US3614856A - Gas transfer device - Google Patents

Gas transfer device Download PDF

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US3614856A
US3614856A US3614856DA US3614856A US 3614856 A US3614856 A US 3614856A US 3614856D A US3614856D A US 3614856DA US 3614856 A US3614856 A US 3614856A
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gas
sample
chamber
device
blood
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Manuel C Sanz
John J J Staunton
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Perkin-Elmer Corp
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    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N7/00Analysing materials by measuring the pressure or volume of a gas or vapour
    • G01N7/10Analysing materials by measuring the pressure or volume of a gas or vapour by allowing diffusion of components through a porous wall and measuring a pressure or volume difference
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10TTECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T436/00Chemistry: analytical and immunological testing
    • Y10T436/25Chemistry: analytical and immunological testing including sample preparation
    • Y10T436/25375Liberation or purification of sample or separation of material from a sample [e.g., filtering, centrifuging, etc.]
    • Y10T436/255Liberation or purification of sample or separation of material from a sample [e.g., filtering, centrifuging, etc.] including use of a solid sorbent, semipermeable membrane, or liquid extraction

Abstract

A DEVICE FOR RECEIVING AN APPROXIMATELY 15 MICROLITER SAMPLE OF BLOOD AND FOR TRANSFERRING GAS FROM THE BLOOD TO A GAS RECEPTOR FLUID THROUGH A GAS PERMEABLE MEMBRANE. THE BLOOD SAMPLE MAY BE STORED IN THE DEVICE WHICH IS ADAPTED TO DELIVER THE RECEPTOR FLUID INTO A MEASURING ELECTRODE. BY CONTRAST IN PRIOR ART SYSTEMS BLOOD GAS ANALYSES WERE MADE IN THE SAME DEVICE IN WHICH THE BLOOD SAMPLE WAS PLACED.

Description

Oct. 26, 1.911 M, Q SANZ ETAL GAS TRANSFER DEVICE Filed Nov. 29. 1968 Af/iff,

Oct. 26, 1971 M Q SANZ ETAL 3,614,856

GAS TRANSFER DEVICE Filed Nov. 29, 1968 2 Sheets-Sheet 11 3,614,856 GAS TRANSFER DEVICE Manuel C. Sanz, Lancy, Switzerland, and John 3. I.

Staunton, Oak Park, lll., assignors to The Perkin-Elmer Corporation Filed Nov. 29, 1968, Ser. No. 779,766 Int. Cl. BOM 53/22 US. Cl. 55-16 lll Claims ABSTRACT OF THE DISCLOSURE A device for receiving an approximately l microliter sample of blood and for transferring gas from the blood to a gas receptor fluid through a gas permeable membrane. The blood sample may be stored in the device which is adapted to deliver the receptor Huid into a measuring electrode. By contrast in prior art systems blood gas analyses were made in the same device in which the blood sample Was placed.

CROSS REFERENCE TO A RELATED APPLICATION This is a companion invention related to a U.S. application entitledMicro-Electrode System by the same inventors, Ser. No. 779,765 led Nov. 28, 1968. Together the specifications describe an entirely new system for measuring partial pressures of gas in a fluid.

BACKGROUND OF THE INVENTION This invention relates to a system for blood gas measurement and more particularly relates to a gas transfer device, which is separate from a measuring microelectrode, and the methods of use of this new device.

Various types of prior art systems exist for the measurements of partial pressures (c g. pCO2 and p02) in blood. These measurements are considered of increasing importance in the diagnosis and treatment of respiratory and metabolic disorders. Present commercially existing blood analysis systems require relatively large samples of blood, 150 microliters or more, for the determination of these partial pressures. Thus, a gas analysis of the blood of small children or premature infants, small animals and many other cases, is rendered impossible because of the necessary large amount of blood sample. Moreover, such systems are slow in producing results because of required initial standardization of the equipment and laborious measurement procedures. In addition, computations are generally required which provide another source of error.

In an attempt to minimize sources of error and reduce the size of the sample required, those skilled in the art have tended to miniaturize blood gas measurement systems. This has resulted in increased initial price and service cost. Moreover, such a construction tends to make the system inflexible and relegated to the technique for Which the system was particularly designed. In addition, most prior art systems are now made of glass or transparent plastics to permit the operator to see through them and decide whether they are properly filled, emptied or rinsed. This introduces the unreliable factor of human visual judgment into the functioning of the equipment. Moreover, the glass construction increases the possibility of breakage especially when a membrane may spring a t. m l

EMS Patented Oct. 26, 1971 leak and the equipment must be dismantled and reassembled.

It is these disadvantages relating to cost, accuracy, and sample size that the present device was conceived to overcome.

