WO1988000708A1

WO1988000708A1 - A clinical chemistry analyzer

Info

Publication number: WO1988000708A1
Application number: PCT/US1987/001724
Authority: WO
Inventors: Gilbert Conover, Jr.; Bruce D. Miller; Thadeous G. Minior, Jr.; John P. Willis
Original assignee: Ilex Corporation
Priority date: 1986-07-21
Filing date: 1987-07-20
Publication date: 1988-01-28
Also published as: AU7785587A

Abstract

A clinical chemistry analyzer which simultaneously dispenses fluid test samples and reference samples into a disposable electrode sensor and determines the activity or concentration of various analytes in the test sample from the electrical characteristics measured across the electrodes of the sensor.

Description

A CLINICAL CHEMISTRY ANALYZER

Description

Related Applications

This application is a continuation-in-part of United States Patent Applications Serial Nσs. 750,671 filed on June 27, 1985 and 750,525 filed on June 27, 1985.

Technical Fields

This invention is in the fields of analytical chemistry, biochemistry and clinical chemistry. In particular, it relates to apparatus for performing tests on serum, plasma, or whole blood samples to determine the concentration or activity of various analytes in the samples.

Background

Ion selective electrodes have been used in the past to conduct potentiometric measurement of the activity of an ion in a liquid sample. The ion-selective electrodes respond preferentially or selectively to a particular ionic species in a liquid. The ion-selective electrodes are used to form one-half of an electro-chemical cell which is formed by contacting a liquid with two such electrodes.

In a typical measurement, the half cell potential of one electrode (the reference electrode) ; which contains a known calibrated sample and that of another electrode (referred to as an indicator or patient electrode) ; which contains an unknown liquid sample varies with the ionic activity of the liquid being analyzed. The electrical potential across the electrodes is proportional to the logarithm of the activity of ions in the solution to which the ion-selective electrode responds.

The well-known Nernst equation describes the logarithmic relationship. This difference in electrical potential is used to determine the ion activity of the liquid, i.e., sample blood solution, dispensed into the indicator electrode.

In the past the measuring apparatus employed utilized either a flow-through process wherein the sample is pumped past a re-usable, limited life electrode or a system in which electrodes are manually dipped into the sample. The flow-through systems require frequent calibration and use expensive electrodes. Also, it is inherently difficult to maintain, effective separation of samples and, hence, sample integrity is such systems. The manual dipping electrode approach is labor intensive and less precise.

Disclosure of the Invention

The apparatus of the present invention is comprised of four interrelated systems or components which result in a clinical chemistry analyzer using an electrochemical sensor system which simultaneously dispenses test samples and reference samples to a disposable sensor and determines the activity or concentration of various analytes in the test sample. 1. Sensor System

In one embodiment of the invention the electrochemical sensor is of the type described in detail in co-pending U. S. Patent Application Serial No. 750,525 filed June 27, 1985. In summary, it comprises at least three ion-selective electrodes, one of which is a reference electrode, another is an indicator electrode, and the third is a calibrant electrode. Each ion-selective electrode consists of a membrane- spaced from a contact element. The membrane is comprised of selectively permeable material having an ionophore selected for the ion whose activity is to be determined. A gel containing a reference material consisting of a solution of the salt of the ion to be determined is disposed in the space between the membrane and the contact element. Fluid samples are dispensed onto the membrane.

Porous wick material is provided between pairs of electrodes to provide a liquid junction between the two fluids while preventing substantial mixing of the fluids.

At least three fluid samples are simultaneously dispensed onto the membranes of separate electrodes. Test samples in fluid form, such as, for example, a blood specimen, which may be either in plasma or whole blood or serum form, are dispensed onto the indicator electrode. Simultaneously, a calibrator fluid sample of known ionic concentration is dispensed onto the calibrant electrode and a reference fluid of known ionic concentration is dispensed onto the reference electrode.

By measuring the EMF generated across the cells formed between the electrodes, the ionic activity of the fluid sample in the indicator electrode can be determined. For this determination to be accurate, it is important that the samples be dispensed substantially simultaneously. If one sample is prematurely dispensed it may travel through the wick and enter the opposite well altering the sample concentration. By dispensing simultaneously the junction occurs somewhere within the wick. To a lesser degree it is important that the correct amount of sample is dispensed.

To dispense such samples simultaneously with uniformity and in an automatic and precise manner, a dispenser mechanism and associated dual pipette dispenser is provided. These elements form the next two structures of the apparatus of the present invention. 2. Dual Barrel Pipette

The dual barrel pipette of the invention is adapted for use in simultaneously dispensing fluid samples of substantially equal amounts. The pipette comprises a pair of substantially identical pipette barrels which are used in conjunction with a pair of substantially identical pistons adapted to be inserted into the barrels.

The barrels have a tapered distal end with a Leur fitting which is adapted to be mated with a standard syringe needle for aspirating fluid samples into the barrel. The barrels are joined together by a web at the proximal ends to form an integral structure. A tab extends transversely to the longitudinal axis of the barrel to serve as a stop mechanism when it abuts with a holder on the dispenser apparatus and also serves as a convenient means of grasping the pipette and for preventing improper insertion of the pipette into the holder.

The pistons or plungers are likewise substantially identical and are adapted to be inserted into the barrels. An integral sealing ring is provided on each of the pistons near the distal end to provide a vacuum seal between the inner walls of the barrel and the piston ring as the pistons are longitudinally extended into or out of the barrel to respectively dispense or aspirate fluid.

