WO1993004371A1

WO1993004371A1 - Analyzer circuitry for analyzing samples on ion sensitive electrodes

Info

Publication number: WO1993004371A1
Application number: PCT/US1992/007100
Authority: WO
Inventors: John R. North; Robert L. Kay
Original assignee: Porton Diagnostics Inc.
Priority date: 1991-08-27
Filing date: 1992-08-26
Publication date: 1993-03-04
Also published as: AU2508292A

Abstract

An analyzer is adapted to receive disposable ion selective electrode sensors. The sensors are used to measure ion concentrations in fluid samples. The analyzer has amplifier circuitry which is protected by relays to prevent the negative effects of static discharge which may arise from the repeated insertion and removal of the disposable sensors. A microcontroller under the control of software controls algorithms for detecting removal of the calibration gel, the application of a sample to the analyzing system and the analysis of that sample.

Description

ANALYZER CIRCUITRY FOR ANALYZING SAMPLES ON ION SENSITIVE ELECTRODES

Background Of The Invention

The present invention relates to circuitry for analyzing samples on ion sensitive electrodes and more particularly to amplifier circuitry within the analyzer. It is known to provide ion selective electrodes (ISE) in the medical field to detect ion levels in fluids. Typically, these electrodes are used in conjunction with an analyzer as part of a diagnostic system. It is also known to provide a disposable sensor including such electrodes on-which a sample of fluid, such as blood, can be placed. Once the sensor is in contact with the analyzer and the fluid is in position on the sensor, the analyzer can provide an indication of an ion concentration in the blood sample, such as an indication of potassium concentration.

An example of a disposable ion sensitive electrode sensor is disclosed in U.S. Serial No. 538,676 entitled METHOD AND APPARATUS FOR SINGLE DETERMINATION BLOOD ANALYSIS. Furthermore, a general description of an analyzer to be used in conjunction with such a sensor is disclosed in the same document. However, the disclosed analyzer does not fully address a number of issues which are unique to the removable sensor/analyzer configuration.

First, because the analyzer is designed to have interaction with single-use sensors, sensors are constantly being attached and detached from the analyzer. This produces static caused by the friction between the sensor and the analyzer during the attachment and detachment operations. Furthermore, static may be transferred to the sensor and/or the analyzer from the body of the operator. This static can destroy an unprotected amplifier circuit in the analyzer, thereby rendering the analyzer device ineffective or unusable. Additionally, the state of the amplifier circuit, from open circuit to closed circuit, changes regularly with the attachment and detachment of the sensor. As a consequence, voltage transients occur in the system which can also negatively influence the measurements taken with the analyzer amplifier circuitry.

Sensors may be subjected to conditions that degrade the quality of the sensor package or possibly render it ineffective prior to its attachment to an analyzer. The known analyzer is unable to detect the quality of the sensor presently attached to the analyzer and is unable to determine if it is necessary to discard a sensor before use.

Additionally, the known analyzer is incapable of detecting the removal of a calibration gel disposed on an attached sensor and is further unable to detect when a sample of fluid has been applied to the sensor.

Summary Of The Invention

The present invention addresses each of the noted problems with the known analyzer by providing amplifier circuitry having a unique configuration and under the control a microcontroller driven by application specific software. As a consequence, the present invention protects the analyzer amplifier circuitry from negative effects of static buildup due to attachment and detachment of sensors with respect to the analyzer. Additionally, the design provides enhanced quality assurance for individual sensors in use with the analyzer. The analyzer accomplishes this by providing the capability of testing each sensor after it is properly positioned in the analyzer. Furthermore, the amplifier circuit of the present invention provides the capability of detecting the removal of a calibration gel associated with the sensor, of detecting a deposit of a sample on the sensor, and of taking certain measurements at fixed time intervals following these detections. In addition, the circuitry of the present invention provides the capability of measuring resistance across the ion sensitive electrode using the smallest possible current flow. This reduces any negative drifting resistance measurements which have been known to arise due to the effect of larger currents on the ion selective electrode configuration. The reduced current in the testing mode reduces the variation of the ISE.

Brief Description Of The Drawings

Fig. 1 illustrates a cross sectional view of a disposable sensor used with an analyzer designed in accordance with an embodiment of the present invention.