SUMMARY OF T HE INVENTION :In a principal aspect the present invention comprises a gas transfer device which is divided into at least two chambers, the size of each chamber depending upon the particular gas analysis to` be performed. The chambers are separated by a gas permeable membrane. The volume of the chambers in one form is` in the range of l5 microliters, and each chamber includes entrance and exit passageways which are preferably restricted in their dimensions so that capillary action will assist in the transfer of the fluids and also assist in maintaining the fiuids within the chambers of the gas transfer device. Blood is placed in one of the chambers of the gas transfer device and a gas receptor `fluid is placed in the remaining chamber or chambers. Gas is then transferred through the gas permeable membrane at the appropriate conditions of temperature and pressure. The gas receptor fluid is then transferred from the gas transfer device to a measuring electrode to determine the partial pressure of the particular gas subject to examination.

It is thus an object of this invention to provide an improved gas transfer device especially adapted for use with blood gas analyses.

It is a further object of the present invention to provide a gas transfer device which is inexpensive to the degree that it may be used with single samples of blood in a blood gas analysis and then discarded.

Still another object of the present invention is to provide a gas transfer device wherein the gas transfer operation, especially in a blood gas analysis, is separated from the electrode measuring operation.

One further object of the present invention is to provide a gas transfer device which is easily constructed and which requires a minimum of human cooperation for operation of the device.

Still another object of the present invention is to provide a gas transfer device which eliminates both cumbersome and expensive equipment and substantially eliminates the necessity of constant calibration of equipment.

`One further object of the present invention is to provide a gas transfer device which may be incorporated in a blood gas analysis system requiring only a small sample typically within the vicinity of `l5 microliters instead of the large samples of microliters as required in prior art gas analysis systems.

One further object of the present invention is to eliminate the necessity of providing expensive measuring electrode instrumentation at the patients location since the sample may be placed in the gas transfer device of the present invention and later sent to a clinical laboratory.

Still another object of the present invention is to provide a gas transfer device wherein a number of samples may be taken and each placed in a separate gas transfer device so that the devices may be transferred to a central testing station where the samples may be tested in a serial manner.

One furthe-r object of the present invention is to provide a gas transfer device which may be used in a gas transfer `system in which anticoagulants, chilling, plasma separation and other procedures necessary with prior art systems, are no longer necessary.

One further object of the present invention is to provide a gas transfer device which eliminates the necessity for frequent cleaning of the measuring electrode in a blood gas analysis system.

These and other objects, advantages and features of the present invention will be more fully set forth by the detailed description which follows:

BRIEF DESCRIPTION OF THE DRAWINGS In the detailed description which follows reference will be made to the drawings comprised of the following figures:

FIG. 1 is a side cross sectional view of a first preferred embodiment of the gas transfer device of the invention;

FIG. 2 is a top cross sectional view of the gas transfer device shown in FIG. 1 taken along the line 2-2 in FIG. l;

FIG. 3 is a top plan view of a second preferred embodiment of the gas transfer device of the present invention;

FIG. 4 is a side cross sectional view of the embodiment of the gas transfer device shown in FIG. 3 taken substantially along the line 4 4 in FIG. 3;

FIG. 5 is a top plan view showing a method of manufacture of a plurality of the devices;

FIG. 6 is a side cross sectional view of an alternative embodiment of the invention, taken substantially along the line 6-6 of FIG. 7;

FIG. 7 is a cross sectional view of the device shown in FIG. 6 substantially along the line 7 7;

FIG. 8 is a side view of a stopper for the embodiment illustrated in FIG. 6; and

FIG. 9 is a partial cross sectional view of a device similar in construction of the device shown in FIG. l including septa for sealing passageways to the interior chambers of the device.

DESCRIPTION OF THE PREFERRED EMBODIMENTS The gas transfer device of the present invention utilizes at least two chambers with transfer of the considered gas, such as CO2 or O2, from the chamber with the sample, such as blood, through an adjacent membrane. The gas reacts with the receptor fluid to change a measurable parameter thereof, such as pH. A portion of the receptor fluid is subsequently withdrawn from the gas transfer device for measurement of the changed parameter in a separate system such as a measuring microelectrode system.

This differs sharply from such well known prior art systems as the Severinghaus electrode system for pCO2 or the Clark electrode system for O2 in which the measuring electrode is physically coupled to the membrane through a thin layer of the receptor fluid. The separation of the transfer and measuring devices provides a host of unexpected advantages hitherto unanticipated and unappreciated.

