Portable analyte measuring system for multiple fluid samples

• US 5,405,510 A
• Filed: 05/17/1993
• Issued: 04/11/1995
• Est. Priority Date: 05/18/1992
• Status: Expired due to Fees

• Current Assignee: Radiometer California, Inc. (Danaher Corporation)
• Original Assignee: PPG Industries Incorporated (Nouryon BV)
• Inventors: Savage, Douglas R., Betts, Ronald E., Leader, Matthew J.
• Primary Examiner(s): Gorgos, Kathryn
• Assistant Examiner(s): Bell, Bruce F.
• Application Number:
  US08/061,969
• Time in Patent Office: 694 Days
• Field of Search: 204/403, 204/409, 204/412, 204/416, 204/415, 204/422, 204/153.1, 204/435, 204/153.12, 128/635, 422/58, 422/61, 422/62, 422/63, 422/68.1, 422/82.03, 422/80, 435/291, 435/817
• US Class Current: 205/782
• CPC Class Codes: A61B 2562/08 Sensors provided with means for identification, e.g. barcodes or memory chips
• CPC Class Codes: A61B 5/14539 for measuring pH
• CPC Class Codes: A61B 5/14542 for measuring blood gases A61B5/14551 takes precedence
• CPC Class Codes: A61B 5/1468 using chemical or electrochemical methods, e.g. by polarographic means A61B5/1486 takes precedence
• CPC Class Codes: A61B 5/15003 for venous or arterial blood
• CPC Class Codes: A61B 5/150221 Valves
• CPC Class Codes: A61B 5/150236 Pistons, i.e. cylindrical bodies that sit inside the syringe barrel, typically with an air tight seal, and slide in the barrel to create a vacuum or to expel blood
• CPC Class Codes: A61B 5/150244 Rods for actuating or driving the piston, i.e. the cylindrical body that sits inside the syringe barrel, typically with an air tight seal, and slides in the barrel to create a vacuum or to expel blood
• CPC Class Codes: A61B 5/150305 Packages specially adapted for piercing devices or blood sampling devices kits for diabetes A61M5/003; packaging in general B65D
• CPC Class Codes: A61B 5/150389 Hollow piercing elements, e.g. canulas, needles, for piercing the skin
• CPC Class Codes: A61B 5/150503 Single-ended needles hollow piercing element tip design A61B5/150396, needle sets for catheters A61M25/06, needles for bringing media into the body A61M5/32
• CPC Class Codes: A61B 5/153 Devices specially adapted for taking samples of venous or arterial blood, e.g. with syringes
• CPC Class Codes: B01L 3/502 with fluid transport, e.g. in multi-compartment structures centrifugal-type cuvettes G01N21/07; analysis by separation into components G01N30/00; automatic analysers G01N35/00
• CPC Class Codes: G01N 33/4925 measuring blood gas content, e.g. O2, CO2 , HCO3
• CPC Class Codes: Y10S 435/817 Enzyme or microbe electrode

Abstract

A portable, ready-for-use analyte measuring device is provided for the measurement of multiple sequential fluid samples. The device has a disposable cartridge, a calibrating fluid external to the cartridge and an analyzer. The cartridge has a housing, inlet for introduction of fluids into the housing, flow cell in fluid connection with the inlet, a waste collection area or reservoir in fluid connection to receive fluids from the flow cell, and at least one flow control means in fluid connection with the reservoir. The flow cell has a flow-through channel with one or more hydrated sensors arranged along the channel that has fluid therein. Also the flow cell has one or more spaced-apart reference electrode containment spaces in conductive contact with a contained quantity of reference fluid for the number of multiple sequential tests for the cartridge. The reference electrode containment space is spaced apart from but in conductive relation with the one or more sensors. The flow cell also has an electric circuit attached for electrical conduction to the one or more sensors and reference electrode and which is electrically isolated from the fluid in the channel. The multi-test device also has signal conveyor connected to the electric circuit of the flow cell to transmit signals responsive to the fluids contacting the sensors to the analyzer. Both the cartridge and the calibrating fluid are associated with an encoded information carrier for sensor performance parameters and calibrant analyte concentrations for inputting into the encoded information reader of the analyzer.

Claims

1. Portable multiple sample fluid analyte cartridge for a fluid analyte measuring device, comprising:

A. housing of the cartridge having the following;

1) at least one fluid inlet supportively connected to the housing for introduction of fluids to the housing;

2) flow cell supportively positioned within the cartridge housing having an opening for fluid communication with the inlet and associated with the inlet to receive fluids from the inlet, wherein the flow cell has a channel for fluid flow through the flow cell and from the flow cell at a second opening and having a sensor containment space and a spaced-apart reference electrode containment space and wherein the flow cell also has;

i) at least one sensor supportively located within the flow cell in the sensor containment space where the sensor is hydrated for sensing contact with fluids in the channel of the flow cell;

ii) reference electrode located in the reference electrode containment space in conductive contact with a contained quantity of reference fluid for the number of multiple sequential tests for the cartridge where the reference electrode containment space and sensor containment spaces are spaced apart from each other and in conductive relation with each other;

iii) fluid occupying the channel of the flow cell where the fluid is selected from the group consisting of storage fluid, hydrating fluid, flush solution, calibrating fluid and sample fluid;

iv) electric circuit means attached for electrical conduction to the sensors and reference electrode and which is electrically isolated from the fluid samples in the channel;

3) signal conveyor connected to the electric circuit means to transmit signals responsive to the fluids contacting the sensors;

4) a expandable waste reservoir contained within the cartridge housing and in fluid communication with the flow cell to receive and retain the multiple sequential fluids passed through the flow cell;

5) at least one flow control means associated with the waste reservoir to retard back flow of the fluids received from the flow cell.