Fig. IA illustrates an enlarged portion of the disposable sensor of Fig. 1.

Fig. 2 illustrates a schematic diagram of a closed loop amplifier circuit in an analyzer in accordance with an embodiment of the present invention.

Fig. 3 is a flow chart for a calibration algorithm implemented with the analyzer of the present invention.

Fig. 4 is a flow chart for a gel cap removal detection algorithm implemented in the analyzer of the present invention.

Fig. 5 is a flow chart for a sample-applied detection algorithm implemented in the analyzer of the present invention. Fig. 6 is a flow chart for a sample measurement algorithm implemented with the analyzer of the present invention.

Fig. 7 is a table describing operational modes available to the analyzer of the present invention.

Detailed Description

Fig. 1 illustrates a cross section of an embodiment of an sensor that uses ion selective electrode technology. Fig. IA shows an enlarged view of a portion of the electrode of Fig. 1. A substrate card 1 includes channels 2 for receiving electrodes 3. Two electrodes are illustrated. However, typically three electrodes will be used. The electrodes may be chlorodized silver electrodes. A bar code 4 is mounted on a bottom portion of the substrate card 1. The electrodes 3 extend through base 5 into chambers 6' and 6' ' in which electrolyte gel 7 is disposed. The chamber is formed in a hollow portion of the body 8 as it is mounted on base 5. The body and the base are sealed together by seal 9 and the base is mechanically bonded to the substrate card 1. A reference junction is provided between chamber 6' and chamber 10. The latter chamber is formed as a hollow region between a cap 11 and the top surface of the body 8. A calibration gel 12 is disposed in chamber 10. A reference junction 13 is disposed to communicate between chamber 6' and chamber 10. Similarly, an ion selective membrane 14 shown enlarged in Fig. IA communicates between the chamber 10 and the chamber 6''. The bar code includes information describing the characteristics of the associated sensor. In particular, the bar code will identify the calibration value associated with the sensor set at the time the sensor is manufactured. The calibration value is related to the salt concentration of the calibration gel. Once the calibration operation is completed as described in greater detail below, the cap is removed and the calibration gel is removed along with the cap. The sensor is now prepared to receive a sample of fluid in the well formed by wall portion 16 above the ion selective membrane and the reference junction. The circuitry of the present invention is designed to detect the removal of the calibration gel and the placement of a sample on the sensor.

Fig. 2 illustrates in schematic form the closed loop electrode amplifier circuit for use with the sensor of Fig. 1. In this circuit 20, two relay coils are provided to control three switches 21, 22, 23. Switches 21 and 22 are under control of a first relay coil (not shown) while switch 23 is under the control of a second relay coil (not shown) . The sensor under test 24 is shown to have three electrodes, a left electrode L, a center electrode C, and a right electrode R. The right electrode is always connected to the pole designated Measure associated with switch 22 while the center electrode is always conducted to the pole designated MeasureCR associated with switch 23. Furthermore, electrode L, when the sensor is positioned on the analyzer, is connected to pole MeasureLR of switch 23. Switch 23 moves between the MeasureCR pole and MeasureLR pole, while remaining connected to the Measure pole of switch 21. Switches 21 and 22 move between the positions Protect and Measure under the control of a single relay such that both switches will either be in the protect mode or in the measure mode at the same time. Pole A of switch 21 is connected to the output of loop integrator U2 which may be a low offset operational amplifier. The output of this amplifier is also connected to an analog to digital converter (not shown) such that digitized signals can be provided to a microcontroller which produces controls for operating the relays. The pole B of switch 22 is connected to the Protect pole of switch 21 and is also connected to the "+" input of sense amplifier Ul providing signal v_sβnsβ along signal line 25. This voltage corresponds to the voltage across resistance R_sensβ- The output of the sense amplifier Ul is also provided to an analog to digital converter for transfer to the microcontroller control circuitry. In addition, the output of sense amplifier Ul is provided as output V_sβnse and is connected to the "- " input of loop integrator U2. The output of the loop integrator U2 is designated V_βlβct. The "+'• input of the loop integrator U2 is connected to a reference voltage supply providing voltage V_rβf. The sense amplifier Ul corresponds to an electrometer operational amplifier.

The operation of this circuit and the relationship between the relays and the microcontroller control for calibrating electrodes and measuring samples will be described in greater detail below.