FIG. l shows a side cross sectional view of a first preferred embodiment of the transfer device. Two similar flanged shells 10 and 12 which may be made of plastic, metal, glass or other rigid material and a membrane 18 are joined to form first and second enclosures or charnbers 22 and 24. The shells 10 and 12 have circumferential flanges 14 and 16 respectively and are mated, as shown, with the thin flat membrane 18 captive between the flanges 14 and 16.

A spun or crimped ring 20 which may be of metal, secures the two shells 10 and 12 and the membrane 18 to form a liquid-tight seal. In practice each chamber 22 and 24 is filled with a different fluid, the fluids being separated by the membrane 18. If the membrane 1S is permeable lo a gas contained in one of the fluids, while being inpervious to charged ions and to the fluids, the gas or part thereof can be transferred from one body of fluid to the other in a predictable manner.

Access to the two chambers 22 and 24 of the enclosure is effected through ports or passageways 26, 27, 28 and 29. These passageways 26, 27, 28 and 29 are frustoconical or tapered, so that they may be easily closed and sealed by Stoppers 32, 33, 34 and 35. The Stoppers 32 through 35 are shown interconnected in pairs, 32 and 33, 34 and 35, for convenience in handling.

The stoppers 32 through 35 are tapered with an angle as wide as practical so that the pressure of insertion will not alter the chamber 22 or 24 volume significantly while the stopper, typically soft rubber, seals the ports 26 through 29 effectively. The Stoppers 32 through 35 may be color-coded to identify which side of the transfer device they seal, i.e. the sample side or receptor fluid side. Means may be provided to hold the Stoppers 32 through 3S sealed in position to prevent loss of fluid or the Stoppers.

In order to completely fill either chamber 22 or 24 of the enclosure, fluid is introduced at one port, for example 26, and allowed to flow into and through the chamber 22 until it emerges at the other port 27. To avoid dea-:l or unfilled spaces, the chambers 22 and 24 preferably have a long and narrow shape, as may also be seen in the plan view of FIG. 2.

While various sizes of this transfer device may be of utility depending on the method of equilibration being practiced, a typical embodiment for pCO2 measurement has the following dimensions:

Mm. Chamber length 12 Chamber width 2 Chamber height 0.6 Membrane thickness 0.025

The volume of such a chamber would approximate 15 al. The membrane 18 is polypropylene although other plastics such as tetrauoroethylene, polyethylene and various silicone rubbers are usable. For the embodiment being considered, namely for pCO2, both chambers 22 and 24 have the same volume.

Continuing with the exemplary embodiment for pCO2, while not in use the chamber 22, which we will designate as the sample chamber, is filled with air or nitrogen free from CO2. If the device is to be stored for a considerable time before use, it is preferable to fill chamber 22 with the same receptor fluid as in chamber 24 to eliminate transpiration of water from the gas receptor fluid in chamber 24 through the membrane 18. Alternatively, air saturated with water is included in chamber 22 t0 eliminate a need to flush the chamber 22 before introducing the sample. A sufhcient amount of NaF to give 10-3 M concentration in the sample may also be included in the sample chamber 22 to check glycolysis if the sample is to be whole blood and measurement is to be delayed.

For a pCO2 measurement chamber 24 would typically be lled with a gas receptor fluid solution comprised of the following:

Isotonic NaCl Trace of sodium phosphate to give a suitable pH, typically approximately 8.

While the value of pH in this solution is a matter of choice, it msut be accurately predetermined.

Prior art devices, for example, the Severinghaus type electrode, must be calibrated before the partial pressure of a sample can be measured. This involves the use of at least two gas mixtures of accurately known composition dispensed from storage tanks or cylinders. Two tanks are essential since both the reading on the measuring instrument, a pH meter generally, for a known partial pressure, e.g. pCO2, and the slope of the electrode, e.g. ApH/ApCO2, must be established. Since gas is being used for calibration, the proper computations to correct for temperature, barometric pressure, etc. must be made.

Such a calibration process typically takes l-15 minutes and must be repeated from time to time.

With the present invention, the time and labor of using gas for calibration is eliminated. Preadjusted buffers certified to represent known partial pressure, e.g. pCO2, values are used. These are most conveniently supplied in transfer devices filled with the same solution in both chambers, i.e. isotonic NaCl plus a predetermined amount of Nal-TC03 for pCO2 measurements. Thus calibration is effected with transfer devices iilled with standard solutions and measurement is -made on samples in similar transfer devices. Gas tanks are eliminated as well as time consuming procedure and calculations.

IFor measurement of p02 a transfer device may be used similar to that used for determining pCO2. However, when the device is in storage and has no sample therein, chamber 22 would be filled with pure nitrogen or another inert, oxygen-free gas. Chamber 24 would be -filled with saturated KCl or another unreducible supporting electrolyte suitable for a polarographic cell. A sample (eg. blood) would displace the inert gas in the chamber Z2 during use of the device.