The two pistons are also joined at the proximal ends by a web member which extends transverse to the longitudinal axis of the pistons. This member forms a convenient handle for grasping the pistons and accurately locates them in relation to the axis of the barrels.

A projection in the form of a small rounded button is formed on the external proximal end of the piston joining web member midway between the longitudinal axis of the two pistons. This project¬ ing button forms a discrete actuating surface which is used by the dispenser mechanism to accurately sense and control the longitudinal displacement of the piston. 3. Fluid Dispenser Mechanism

The function of the dispenser mechanism is to precisely and simultaneously dispense equal amounts of calibrant liquid, reference liquid and patient sample liquid onto the respective calibrant, reference, and indicator electrodes mounted in the sensor body.

The dispenser is adapted to be employed with the above-referenced dual pipette. It consists of the following the main elements: a holder for holding the pipettes in a longitudinally upright position over the sensor body such that the distal ends of the pipette barrels are disposed directly over the respective electrodes; and a pipette dispenser actuator having actuating arms adapted to be moved from an extended position laterally away from the top of the pipette to an actuating position over the projecting button on the pipette piston.

The pipette dispenser actuator consists of a hollow shaft and an actuating arm disposed on one end of the shaft and extending transverse the longitudinal axis of the shaft. A grooved cam surface is formed on the external surface of the shaft. Electrical wires are connected through the hollow shaft to a membrane-type switch mounted on the bottom surface of the dispenser actuating arm. A support member holds the shaft for rotation about the longitudinal axis of the shaft in a plane displaced and parallel with the longitudinal axis of the pipette barrels. A projecting member is provided in the body of the support member which extends transverse the longitudinal shaft axis and projects into the grooved cam surface on the shaft to control the rotational movement of the shaft along the path of the grooved cam surface. The cam surface enables the arms to be placed in two positions. In the first position, the arms are vertically extended along the longitudinal shaft axis while being laterally rotated away from the piston actuating surface or projection formed on the pipette piston. In this position, the pipette can be easily inserted into the holder without interference from the arms. In the second, or actuating position, the actuator arm is distended longitudinally and constrained to rotate laterally- over the piston actuating projection.

A membrane switch, mounted in a recess in the bottom of the arm, senses when the arm is in contact with the piston projection. In the event the dual pipette should be mounted improperly, the recessed switch in the arm will not make contact with the projection and, therefore, the dispenser will not operate. The dispenser mechanism is also provided with a slideable drip catcher tray for collecting fluids which might inadvertently be dispensed from the pipette when the sensor body is not in position beneath the holder.

The shafts are driven by a microprocessor controlled stepping motor through a precision lead screw mechanism. This mechanism allows the shafts to be raised or lowered very precisely to control the amount of fluid dispensed. Also the acceleration or deceleration can be controlled to eliminate hanging drops on the ends of the pipette and to eliminate splashing. The amount of sample fluid dispensed is determined by the number of steps taken by the stepping motor and can be readily changed by the microprocessor. Also the microprocessor i^ provided with several additional signals which signify whether sufficient sample reference, calibrant and indicator fluid is available before dispensing thereby assuring that all tests are conducted with the correct volume of fluids. 4. Potentiometric/Amperometric Measurement System

The sensor apparatus of the present invention includes a magnetic strip which can be read to provide information to the measurement circuitry with respect to the type of test under measurement test card expiration date and in some cases, calibration data. The contacts on the ion-selective electrodes on the sensor body provide contact points across which either a voltage, i.e. , potentiometric measurement, may be conducted, or in an alternate embodiment of the sensor body, a current, i.e., amperometric measurement, may be accomplished. The analyzer is provided with sufficient flexibility to accomplish either of these measurements depending on the instrumentation mode programmed via a microprocessor responsive to the information provided from the magnetic strip.

In the potentiometriσ mode of operation, the voltage across selected cells formed of two ion selective electrodes is measured and converted from an analog signal to a digital signal in an A-D converter. In the amperometric mode, the current differential between the selected cell^'s is similarly measured and converted.

The details of the above instrumentation will now be described in detail in connection with the drawings.

Brief Description of the Drawings

Fig. 1 is a perspective view of the top of a typical sensor 30 of the invention.

Fig. 2 is a perspective view of the bottom of the sensor of Fig. 1 showing the magnetic stripe 8 on the card handle 5 of the sensor 30.

Fig. 3 is an exploded perspective view showing the individual components of a sensor 30 of the invention.

Fig. 3A is an enlarged partial sectional view of the sensor body 10 taken through one of the ion-sensitive electrodes. Fig. 4 is a perspective view of the dispensing mechanism of the invention showing a dual pipette in place on the holder 44 of the dispenser.

Fig. 4A is a partial top view of a portion of the dispenser.

Fig. 5 is a partially sectionalized side view of the piston 42 for the dual pipette.

Fig. 6 is a top view of the piston 42 of Fig. 5.

Fig. 7 is a partial enlarged sectional view of the piston taken along the lines 7-7 of Fig. 6.

Fig. 8 is an enlarged sectional view taken along the lines 8-8 of the enlarged section of Fig. 7.

Fig. 9- is an enlarged sectional view taken along the lines 9-9 of Fig. 5.

Fig. 10 is an enlarged sectional view taken along the lines 10-10 of Fig. 5.

Fig. 11 is a side view taken along the lines 11-11 of Fig. 5.

Fig. 12 is a side view taken along the lines 12-12 of Fig. 5.

