CA1313486C - Product for chemical measurement of blood and method for producing same - Google Patents

Abstract

ABSTRACT

A flexible gas-impermeable package containing a blood facsimile reference solution for use in blood gas electrolyte analysis comprises ionic potassium and calcium, tonometered at elevated temperature with oxygen and carbon dioxide. The package content is free of voids. The solution is produced by constituting an aqueous buffered solution containing ionic potassium at a predetermined concentration and subjecting the solution to tonometry with said gases.
Following start of tonometry, ionic calcium is admixed in a predetermined amount with the tonometered solution. During the packaging process the solution is maintained at subatmospheric pressure ranging from 625 to about 700 mm Hg and at a temperature higher than the use temperature.

Description

3 ~ 8 ~

This invention relates to a pacl~age containing a blood facsimile reference solution for use in blood gas electrolyte analysis and a method or producing a packaged blood facsimile reference solution. This ~ 5 application is a di~ision of Canadian patent : application serial No. 504,268 filed March 17, 1986.
In a variety of clinical situations it is ; important to measure certain chemical characteristics of the patient's blood quch as pH, concentrations of calci.um, po-tassium ions and hematocrit, -the partial pres ure of 02 and C02 and the lilce. (See, for example, Fundamentals of Clinical Chemistry, Tietz, Edi-tor, page 135 et seq., Electrochemistry; page 849 et seq., Blood Gases and Electrolytes; 1976, Saunders ~` 15 Company, Phila.). These situations range from a routine vi~it of a patient in the physician's office to monitoring during open-heart sur~ery for which situa-tions of the required speed, accuracy and similar performance charac-teristics vary with each situation.
Measurement of chemical characteristics of blood during open-heart surgery provides the most demanding set of criteria. Presently, blood gas analysis during major surgery is provided by repeated tra.llsfer of ~ ~k ...
,, ~ 3 ~ 3 ~

discrete blood samples -to a permanent lab-based blood gas analyzer or by use of sensors placed in-line with the extra-corporeal blood circuit of a hear-t-lung machine employed -to bypass the patient's heart.
The transfer of discrete blood samples, required by blood-gas analyzers inheren-tly increases the risk oE
contaminating the blood sample with the ambient airl whicll may alter certain of the monitorecl oharaoteristics. ~dditionally, since such analyzers are complex and aostly clevices, they are typic:ally located only in the hospital ].ab where -they need to be operated by a skilled technician, resulting in undesirable delay during surgery, critical care or intensi~e care. Furtherg such analyzers employ bubble tonometers to generate a suitable electrolyte referent mixture by dissolving quantities of gases, stored in pres~urized free~standing tanks, into -the electrolyte solution. ~hile replacemen-t o-f theses gas tanks is infrequerltly required, it is a cumbersome procedure.
Finally, these existing analyzers require cleaning to decontaminate all exposed portions from the prior patient's blood prior to subsequent use.
hlthough use of in-line sensors minimized the risk _ 3 _ ~ 3 ~

of contamination during transfer and of delay, they have a response wh:ich normally varies or "drifts"
during use; moreover this drift is not at a constant rate. Present in-line sensors can only be calibrated before they are placed in -the extra-corporeal circuit.
Thus, the inherent drift of these in-line sensors cannot be monitored, resulting in reading of ever decreasing reliability as time passes.
The system disclosed herein provides quicll, on-si-le oontemporaneoll~ blood chernis-try analysis, with minilnal risl~ o~` contamina-tion, and maintains its accuracy over its useful life.
According to the present invention, -there is provided a blood facsimile reference solution for use in blood ~as electrolyte analysis, comprising ionic po-tassium and calcium and tonometered at e]evated -temperature l~ith oxygen and carbon dioxide, the package content being free of voids.
According to another aspect of the invention, there is provided a method of producing a packaged blood facsimile reference solution containing oxygen gas, carbon dio~ide gas and ionic potassium and calcium, comprising constituting an aqueous buffered 3 ~ 3 ~