Again, for p02, no tank gas with its complications for calibration would be required; whereas, the prior art Clark-type cell requires two gases, usually combined with the CO2 mixtures, one of which contains no oxygen, the other of which contains a known amount of oxygen. The usual conversions for temperature and barometric pressure would also be necessary using the old system and devices. The new system of the present invention uses a pre-calibrated transfer device to establish the up-scale oxygen point. Thus, in a standardizing transfer device, chamber 22 is filled with a sample containing a mixture of nitrogen and oxygen of yknown ratio suitable to the scale range to be established. Chamber 24 is filled with saturated KCl. For the zero point, which should also be checked, an oxygen-free sample in a transfer device is used.

The separate gas transfer device of the present invention lends itself well to simplification of equipment and technique not readily associable with prior art unified electrode systems. A typical method of use of the transfer devices of the present invention will now be set forth. This will serve to point up certain differences in theory and operation between the present invention and prior art electrodes and measurement systems.

First a technician or nurse will take a sample from the patient by finger puncture. Proper techniques for this, known to the art, should be followed. One drop of blood is enough (about 40H1.) for both a pCO2 and a p02 sample in a transfer device of the invention. Transfer is best made by a micro-pipette or injector such as that described in our copending application previously cited, although a capillary may be used. Filling of the sample chamber 22 must be effected quickly and completely and the Stoppers inserted to displace a small amount of the sample so no air bubble is included in the chamber 22. The use of an injector makes this operation rapid and automatic, not requiring visual check, whereas use of a capillary for transfer depends on capillary action for transfer of the sample to the chamber and is less certain. The filled transfer devices with samples therein, properly labeled, are then sent to the laboratory for analysis.

Since pCO2 and p02 are functions of temperature, the device, shortly before measurement, is placed on a thermostated hot plate and brought to approximately 37 C. A metal ring into which the capsule is fitted serves as a heatsink to facilitate heat transfer and holds a steadywithdrawn from chamber 24 using an injector and it is delivered to the measuring electrode. For pCO2 this electrode may be a pH electrode such as is described in the copending application referred to above. Any temperature change in the sample during transit in the injector will be nulliiied in a few second after the sample is in the electrode. A pH measurement may therefore be taken without a long equilibration delay such as is experienced with the Severinghaus type of electrode.

Since the sample introduced into the pH electrode is a nonorganic aqueous solution, no dithculty is experienced in keeping the electrode clean, unlike prior art electrodes which receive whole blood or plasma samples. Moreover, once the transfer device has been used, it is simply discarded, thereby eliminating the necessity to clean the device.

One important difference between the present invention and prior art devices in measuring pCO2 results from the fact that the volume of chamber 24 is preferably the same as that of chamber 22. Thus, equilibration reduces pCO2 in chamber 2.2 while raising it in chamber 24. The nal pCO2 will be 0.5 the initial pCO2 of the sample, all other factors being constant. The calibration curve ApHzKA log pCO2 is a straight line. However, the slope will now be less than the theoretical value because the pCO2 being measured is only half that of the original sample. This is not serious. The precision of modern pH meters is ample to overcome the loss in slope.

It is important, however, to accurately maintain the volume ratio of chambers Z2 and 24. Accurate control of the size of the two shells 10 and l2 and control of the amount of solution loaded into chamber 24 as exactly half of the total volume at 37 C. provides adequate volume control. In this way the ratio of Volumes can be maintained even though one side of each chamber 22` and 24 is a flexible membrane 18.

Measurement of the p02 sample also involves equilibration on a thermostated hot plate. The sample is then transferred by an injector to a microelectrode polarographic cell and measured at -0.6 to 0.8 volt. The diffusion current passing through the cell develops a voltage across a resistor. Typically the resistor will be 106 ohms and the microelectrode is of such a size that the current through the resistor is of the order of lO-7 amp. Thus a voltage of about 0.1 volt is developed across the resistor. The same pH meter can then be used to give a readout for p02.

As an alternative to withdrawal and transfer of the sample from the transfer device, a pair of electrodes consisting of a chlorided silver wire and a sheathed platinum wire with the tip exposed could be plugged into the ports 28 and/ or 29 to form the polarographic cell in chamber 2.4L of the device. This procedure is simple and fast and provides satisfactory accuracy partially because the temperature coeficient of the cell is relatively low being about i0.5% pO2/ C.