Fig. 13 is a side view of a dual pipette barrel 46 of the invention.

Fig. 14 is a bottom view of the dual pipette barrel of Fig. 13.

Fig. 15 is a sectional view of the dual pipette barrel of Fig. 13 taken along the lines 15-15 of Fig. 13. Fig. 16 is a sectional view taken along lines 16-16 of Fig. 13. ^'

Fig. 17 is an end view taken along the lines 17-17 of Fig. 13.

Fig. 18 is a front elevational perspective view cf a shaft and actuating arm 72 of the invention.

Fig. 19 is a side view of the shaft and actuating arm 72.

Fig. 20 is a planar view of the bottom of a membrane switch 88 utilized in the actuating arm 72.

Fig. 21 is a partly schematicized view of the dispensing mechanism and associated electronics.

Fig. 22 is a block diagram of the electronic portions of the invention.

Fig. 23 is a side sectional perspective view of an alternate sensor body 10' used for amperometric measurements, including a schematic showing the external connections to the bottom of the sensor.

Fig. 24 is a schematic showing the internal connections of the sensor body 10' of Fig. 23.

Referring now to the drawings, the details of the apparatus of the invention will be explained in connection therewith.

Best Mode of Carrying Out the Invention

The clinical chemistry analyzer of the invention is comprised of several elements, chief of which are the sensor shown in Figs. 1-3A, the dispenser mechanism shown in Figs. 4 and 21, the dual disposable pipette shown in Figs. 5-17 and the "top-of-pipette" sensing mechanism shown in Figs. 18-20. These elements of the invention will now be described in detail below. 1. Sensor

As shown in Figs. 1 and 2, the sensor 30 consists, in general, of a disposable test card comprising a sensor assembly 10 and a card 5. Sensor 30 is used to perform many of the commonly occurring clinical chemistry tests on liquid samples and, in particular, on blood samples which may be in serum, plasma or whole blood form. Each test card 30 performs a single discrete test.

Typical tests are the determination of the concentration of either potassium, sodium, chloride or BUN (Blood Urea Nitrogen) or Glucose in a blood sample. The holder or card 5 is made of thin plastic material with a bottom stripe 8 of material upon which information may be stored in machine readable form concerning the type of test to be performed with a specific sensor and also the expiration date of the sensor and in some cases calibration data. Stripe 8 may take the form of a magnetic bar code.

The sensor body 10 is affixed to the card 5. Body 10 comprises a rectangular, square, or clover leaf light transparent, plastic, frame having an upper and a lower section 12 and 14, respectively. The upper and lower frames are attached to each other by ultrasonic welding. The body 10 forms a holder for a plurality of ion selective electrodes 31. As shown in Figs. 3-3A, each such electrode 31 comprises an electrically conductive contact element 22 and an ion selective membrane 18 displaced from each other by a hollow plastic cylindrical retaining ring 24. A gel 19 is enclosed within ring 24. Gel 19 incorporates a reference material consisting of a solution of the salt of the ion to which the membrane is selective.

The body 10 of the holder 30 has planar top and bottom surfaces 10a and 10b. The electrically conductive contacts 22 of each ion sensitive electrode 31 have an exposed surface 22a which is located co-planar to the bottom surface 10b of the holder body 10 and card 5. As will be explained later, this facilitates making electrical contact in the dispensing mechanism with the ion sensitive electrodes 31.

The disc-shaped ion selective membrane 18 is preferably formed of an ion-selective compound, i.e., an ionophore, a thermoplastic resin and a plastisizer, all of which are soluble in an organic solvent. Each ion-selective electrode 31 thus forms one-half of an EMF generating cell formed when two such electrodes are coupled to one another via liquid flow through porous rods 17 disposed in grooves 6 formed midway between the planes of the contacting top surface of frame 14 and the bottom surface of frame 12. These grooves 6 extend between the wells 4 of certain selected pairs of ion-sensitive electrodes to provide fluid ionic communication between such pairs to complete the cells. The wells 4 extend from the top frame 12 of the body 10 to the membranes 18.

In the preferred embodiment of the invention, three ion-selective electrodes 31 are utilized with a fourth optional electrode. The function of the optional electrode is to provide flexibility for additional types of testing. For example, two independent tests could be performed, concurrently, by coupling two electrodes together with one wick and two other electrodes via another wick. The three electrodes 31 are labelled CA, REF, and IND, representing the calibrant electrode, CA, the reference electrode, REF, and the patient sample electrode, IND. The optional electrode is labelled OPT. The test card is adapted to be inserted into the dispenser, as will be described in detail later, with the electrodes symmetrically positioned within the holder, as shown in Fig. 1, such that simultan¬ eous amounts of patent, reference and calibrant samples may be disposed in the respective patient (indicator) , reference, and calibrant electrodes when the test card is positioned beneath the dual pipette 41, as shown in Fig. 4. 2. Dual Barrel Pipette Fluid Dispenser

As related previously, it is important for proper operation of the apparatus of the invention, that a capability be provided for simultaneously dispensing fluid samples to the patient, reference and calibrant electrode of the sensor.

This problem is solved in the present apparatus by providing a dual barrel pipette 41 (See Fig. 4) which is comprised of two separate plastic components; a plunger or piston mechanism 42 shown in detail in Figs. 5-12 and a barrel mechanism shown in detail in Figs. 13-17. These components will now be described in detail.