2. Cartridge of claim 1 wherein the flow cell is oriented in the cartridge housing so that the conductive contact between the reference electrode containment area and the sensor contacting the channel of the flow cell are not totally in the same horizontal plane within the housing.

3. Cartridge of claim 1 wherein the flow cell has a reference electrode containment area that is in conductive communication with a sensor and the flow cell is oriented in the cartridge housing with an acute or obtuse angle in relation to the horizontal plane through the cartridge housing.

4. Cartridge of claim 1 wherein the reference electrolyte is a gel.

5. Cartridge of claim 1 wherein the sensor is a Clark cell.

6. Cartridge of claim 1 wherein the sensor is a sensing means.

7. Cartridge of claim 1 wherein the waste reservoir is an expandable bag.

8. Cartridge of claim 1 wherein the waste reservoir is a waste reservoir means.

9. Cartridge of claim 1 wherein the inlet is adapted to receive the needleless fitting of a syringe.

10. Cartridge of claim 1 wherein the sensors are sensor means including thick-film sensors, thin film sensors or both.

11. Cartridge of claim 1, where the sensor has a plurality of different analyte measuring electrodes in the channel to measure blood gases and/or electrolytes.

12. Cartridge of claim 1, where the flow cell has at least two sensors and one is a Clark cell arranged for sensing contact within the channel.

13. Cartridge of claim 1, where the flow cell is oriented in relation to the inlet to facilitate gravity flow through the channel of the fluids introduced at the inlet.

14. Cartridge of claim 1, where the flow control means is a unidirectional valve in the flow path between the flow cell and the reservoir arranged to allow fluid flow from the flow cell to the reservoir and where the valve assists in maintaining fluid in the flow cell to keep the sensor hydrated.

15. Cartridge of claim 14, which includes a second unidirectional valve arranged in fluid communication between the inlet and the flow cell.

16. Cartridge of claim 14, where the valve is a check valve of polycarbonate with a silicone rubber diaphragm.

17. Cartridge of claim 1, where the section of the electrical circuitry in the containment space is printed wiring circuitry connected to the electrodes on a nonconducting substrate and the section leaving the cartridge is a cable means.

18. Cartridge of claim 1, where the cartridge housing has at least one vent for atmospheric gases.

19. Cartridge of claim 1 wherein the sensor includes a measuring electrode and the reference electrode wherein the reference fluid is in constant contact with the reference electrode.

20. Cartridge of claim 19 wherein the reference containment area only communicates with the channel with the at least one sensor for ionic contact between the at least one sensor and the reference electrode.

21. Cartridge of claim 1 wherein the electrodes comprise a Clark cell with an anode and a cathode.

22. Cartridge of claim 1 wherein the reference fluid in contact with the reference electrode remains in contact with the electrode through the multiple sampling at the inlet where the reference fluid is in liquid junction contact through a capillary chamber of the channel or where the reference fluid is a different viscosity or density than fluids in the channel to remain in contact with the reference electrode.

23. Cartridge of claim 22 wherein the liquid junction contact is through a capillary channel from the reference electrode containment area intersects with channel with the at least one sensor.

24. Cartridge of claim 22 wherein a second reference electrode is present in spaced apart relation to the first reference electrode with each reference electrode having a separate channel intersecting with the main channel having the at least one sensor.

25. Portable system for the measurement of at least one analyte in multiple fluid samples, comprising:

A. a cartridge having;

1) cartridge housing having the following;

2) at least one fluid inlet supportively connected to the housing for introduction of fluids including calibrant and optionally flush solution from sources external to the housing;

3) flow cell supportively positioned within the cartridge housing in fluid flow connection with the inlet and having a flow channel to provide for the flow through of the multiple fluids introduced at the inlet into the flow cell and having a containment space for at least one sensor, where the space is arranged to provide access of the sensor to the channel and to support the sensor in signal processing connection with a signal conveyor in the cartridge housing;

4) sensors positioned in the flow cell in the containment space and in sensing engagement with the channel for measuring at least one analyte;

5) signal conveyor connected to the sensor to transmit signals responsive to the fluids contacting the measuring sensor;

6) a waste reservoir contained within the cartridge housing to receive the fluids passed through the flow cell;

7) at least one fluid flow control means in fluid communication with the channel of the flow cell at the end away from the inlet and with the reservoir to retard back flow of the fluids from the reservoir;