For the p02 transfer device, the requirement for maintenance of volume ratio is like that for pCO2 device. However, the polarographic readout method consumes the oxygen content of the sample, unlike the pH readout of pCO2. Hence the readout indication tends to slowly drop toward a lower value. By using Faradays laws it may be calculated that the rate of drift will be about 0.1%/minute for the Volume of 15rd. with which we are concerned at the 10H7 amp. previously quoted. This is practical rate which can be bettered if required. It is an advantage of the present transfer device that this drift does not start until measurement is initiated.

In the prior art Clark cell this drift is normally much greater because of higher currents. Moreover, drift was balanced partly against continuing diffusion through the membrane ybecause of the small amount of supporting solution used. Thus, two variables must balance in the Clark device and as a result the possibility of error increases. In the present device continuing diffusion during readout is negligible because the reduction in p02 of the liquid in chamber 24 is negligible.

Reference to FIGS. 3 and 4 shows another embodiment of the device wherein the construction permits filling by capillary action and the device can be squeezed to empty it thus acting as its own injector for transfer to a measuring electrode.

Two plastic shells 40 and 42 are sealed peripherally to membrane 44 as shown in FIGS. 3 and 4. Shell 40 is formed with an entrance passage 46 in an entrance nipple 47 and vent 48. Thus, entrance passage 46 can be introduced to a drop of blood or other sample which then proceeds to be inducted by capillary action to 'fill chamber 5t). Chamber 52 is prefilled through orifice 54 in discharge nozzle 55 which may then be sealed by any suitable means. Optionally, a discharge tip 56 may be flexible to form a self-closing orice 54 or may be snipped off to reopen orifice 54 if the orifice 54 has been sealed.

A further option is to package the capsule in an impervious envelope or container as at 58 in FIG. 4 filled with water-saturated air or a nitrogen-oxygen mixture of known ratio. With this option it would not be necessary to close orifice 54 since loss of water by evaporation would be nil. The package must, however, be designed so that liquid cannot be lost at the orifice 54 by contact with the walls or other contents, if any, of the container SS.

This embodiment preferably, includes ribs 60 formed in chamber 50 to support the membrane 44 especially when squeezing the flat sides of the shells 40 and 42 to expel the liquid in chamber 52 into a measuring electrode. The device then serves the added function of being its own injector. To effect a junction with the electrode, the tip 56 has a tapered outer surface. This male taper is received by a female receptacle on the electrode (not shown) as described in our copending application referred to above.

The solutions used to fill this embodiment and the general technique of use is typically the same as for the embodiment described above. The advantage of this second embodiment is the elimination of the initial sample transfer from finger puncture to capsule by a capillary or injector. In addition, the manipulation of this second embodiment is easier and the second transfer to an injector for insertion in the electrode is also eliminated. These advantages increase convenience and speed of use. On the other hand, the first described embodiment is especially flexible for adaption to changing techniques, and, if need be, the samples therein can be introduced and removed more than once.

Either of the cited embodiments, as shown in FIGS. 1 and 2 or FIGS. 3 and 4 may be manufactured advantageously in a form wherein a plurality of devices are disposed side by side along a continuous strip of diaphragm material. FIG. 5 shows such an arrangement. A plurality of devices. as at 62 and 64, are arranged side by side along diaphragm material 66. The separate devices, as at 62 and 64, may be connected if a rigid strip of device is preferable. The devices are broken apart if individual units are required. Alternatively the diaphragm material 66 alone may serve to connect devices. This permits the strip to be folded or coiled. Perforations in the diaphragm material along a line between devices facilitate separation of devices. The devices in strip form are pre-loaded with receptor fiuid in the same manner as previously described for individual devices.

Advantages of the strip form include ease of storage and dispensing; ease of identification of the type of test, i.e. pCO2, p02, dual-purpose, standardizing by a given Strip; ease of manual handling when loading a sample, placing on hot plate, etc.; and positive sample identification when a definite order is required since order is determined by the strip. These advantages and others make the strip form more than just a manufacturing convenience.

The strip form also lcnds itself to manufacture of a closely related alternative embodiment to the embodiment shown in FIGS. l and 2. FIGS. 6 and 7 illustrate this alternative form. Shells 68 and 69 forming the device are shaped by stamping, rolling or embossing a continuous strip of plastic, for example. Passageways 70 and 71 for filling and emptying are pierced in the same operation and may be 'formed with a raised sealing lip 72 of suitable diameter to mate with an injector. Notches 74 formed between devices facilitate subsequent separation. To assemble the devices, identical strips 68 and 69 are aligned in Opposition as shown in FIG. 7 with a strip of diaphragm material 66 between the mated flanges. The three-part assembly is joined by suitably applied pressure and/or heat or ultrasonic welding impulses. Alternatively a suitable cement may be applied to the flanges to provide a sealed assembly.