The pipette 41 is of syringe-type construction having a dual piston member 42 comprised of a pair of substantially identical pistons 208 and 210 (Fig. 5) adapted to be inserted into the barrels 300 and 310, respectively, of the dual barrel 46 (Fig. 13) . The pistons or plungers 208 and 210 are joined at their proximal ends by a piston-joining member 204 comprising a web .of plastic integrally formed transverse to the longitudinal axis of the pistons 208 and 210. The piston-joining member 204 provides a convenient 'handle for inserting and extracting the pistons .

An actuating means 200 in the form of a button or projecting knob 200 is integrally formed on the external planar surface 202 of piston-joining member 204 midway between the longitudinal axis of the two pistons 208 and 210. As will be described in detail in connection with the piston actuating arm and membrane switch, the actuating button 200 on the piston 42 forms a discrete location on the piston for determining the presence of the piston which actuates a membrane sensor in the dispenser arm which, in turn, applies a longitudinal force to actuate the pistons a predetermined distance into the barrels, thereby to expel fluid samples of equal amounts from the distal ends 303 of barrels 300 and 310 (Fig. 13) .

Near the distal end of the pistons a pair of sealing rings 214 are formed in the shape of re-entrant flexible structures with outer cylindrical tapered walls 222 which have a sufficient peripheral diameter to mate with the inner walls of the barrels and form a vacuum-tight seal therebetween.

As shown in the cross-section of Fig. 9, the iston rods 208 and 210 are of generally cruciform cross-section providing good rigidity. Web 204, as shown in Fig. 10, joins the two cruciform sections at the mid-planes. A portion of the cruciform sections are extended in diameter and rounded off at the extremities, near the sealing ring portion of the piston rods 208 and 210, as shown in Fig. 7. The purpose of this extended transition portion is to eliminate side-play at the top of the piston when fully extended.

A close, but not interference fit with the pipette barrels is thus provided so that the pistons remain in the same axis as the barrels, even when the piston is at the very top of its stroke. This ensures that the button 200 lines up with the membrane switch sensitive area 94 (Fig. 20) . The twin barrel member 46 making up the other half of the dual barrel pipette syringe 41 is shown in Figs. 13-17. As shown therein, the dual barrels 300 and 310 comprise longitudinally extending substantially identical pipette barrels with an integral web member 314 joining the proximal ends of the barrel together.

A leur-type fitting or nipple 302, 312 is formed at the distal end of each barrel. An opening 303 is provided on the distal end of each fitting. A tapered entrance structure 316 is formed at the proximal ends of the barrel having a transversely extending abutment plate or tab 304.

Tab 304 serves as a convenient mechanism for placing the dual pipette in the dispensing mechanism holder and for preventing insertion of the pipette mechanism in an incorrect position. It also serves as^' a stop so that the barrel is at a precise height. This is important since it enables a microprocessor to determine the amount of sample left by knowing the piston height.

Preferably, pipette barrel 46 is made of plastic material of somewhat less rigidity than that of the material of the pistons 42. A"preferred choice of plastic material would be the use of polypropylene for the barrels 46 and high density polyethylene for the pistons 42. 3. Dual Pipette Dispenser Mechanism

The details of the dual pipette dispenser mechanism will now be described in connection with

Figs. 4 and 18-21.

Referring now to Fig. 4, which is a perspective view of the dispenser mechanism 40, the dispenser mechanism 40 comprises, in general, a pipette holder

44 mounted on a vertical support member 43. Right and left pipette dispenser actuators consisting of left actuating shaft 72 and right actuating shaft 62 and right actuating head 64 and le - actuating head 74 are rotatably disposed within the support member 43.

A pair of dual barrel pipettes, each comprising a dual piston or plunger 42 and a dual barrel 46, are disposed within longitudinally extending bores

45 formed in holder 44. For clarity and simplification in the drawing, only one such dual pipette assembly 41 is shown in Fig. 4. It should be understood, however, that in normal operation, a left and right dual pipette would be disposed in the holder 44.

Support 43 is affixed to horizontal frame plate 63 which has an outer extending lip 61 with a pair of guide rails 58 formed thereon for guiding the horizontal insertion of card 5 of sensor 30 into the dispenser mechanism in the direction shown by the arrows.

A pair of openings 57 and 59 (shown in dotted lines) are formed in member 63. Spring loaded electrical contacts 56 (shown in phantom) mounted accurately in a housing or block 56 extend through opening 57. A magnetic pickup head 60 extends through opening 59. A drip catcher tray 48 with disposable absorbent material (not shown) is mounted on member 63 to catch any fluid dispensed inadvertently from the dual pipette 41 to prevent such fluid from accumulating and damaging the contacts 56 mounted below the holder.

As shown more clearly in the side elevation view of Fig. 21, tray 48 is mounted in a track 49 loaded against a spring 120 that normally keeps the tray directly under the pipette holder 44. When a sensor test card 30 is inserted into the instrument in the direction of the arrows, the body 10 of the sensor test card 3.0 abuts the tray 48 moving the tray horizontally until the sensor body 10 is positioned directly beneath the pipette holder, whereupon the contact elements on the bottom of the four ion-sensitive electrodes labelled REF. CA, IND. and OPT., make contact with separate spring-loaded contacts 56 disposed in the opening 57 provided in member 63.

An opaque interrupt tab 122 is affixed to the bottom of track 48 which extends through a slot (not shown) formed in member 63. Interrupt tab 122 therefore slides in the direction of the arrows along with the tray 48 and in the process, interrupts light focused on photodetectors 152 and 150 mounted on the bottom of the member 63 in the path of the interrupt member 122, thereby generating start and stop signals, respectively, on leads 112 and 110, which are coupled to an In/Out Card Circuit 104.