solution containing ionic potassium at a predetermined concentration, subjecting the resulting solution to tonometry with said gases, and following initiation of tonometry admixing ionic calcium in predetermined amount with the tonometered solution.
According -to a further aspect of the invention, there is provided a method of producing a package of an electrochemioally stable tonometered blood ~acsimi:Le solution for storage and for use in b]ood/gas monitoring at atmospheric pressure, comprising ~ packaging the solution in a sealed flexible gas-; impermeable envelope free of voids while maintainirlg the solution at sub-atmospheric pressure ranging from about 625 to about 700 mm Hg and at temperature higher 16 than said use temperature.
A preferred blood chemistry analysis machine is adapted to be connected to a blood collection device, an extracorporeal shun-t, or arl ex vivo blood ~ource such as a heart/lung machine used to sustain a patient during surgery, intensive care, critical care and the like. The machine is designed to allow small test samples of flowing live ex vivo blood to be diverted off-line from either the venous or arterial flow lines :L3tl. 3~-$~

of a flowing blood source such as a heart/lung machine directly in real time -to a chamber exposed to a bank of solid state micro-electrodes which generate electr,~ical signals proportional to chemical characteristics of the real time flowing blood sample.
; The bank of eleotrodes is housed in a disposable cartridge, adjacent to a thermal plate whicll maillt,airls the tes-t sample at a constant temperature. Upon insertion of the cartridge ;.nto a challlber of suitably adapted blood chemistry analysis mac}lh~e, the electrodes conneot l;o an electrode inter~ace wll,ic selects on of` the plurality of electricul si~nals generated by the sensors and passes the selected si~nal to a microprocessor in the machine ~here it is converted from analog to digital form suitable for analysis, storage and display.
A metal plate in the cartridge connects -to a thermal unit in the machine l~hich moni-tors the -temperature of and genera-tes and -transmits heat to the plate and through it to the sample in -the adjacent electrode chamber in order to maintain the sample at a constant temperature.
The car-tr,idge also contains at least one, and .

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preferable two containers of reference or calibrating electrolyte solution (i.e., solution serving for purposes of quality control including calibration, sometimes referred to hereinafter as control or calibration solution), as well as a reservoir suitable to collect waste Eluids following assay. ~pon insertion o-f the cartridge, a selec-tion valve in the cartrid~e connec-ts to a shaft in the machine, con-trolled by the microprocessor, to selectively all.ow either oE the calibrati.rlg solutions or the test sampLe to flow across the eleotrodes.
The force driving the fluid flow through the cartridge (eg, by positive pressure or suc-tion) is provided by a peristaltic pump formed when a set of rotatable drive rollers in the machine pinch exposed por-tions of tubing against the curved wall of the pump slot on the cartridge. The rotation of the rollers forces either the calibrating solutions or a test sample from their respective sources through the cartridge tubing across the electrode chamber and into the was-te collec-tion reservoir. The rotation of the drive rollers is controlled by the microprocessor.
In addition to the features already mentioned, the ~ 7 ~ ~3~

analysis machine houses an internal digital clock which provides a time base for the operation of the system, a bacl~-up battery power source, an operator keyboard, a display and a printer.
In operation, after all connections are suitably made, the selection valve and drive rollers cooperate to cause the calibrating solution to flow into the electrode chamber where a reading is taken and stored in the microprocc?ssor. Subsequenl.Ly all(J in a s.illl;lar manrler, a read.ing o:l` the test sample is taken, anal~zecl by -the microprocessor and displayed. The assa~ed fluids are directed into the waste collection reservoir. The microprocessor controls and repeats this cycle oE calibration and test sample assay at a rate preselected and entered by the operator through the control ]~eyboard. The keyboard also allows the operator to take an immediate asqay at any time, e~en while the machine is in its automatic cycle mode, li.mited only by the recycling time of be-tween two and three minutes. Following surgery, the cartridge and the tubing connecting the venous and arterial flows of the heart-lung machine to the cartridge are discarded and the machine is ready for use with a new cartridge.

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Further features and advantages will be more apparent upon reading the following de-tailed description and by reference to the drawings in which:
FIGURE 1 is a schematic diagram showing the major components of a preferred embodiment of a blood gas analysis system;
FIGURE 2 is an elevated side view of one embodiment of the cartridge useful wi-th the system of FIGURE 1; showirlg the insertiorl end Or tlle curtriclge in tlle foreground;
FIGURE 3 ls a fragmentary perspeotive view of this embodimen-t of the car-tridge;
FIGURE 4, which appears on the same shee-t as FIGURE 2, is a side view of the trailing end of this embodiment of the cartridge;
FIGURE 5 is an exploded view of the selection valve contained in this embodiment of the car-tridge;
FIGURE 6a is a frontal view of -the elec-trode card contained in this embodiment of' the cartridge;
20FIGURE 6b is a cross sectional view of this electrode card; and FIGURE 7, which appears on the same sheet as FIGURES 2 and 4, is a fragmentar~ side view of -the end :