With the device shape shown in FIGS. 6 and 7 closure may be effected by a semi-captive stopper 76 such as shown in FIG. 8. The stopper 76 includes shallow plugs 78 and 79 which mate with passageways as at 70 and 71. The plugs 78 and 79 are connected by a flexible bar 8f) which has a thin middle portion to facilitate bending. A pressure sensitive adhesive on the inside or plug side of the stopper 76 holds the stopper 76 against the device but permits peeling up the ends of the stopper 76 in order to open the passageways 70 and 71 for filling.

Other types of seals such as perforable septa may also be used in combination with the embodiments shown in FIGS. l and 6. FIG. 9 shows in a partial cross sectional view an embodiment similar to the embodiment of FIG. l and adapted for a septum type closure 82. The closure 82 is perforated with a slit 84 so that the device can be filled with either a plastic or a metal-tipped injector or a capillary. A constricted opening 86 at the bottom of the neck of a straight, uniform cross section passageway 27a prevents the tip of an injector or capillary from passing into the fluid chamber and damaging the diaphragm material 66 when filling. Septum type closures for the embodiment of FIG. 6 may be cemented or heat-sealed to the device. Alternatively the notches 74 could extend far enough in from each edge of the strip as open slots so that thin elastomeric bands encircling the end of the device could provide the closure.

While the emobdiments and methods heretofore de scribed refer to static handling during the diffusion process of a single sample at a time, the scope of this invention also includes the handling of fiowing streams of sample and receptor fluid. For this purpose a series of samples of blood, for example, may be fed through one channel of a device in succession. The device or capsule would be of a construction and orientation suitable to such service and would be maintained at the proper temperature, typically 37 C. The receptor fiuid would be fed as a second stream through the other channel of the capsule. Transfer of the gas, CO2 or O2 would take place in the capsule under the proper equilibration conditions. Flow rate would be dictated by the required diffusion time to equilibrate at the 37 C. temperature. The process is essentially different from dialyzer action as exemplified in a contemporary flowing stream analysis device. The points of difference may be set forth as follows:

brano? ln a continuous process embodiment of the invention, the fiowing stream of receptor fluid, after leaving the capsule, will be passed through a suitable electrode held at 37 C. for measurement of either pH (for pCO2 determination) or polarographic diffusion current (for p02 determination). If the connecting conduit is also maintained at or near 37 C. this process will be expedited as thermal re-equilibration will not set limits on flow rate. A suitable pH electrode is described in the previously cited copending patent application. In the case of p02 it is practical to use a separate polarographic cell with a platinum microelectrode such as are described in texts on polarography. Alternatively the built-in electrode, previously described herein, can be used. If the platinum electrode is placed in the outlet of the capsule channel the' p02 measured will be that of the equilibrated stream and the reading will be enhanced because of the stirring action of the iiowing stream.

Numerous other dispositions within the scope of this invention are also apparent. For example, both the pCO2 and the p02 chambers may be disposed adjacent to each other and to the same sample chamber thus using regions of the same membrane and the same thermostating equipment. lIt is also possible, if a suitable supporting electrolyte is used as receptor solution, to make both p02 and pCO2 determinations on the same receptor solution using only a single chamber for both but separate electrode systems as heretofore set forth. The 0.163M or isotonic salt solution makes a suitable supporting electrolyte for both p02 and pCO2 in this simplified practice of the invention where one device and a single sample is used for both p02 and pCO2. Such a solution is dened in the claims as a dual purpose gas receptor fluid. To carry this to a further degree, it will be seen that a pH determination may be made on the sample before transferring it to the capsule thus completing the trio of tests; pH, p02 and pCO2.

What is claimed is:

1. A method for determining simultaneously both pCO2 and p02 in a minute sample of blood which comprises enclosing the blood sample on one side of a semi-permeable membrane,

enclosing a dual purpose gas receptor fluid on the opposite side of said membrane, causing gas in said blood sample to pass through said membrane to establish partial pressure equilibrium across the membrane, whereby the portion of the gases traversing said membrane changes physical, measurable parameters of said receptor fluid,

transferring said receptor iiuid to a separate gas measuring electrode, and

measuring said parameters.

2. A gas transfer device for receiving samples of fluid and transferring gas from said iiuid to a receptor fluid comprising, in combination:

first and second enclosed chambers wherein each of said chambers are defined by flexible walls and said first chamber comprises a sample fluid chamber and said second chamber comprises a gas receptor fluid chamber,

a gas permeable membrane separating said chambers,

a capillary opening between said Walls comprising an entrance to said first chamber, and

a vent opening for said first chamber distal from said capillary opening.