Thus, as the disposable sensor card is inserted beneath holder 44, along the lines of the arrow within tracks 58, the slideable tray 48 provides a start signal on leads 112 and a stop signal on leads 110 when the sensor body is properly positioned beneath the dual pipettes and contact is established between the electrodes and the four contact pins 56.

Two "pipette-in" sensor switches, in the form of a spring-loaded microswitch, are mounted in the rear wall of holder 44 extending into the bores 45. Each "pipette-in" sensor is coupled to a "pipette in" circuit- 103 to provide a signal to a microprocessor 514 (Fig. 22) indicating that the pipettes are loaded into the holder. One such sensor 512 is shown in Fig. 21.

With the dual barrel pipette properly loaded in the holder 44, in the position shown in Fig. 4, ^"the tab 304 on the pipette barrel 46 extends transverse the longitudinal axis of the holder and the barrels and prevents the pipette from being extended too far into the holder. It also serves to prevent the pipette barrel from being positioned at a 90° angle to the position shown in Fig. 4 with the tab extending in the direction of the support member 43. It is possible, however, to improperly mount the pipette with the tab extending forward of the holder at a 90° angle from the position shown in Fig. 4. In this event, however, a "top-of-the-pipette" detect mechanism will not be activated, as will be described below.

A membrane actuator switch mechanism is located in the arms 64 and 74 which are affixed to the rotatable shafts 62 and 72, respectively, each of which are adapted to partially rotate about a fixed longitudinal axis within a longitudinal bore 430 (shown in dotted lines in Fig. 4) provided in support member 43. At the same time, the shafts move in an axial direction, in and out of the bore 430. This axial and rotational movement of the actuator arms is dictated by the grooved partial spiral cam surface 82 formed in the external peripheral surface of shaft 80, as shown more clearly in Figs. 18 and 19. Guide studs 70 are inserted through a side wall of support member 43. The ends of the studs project into the grooves 82, restraining the path of rotation of the shaft 80 along the grooved cam surface.

In the fully extended position of the shaft, the actuator arms 64 and 74 are in the position shown in Fig. 4A with the left arm 74 fully rotated away from the pipette holder 44. Likewise, the right actuator arm 64 is fully rotated away from the holder in the position shown in solid lines. In the actuation position of the actuator arms, the arms are rotated to the position shown in dotted lines such that the actuator arms are displaced over the holder with the contact elements 94 of the membrane switch 88 centered between the two longitudinal bores 45 of the holder 44.

' Stepping motors A and B, shown in Fig. 4, drive lead screws affixed to the shafts to rotate the arms from the extended to the actuating positions in response to signals received from an electronic control system (not shown) . Each actuator arm, more clearly shown in Figs. 18 and 19, is comprised of a housing 94 affixed to one end of shaft 80. The housing is provided with a stepped inner recess 85 for accepting membrane switch 88. Switch leads 92 are coupled to terminals 90 and pass into the bore 99 in shaft 80 and extend through the exterior end thereof.

Within recess 85 is a circular sensitive area of the membrane switch wherein the membrane may be deflected by the button or projection 200 provided on the pipette piston. Only when the piston is properly placed in the position shown in Fig. 4, will the membrane switch 88 be actuated, because alignment with the projection 200 only occurs in this position.

A groove 86 is provided on the lower end of shaft 83 to facilitate a snap ring to attach the shaft to the lead screw. Thrust washers and a wave washer are used to eliminate any axial play and permit smooth radial movement at the attachment point.

A "top-of-travel" sensor 100 is provided adjacent each actuator arm shaft 62 and 72. Each sensor may comprise an opto-electronic switch to provide a signal to the "top-of-travel" circuit 127 as an input to microprocessor 514 (Fig. 22) to indicate when the actuator is at its highest extended position.

4. Electronics Circuitry

Referring now to Fig. 22, further details of the electronics associated with the system will now be described. The potentiometric sensor body 10' containing the four contacts 22, labelled OPT, IND, CAL and REF, are individually externally electrically coupled to respective microprocessor controlled electronic switches SI, S2, S3, and S4. Each contact forms one-half of a cell capable of being coupled together via wicks 17 to form a complete cell. When the magnetic read/write circuit 108 detects that a potentiometric-type sensor has been inserted, then the microprocessor 514 causes switches SI and S4 to be in the "POT" position. S2 and S3 are in the "ON" position.In the potentiometric sensor body configuration 10' shown in Fig. 22, wicks 17A connects the IND and REF electrodes and wick 17B connects the REF and CAL electrodes. Dummy wick 17C is hydrophobic, affecting an open-circuit between the OPT electrode (not in use) and the IND electrode.

The difference in potential between the CAL and REF electrodes is conducted through switch S3 to amplifier A2. The difference in potential between the IND ^'and REF electrodes is conducted through switch SI to amplifier Al. Amplifiers Al and A2 are very high input impedance ("electrometer") non-inverting amplifiers consisting of two op-amps and associated circuitry which allow them to amplify either current or voltage (potential) inputs, perform both "zero" and "full scale" calibrations, and to select various gains. All of these parameters are under the control of microprocessor 514 via lead 509. Switches S2 and S3 are "off" when the amplifier is being calibrated.