- 9 - ~ 3 ~ 3 wall a-t the inser-tion end of this embodiment of -the cartridge, showing the peristaltic pump slot;
FIGURE 8, which appears on the same sheet as FIGURE 3, is an elevated side view of that portion of the blood gas analysis machine useful with the system of FIGURE 1, adapted to receive and connect suitably -to certain features of -this embodiment of the cartridge;
and FIGURE 9 is a rrontal view o~ one embo(lilllerlt of the oontrol panel of the blood gas analysis machine showing -the display and keyboard.
While the apparatus for chemical measurement of blood charac-teristic of the present invention may be used in a variety of clinical and experimental environments, the preferred embodiment of the inven-tior is described as being used in major surgery. This description should not be taken to limit the applicability of` the presen-t invention.
FIGURE 1 shows in schematic form a blood gas analysis system suitable for use during surgery in which a patient lO is sustained by a heart/lung machine 12.

lo ~ c $ ~) This system allows a test sample of blood to be diverted from either the venous flow 14 or the arterial flow 15 of the heart/lung machine 12, as selected by the system using a two-way valve 18, directly to a cartridge 20 containing a bank of sensing electrodes fi2-69~ These electrodes 62-69 generate electrical signals proportional to distinct characteristics of the blood sample. These signals are transmitted to a microprocessor 100, contained within a blood chemistry analysis machine 80 into which the cartridge 10 has been inserted. After analyzing these signals, the microprocessor 100 controls a display 104 to display the values of these parameters of the blood sample to provide the surgeon with information on the status of the patient 10~
: The system operator uses a keyboard 102 to program the microprocessor 100 with the desired frequency of assays to be made by the system during surgery~ The microprocessor 100 then controls the selection valve driver means 82 in the machine 80 to cooperate with a selection valve 40 in the cartridge 20 to allow the sequential fluid flow from a calibrating solution bag 22 and a calibrating solution bag 24, both contained in the cartridge 20, and then from the venous :

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flow 14 or arterial flow 15, into an electrode channel 61 exposed to a bank of electrodes 62-69. The distinct reference solutions from the bags 22 and 24 provide a two-point calibration of the electrodes 62-69. In a similar manner, at the selected intervals, subsequent assays of blood samples are made, most preceded by one-point calibration, with occasional two-point caLibration made to ensure continued accuracy. Upon completion of the surgery or depletion of the calibrating solutions, the cartridge 20 is discarded and replaced by a new cartridge 20 Eor subsequent use of the system.
All of these features and additional features are explained more fully herein.

Referring now to the FIGURES 2 and 3, there is shown a box-like cartridge 20 which is preferably made of rigid plastic. The dimensions of the cartridge allow insertion into a blood gas electrolyte analysis machine 80, shown in FIGURE 1, appropriately engaging features to be described herein.
The main body of cartridge 20 is partially enclosed to provide protection of its contents, flexible bags which are two calibrations solution bags - 12 - ~ $

22 and 24, and a waste collection bag 28. The calibrating solution bags 22 and 24 have zero head space and contain solutions and dissolved gases therein that preferably are specially formulated as described hereinafter, having known, distinct electrochemica1 characteristics. For a description of the technology of packaged reference or calibration solution, see U.S.
Patent No~ 4,115,336. The third bag 28 or waste collection bag begins in an empty state and is intended to collect waste calibrating solution and blood products following assays. Preferably, the calibrating solut~on bags 22 and 24 are encircled by the two sides of waste collection bag 28, as shown in FIG~RE 4.