3. The device of claim 2 wherein said volume of each of said chambers is approximately ll5 microliters.

4. The device of claim 2 wherein said gas permeable membrane is a plastic film.

5. The device of claim 2 wherein said gas receptor fluid chamber has entrance and exit means comprising a single channel formed by said exible walls through which fluid may be expelled by squeezing said flexible wall portions surrounding said gas receptor fluid chamber.

6. The device of claim 5 wherein said channel from said gas receptor fiuid chamber includes a self-sealing oritice.

7. The device of claim 6 including juncture means on said orifice to facilitate expulsion of gas receptor fiuid to a measuring electrode.

8. The device of claim 2 enclosed in a Water vapor impervious envelope, said envelope being filled with water saturated air.

9. The device of claim 2 enclosed in an envelope containing a nitrogen-oxygen mixture of predetermined ratio.

10. A gas transfer device for receiving samples of fluid and transferring gas from said fluid to a gas receptor uid comprising in combination a pair of pan-like shell members, each having a peripheral ange, said members being disposed face to face with their fianges superimposed,

a gas permeable membrane clamped between said flanges to divide the interior of said members into a sample chamber and a receptor chamber,

a pair of openings through the wall of each of said members which is opposite said membrane for providing fluid entrance and exit passageways to said sample and receptor chambers,

a neck projecting outwardly from said members surrounding each of said openings, and

plug means for each pair of openings comprising two interconnected Stoppers which fit into said necks.

11. A method for measuring the partial pressure of a gaseous constituent present in a microsample of blood which comprises (a) providing a minute anaerobic sample of blood (b) enclosing said sample completely in a chamber formed adjacent one side of a gas permeable membrane with said sample in contact with said membrane (c) enclosing a gas-receptor liquid in a similar chamd ber adjacent the other side of said gas permeable membrane (d) maintaining the temperature of said sample and said liquid at a constant predetermined value While permitting the partial pressure of the gaseous constituents in the blood and receptor liquid to equilibrate through said membrane (e) transferring said gas receptor liquid to a separate gas measuring electrode (f) and determining the partial pressure of said gas in said liquid.

References Cited UNITED STATES PATENTS 3,055,504 9/1962 Schultz 210-321 X 3,212,498 10/1965 MCKirdy et al. 210-'321 X 3,404,962 10/1968 Medlar et al. ZIO-32:1 X 3,459,176 8/1969 Leonard 210-321 X JOHN ADEE, Primary Examiner U.S. Cl. X.R.

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Cited By (22)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3751879A (en) * 1971-04-26 1973-08-14 Instrumentation Specialties Co Apparatus for reducing the dissolved gas concentration in a liquid
US3778971A (en) * 1970-09-29 1973-12-18 Rhone Poulenc Sa Device for purging gas from a liquid
US3828527A (en) * 1972-09-28 1974-08-13 Varian Associates Leak detection apparatus and inlet interface
US3907687A (en) * 1968-12-07 1975-09-23 Baxter Laboratories Inc Plate dialyzer
US3909302A (en) * 1973-06-21 1975-09-30 Tyco Laboratories Inc Vent cap for batteries
US4164524A (en) * 1974-05-31 1979-08-14 Ward Charles A Treatment of blood containing vessels
US4197206A (en) * 1978-09-13 1980-04-08 Karn William S Heat sealable ion permeable membranes
US4516984A (en) * 1983-11-08 1985-05-14 Emory University Degassing process and apparatus for removal of oxygen
US4529419A (en) * 1983-05-03 1985-07-16 Sartorius Gmbh Filter for gas filtration
US4632677A (en) * 1981-10-27 1986-12-30 Blackmer Richard H High humidity oxygen enricher apparatus
US4965989A (en) * 1989-04-10 1990-10-30 Lamar Ellis In-line molecular sieve bed conversion kit
US5238853A (en) * 1990-09-14 1993-08-24 Instrumentation Laboratory S.R.L. Process and apparatus for the electrochemical determination of oxygen in a blood gas analyzer
US6326211B1 (en) * 1995-06-29 2001-12-04 Affymetrix, Inc. Method of manipulating a gas bubble in a microfluidic device
US6352577B1 (en) * 1994-07-29 2002-03-05 Battelle Memorial Institute Microchannel laminated mass exchanger and method of making
US20020144600A1 (en) * 2000-06-06 2002-10-10 Tegrotenhuis Ward E. Conditions for fluid separations in microchannels, capillary-driven fluid separations, and laminated devices capable of separating fluids
US6666909B1 (en) 2000-06-06 2003-12-23 Battelle Memorial Institute Microsystem capillary separations
US20050098032A1 (en) * 2003-11-12 2005-05-12 Tsai George P. Devices and methods for performing array based assays
US20070099288A1 (en) * 2005-11-02 2007-05-03 Affymetrix, Inc. Microfluidic Methods, Devices, and Systems for Fluid Handling
US20070267782A1 (en) * 2005-11-02 2007-11-22 Affymetrix, Inc. System and Method for Making Lab Card by Embossing
US20080038714A1 (en) * 2005-11-02 2008-02-14 Affymetrix, Inc. Instrument to Pneumatically Control Lab Cards and Method Thereof
US20080311585A1 (en) * 2005-11-02 2008-12-18 Affymetrix, Inc. System and method for multiplex liquid handling
US8075852B2 (en) 2005-11-02 2011-12-13 Affymetrix, Inc. System and method for bubble removal