8) encoded information carrier for the values of the sensor'"'"'s performance parameters for later retrieval by a microcomputing means;

B. calibrator having;

1) a calibration fluid having a known amount of the one or more analytes to be measured by the sensors for introduction into the inlet and for contact with the sensor to determine a set point for calculating the unknown amount of the one or more analytes to be measured;

2) encoded information carrier for the values of the calibration fluid information for later retrieval by a microcomputing means when the calibrant is introduced at the inlet of the cartridge and over the sensor in the cartridge;

C. flush solution for introduction to the inlet of the cartridge to prepare the sensor for the measurement of another sample;

D. analyzer having;

1) electronic interpreter for the signals sent from the sensor for the calibrant and for the multiple samples having one or more analytes to calculate the amount of the one or more analytes in the multitude of fluids introduced into the cartridge for measurement;

2) reader for encoded information to place the encoded information for the sensor and the calibrant into the microcomputing means for use in calculating the values of the amounts of the analytes in the multiple samples introduced into the cartridge;

3) connector with the signal conveyor of the cartridge;

4) display means for displaying at least the calculated value of the analyte.

26. Portable system of claim 25 wherein the flush solution is present in a gas impermeable wrapper having a known equilibrated atmosphere for carbon dioxide and oxygen suitable to precondition the electrodes prior to sample introduction.

27. Portable system of claim 25 wherein both encoded information carriers are the same means for encoded information.

28. Portable system of claim 27, where the encoded information means is a bar code.

29. Portable system of claim 25 wherein the calibrant and flush are in a kit.

30. Portable system of claim 25, where the cartridge is packaged in a foil sealed container having a known equilibrated atmosphere for carbon dioxide and oxygen which precondition the electrodes prior to sample introduction and having the encoded information carrier for the cartridge and the kit has the encoded information carrier for the calibrant.

31. Portable system of claim 25 wherein the calibration fluid is introduced into the inlet of the cartridge before each sample fluid.

32. Portable system of claim 25 wherein the cartridge housing has at least one vent for atmospheric gases.

33. Portable system of claim 25 wherein the analyzing means includes a printer means for displaying a hard copy of the calculated values.

34. Portable system of claim 25 wherein the electronic means is a microprocessing means.

35. Portable system of claim 25 wherein the microcomputer means also regulates the temperature of the board and the sample through a heater located in the electric circuit means of the sensor substrate.

36. Method of measuring a multitude of samples having unknown values of known analytes, comprising:

A. entering into a computer means encoded information of a sensor in a cartridge wherein the cartridge has;

1) cartridge housing having the following;

2) at least one fluid inlet supportively connected to the housing for introduction of fluids including calibrant and optionally flush solution from sources external to the housing sources;

3) flow cell supportively positioned within the cartridge housing in fluid flow connection with the inlet and having a flow channel to provide for the flow through of the multiple fluids introduced at the inlet into flow cell and having a containment space for at least one microsensor, where the space is arranged to provide access of the microsensor to the channel and to support the sensor in signal processing connection with a signal conveying means in the cartridge housing;

4) sensors positioned in the flow cell in the containment space and in sensing engagement with the channel for measuring at least one analyte;

5) signal conveying means connected to the sensor to transmit signals which are responsive to analyte concentration in the fluids contacting the measuring sensor;

6) a waste reservoir contained within the cartridge housing and in fluid communication with the valve to receive and retain the fluids passed through the flow cell;

7) at least one flow control means in fluid communication with the flow cell to prevent bi-directional flow of the fluids from the waste reservoir to the flow cell;

B. enter into a microcomputer means encoded information of predetermined analyte values of a calibrant contained in a calibration means having;

1) a calibration fluid having a known amount of the one or more analytes to be measured by the sensors for introduction into the inlet and for contact with the sensor to determine a set point for calculating the unknown amount of the one or more analytes to be measured,

2) means for encoding the values of the calibration fluid information for later retrieval by a microcomputing means when the calibrant is introduced at the inlet of the cartridge and over the sensor in the cartridge;

3) flush solution for introduction to the inlet of the cartridge to prepare the sensor for the measurement of another sample;

C. introducing calibrant into the cartridge that is electronically connected to the microcomputer and analyzing means having;

1) electronic means to interpret the signals sent from the

sensor for the calibrant and for the multiple samples having one or more analytes to calculate the amount of the one or more analytes in the multitude of fluids introduced into the cartridge for measurement;

2) reading means for encoded information to place the encoded information for the sensor and the calibrant into the microcomputing means for use in calculating the values of the amounts of the analytes in the multiple samples introduced into the cartridge;

3) connecting means with the signal conveying means of the cartridge;

4) display means for displaying at least the calculated value of the analyte;

D. introducing sample into the cartridge and obtaining the value of the one or more analytes from the microcomputer and analyzing means;

E. introducing flush solution into the cartridge to clear the previous sample from the flow cell and to maintain the membrane of the sensor in a hydrated state;

F. introducing another amount of calibrant to fill the flow cell to recalibrate the sensor; and

G. introducing another sample into the cartridge for testing.