To protect the amplifiers from the potentially damaging effect of static charge buildup, the relays are controlled to isolate the amplifiers from the control electrodes until such time as there has been some dissipation of the static charge. In particular, before a sensor is inserted into the analyzer the relays control switches 21 and 22 to be in a Protect mode so that both switches are in contact with the respective protect poles. This protects the amplifiers from the actual process of the generation of static charge. Thus, any negative impact of such a charge generation mechanism is avoided.

Once the sensor is in position, the analyzer microcontroller then implements a control routine whereby the relay positions are altered with a specific timing and measurements are taken using low bias currents to determine the characteristics of the sensor. In addition, a bar code reader reads the assigned characteristics of the sensor from the bar code associated with that sensor and stores that information in a memory associated with the microcontroller. This information is used in calculating calibration compensation.

This closed loop configuration for the amplifier circuitry has many advantages. First, the closed loop amplifier requires only the two amplifiers and the two relays to accomplish the same tasks as an instrumentation amplifier. This offers a savings in printed circuit board area. Furthermore, where resistance measurements may occur at currents higher than 100 pA with an instrumentation amplifier, much smaller currents are utilized in the closed loop amplifier circuitry, thereby avoiding the negative effect which can arise by exposing the electrodes to higher currents over a period of time. The closed loop amplifier can also be made to respond to a self test while it is being protected from static discharge. In its protected state, the electrode is completely disconnected from the amplifier and the loop output V_βlβct is basically connected directly to its input v_sβnsβ. If the resistance current input is changed, the various loop amplifiers will change output level accordingly. A key aspect of the closed loop design is that if any component in the loop fails, the loop integrator will saturate. If the loop integrator, U2 in Fig. 2, is monitored by the microcontroller, then the general health of the loop can be determined by its response to a change in the resistance current input. If the loop response during self test does not correspond to an expected value, it can be deduced that there is a degraded or completely failed component in the loop. A failed component would likely trigger loop saturation while a component degradation would produce a response which differs from the normal response without causing loop saturation. Analyzer software can perform an auto calibration of the gain of the closed loop amplifier. Thus, a gain correction can be made that utilizes the same voltage reference as the microcontroller uses to calibrate out any gain drift or initial error. It is also possible to roughly measure the bias current of the electrometer.

Thus, the closed loop amplifier capability provides a self test capability that can verify all amplifier components with the exception of the two relays and the actual electrode contacts.

As described above, the amplifier circuit operation is under the control of a microcontroller. The microcontroller controls the amplifier circuit in accordance with previously stored software programs which cause the microcontroller to produce the necessary control signals for carrying out desired operations with the amplifier circuit. Various software controlled operations and the reasons for carrying out these software operations are described below.

First it is desirable to perform a control check of the newly inserted sensor when it is first attached to the amplifier circuit. The electrical resistance across the entirety of the sensor should be within certain limits. If the resistance is too high, this indicates a broken connection or a defective membrane with insufficient charge carrying ability. If the electrical resistance is too low, this indicates a perforated membrane with no ion selectivity. The voltage output using one of these damaged ISE devices would not reflect the concentration of the selected ion and could lead to an inappropriate medical diagnosis. Furthermore, the electrical resistance between the center electrode and the right electrode must also be between certain limits. Too high a resistance indicates a broken connection whereas too low a resistance would represent a short circuit. An additional feature of the reference electrode resistance is that its value is a function of the salt concentration in its electrolyte gel and in the calibration gel. Since ions can diffuse freely between these two gels, their salt (electrolyte) concentrations will be the same. The concentration of the selected ion in the calibration gel directly determines the calibration "set point" of each individual sensor. This calibration value must be known for accurate readings. The calibration value is provided to the analyzer in the form of the bar code printed on each sensor. By accurate measurement of the right-center RC resistance, any change in the salt concentration of the calibration gel can be detected and compared to that when the sensor was manufactured. Such changes could occur as a result of water loss from the electrode. Where a small change has occurred in the RC resistance, and therefore in the calibration gel salt concentration, a correction factor is applied to the calibration "set point". Where a change is larger than a limit value, the sensor fails its quality control/calibration test and must be discarded by the user. Thus, the system reduces the risk of a miscalibration from a partial drying of the calibrant. This condition would otherwise be undetectable without this resistance measurement because the user has no access to make an independent calibration check. The microcontroller, under software control, controls the amplifier circuit to perform the necessary quality control checks of the overall electrical resistance RL of the electrode and the reference resistance RC. Drawing Fig. 3 illustrates a flowchart for the algorithm for calibration of the electrode. This is one possible algorithm using a fixed time interval between measurements so as to allow current and voltage settling of the device to account for transient conditions. In step 301 the microcontroller sets the amplifier relays to the RL voltage mode. In this mode, switches 21 and 22 are moved to contact the respective Measure poles and switch 23 is moved to contact the pole MeasureLR. In step 302, the microcontroller sets a wait period based on a projected settling time for removing transients. In one embodiment, this wait period is set as 19 seconds. The voltage at V_βlθCt is then measured four consecutive times as indicated in step 303. An average of these four values is calculated in step 304 and is stored in the microcontroller related memory as V_cap. It is noted that a gain of approximately ten is present in this voltage and must be accounted for before using it in a Nernst equation for detecting ion concentration. However, the gain need not be accounted for in the resistance computation.

