Calibration medium containment system

A method and apparatus which contemplates coverage control, and collateral containment of calibration media with respect to diverse electrodes in a flow-through calibration and measurement cell during storage and sensor calibration and in which the calibration media are displaced by the entry of a subsequent sample to be tested. The system is associated with a disposable cartridge insertable into a portable instrument that contains all of the electronics and other end support equipment associated with automated calibration and sample measurement.

BACKGROUND OF THE INVENTION 
I. Field of the Invention 
The present invention is directed generally to a self-contained, disposable 
cartridge-type electrochemical test cell for use with an associated test 
instrument having an integral temperature stabilized autogenous electrode 
calibration and measurement system and, more particularly, to a method and 
system for controlling and stabilizing the location of the calibration 
material with respect to the electrode system so that calibration can be 
accomplished automatically and thereafter displacement of the calibration 
medium by the sample readily accommodated. 
II. Description of the Related Art 
The field of diagnostic medicine is fast becoming more sophisticated and 
complex. The ability to make rapid or immediate diagnostic determinations 
characteristic of the current condition of a patient so that the proper 
emergency steps may be taken in a timely manner to improve or stabilize 
the condition of the patient, for example, during surgery or during the 
treatment of traumatic injury has become very important. Blood gas 
determinations including the partial pressures of oxygen (PO.sub.2), 
carbon dioxide (PCO.sub.2), acidity or alkalinity (pH) and concentration 
of certain electrolyte species such as potassium (K.sup.+) in the blood 
are examples of extremely important instantaneous indications of 
respiratory deficiency, efficiency of inhalation therapy, renal function 
and other vital bodily processes. 
Blood gas determinations heretofore have been made utilizing stationary 
clinical laboratory instruments that have large reference electrodes and 
pH, CO.sub.2 and O.sub.2 electrodes. The instruments must be periodically 
calibrated using a calibration system which is cumbersome in size and 
intended for use only at a specific temperature. Operation of the 
instrument is also generally restricted to a specific known temperature, 
e.g., 37.degree. C. The reference and pH electrodes must be calibrated 
using a liquid system. The CO.sub.2 and O.sub.2 electrodes can be 
calibrated using either a liquid medium or a calibration gas. In addition 
to periodic recalibration of the instrument, control samples also need to 
be analyzed to ensure continued proper operation; these samples also have 
restrictive temperature ranges for use. The specific composition of 
typical liquid control or calibration fluid systems is such that the 
reference or known equilibrium partial pressures of oxygen and carbon 
dioxide are temperature dependent and so occur only at the specific 
storage temperature. Operating or using a liquid-based calibration system 
at a temperature other than the designed temperature may introduce a 
decided amount of error into the readings. Gaseous CO.sub.2 and O.sub.2 
may also be used to calibrate CO.sub.2 and O.sub.2 sensors in such 
instruments, but that requires the need for obtaining and for storage of 
cylinders of compressed gases. 
A calibration and measurement system which is small and portable and that 
makes use of a calibration system that is temperature independent would be 
very desirable. Reducing the temperature dependence of the calibration 
system as by temperature stabilization of the amount of contained 
dissolved or dissociated gaseous species of interest in media for a 
variety of applications has been demonstrated. 
In this regard, it has been found possible to create a packaged system that 
provides a stable concentration of a gas in a calibration medium despite 
changes in the temperature of the calibration medium or solvent within a 
reasonable range of ambient temperature. Such a system is illustrated and 
described in copending application Ser. No. 07/806,495 of David W. Deetz 
and Russell L. Morris, filed Dec. 13, 1991 and assigned to the same 
assignee as the present invention. To the extent necessary for an 
understanding of the present application, material from that application 
may be deemed incorporated by reference herein. That 
temperature-independent system involves the use of an additional separate, 
reversible equilibrium compensating source containing an amount of the gas 
or gases of interest packaged along with the calibration medium. The 
additional source known as a "reservoir" acts in the manner of a buffer to 
control changes in the partial pressure of the gas or gases of interest in 
the atmosphere of the package including the atmosphere contacting the 
calibration liquid. The changes in partial pressure can be tailored to 
compensate for changes in the solubility of the gas or gases of interest 
in the calibration medium over a designed range. The system can also be 
used to control change in the partial pressure of a species of interest as 
a function of temperature change. 