The amplified analog signals from Al and A2 are coupled to respective analog to digital converters 504 and 506 and the digital signal is fed to microprocessor 514 wherein the signals are compared to acceptable operating limits to verify^' that the sensor is operating correctly and then the concentration of the analyte in the IND electrode is calculated mathematically using pre-programed equations and, also in some cases, additional calibration data read from the sensor card mag stripe 8.

An optional input to the amplifier circuitry utilizes sensor body 10' for ampero¬ metric sensing and measurement. In this system, current activity is measured. When the magnetic read/write circuitry 108, in the READ mode, 108 detects an amperometric-type sensor card has been inserted, then the microprocessor 514 causes switches SI and S4 to be in the "AMP" position. S2 and S3 are on. The outer half circle represents the anode of a cell and the dot, the cathode. Four such cells are formed, as shown, an OPT cell, an IND cell, a CAL cell and REF cell externally connected as in Fig. 22. A measurement is made when a cell is biased with a characteristic potential supplied by the positive bias circuit 500 conducted through SI and the negative bias circuit conducted through S4. Chemical activity in the cell related to the fluid sample in the cell produces a current flow from anode to cathode, for example, II, as shown. With two cells, CAL and REF, coupled in series; a current 12 also flows into the anode of the REF cell. If II is not equal to 12, a difference current I 1 is generated and coupled through S3 to amplifier A2 in the amperometric embodiment. Similarly, a difference current I 2 is generated between OPT and IND cells and is coupled to S2 for amplification in Al. The delta signals from amplifiers Al and A2 are then converted and processed, as previously described in connection with the potentiometric description.

As may be seen in Fig. 22, the amperometric circuitry uses the same external contact points as are used for potentiometric measurement so that the measurement appears transparent to the operator.

Keyboard 516 of Fig. 22 is utilized to input command functions to microprocessor 514 which controls the operation of step motors A and B (508 & 510) to drive the plunger shafts 80 (Fig. 19) . Initially, the plunger arms are at their very top-most position. The "top-of-travel" actuator switches 100A and 100B confirm with the microprocessor that the arms are in that position.

Now, after the pipettes have been inserted in their holders, as sensed by "pipette-insert" switches 512A and B, the microprocessor 514 will send step signals out to the stepping motors. For each step, there is a definite known downward motion of the plunger arm. So, by storing in memory the number of steps that are taken, the microprocessor can determine the exact position of the plunger arm.

The microprocessor 514 will continue to give the stepping motor step signals until the plunger sensing switches 88A and 88B detect that the plunger actuating arm have come in contact with the top of the pipette, at which time it will stop the stepping motor.

Depending upon how many steps have been given to get to that position, the microprocessor knows the exact height of the plunger and can calculate how much sample is left in the plunger. After it calculates how much is left, it can determine how many tests may be made with that amount of sample. Now, when a sensor body card 30 is slid in through the test card track (Fig. 4) , after the coded data oh the card has been read by the magnetic read head (60) and stored in the microprocessor and the card is in the fully seated position, as sensed by the card end travel switch 150, the microprocessor 514 will give a fixed number of steps to the stepping motors 508 and 510 which pushes the plungers down a known amount, simultaneously dispensing a predetermined known amount of fluid sample into each of the sensor body wells.

When the test card is manually removed, as sensed by "card end" switch 150, and, through the keyboard input instruction, the operator indicates that no more tests are to be run on that sample, the microprocessor will give step signals which will cause the stepping motors 508 and 510 to rotate in the opposite direction and thus move the actuator to the fully "up" position and it will keep giving steps until the top-of-travel switches 100A and B tell the microprocessor 514 that the plunger arms are in the fully "up" position. Note that when the test card is inserted, as sensed by "card begin" circuit 152, the microprocessor 514 is programed to instruct the mag-head 60 to operate in the WRITE mode to erase whatever information is on the magnetic stripe 8, thereby rendering the test card inoperative for future use. When the card is removed, as sensed by "card end" circuit, the magnetic head is caused to resume operation in the READ mode.

Fig. 23 shows a cross-sectional partial perspective view through an amperometric sensor body 10' having four bottom electrode elements, OPT, IND, CAL and REF, internally connected, as shown in Fig. 24. Thus, the anodes A of the CAL and OPT electrodes are connected together by conductive wire 800a; the cathodes K of electrodes REF and IND by wire 800c; the cathode K of CAL electrode element to the anode A of REF electrode by wire 800d and the anode A of IND to cathode K of OPT.

Note that only the OPT and CAL elements are shown in cross-section in Fig. 23 and it should be understood that the IND and REF elements are constructed on the same body 10' adjacent thereto in the same manner. Amperometric body 10' is constructed similar to the body 10 of Fig. 3A and is dimensioned so as to be interchangeable therewith, so that external pick-up spring contacts 56 will be coupled to the same locations on each type body. However, as shown in Fig. 23, the pick-up contact 56 leading to switch SI is coupled to the half-ring anode A of CAL and the pick-up contact 56 leading to S2 is coupled to the cathode K of the OPT electrode.