The amplifier relays are then set to the RL resistance mode in which the relays are placed in the same measuring positions but a resistance measurement is carried out, step 305. In step 306 the microcontroller enters a wait mode for settling. This can be 9 seconds. After the wait period has elapsed, the value of the voltage at V_βlβct is again measured four consecutive times as indicated in step 307. An average of these four values is calculated in step 308 and stored as Vlcl. In step 309 the amplifiers are set for the RC voltage mode whereby the switch 23 is moved to the MeasureCR pole. The device then enters into a wait mode as in step 310, which can be 19 seconds, to allow for settling. The value at V_βlβct is measured four consecutive times at step 311 and an average of these four values is calculated and stored as Vrcl in step 312. The amplifier relays remain in the same positions and the RC resistance operation is set in step 313 and the device enters another wait mode 314 to allow for settling. This wait period can be 9 seconds. In step 315 the voltage at ^vβiβ_c i^s measured four consecutive times. The average of these four values is calculated at step 316 and stored as Vrc2. Then in step 317, the amplifier relays are set into the PROTECT BIT NO. 1 mode where both switches 21 and 22 are moved to be in contact with their Protect poles. The microcontroller then, in step 318, takes the detected values and calculates the resistances for RC and LC, using the following equations: the resistance of RC = (Vrc2 - Vrcl - 0.2264)/1.132 x 10^"9; the resistance of LC = ((Vlr - Vcap - 0.2264)/ 1.132 x 10^"9) - the resistance of RC.

Using these calculated values, the microcontroller compares the values to resistance values that define an acceptable resistance range. If the resistance values are outside of the acceptable range, the sensor must be discarded without being used. Additionally, the resistance value of the RC connection is used as a representation of the ion concentration of the calibration gel. The microcontroller can provide calibration adjustments based on differences between the detected ion concentration and that which it expects to see in view of the information appearing on the sensor bar code.

This same calibration process can be carried out using a drift rate threshold algorithm rather than a fixed rate algorithm. In the drift rate algorithm, rather than providing explicit wait time periods for the settling of the measured values, the device detects when settling has occurred. Consecutive measurements are made after the device is placed in the appropriate measurement mode and when a difference voltage value between seven of eight consecutive measurements is less than plus or minus 1.00 mV as measured at the A/D input it is detected that the system has undergone settling. This is indicative that the voltage is considered stable. Four consecutive values are then measured and averaged as in the fixed time algorithm. All of the resistance values of interest in the calibration mode may be detected in this manner. The same ultimate calculations for the resistance of RC and LC can then be carried out in the same manner as in the fixed time algorithm. The software in the microcontroller also controls a determination of gel cap removal as well as a determination of the application of a sample to the sensor. The flow chart of Fig. 4 illustrates the steps involved in testing for gel cap removal. First, the amplifier relays are set to the RC resistance mode in step 401. The value of V_βlβct is measured at step 402. The value is compared to a standard value of 1.200 volts in step 403. If the value of V_βlβct exceeds 1.200 volts, representing the saturation of the integrator, the cap is detected as being off, step 404. The amplifier relays are then returned to the PROTECT BIT no. 1 mode, step 405. This last step is important because after cap removal, the amplifier inputs are susceptible to electrostatic events should the user touch the electrode top. If V_βlβct is not greater than 1.200 volts, steps 402 and 403 are repeated.