The bags 22 and 24 each are gas impermeable and contain an aqueous reference (i.e., calibration or control) solution (a solution electrochemically resembling blood with respect to dissolved gas and electrolyte) having known values of the chemical characteristics over a range of values that the system is intended to monitor. The values of those characteristics are different in the two bags so that by sequential passage of the two calibrating solutions over the electrodes 62-63, a two point calibration or bracket - 13 - ~3~3~3 (e.g~ high and low) calibration of the measurement characteristics of the electrodes may be made~
In order to maintain the concentratlon of gases, such as oxygen and carbon dioxideg at a known constant level in the bags 22 ancl 24, independent of variations in ambient pressure and temperature, the ~ gases are added to the solutions~ during their : packaging, in a special manner~ As a feature of the invention, the packaging in one embodiment to be described is performed under conditions of pressure and temperature which are different from those that will be encountered during normal use of the solutions, so that advantageously the solutions may be fully saturated with the gases at the time of packaging with the important but hitherto unrealized result that these same solutions will be suitably unsaturated during use~ Typically, both the temperature will be higher and the ambient pressure lower during the packaging procedure than will ever be encountered in use~ For example, for a blood facsimile formulation tonometered with oxygen, CO2 and nitrogen, packaging may occur at a pressure above about 625 mgs~ to about 700 mm. Hg and at elevated temperatures in the approximate range from 45 to 50 C~, higher temperatures being unnecessary~ During - 14 ~ 3l~3 packaging, the 1iquids are fully saturated with the gases and the packages are sealed in an effort to minimize entrapped air. It is found that later when the temperature and ambient pressure are at normal use values, the packaged solutions will not be saturated but their analyte concentrations will sti1l be at the known values achieved during initial filling process. Since the solutions are unsaturated, there is no tendency for the gases in the solution to outgas into any gas bubbles formed during use~
By way of illustration but without limitation, a preferred embodiment of reference solutions for dual monitoring as described above, comprises the following solutions designated A and B and their respective methods of tonometry~

Formulations And Tonometry Procedure Calibration Reference Solution A: Na+, Ca+~, pCO~, P~

Prepared at 37C and at atmospheric pressure tonometered with ~% CO2 -N2 gas~
All cornpounds are weighed, combined, and diluted to volume except the calcium salt which is added after tonometering has started~

. 15 ~ 3~ 3 ~L ~ ~

COMPOUND CONCENTRA~ION ~SS. 1.0 L
Buffer, 3-Morpholinopropane- 14.0 mmol/l 2.926 g sulfonic Acid (MOPS) Buffer, NaMOPS 36O0 mmol/l 8.316 g ~ suffer~ NaHC03 14.5 mmol/l 1.218 g NaCL 110 mmol/l 6.430 g NaN3 .01~ w/w 007 g KCl 6.0 mmol/l .447 g CaC~2-2~2 1.25 mmol/l .184 ~
1J 1. ON HCl ca 8 mmol/l ca 8 ml 25 wt. % Surfactant (BRIJ
35) aq. soln.
This gives parameter levels of:
mmol/l . .
L5 pH PCO~ mm Hg PO~ mm Hg K~~-Radiometer K~-Beckman Ca++
7.330-7.3~5 15.5-19.0 116-120 5.6-5.8 5.60-5.75 .85-.95 Calibration Reference Solution 8: Na~ ~ ~ ; pH
Prepared at 50~C and at 700 mm Hg absolute pressure tonometeted with 21~ 2 ~ 4~ C02-N2 gas.
All compounds except the calcium salt are weighed, transferred and combined, and diluted to volume with H20. The calcium salt is added after tonometering has started.

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COMPOUND CONCENT.RATION MASS. 1.0 L
Buffer: Imidazole 50 mmol/1 3.405 ~
Na~SO3 10 mmol/1 1~250 g NaHC03 11.5 mmol/1 0~966 g NaC1 93 mmol/1 5~44 ~
NaN .01~ w/w .007 g KC13 2.0 mmol/1 .149 g CaC12!2H20 0.25 mmol/1 ~037 1.0N HC1 23 mmol/1 23 ml 25 wt. ~ Surfactant (BRIJ ~.25 ml/1 35) aq. soln.
This gives parameter levels of:
mmol/1 -pE~ PCO~ mm Elg ~2~ Ig K~-Radiometer K~~-Beckman _A~-~
6.890-6.910 4~-48 n.o 1.9~-1.9 1.83-1.98 .18-.22 Thus, the reference solution in packaged form for use in blood/gas measuring or monitoring equipment according to a preferred embodiment of the invention comprises a flexible gas-impermeable void-free package ~20 of an aqueous solution electrochemically resembling arterial blood or venous blood. The solution contains electrolyte (ionic potassium and calcium) and dissolved gas at known partial pressure~ The mentioned packaged solution may thus be regarded as an electrochemical facsimile of blood in a stable form such as that exempliEied by reference solution B above~ The total gas pressure in the packaged solution is in the range from about 0.82 to about 0.92 atmospheres (625 to 700 mm ~3 ~ 3~$~

