and displaced into the
receiving coil which is also formed of a fiber oxygenating
tubing and from which it is flushed with additional buffer drawn
from the buffer bag 132 through line 134 into the syringe 126
for displacement to the differential oxygen~glucose electrode
136 for evaluation7 as previously described. The material is
flushed to the waste bag 110 before a next cycle of operation
is initiated.
Temperature equilibration is effected by housing the
buffer bag 132 and the coils 128 and 130 in a temperature con-
trolled environment~such as at a temperature of 37C, as outlined
by the broken lines in Figure 2 of the drawingO
In the modification illustrated in Figure 2, themixing coil 130 may be dispensed with along with syringe 124
whereby syringe 126 operates to draw the equilibrated blood
sample from the coil 128 along with the additional buffer for
admixture therewith before introduction into the analyzing unit.
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To -the presen-~ th~ deter~in~tion of blood (~hole
blood plasma or serum) has been made wi-tn a ~lucose o~idase
enzyme reac3ent, as described in Clin~ Chem. 1~ 116(1968). ~;hen
glucose is added to the enzyme reagent in a stirred thermostated
cell, ylucose reacted with -the oxygen in the pxesence of glucose
o~idase in accordance with the reaction
O Glucose oxidase > Glucc?nic Acid ~ H2O2
The amount of glucose is measured indirectly by
measuring the amount of dissolved oxygen in the reaction
solution.
Such techni~ue, which makes use of glucose oxidase
enzyme reagent, finds a number of objections from the stand--
point of cost of the reagent and the time consumed for making
a determination.
An important factor in the test procedure and apparatus
described resides in the utilization of an electrode in which a
small amount of glucose oxidase enzyme is irnrnobilized on the
membrane of the oxygen electrode thereby to eliminate the
need for an enzyme reagent and markedly to increase the response
and speed for making a determination.
An important inventive concept resides there-fore in
the -fabrication o-f an electrode having a membrane of hydrophobic
material, such as Teflon, a portion of which, preferably at
the electrode tip, is converted to a hydrophilic surface on
which the glucose oxidase enzyme can be imrnobilized as by a
stable covalent bond. The result is an oxygen sensor in which
the only element that would penetrate the membrane is oxygen
since others of the elernents are either no_ volatile enouyh-
andJor are too polar.
Oxygen a-t the electrode tip is consumed in the pres-
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ence of glucose oxidase. Under such circumstances, use can be
made of a rate de~ermination based upon the c:urrent output of
the electrode due to the presence of glucose in the sample being
tested. Under such circumstances, the electrode can exhi.bit
some slow baseline drift while an accurate determination can be
made within a few seconds. All that is required is the blood sampl
be diluted in a suitable buffer and equilibrated to room tempera-
ture and ambient oxygen level before the analysis is made.
Thus the blood sample is drawn from the patient and
equilibrated from the standpoint of temperature and oxygen by
exposing the sample to oxygen in air, as by the bubble method
oE the equilibration chamber 56 or by the diffusion method of
the equilibration coils 12~ to give the sample the oxygen
tension that is ambient. Thus when initially pulled by the
electrode, the electrode will read the starting oxygen tension.
If ~lucose is present, the o~ygen at the electrode tip is
consumed, the effect of which is to enable a rate determination
to be made from the flow of electrons based on oxygen penetra-
tion to the cathode tip of the electrode.
Briefly described, the hydrophobic electrode membrane~
such as a membrane of Teflon* or otherhydrophobic plastic mater=
ial, is etched to convert the hydrophobic surface to one that is -
hydrophilic. This can be accomplished, for example, with a
commercial preparation of metallic sodium in naphthalene/
tetrahydrofuran, such as marketed by Loctite Corporation of
Newington, Connecticut. The smaller the area covered by the
glucose oxidase, the more effective the analysis, since sur-
face area is not critical when use is made of a stirred solution
of the material being tested. In fact, it is sufficient if
only the tip, such as a round area 25 ~ 200 microns in diameter,
is treated.
* Trade ~ark
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For this purpose, a drop of the etchant can be
placed on the men~rane tip for l minute and then rinsed
with acetone and ~ater,~ollowed by drying.
Next, the enzyme is mobiliæed as by covalent bonding
the treated surEace. Attachment is made with f_he aid of a
thin layer of protein gel containiny glucose ox dase enzyme.
A solution o~ yelling protein, glucose oxidase and fixative
is prepared immediately before application to the etched
surface of the membrane. The following is an example of a
~ 10 formulation which may be used:
4 volumes o-f Glucose Oxidase solution, Type VI,
available from Sigma chemffcal Company,
St. I,ouis, Missouri
1 volume of 20% by weight Bovine Albumin in
solution in water
1 volume of a 4% of a paraformaldehyde solution
in water
A drop of the solution is placed on the etcF~lng
area of the membrane, as with a plastic micropipet tip. The
tip o~ the pipet is emptied of solution and used to remove
as much solution as possible from the drop on the membrane.
The remaining thin layer of solution is aried at room tem-
peratu~e for l minute and then drying is continued while the
treated membrane is refrigerated at 4~C ~or several hours.