The algorithm for detecting the presence of a sample is similar to that for detecting removal of the gel cap. Again, the amplifier relays are set to the RC resistance mode in step 501 and the voltage value at ^vβiβ_c is measured at step 502. The measured voltage value is compared to a standard value of 1.200 volts in step 503. If the voltage value is greater than 1.200 volts, then no sample is present and steps 502 and 503 are repeated. If the measured voltage value is less than 1.200 volts, a sample is present and the device returns to the PROTECT BIT no. 1 mode in step 504. This last step is important because the amplifiers are susceptible to electrostatic discharge events should the user touch the electrode top.

Once a sample is applied, a measurement of the sample is carried out. There are two possible algorithms for carrying out this measurement. A fixed time algorithm is illustrated in a flow chart of Fig. 6. In step 601, the amplifier relays are set to the LR voltage mode. The device then is placed in a wait mode for 60 seconds to allow for settling with respect to transients in step 602. The voltage value at V_βlβct is measured four times consecutively in step 603. The four values are used to calculate the V_sol using a simple arithmetic average of the four measured values, step 604.

The alternative to the fixed time sample measurement algorithm is a drift rate threshold algorithm. This algorithm is the same as that for the fixed time algorithm except that instead of setting a fixed time for settling of transients, the voltage is measured immediately upon entering the voltage mode and is repeatedly measured until such time as a voltage difference between 7 of 8 consecutive measurements is less than plus or minus 1.00 mV at which point the voltage is considered to be stable. Then, the multiple measurements and average calculations steps can be executed for determining the voltage with the sample present, V_sol.

Fig. 7 illustrates a table for describing a matrix with respect to the mode of operation and the states of the amplifier relays and the types of measurements to be conducted. In the PROTECTED BIT no. 1 mode, the amplifier relays are set to the protect mode so that there is no actual measurement. The switch for controlling either RL or RC connections is set to the RL position and the device is generally set to a resistance measurement mode while no actual measurement is carried out. A PROTECTED BIT no. 2 mode similarly sets the amplifier relays into the protect mode and provides the RL connection as opposed to the RC connection. In this mode, a voltage measurement operation is set, but not carried out due to the status of the amplifier relays. When the RL voltage measurement mode is selected, the amplifier relays are placed in the measurement position, switch 23 is set to the MeasureLR pole and the device is placed in a voltage measurement state. For a RC voltage measurement status, the device is the same as in the RL voltage measurement status, except that the switch 23 is now placed into contact with the MeasureRC pole. For the RL resistance measurement and the RC resistance measurement, the device is set in the resistance measurement mode and the amplifier relays are set in the measurement position. For the RL measurement, the switch 23 is placed in contact with the MeasureLR pole while for the RC measurement the switch contact is placed in contact with the MeasureRC pole. There are two disallowed modes shown in the chart. This indicates that when the amplifier relays are set in the protect mode, the switch 23 cannot be in contact with the center pole C.

There are a number of quite distinct purposes for electrode resistance testing. The center-right (RC) resistance is the resistance of the center wire, the calibration gel, the reference junction, the reference gel and the reference electrode circuit. It must be measured by the analyzer for two purposes, with different specifications. First, there should be a low accuracy measurement with low enough current to permit continuous monitoring for up to five minutes without polarization effects. This is carried out for the detection of the removal of the calibration gel and for the indication of the application of a sample. Additionally, there must be a high accuracy measurement having a better than 10 Koh resolution in 1 to 5 x 10⁶ resistance. Current is limited by the polarization limit of the center wire and the reference wire. This is carried out to detect gel resistance for the purposes of calibration and to correct for the drying of the calibrant and changes in ion concentration. The center-left (LC) resistance includes wires and gels but is dominated by the membrane resistance. This resistance is measured during development to establish the required amplifier characteristics and to ensure that procedures are available to cast membranes with consistent resistance. In this mode, the current should be minimized to avoid the effects of anomalous conductance mechanisms and intramembrane polarization which might affect subsequent membrane performance. This resistance is also checked by the analyzer during the calibration state to ensure that the membrane has resistance greater than the minimum resistance for an integral, puncture-free membrane. This requires a low accuracy and low current reading. Finally, this resistance is checked by the analyzer after the application of a sample to check that a sample is covering or contacting the membrane. This is also carried out with low accuracy and low current requirements.