Hg) at use temperature, i.e., temperature encountered during storage and monitorir,g~ The package may be a ilexible bag, as indicated, or other suitable container package~
It is found that the preparation of the above-mentioned packaged blood facsimile involves previously unrealized compatibility problems. In this regard, when constituting the solution by conventional tonometry procedures, one finds that the compounds are incompatible in that ionic calcium separates unmanageably Erom the solution as a non-ionic precipitate~
Therefore, another preferred aspect of the invention eesides in a method of producing a packaged blood facsimile reference solution containing oxygen gas, carbon dioxide gas and ionic potassium and calcium, without the unwanted precipitation of calcium~ The method comprises constituting an aqueous buffered solution containing ionic potassium at a predetermined concentration, subjecting the resulting solution to tonometry with the gases, and following initiation of tonometry admitting ionic calcium in predetermined amount with the tonometered solution, whereby the resulting solution is stable with respect to the desired - 18 - ~3~

ionic parameters and the solution can be suitably packag~d~
Still another preferred method aspect of the invention concerns a method of producing a package of an electrochemically stable tonometered blood facsimile solution, as indicated, for storage and for use in blood/gas monitoring a~ normal atmospheric pressure. The method comprises packaging the solution in a sealed flexible gas-impermeable envelope free of voids (i.e., zero head space) while maintaining the solution at sub-atmospheric pressure and at temperature higher than said use temperature, as described hereinbefore. The packaging can be done in any suitable way by packaging art means which per se may be conventional.
A preferred embodiment of the package aspect of the invention concerns a flexible gas-impermeable package~ The package contains a blood facsimile reference solution for use in blood gas electrolyte analysis, comprising ionic potassium and calcium and tonometered with oxygen and carbon dioxide, the package contents being entirely liquid and free of voids or bubbles under conditions of use.
Both calibrating solution bags 22 and 24 contain tube fittings 26, as shown in FIGURE 3 and 4, which connect in turn to their calibrating solution 19- ~3~

tubes 23 and 25 respectively. The ca1ibrating solution ; tubes 23 and 25 subsequerltiy connect to a selection valve 40 as described later.
The waste collection bag 28, suitable for collection of waste blood products and calibrating solutions following assay, is formed of a materia1 which is semi-permeable to gases but impermeable to the liquid component of blood and to the calibratillg solutions. It is thus intended that only the liquid component of blood and of the caLlbrating solution will occupy space in the waste collection bag 28. In the preferred embodiment, the bags 22, 24 and 28 are contained in the main body of the cartridge 20 such that as the waste collection bag 28 fills, it will occupy the space created by the emptying of the calibrating solution bags 22 and 24.
The waste collection bag 28 also has a tube fitting 26, shown in FIGURE 4J connected to a waste tube 76, which originates at the discharging end of the electrode card 60. A check valve 77 (FIGURE 3) is disposed in the flow line to the collection bag 28 to prevent back-flow~
The trailing end of the cartridge 20, bei~g the end opposite to the cartridge which is inserted into - 20 - ~ 3~

the blood gas analysis machine 80, contains a blood intake port 30, shown in FIGURES 2 and 3, connected by tubing 16 to either the venous blood flow 14 or the arterial blood flow 15 of a heart/lung machine 12 used to sustain the patient 10 during surgery~ The system operator controls the selection of a blood sample from either the venous flow 14 or the arterial flow 15 by use of a valve 18 in the tubing 16~ The blood intake port 30 is connected by a blood intake tube 32, passing through the interior of the cartridge 20 between the bags 22 and 24, to the selection valve 40 at the insertion end of the cartridge 20.
; As shown in FIG~RES 2 and 3, the insertion end of the cartridge 20 includes a selection valve 40, an : 15 electeode card 60, a peristaltic pump slot 74, and a metal plate 70 In the preferred embodiment, this insertion end of the cartridge 20 is protected by the overhanging sides and top of the plastic encasing material of the cartridge 20 but is exposed to the connecting portions of the blood gas analysis machine 80.
Referring to FIGURES 2 and 3, the selection valve 4~, the electrode card 60, and the peristaltic pump slot 74 are all intended to connect with appropr;ate contacts in the blood gas analysis machine - 21 - ~3~3~