Cited By (28)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3907687A (en) * 1968-12-07 1975-09-23 Baxter Laboratories Inc Plate dialyzer
US3778971A (en) * 1970-09-29 1973-12-18 Rhone Poulenc Sa Device for purging gas from a liquid
US3751879A (en) * 1971-04-26 1973-08-14 Instrumentation Specialties Co Apparatus for reducing the dissolved gas concentration in a liquid
US3828527A (en) * 1972-09-28 1974-08-13 Varian Associates Leak detection apparatus and inlet interface
US3909302A (en) * 1973-06-21 1975-09-30 Tyco Laboratories Inc Vent cap for batteries
US4164524A (en) * 1974-05-31 1979-08-14 Ward Charles A Treatment of blood containing vessels
US4197206A (en) * 1978-09-13 1980-04-08 Karn William S Heat sealable ion permeable membranes
US4632677A (en) * 1981-10-27 1986-12-30 Blackmer Richard H High humidity oxygen enricher apparatus
US4529419A (en) * 1983-05-03 1985-07-16 Sartorius Gmbh Filter for gas filtration
US4516984A (en) * 1983-11-08 1985-05-14 Emory University Degassing process and apparatus for removal of oxygen
US4965989A (en) * 1989-04-10 1990-10-30 Lamar Ellis In-line molecular sieve bed conversion kit
US5238853A (en) * 1990-09-14 1993-08-24 Instrumentation Laboratory S.R.L. Process and apparatus for the electrochemical determination of oxygen in a blood gas analyzer
US6352577B1 (en) * 1994-07-29 2002-03-05 Battelle Memorial Institute Microchannel laminated mass exchanger and method of making
US6533840B2 (en) 1994-07-29 2003-03-18 Battelle Memorial Institute Microchannel laminated mass exchanger and method of making
US6326211B1 (en) * 1995-06-29 2001-12-04 Affymetrix, Inc. Method of manipulating a gas bubble in a microfluidic device
US20050229553A1 (en) * 2000-06-06 2005-10-20 Tegrotenhuis Ward E Conditions for fluid separations in microchannels, capillary-driven fluid separations, and laminated devices capable of separating fluids
US6666909B1 (en) 2000-06-06 2003-12-23 Battelle Memorial Institute Microsystem capillary separations
US6875247B2 (en) 2000-06-06 2005-04-05 Battelle Memorial Institute Conditions for fluid separations in microchannels, capillary-driven fluid separations, and laminated devices capable of separating fluids
US7344576B2 (en) 2000-06-06 2008-03-18 Battelle Memorial Institute Conditions for fluid separations in microchannels, capillary-driven fluid separations, and laminated devices capable of separating fluids
US20020144600A1 (en) * 2000-06-06 2002-10-10 Tegrotenhuis Ward E. Conditions for fluid separations in microchannels, capillary-driven fluid separations, and laminated devices capable of separating fluids
US7022157B2 (en) * 2003-11-12 2006-04-04 Agilent Technologies, Inc. Devices and methods for performing array based assays
US20050098032A1 (en) * 2003-11-12 2005-05-12 Tsai George P. Devices and methods for performing array based assays
US20070099288A1 (en) * 2005-11-02 2007-05-03 Affymetrix, Inc. Microfluidic Methods, Devices, and Systems for Fluid Handling
US20070267782A1 (en) * 2005-11-02 2007-11-22 Affymetrix, Inc. System and Method for Making Lab Card by Embossing
US20080038714A1 (en) * 2005-11-02 2008-02-14 Affymetrix, Inc. Instrument to Pneumatically Control Lab Cards and Method Thereof
US20080311585A1 (en) * 2005-11-02 2008-12-18 Affymetrix, Inc. System and method for multiplex liquid handling
US8007267B2 (en) 2005-11-02 2011-08-30 Affymetrix, Inc. System and method for making lab card by embossing
US8075852B2 (en) 2005-11-02 2011-12-13 Affymetrix, Inc. System and method for bubble removal

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