Both the calibration medium and the reservoir are contained in separate 
gas-permeable enclosures within an outer, common enclosure such that 
gaseous species may be readily exchanged with respect to the common 
atmosphere of the sealed outer enclosure but such that the media 
themselves do not contact each other. The reservoir equilibrium is 
designed to have a more sensitive temperature dependence and the enclosure 
of the reservoir to be more permeable to the gas(es) of interest than 
those of the calibration system and container in order that the reservoir 
system react more quickly to temperature changes and thus to dominate 
changes produced in the calibration container. Temperature changes which 
produce an increase or decrease in the partial pressure of a species of 
interest in the reservoir medium will cause a corresponding increase or 
decrease in the partial pressure of that species in the common atmosphere 
at a rate that will, in turn, anticipate and compensate changes in the 
calibration system material. 
For example, the reservoir medium is designed, upon heating, to expel 
amounts of a gas or gases into the package atmosphere anticipating the 
reaction of the sample by raising the partial pressures of these gases in 
the common atmosphere at a somewhat faster rate than they would be lost 
from the calibration medium, thereby preempting the thermodynamic driving 
force for the gases to leave through the permeable shell of the 
calibration container. Conversely, if the system cools and the solubility 
of the gases of interest in the calibration medium increases, the 
reservoir acts to reverse the phenomena of the heating mode and reabsorbs 
the gas or gases into the reservoir medium from the package atmosphere at 
a somewhat faster rate than the reabsorption in the calibration medium 
thereby lowering the partial pressure of the gas or gases of interest in 
the common atmosphere to eliminate any driving force for the gas or gases 
of interest in the common atmosphere to permeate the calibration enclosure 
and dissolve in the calibration medium. This preserves the resulting 
concentration of each such species of interest in the calibration medium 
regardless of the direction of temperature change within a designed 
limited ambient temperature range. 
Typically, the calibration medium and/or the reservoir medium are solutions 
of selective solvents with or without complexing agents or buffers. In the 
case where CO.sub.2 is the species cf interest, both the reservoir and the 
sample media may be aqueous solutions of CO.sub.2. A system where the 
sample pH is 7.4 and the reservoir is buffered to a pH of 8.6, for 
example, exhibits good temperature/concentration or (pCO.sub.2) stability 
in the 20.degree. C. to 30.degree. C. range; but (pCO.sub.2) is quite 
temperature dependent for a reservoir pH above 9.0, or below 8.2. 
It being further recognized that while the copending cross-referenced 
application addresses the physics and chemistry of temperature related 
calibration media composition stabilization and control, it remains 
necessary to stabilize and control the locus of the calibration media 
materials themselves with respect to the sensor electrode system to 
achieve proper electrode function and automate calibration. In this 
regard, it is desirable that the calibration medium or media be stored or 
available over one or more of the electrodes as required for automatic 
calibration. In addition, the calibration materials must be readily 
displaceable for the subsequent sample to be subjected to analysis just 
after calibration so that the sample and calibration media do not 
interfere with each other. 
Accordingly, it is a primary object of the present invention to provide a 
disposable, self-contained automated calibration and sample testing 
enclosure that stabilizes the calibration material in contact with 
selected electrodes until calibration is concluded, yet allows easy 
displacement by the sample solution to be analyzed. 
Another object is to provide a calibration media of a consistency 
commensurate with maintaining a desired location during storage and 
through calibration. 
A further object of the present invention is the provision of flow control 
and storage volumes for used displaced calibration fluid. 
A still further object contemplates a containment system that maintains 
calibration material over sensors in a disposable test cartridge used for 
measuring blood gases and pH, as well as other analyses. 
An additional object of the invention is to provide a containment system 
that maintains calibration fluid over the sensors of a disposable test 
cartridge by the provision of a flow cell region over the sensors with 
flanking constrictions sufficient to contain an aqueous or other 
calibration fluid, yet large enough to allow blood flow. 
Yet an additional object contemplates a containment system that maintains 
calibration material over sensors in a disposable test cartridge used for 
measuring blood gases and pH using both aqueous and non-aqueous 
calibration material solvents. 
Yet still another object contemplates a containment system that maintains 
calibration material over sensors in a disposable test cartridge used for 
measuring blood gases and pH using a gel stabilized dispersion of aqueous 
and/or non-aqueous calibration materials. 
These and other objects will become apparent to those skilled in the art 
who persevere through this specification in light of the drawings and 
claims. 