80b The insertion end wall 50, formed of plastic, serves to provide partial protection to the bags inside the main body of the cartridge 20, and to provide well-positioned contact between the appropriate portions of the cartridge 20 and the blood gas analysis machine 80 upon insertion of the former~
As shown in FIGURE S, the selection valve 40 has a rotating plug 42, formed of a thick ring of plastic, which houses the electrode input tube 58, cunning ultimately to the input end of the electrode channel 6l. The rotating plug 42 is held flush against the insertion end wall 50 by a bolt 46 passing through the center of the plug 42 and through the end wall 50 into the interior of the cartridge 20. As the bolt 46 extends into the interior of cartridge 20, it passes through a spring 48 ~hich seats against a nut 47 which in turn serves to seat the plug 42 flush against the head 44 of the bolt 46. The spring 48 thus serves to urge the rotating plug 42 against the insertion end wall 50~ The exterior end of the bolt head is recess le~g., Allen-recess) adapted to receive a drive shaft 84 in matching relation when the cartridge 20 is inserted into the machine 80~

. .

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The rotating plug 42 seats against that portion of the insertion end wall 50 having three ports 52l 54 and 55~ A blood sample por~ 52 connects in the interioe of the cartridge 20 to the blood intake tube 32; the calibration solution ports 54 and 55 connect in the interior of the cartridge 20 to the ca1ibration solution tubes 23 and 25 respectively~ Each end of the ; ports 52, 54 and 55 which contacts the rotating plug 42 is sealed by a rubber ring 56 to provide a leakproof connecti.on to an electrode input tube 5B~
As seen in FIGURE 5, the selection valve 40 allows the microprocessor to direct the rotating plug 42 into a position aligning the electrode input tube 58 with either the blood intake tube 32, the calibrating solution tube 23, or the calibrating tube 25; when aligned with one of these tubes, the rotating plug 42 blocks the flow from the other two tubes~
Another feature of the insertion end of the cartridge 10 is the electeode card 60, best shown in FIGURES 6a and 6b. The electrode card 60 .is formed of polyvinylchloride in a generally rectangular shape and contains a bank of electrodes 62-69~ The electrode card 60 is fastened to the insertion end wall 50 such that the electrode bank protrudes and connects with an , .
., , , , , ~

:~3~ 3~

electrode interface 94, within the blood gas analysis machine B0.
Preferably, each of the electrodes 62-69 are distinctly formed planar solid state electrodes which allow assay of different characteristics of human blood~
The distinct construction of each electrode 62-69 produces a plurality of voltages or currents proportional to differerlt chemical characteristics of a test sample~
The electrodes 62-69 are formed in preformed circular slots in the electrode card 60. These solid state electrodes may be either of the ion-selective membrane type, as is preferable, of the metal/metal-oxide type, or of polarographic type, as is also preferable, all well known to the prior art. Once the electrodes 62-69 are formed, their interior analyte sensing ends remain exposed to an electrode channel 61 and to any sample contained therein. The electrode channel 61 is connected at one end to the electrode input tube 58 and at the other end to the waste tube 76 and is adapted to contain a sample being exposed to the electrodes 62-69.
In one preferred embodiment the flow path of the electrode channels is rectilinear in cross-section (e.g., lmm x 2mm~ having a total volume of ca. B0 ul.
The electrode card 60 is backed by a metal ; 25 plate 70 disposed adjacent to the electrode channel 61 :~3~ 3~$~
- 2~ -which makes contact with a thermal unit 96 in the machine 80, allowing the microprocessor lO0 to monitor and control the temperature of the sample while in the channel 61.
: 5 The exterior end of each of electrodes 62-69 is topped with an electrically conductive material.
This conductive material is then drawn out to the distal end of the electrode card 60 to complete, upon insertion : of the cartcidge 20, the contact between the electrodes; 10 assaying the sample and the electrode interface 94 which connects to the microprocessor lO0 contained in the machine 80. The microprocessor lO0 is programmed to monitor, store, and display the assay results, among its other functions.
FIGURE 7 illustrates the peristaltic pump slot 74 which is disposed in the insertion end of the cartridge 20~ The peristaltic pump slot 74 is a concave slot in the insertion end wall 50. The waste tube 76 running from the output end of the channel 61 to the bag fitting 26 of the waste collection bag 28 is brought out of the main body of the cartridge 20 through the ; insertion end wall 50 and suspended across the peristaltic p~mp slot 74. ~pon insertion of the cartridge 20, the drive rollers 90 in the machine 80 -- 25 - ~3~ 3~

pinch the exposed portion of the waste tube 76 against the concave wall of the slot 74. The rotation of the rollers 90 thus forces the test sample across the channel 61 of the electrode card 60, through the waste tube 7G, and into the waste collection bag 28.