The prepared glucose oxidase membrane is used in place
of regular Te~lon*membrane in a commercial glucose analyzer
instrument, such as marke.ed by seckman Instrument Company
o, Fullerton, California, wlth no substantial alteration of
the analyzer or the sample size of the plasma required for
analysis The membrane, stored at 4C, has a shelf life of
at least 8 n~onths and its useful life will depend some~hat on
the steps taken to prevent growth oE microorganism
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Covalent bonding of the enz~ne-gel preparation occurs
by reaction with groups on -the treated hydrophilic surface of
the hydrophobic membrane, such as with carbonyl, hydroxyl and
carboxyl groups. Instead o-E paraformaldehyde for immobilization
and fi~ing of the enzyme, the enzyme can be immobilized on the
membrane by the use of o-ther bifunctional compounds having
one group that attached to the etched surface and one or more
other groups that provide sites for attachment of the enzyme,
Representative of such other fixatives or immobilizing agent
are butyraldehyde, carboxiimide, formaldehyde and other well
known bifunctional coupling agents. The protein carrier gel
may not be essential to the fixation of the enzyme onto the
treated surface, since it can be entirely eliminated or other
carriers can be employed.
Example 1
The precision, accuracy and linearity of the automated
glucose analyzer is demonstrated, using standards made up in
distilled water and whole blood by addition o~ appro~riate
amounts of gravimetrically determined glucose. The aqueous
standards were prepared by dissolving lO grams of dextrose in
l liter of distilled water, 24 hours was allowed for muta-
rotation. Serial dilutions were then prepared to produce 50 ?
100, 200, 300, 400 and 500 mg/dl standard. The whole blood
samples were anti-coagula-ted with 200 mg ethylene diamine
tetramine (EDTA) per liter of whole blood.
An anesthetized dog was used for the analysis. The
analyzer was connected to ~he right jugular vein of the dog
with a 21 gauge pediatric scalp vein needle, The left jugular
~ein was canulated to allow discrete blood sampling for refer-
ence glucose analyzing~ and for infusion of glucose and insulin.
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Reference glucose determinations were made on a Beckman glucose
analyzer.
At the start of the experiments, the automated glucose
analyzer was calibrated with 100 mg/dl glucose s~andard. A graph
representing the data from a typical experirnent is presented in
Figure 3 of the drawings. As indicated in the graph, 37 minu-tes
after the experiment started, a 16 gram glucose bolus was given
intravenously. 67 minutes after the start of the experiment,
16 units of regular insulin was given intravenously. At 90
minutes after the start of the experiment, 16 grams of glucose
was infused.
It will be noted from the graph that the amount oE
glucose detected in the blood rose precipitously each time upon
infusion of glucose and that the amount of glucose in the blood
was determined as having fallen to lower levels in response to
the infusion of insulin.
~ ith daily use of the instrument described, sufficient
enzyme activity remained îmmobilized on the membrane having the
electrode so that it was necessary to change the membrane only
after two to :Eour wee~s, providing the membrane surface contact
and antibacterial solution such as a solution of benzoic acid
in 0.2 M phosphate buffer at pH 7.4. If the same enzyme membrane
is used briefly daily and stored at 4C when not in use, loss
of enzyme activi~y over a one month period will be found to be
less than 5%.
The electrode employed in the practice of this inven-
tion, with the enzyme immobilized on the surface of the membrane,
is illustrated in Fig. 4 wherein the base of the electrode com-
prises a glass rod 150 having a cathode in the form of a platinum
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electrode 152 whicl~ extends to the tip of the rod 150, and
anodes in ~he form of silver chl.orlde reference electrodes 154
~hich extend into the space between the encl port:ion of the glass
rod a-nd a Teflon membrane ]56 that is secured onto the end of
the electrode ~ith a space 158 in between that is filled with
elect~olyte 160. Tl~e membrane of Teflon is releasably mounted
onto the end portion of the glass rod by means of an O-ring 162
which seats in an annular groove 164 of the rod sealably to
engage portions of the membrane 156 which span the groove. The
enzyme is immobilized on the gel layer 166 bonded, as heretofore
described, on the outer surface of the membrane layer, at the
tip portion of the electrode. The electrode is similar in con-
struction to that described in U.S, Pa-tent No. 3,5~l2,662 except
for the membrane with the enzyme immobilized in a layer bonded
to the outer surface of the membrane at the tip of the electrode.
As previously described, the blood glucose analyzer
of this invention is based on a polargraphic detection system
in which the specificity for oxygen is e~cellen-t since oxygen
is the only electro-active substance in blood defusible through
a Teflon*membrane for reaction at the elec-trode. The specifi-
city of glucose oxidase for glucose has also been established.
By operation of the glucose sensor in a rate determination
mode, any base line drif-t in the oxygen electrode is eliminated, -
There are a number of distinct advantages to the
invention described and claimed? namely: the blood samplingcan be carried out on frequent intervals, such as 150 seconds~
This minimi.zes the amount of blood removed from the patient
for analysis and facili~ates the maintenance of a clot-free
sampling system by comparison with continuous sampling, The
* Trade Mark
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amount of heparin infused into the patient between sampling
cycles is not sufficient to cause any significant deyree of
systematic heparnization~ By avoiding infusion of the sample
blood back into the patient,the chance of sepis is greatly
reduced. The use of an immobilized enæyme clectrode in the
glucose detector permits miniaturization and simplification
of operation with minimal reagent requirement. Within seconds
after sampling, the result can be secured for the glucose
concentration in the patient's blood.
It will be apparent from the foregoing that a
significant improvement is provided in a system for blood
glucose analysis and in elements employed in analysis e~uip-
ment whereby rapid and accurate determinations of blood glucose
can be made on site for monitoring glucose levels in a patient's
blood.
It will be understood that changes may be made in
the details of construction, arrangement and operation, without
departing from the spirit of the invention, especially as
defined in the following claims.
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