SUMMARY OF THE INVENTION 
The present invention involves a self-contained, disposable cartridge 
system including a flow-through cell containing the sensors used for blood 
gas analysis including pH, pCO.sub.2, pO.sub.2 and possibly K.sup.+ 
sensors, in a configuration in which the blood gas analysis is designed to 
be carried out after automatic calibration of the sensor electrodes. The 
disposable cartridge is designed to be inserted into an instrument that 
contains all of the electronics and other support equipment to accomplish 
the calibration and measurement using the electrode system contained in 
the disposable cartridge. The disposable cartridge, then, is designed to 
contain a system which automatically calibrates the electrodes after the 
cartridge is inserted in and engaged in conjunction with the operation of 
the portable instrument. Combinations of calibration media and disposable 
cartridge electrode and media containment and storage design are 
contemplated such that the calibration material is contained over the 
sensors as required in the flow-through cell chamber during storage and 
shipment and up to the time of calibration but is thereafter readily 
displaced by the injection of the sample of interest, normally blood. 
It is contemplated with respect to the present invention that the media 
supporting calibration may take a variety of forms. These include highly 
fluid aqueous solutions; highly fluid non-aqueous solutions, which may or 
may not be miscible with aqueous media may be used. Variations in the 
viscosity of the media are clearly also contemplated. Gels or even solids 
exhibiting the properties required with respect to taking on and giving up 
the species necessary for accurate calibration may be employed. A gel 
stabilized dispersion of aqueous and/or non-aqueous calibration material 
may also be used. The gel may be based on natural materials such as agar, 
collagen, agarose, other natural polysaccharide materials or any of 
numerous compatible synthetic polymer based materials. An amount of 
surfactant may be used to enhance the temperature and/or time stability of 
the dispersion if required. 
The environment of calibration, and hence that of sample determination, is 
that of a disposable cartridge unit having a plurality of electrochemical 
electrode sensors to perform each contemplated function. One embodiment 
contains sensors for determining CO.sub.2, O.sub.2, pH and K.sup.+ 
together with a reference electrode. These are contained in a hollow 
flow-through cell channel or chamber within the disposable cartridge. 
Provision is made to maintain the presence of the calibration material 
over the required some or all of the electrodes during shipment, storage 
and calibration. The system may take any one of several configurations 
depending on the combination of electrodes and calibration materials 
contemplated. For example, the calibration material may need to allow 
ionic conduction between the pH and reference electrodes or between the 
CO.sub.2 and pH and the reference electrode in certain configurations. The 
oxygen electrode, on the other hand, may be designed to operate with a 
specific in situ calibration material or may be calibrated to atmospheric 
oxygen using only a wetting medium to support ionic conduction. 
The containment means itself may take one of several forms. If the use of 
an aqueous or non-aqueous calibration fluid that is of low viscosity be 
contemplated, the flow-through cell channel or chamber region including 
the sensors is provided with constrictions on each end sufficient to 
contain the fluid based on surface tension, yet large enough to allow 
blood flow. If, on the other hand, a gel stabilized or highly viscous 
system be used, physical members for flow restriction may not be required. 
The disposable cartridge contemplated by the invention consists of an inlet 
port addressing the flow-through cell, passage or sample chamber having a 
cell volume and which carries the electrodes in communication with the 
interior thereof. This chamber also is designed to retain the calibration 
medium or media prior to injection or insertion of the sample. The 
cartridge further includes an outlet passage, exit or egress flow path in 
fluid flow communication with the sample chamber and with a used 
calibration fluid disposal chamber such that the insertion or injection of 
the fluid sample into the sample chamber displaces the calibration medium 
from the sample chamber into the used calibration fluid storage chamber to 
prevent interference with sample measurement. 
As a physical medium, a calibration material having multiple phases 
including aqueous and non-aqueous phases may also be used. Likewise, a gel 
system may be designed to melt at a temperature close to body temperature 
such that it is either liquified at operating temperature or gelled in a 
manner such that it may be displaced by the blood sample as a solid or 
plug. Solids may include high average molecular weight polymers or other 
materials which reversibly transceive the species of interest. Of course, 
an aqueous or non-aqueous gel may also be used.

DETAILED DESCRIPTION 
As is evident from the summary above, the electrode array and so the 
calibration media associated with the disposable cartridge of the present 
invention may take any of many forms and the description of the detailed 
embodiments herein are decidedly intended by way of example rather than 
limitation. Accordingly, there is shown in FIG. 1 generally at 10 a 
disposable cartridge unit that is designed to be inserted into an 
instrument (not shown) that contains the power supply for and all of the 
electronics and other support equipment to utilize the cartridge of the 
invention in the manner intended, yet which itself does not form a part of 
this invention. This includes means to calibrate all of the electrodes 
and, upon the insertion of a sample, make all the measurement 
determinations with respect to that sample. The cartridge 10 is intended 
to be employed as a disposable on a one-time basis which includes 
insertion, automatic calibration and sample measurement by the associated 
instrument. 