In the preferred embodiment, the blood gas analysis machine 80 houses a selection valve driver means 82, a peristaltic pump driver means 88, a thermal unit 96, an electrode interface 94, a microprocessor lO0, an operator keyboard 102, a printer 106, a display 104l an internal digital clock 108, and a back-up powèr soùrce 110, as seen in the schematic diagram of FIGURE 1~
Power is provided to the blood gas analysis machine 80 by connection to a standard electrical outlet. A back-up power source 110, comprising a standard battery device which can power the system to maintain calibration for up to 30 minutes, is contained within the machine 80.
An internal digital clock 108 contained in the machine 80 is of standard design and provides a time base for the operation of the system.

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The valve driver means 82, shown isl FIGURES l and 8, which selectively directs either of the calibrating solutions or the test samp1e to the electrodes 62-69, preferably includes a rotatable shaft . 5 84 which fits into the end of the bolt 46 of the selection valve 40. The position of the shaft 84 is controlled by the microprocessor lO0 through a solenoid 86.
The peristaltic pump driver means B8, shown in FIGURES 1 and 8, which drives the fluid flow through the cartric3ge 20 comprises the rotatable peristaltic pump driver rollers 90 which contact a portion oE the waste tube 76 suspended across the pecistaltic pump slot 74 when the cartridge 20 is inserted into the blood gas analysis machine 80. The rotation of the driver rollers 90, powered by a motor 92, is controlled by the microprocessor lO0.
The thermal unit 96 includes a resistance heater and a thermistor which are controlled by the n,icroprocessor lO0 to obtain a constant, predetermined temperature of samples in the electrode channel 61.
Heat generated by the thermal unit 96 is conducted to the metal plate 70 adjacent to the channel 61.
The electrode interface 94, within the machine 80, connects to the electrodes 62-69 when the cartridge '"' . ' - 27 ~ 3~

20 has been inserted and selects one of the plucality of signals generated by the electrodes 62-69~ This selected signal passes through to the microprocessor 100 which converts the signal from analog to digital form and then further processes the signal~
The microprocessor 100 is programmed to control those means described above and to control the printer 106 and the display 104; additionally, the microprocessor 100 receives, analy~es, and stores the calibrating and test sample signals from the electrodes 62-69.
The keyboard 102 is a standard keyboard device having a touch sensitive membrane which is mounted on the front panel and has a format as shown in FIGURE 9 The keyboard 102 allows the opecator to initiate the input of the calibrating solution or the test sample , to enter patient and operator identification information, to initiate print or display functions, to set the clock, to set the temperature, and to enter such data.
In the preferred embodiment, the display 104 is a standard, commercially available LED device, having a format shown in FIGURE 9~ The display 104, controlled by the microprocessor 100, provides a constant reading .,.. , .;. ,,~

28 - ~3~

of pH and of CO2 and 2 pressures in mmHg for the last sample from both the venous flow 14 and the arterial flow 15, as well as the operator's choice of hematocrit, K~ or Ca++ readings of the last sample. The display 104 can also provide readings of the current temperature9 oxygen saturation, base e~cess, total CO2, bicarbonate, oxygen consumption rate, or total blood volume consumed to date, as well as the status of the back-up power system, all available at the operator's discretion~
The printer 106 is a standard printer, such as a dot matrix or thermal printer, adapted to provide a hard copy of the time, date, patient and operator ID
numbers, and temperature, as well as the values of all parameters of blood characteristics which can be the displayed by display 104, as described above.

In operation, power is provided to the blood chemistry analysis machine 80, and a cartridge 20 is inserted therein. The blood intake valve 30 is connected by the tubing 16 to the venous blood flow 14 and the arterial blood flow 15 of a conventional heart/lung machine 12 sustaining a surgical patient 10.
An automatically operated valve 18 allows the operator , ~