Body 10 ' forms a holder for the four electrode elements, each of which comprises a circular planar membrane 18' displaced by ring 24' from half-ring planar anode A and a planar circular cathode K within the half-ring. The anodes and cathodes each have an exposed bottom surface facing the pick-up contacts 56. A plastic transparent frame having upper and lower sections 12' and 14', respectively, forms a holder for the four electrodes. A reference gel 19' is disposed in the space between membrane 18* and the anode and cathode. A well 4' is provided in upper frame 12' into which appropriate samples are dispersed, as previously described. Membrane 18' may comprise a suitable enzyme/0_ permeable membrane, as described in pending U. S. Patent Applications, Serial No. 750,671 and 750,525, previously mentioned. Note that no wicks are utilized in this embodiment and the cathode and anode contacts are insulated from each other and from the lower frame 14' by insulator rings 824 and 822, respectively. The half ring anode A of the OPT electrode is coupled via lead 800a, which extends through insulator 822 and frame 14' to the anode A of the CAL electrode. Similar internal wires (not shown) connect the other electrode elements as shown in Fig. 24.

Equivalents

Those skilled in the art will recognize or be able to ascertain using no more than routine experimentation many equivalents to the specific components, materials and apparatus described herein. Such equivalents are intended to be encompassed in the scope of the following claims.

Claims

1. A clinical chemistry analyzer comprising: a. a disposable electrode sensor for accepting liquid samples for analysis of analytes in said samples, said sensor containing electrodes adapted to be internally connected with an analyte sensitive membrane covering each of said electrodes; b. dispenser means for simultaneously dispensing a predetermined amount of said liquid samples onto said membranes; and c. measurement means coupled to said electrodes for measuring an electrical parameter produced by s'aid fluid samples to determine a characteristic of said analytes.

2. The analyzer of Claim 1 wherein the sensor is a potentiometric sensor and at least two of said electrodes are coupled together by porous members which are wetted by said samples to thereby form a voltage generating cell the potential of which is measured to determine the presence of said analyte.

3. The analyzer of Claim 1 wherein the sensor is an amperometric sensor and the electrodes are divided into cathode contacts and anode contacts and in which pairs of adjacent electrodes are coupled in series such that the anode contact of a first such electrode is coupled to the cathode contact of a second such electrode; and wherein the measurement means provides a positive voltage to the anode of the second electrode and a difference current is coupled from the connection between cathode and anode contacts for measuring the current to determine a current carrying characteristic of said analyte.

The analyzer of Claim 1 wherein the dispenser means comprises: d. a pair of substantially identical longitudinally extending pipette barrels containing said test samples and having proximal and distal ends wherein the proximal ends are joined together; e. a pair of substantially identical pistons adapted to be displaced into or out of said barrels, each having proximal and distal ends wherein the proximal ends are joined together with sealing means for providing a vacuum seal with an inner wall of said barrel as the pistons are longitudinally displaced into or out of the barrels.

The analyzer of Claim 4 including actuating means on the external proximal end of said joined pistons forming a discrete location on said pistons for determining the presence of said pistons.

The analyzer of Claim 5 wherein the actuating means actuates a sensor in an arm which is adapted to apply a longitudinal force to insert said pistons a predetermined distance into said barrels, to simultaneously expel fluid samples of equal amounts from each of said pipette barrels.

The analyzer of Claim 5 including: a. holder means for holding said pipette in a longitudinally upright position over said electrode sensor; and b. actuator means comprising a shaft and an arm extending transverse the longitudinal axis of the shaft, said actuator adapted to move from a first extended position to a second actuating position, said actuator shaft being disposed adjacent the longitudinal axis of said pipette; c. a vertical support member for holding said actuator shaft for rotation about the longitudinal axis thereof and for displacement along the longitudinal axis thereof; d. restraining means for restraining the rotational movement of said shaft along a path such that when said pipette is held in said holder means and said actuator is in a vertically extended position, the arm is laterally rotated away from the piston means of said pipette and when said actuator is in a non-vertically extended actuating position, the arm is laterally rotated over said piston means; and e) switch means mounted in said arm for sensing when said arm is in contact with said piston means.

8. The analyzer of Claim 5 further including a drip catcher means for collecting fluids inadvertently dispensed from said pipette when said sensor is not in position beneath said holder means.

9. A dual barrel pipette for use in simultaneously dispensing fluid samples of substantially equal amounts comprising: a. a pair of substantially identical longitudinally extending pipette barrels having proximal and distal ends wherein the proximal ends are joined together; b. a pair of substantially identical pistons adapted to be displaced in or out of said barrels, each having proximal and distal ends wherein the proximal ends are joined together with sealing means for providing a vacuum seal with an inner wall of said barrel as the pistons are longitudinally displaced into or out of the barrels.

10. The pipette of Claim 9 including: c. actuating means on the external proximal end of said joined pistons forming a discrete location on said pistons for determining the presence of said pistons.

11. The pipette of Claim 9 wherein the actuating means actuates a sensor in an arm which is adapted to apply a longitudinal force to insert said pistons a predetermined distance into said barrels, to simultaneously expel fluid samples of equal amounts from each of said .pipette barrels.

12. The pipette of Claim 11 wherein the pistons are of generally cruciform cross-section and an enlarged cruciform cross-section is provided near the sealing means.

13. The dual barrel pipette of Claim 9 wherein the the pistons are joined by a piston-joining member extending transverse the longitudinal axis of the pistons wι:_ch comprises a solid cross piece extending between the two pistons with ribbed means affixed thereto forming a convenient handle.

14. The pipette of Claim 9 wherein the pipette barrel is provided with a proximal end of generally funneled shaped cross-section having an abutment tab extending transversely therefrom.

15. The dual barrel pipette of Claim 9 wherein the distal end of the barrels is provided with a leur-type nipple on the distal ends thereof.