Since the resistance of the electrode is known to vary as the magnitude of the electric current applied to it varies, it is important to determine the resistance of the electrode at minimum current levels. A precision, voltage controlled current source in the range of 10 pico amp to 1 naήo amp is required. The system of the present invention uses a simple control loop that forces the output of amplifier Ul to be equal to the reference input V_rβf to amplifier U2, as shown in Fig. 1. Amplifier Ul measures the voltage across the reference resistor R_sβ_nsβ* ^AnY voltage appearing across ^R _sβ_nse is ^{t e} result of current flowing through that resistor and the electrode under test. Thus, the control loop will force a current through R_sβnsβ and the electrode under test to make V_sβnεβ equal to V_ref.

In the special case where the reference voltage is equal to zero, the loop is commanded to make the current through R_sβnsβ equal to zero. That does not exactly happen due to error sources in the amplifiers. The bias currents of amplifier Ul appear to the loop as a current through R_sβnsβ. Thus, the loop will produce an equal, but counter current that results in V_SΘIJse equal to V_rβf. This current cannot be prevented from flowing through the parallel network formed by R_Sθnεe and the electrode under test. Thus, the bias current from amplifier Ul is the minimum current possible in this design. For this reason, amplifier Ul was chosen to be an electrometer amplifier as it has the lowest possible currents, 75 fA.

A second error source is the input offset voltage of amplifier 1. Input offset voltage is the amplifier's residual imbalance at its input (that is, zero volts output is produced when the input is equal to its offset voltage) . Thus, the loop will force current through ^R _sβ_nse until the resulting voltage at the positive input of amplifier 1 produces V_Sθnse to be equal to V_rβf. This error can be measured and corrected.

If V_rβf is adjusted to a value other than zero, the loop will still force V_sβnsθ equal to V_rβf. This will produce a controlled current through R_sβnsβ- That current will be equal to V_rβf/(Kl x R_sβn8β) . A key advantage of this circuit is the ability to change the effective value of R_sβnsβ or (or inversely, V_rθf) by changing the gain, Kl. If R_sβnsβ and Kl are calibrated and measured in advance, the resistance of the device under test can be determined by measurement of V_βlθCt and V_rβf. Additionally, if the device under measurement contains a voltage source (for example, a chlorodized wire) , the effects introduced can be removed by simply measuring the voltage and utilizing that measurement in the calculation of the resistance under test. The gain of amplifier Ul has been optimized to minimize the offset voltage effects from amplifier U2. Thus, amplifier Ul becomes the major error source in the system. The effects from amplifier Ul bias currents and offset voltage drive the basic system accuracy. The gain of amplifier Ul is set high enough to make these error sources dominant over the equivalent sources in amplifier U2. An additional benefit of providing amplifier Ul with gain is the scaling effect that it has on the reference input V_rβf and the reference resistor R_sense . As the gain is increased, the effect of V_rβf is reduced by an equal amount. This allows precision control of the set current. Further, this can be shown to be equivalent to increasing the value of R_6βnse by th gain. This allows simulation of much higher resistances if necessary. The gain of amplifier Ul must be known to compute the magnitude of R_sβnSe« ^Tne accuracy requirement is directly proportional to the desired accuracy for resistance measurement. However, the gain accuracy of amplifier Ul is not significant when V_rβf is zero and an electrode voltage is being measured. An important design parameter of control loop systems is loop stability. Inattention to this characteristic can be lead to inaccuracy, long settling times, or actual oscillations. It is important to consider that the attachment of the electrode and the setting of the relay switches to close the loop inserts a complex impedance inside of the loop. The parallel resistor-capacitor elements of the electrode can significantly complicate the stability analysis unless a set of simplifying assumptions are adhered to, such as: 1. the dominant pole of the nonelectrode portion of the control loop is always forced to be one decade above or below the high and lowest pole of the electrode (that is, make the loop faster or slower than any response from the electrode. A pole is essentially a low pass filter. The pole frequency is the point at which higher frequency components start to be attenuated.)