~3~

to select between the venous flow 14 or the arterial flow 15~ Inside ~he cartridge 20 and passir3g between the calibrating solution bags 22 and 24, a blood intake tube . 32 connects a blood intake vaLve 30 to a selection valve 40.
Upon insertion of the cartridge 20 into the blood gas analysis machine 80, the bolt head 44 of the selection valve 40 connects to a shaft 84 in the machine 80, the electrode card 60 connects to the electrical contacts 9S in the machine 80 which lead to a microprocessor lO0 contained therein, and the peristaltic pump slot 74 connects to the rotating drive rollers 90 in the machine 80. A metal plate 70 in the cartridge 20 connects to a thermal unit 76 of the machîne 80, to monitor and control the temperature of samples in the electrode channel 61.
To initiate the automatic cycle of periodic analyses of the blood samples, the operator uses a keyboard 102 to enter the desired frequency of assays into the microprocessor lO0~ The microprocessor lO0 ~hen directs the shaft 84, which is in contact with the nut 44, to rotate a pluy 4? of a selection valve 40, aliyning an electrode input tube 58 with one of the calibrating solution ports 54 or 55. The port 54 is connected by tubing to one calibrating solution bag 22;

_ 30 ~ ~ 3~3~$~3 the por~ 55 is connected to another calibra~ing solution bag 24. The microprocessor 100 selects first the : calibrating solution in the first bag 22 and then the calibrating solution in the second bag 24 to establish a two-point calibration of the electrodes 62-69~ Once the rotating plug 42 is appropriately positioned, the rotation of the rollers 90 along a portion of a waste tube 76, suspended across the peristaltic pump slot 74, draws the appropriate calibration solution into the channel 61 of the electrode card 60.
When either calibrating solution is in contact with the electrodes 62-69, a plurali~y of voltages or currents proportional to distinct ionic characteristics or gas concentrations of the solution pass from the electrodes 62-69 to an electrode interface 94 which selects one of the plurality of the signals. This selected signal passes to the microprocessor 100 which converts it from analog to digital fo[m. In subsequent . turns, the electrode interface 94 selects each of the 2~ other voltage signals~ After the two-point calibration, the microprocessor 1~0 causes the rotating plug 42 to align the electrode input tube 58 with the blood sample port 52~ The drive rollers 90 then draw a blood sample into the channel 61, at the same time Eoccing the ~ 3~3~ ~3j calibration solution through the waste tube 76 and into the waste collection bag 28~ The several vol~age and current signals of the blood sample are measured, the distinct parameters are valued according to the two-point calibration and are displayed through appropriate means on the blood gas analysis machine 80~
Additionally, the values of the distinct parameters of the blood sample may be stored in the microprocessor 100 for subsequent recall and display.
Constant temperature of samples in the channel 61 is insured by preprogramming the microprocessor 100 to monitor and control the temperature of a metal plate 70 through a thermal contact 97 and a thermal unit 96.
The calibration solution and blood sampLe assay sequence is repeated at intervals previously selected by the operator~ For most subsequent interval assays, a one-point recalibration of the electrodes 62-69 is made; occasionally, a two-point recalibration is initiated by the microprocessor 1~0 to ensure continued accuracy Alternatively, a discrete blood sample may be connected to the blood intake port 30 and subjected to the above-outlined sequence, enabling the system to operate as a standard lab-based blood gas analyzer~

_ 32 ~

Following the exhaustion oE calibrating solutions or following the termination of the surgical procedure of a particular pa~ient, the spent cartridge 20 may be discarded and replaced with a new cartridge for subsequent use of the blood gas analysis system.
Therefore it is seen that this blood gas analysis system provides an economical, highly automated, contamination-free means to provide a surgeon with almost immediate inEormation on the surgical patient's blood characteristics, which in turn reflects the patlent's status.
.

Claims

The embodiments of the invention in which an exclusive property or privilege is claimed are defined as follows:

1. A flexible gas-impermeable package containing a blood facsimile reference solution for use in blood gas electrolyte analysis, comprising ionic potassium and calcium and tonometered at elevated temperature with oxygen and carbon dioxide, the package content being free of voids.
2. A method of producing a packaged blood facsimile reference solution containing oxygen gas, carbon dioxide gas and ionic potassium and calcium, comprising constituting an aqueous buffered solution containing ionic potassium at a predetermined concentration, subjecting the resulting solution to tonometry with said gases, and following initiation of tonometry admixing ionic calcium in predetermined amount with the tonometered solution.
3. A method of producing a package of an electrochemically stable tonometered blood facsimile solution for storage and for use in blood/gas monitoring at atmospheric pressure, comprising packaging the solution in a sealed flexible gas-impermeable envelope free of voids while maintaining the solution at sub-atmospheric pressure ranging from about 625 to 700 mm Hg and at temperature higher than said use temperature.