The disposable cartridge 10 is constructed of a polymer material such as 
polycarbonate and includes an integral handle 12 provided to grasp the 
cartridge and guide members 14 which aid the insertion of end 16 into the 
corresponding associated portable diagnostic instrument (not shown). The 
cartridge is provided with an array of functional electrical conductors as 
at 18 which provide the required cartridge/instrument interconnect 
including all necessary input and output conductors. The conductors may be 
constructed in any well-known manner. They may be deposited on the surface 
of the polymeric material utilizing thick or thin film technology or any 
other appropriate technique as many such are readily available to those 
skilled in the art. The cartridge unit itself contemplates a plurality of 
internal passages or chambers including a calibration and measurement 
flow-through cell chamber 20 and a used calibration medium and excess 
sample storage chamber 22 which may have a plurality of partitions 24 
thereby defining a tortuous maze. The compartment 22 is connected with the 
electrode-containing measurement compartment 20 via a fluid passage 25. 
The system also includes a sample inlet port at 26 and a plurality of 
sensor electrodes including a reference electrode 28, pH electrode 30, 
CO.sub.2 electrode 32, potassium (K.sup.+) electrode 34 and O.sub.2 
electrode 36. The electrode arrangement in the system, of course, may vary 
with application. 
FIG. 4 depicts an embodiment similar to that of FIG. 3 except that the 
ingress and egress to the compartment 20 is further limited by pairs of 
flanking, oppositely disposed flow restriction devices as at 40 and 42. 
These devices are designed to permit flow through the openings 44 and 46 
only upon the application of an external force such as that which could be 
provided by a syringe. This enables the system to contain even low 
viscosity aqueous calibration solutions during storage and through 
calibration by relying on surface tension for retention. Forcible 
injection or insertion of a blood or other fluid sample into port 26 will 
readily displace the calibration media from the volume 20 into the volume 
22, through openings 44 and 46. 
The system of the present invention contemplates a method of providing an 
automated calibration system for a disposable cartridge of the class 
described in addition to the apparatus itself. The method includes 
providing means commensurate with the composition and viscosity of the 
calibration medium or media to provide proper containment during storage 
and calibration which is then receptive to displacement by the in-flow of 
the sample solution which thereby then makes use of the same 
electrochemical sensor system. 
The system of the present invention, as introduced above, contemplates 
calibration materials of several forms. In this manner, a non-aqueous 
phase may be sandwiched between two aqueous phases with one of the aqueous 
phases placed over the pH, CO.sub.2 and reference electrodes and the 
non-aqueous phase over the O.sub.2 sensor, it being recognized that the 
electrodes of the system can be placed in any desired order and they are 
suitably connected through he conductors as at 18 to the instrument upon 
the insertion of the disposable cartridge 10. For example, if the O.sub.2 
sensor is designed for use with a perfluorocarbon non-aqueous calibration 
phase, the aqueous phases might be placed at each end to contain the low 
surface-tension, non-aqueous perfluorocarbon phase in the embodiment of 
FIG. 4. The flow-through channel 20 must be small enough, however, to 
prevent the phases from moving relative to one another during shipping and 
handling. 
With respect to gel systems, a gel stabilized dispersion or solution of 
aqueous and/or non-aqueous calibration material can be employed in which 
the gel is a natural material such as agar, agarose, collagen or any 
suitable polysaccharide, the gel can also be based on one or more 
synthetic polymers such as polyvinyl alcohol (PVA), polyvinyl pyrrolidone 
(PVP) or the like. An amount of surfactant may be used to enhance the 
temperature and time stability of a dispersion. The gel system may be 
signed to melt at a temperature slightly below 37.degree. C. so that it is 
in liquid form at body temperature which is normally the contemplated 
operating temperature of the sample determination system of the 
instrument. The gel system may be designed to melt at a temperature higher 
than 37.degree. C. so that it is displaced by the blood or other sample as 
a solid or plug which can be squeezed from the electrode chamber into the 
used calibration fluid chamber as a solid. The gel or other electrolyte 
calibration systems can be utilized with a subset of sensors that contains 
materials and/or salts necessary to calibrate the sensors over which it is 
placed. 
This invention has been described in this application in considerable 
detail in order to comply with the Patent Statutes and to provide those 
skilled in the art with the information needed to apply the novel 
principles and to construct and use such specialized components as are 
required. However, it is to be further understood that the invention can 
be carried out by specifically different equipment and devices and that 
various modifications can be accomplished without departing from the scope 
of the invention itself. For example, the cartridge system described may 
also be used with other types of chemical sensors. These include optical 
sensor systems.