2. the control loop is constrained to a first order, type 1 system (that is, one loop integrator only) .

By integrating these design considerations into the closed loop circuitry of Fig. 1, there is an overall enhancement of the characteristics of the detection circuit. In addition, the interaction of the software driven microcontroller control of the amplifier circuit expands the capabilities of the circuitry to provide additional features such as calibration, calibrating gel removal, sample application and sample analysis. At the same time, the circuit design protects the amplifier circuitry from damage due to static which can arise through the multiple insertions and removals of the disposable sensors which are constituted by ion selective electrodes.

Claims

What Is Claimed Is: 1. An amplifier circuit in a sensor analyzer device comprising: a loop circuit selectively connected to a sensor; a sensor receiving station adapted for the insertion and removal of sensor devices; and a switching circuit disposed between said loop circuit and said sensor reciving station wherein said switching circuit controls an electrical connection of said loop circuit to said sensor receiving station.

2. The amplifier circuit of claim l wherein said switching circuit comprises two switches under the control of at least one relay coil, a condition of said relay coil causing said two switches to be in either a protect mode position where the loop circuit is electrically isolated from said sensor receiving station or a measure mode portion where the loop circuit is electrically connected to said sensor receiving station.

3. The amplifier circuit of claim 2 wherein said loop circuit further comprises a plurality of amplifiers, a first one of said amplifiers comprising a loop integrating amplifier and a second one of said amplifier comprising a sense amplifier.

4. The amplifier circuit of claim 1 wherein said loop circuit further comprises a plurality of amplifiers, a first one of said amplifiers comprising a loop integrating amplifier and a second one of said amplifier comprising a sense amplifier.

5. The amplifier of claim 4 wherein said sense amplifier comprises an electrometer operational amplifier.

6. A method for testing the quality of an ion selective sensor that includes a plurality of electrodes and a calibration gel cap comprising the steps of: selectively coupling the sensor to an electronic analysis circuit via a plurality of switches; measuring a first average voltage in a first voltage measurement mode with a first electrode and a second electrode of said plurality of electrodes connected to said electronic analysis circuit; measuring a second average voltage in a first resistance measurement mode with said first and second electrodes being connected to said electronic analysis circuit; measuring a third average voltage in a second voltage measurement mode with a third electrode and said second electrode connected to said electronic analysis circuit; measuring a fourth average voltage in a second resistance measurement mode with said third and said second electrodes connected to said electronic analysis circuit; calculating a first resistance between said first and second electrodes and a second resistance between said second and third electrodes using said first, second, third and fourth average voltage values; comparing said first and second resistances to first and second reference resistances respectively and identifying when a difference between a detected and a corresponding reference resistance is greater than a predetermined tolerance range.

7. The method of claim 6 wherein said steps of measuring average voltage comprise measuring the voltage a plurality of times and calculating a simple average voltage from said plurality of measurements.

8. The method of claim 7 further comprising the step of delaying measurement of the average voltage until voltage transients have settled.

9. The method of claim 8 wherein said step of delaying comprises entering a wait mode for a fixed time interval.

10. The method of claim 8 wherein said step of delaying comprises implementing a drift rate threshold operation, said operation comprising: detecting the voltage at the desired measuring location a plurality of times; inhibiting uses of said detected voltage in an average voltage measurement until a difference voltage value between a predetermined number of consecutive detected voltages is below a reference threshold.

11. The method of claim 6 wherein said second resistance is indicative of an ion concentration in the calibration gel electrolyte.

12. A method for detecting the presence or absence of a calibration gel electrolyte on an ion selective sensor that includes a plurality of electrodes, comprising the steps of: selectively coupling a first electrode and second electrode of the plurality of electrodes to an analyzing circuit; measuring a first voltage at a detection point coupled to said first electrode; comparing said first voltage to a threshold voltage; and indicating that the gel cap has been removed when the first voltage exceeds said threshold voltage.

13. A method for detecting the presence or absence of a sample on an ion selective sensor that includes a plurality of electrodes comprising the steps of: selectively coupling a first electrode and second electrode of the plurality of electrodes to an analyzing circuit; measuring a first voltage at a detection point coupled to said first electrode; comparing said first voltage to a threshold voltage; and indicating that the sample has been applied when the first voltage is less than said threshold voltage.