16. Dual pipette dispenser apparatus for simultaneously, dispensing fluid samples of substantially equal amounts to a fluid sensor comprising: a. A dual barrel pipette having a pair of pipette barrels and pistons, each having proximal and distal ends, said pistons being inserted into said barrels for dispensing fluid samples from the distal ends of said barrels, and piston location means formed on the exterior proximal end thereof; b. holder means for holding said pipette in a longitudinally upright position over said fluid sensor; c. a pipette dispenser actuator comprising a shaft. and an arm extending transverse the longitudinal axis of the shaft, said actuator adapted to move from a first extended position to a second actuating position, said actuator shaft being disposed adjacent the longitudinal axis of said pipette; d) a vertical support member for holding said actuator shaft for rotation about the longitudinal axis thereof and for displacement along the longitudinal axis thereof; e. restraining means for restraining the rotational movement of said shaft along a path such that when said pipette is held in said holder means and said actuator is in a vertically extended position, the actuator arm is laterally rotated away from the piston means of said pipette and when said actuator is in a non-vertically extended actuating position, the arm, is laterally rotated over said piston means; f) first switch means mounted in said arm for sensing when said arm is in contact with said piston locating means; and g) second switch means mounted in said holder for sensing when said pipette is in said holder.

17. The apparatus of Claim 16 further including a drip catcher means for collecting fluids inadvertently dispensed from said pipette when said sensor is not in position beneath said holder means.

18. The apparatus of Claim 16 wherein the drip catcher means comprises a disposable tray positioned beneath said holder means and adapted to slide along a track in a horizontal direction transverse the longitudinal upright position of said pipette, when said sensor is inserted beneath said holder.

19. The dispenser apparatus of Claim 16 wherein the first switch means comprises a membrane switch mounted on said actuator arm.

20. The apparatus of Claim 18 wherein an opaque member is attached to said tray and further including optoelectronic switches in the path of said opaque member for providing an electrical signal when said tray is horizontally moved from a first position to a second position.

21. The apparatus of Claim 18 further including a horizontal support member having a transversely extending lip portion provided with laterally extending horizontal guide grooves for guiding said sensor into contact with said tray and to center said sensor beneath said holder means.

22. The apparatus of Claim 18 wherein said support member is provided with openings into which a read/write device is inserted to read informa¬ tion stored on the sensor and to erase or write over such information.

23. A clinical chemistry analyzer comprising: a. a disposable electrode sensor having at least a pair of electrodes adapted to be conductively connected by a porous member where said porous member is wetted by fluid test samples dispensed onto said electrodes; b. dispenser means for simultaneously dispensing fluid samples onto said electrodes; and c. measurement means for measuring an electrical characteristic across said electrodes to determine a characteristic of an analyte in said test sample.

24. A fluid sample sensor apparatus for use in determining the concentration of certain substances in a fluid sample by measuring electrical properties produced when said sample forms a conductive path between two electrodes, one of which is a reference electrode and the other is an indicator electrode comprising: a. an electrode holder means formed of a body of material with planar top and bottom surfaces with at least a reference electrode, a calibrant electrode, and an indicator electrode; each separately retained in separate bores extending transverse to said planar surfaces of said body, each of said electrodes having an electrically conductive contact element with an exposed surface co-planar to the bottom surface of said holder, said electrode having a membrane. displaced from said contact and disposed in said bore and exposed to the atmosphere via said bore and grooves formed in said body extending in fluid communication between certain pairs of electrodes and adapted to contain porous wicks therein; b. card means extending laterally from the body of said holder means for storing information in machine readable form concerning the type of test to be performed with a specific sensor; c. pipette means for simultaneously dispensing fluid samples onto the exposed surface of each of said membranes; and d. coupling means for coupling the contact elements to a measurement means for determining the electrical properties between selected contacts resulting from the introduction of said samples onto said electrodes.

25. The apparatus of Claim 24 wherein the pipette means comprises: e. a pair of substantially identical longitudinally extending pipette barrels containing said fluid samples having a proximal and a distal end with the proximal ends joined together; f. a pair of substantially identical pistons adapted to be inserted into said barrels, each having a proximal and distal end with the proximal ends joined together; and g. locating means on said pipette means for actuating a dispenser means for inserting said pistons a predetermined distance into ■said barrels to simultaneously expel a predetermined amount of said samples.

26. The apparatus of Claim 17 wherein the dispenser means comprises: h. a shaft and actuator arm transverse the shaft axis; i. holding means for holding said shaft for rotation about the longitudinal axis thereof and for displacement along the longitudinal axis thereof; j . restraining means for restraining the rotational movement of said shaft along a path such that when said pipette is held in said holder means and said actuator is in a vertically extended position, the arm is laterally rotated away from the locating means of said pipette and when said actuator is in a non-vertically extended actuating position, the arm is laterally rotated over said locating means; and k. switch means for sensing when said arm is , in contact with said locating means.

27. A fluid sample sensor apparatus for use in determining the concentration of certain substances in a test fluid sample by measuring the current difference produced when said sample is introduced between the anode and cathode of a first electrode while simultaneously a calibrated fluid sample is introduced between the anode and cathode of a second electrode, comprising: a. an electrode holder means formed of a body of material with planar top and bottom surfaces with at least a first electrode and a second electrode; each separately retained in separate bores extending transverse to said planar surfaces of said body, each of said electrodes having a pair of electrically conductive contact elements, one of which is an anode and the other a cathode, each with an exposed surface co-planar to the bottom surface of said holder, said electrode having a