Analysis system having a removable reaction cartridge and temperature control

• US 5,133,937 A
• Filed: 06/01/1989
• Issued: 07/28/1992
• Est. Priority Date: 06/01/1989
• Status: Expired due to Fees

• Current Assignee: Il Holding SpA (Werfen SA)
• Original Assignee: Iniziative Marittime 1991 SRL
• Inventors: Frackleton, John J., Milesky, Lawrence, Rasmussen, James E.
• Primary Examiner(s): Hill, Jr., Robert J.
• Assistant Examiner(s): Chan, William
• Application Number:
  US07/360,008
• Time in Patent Office: 1,153 Days
• Field of Search: 422/81, 422/67, 422/289, 204/409, 436/52, 435/288, 435/286, 435/290
• US Class Current: 422/81
• 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: B01L 7/00 Heating or cooling apparatus autoclaves B01J3/04; Heat insulating devices
• CPC Class Codes: G01N 33/48 Biological material, e.g. blood, urine G01N33/02, G01N33/26, G01N33/44, G01N33/46 take precedence; Haemocytometers counting blood corpuscules distributed over a surface by scanning the surface G06M11/02
• CPC Class Codes: G01N 35/00 Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
• CPC Class Codes: Y10T 436/117497 with a continuously flowing sample or carrier stream

Abstract

An analysis system for analyzing a biological fluid or the like for a constituent of the interest includes metal body structure with sample flow path channel structure that serially interconnects heater chamber structure, recess structure for receiving a reaction chamber cartridge and an analysis region to which a measuring system is coupled. The reaction chamber cartridge preferably includes reaction chamber structure with an immobilized enzyme in the reaction chamber that is capable of converting the constituent of interest to a constituent detectable by the measuring system. Cooperating with the metal body structure is a transparent face plate structure which permits visual observation of the sample flow path in the metal body structure. Thermally coupled to the metal body immediately adjacent the analysis region are a temperature sensor that provides a temperature signal to a control unit and a thermal source that receives control signals from the control unit as a function of signals from the temperature system for stabilizing the temperature of the metal body structure (including the reaction chamber structure, the heater chamber and the analysis region) at a desired analysis temperature.

Claims

1. An analysis system for analyzing a biological fluid or the like for a constituent of interest comprising

metal body structure defining an inlet port, a heater chamber, an analysis region, recess structure for receiving a reaction chamber cartridge, and passage structure for serially interconnecting said heater chamber, said recess structure and said analysis region, said passage structure including an outwardly open flow path channel in a planar surface of said metal body structure, said channel being coated with a thermally conductive, corrosion resistant dielectric material, and further including a transparent gasket member seated against said planar surface of said metal body structure,

a thermal source thermally coupled to said metal body structure immediately adjacent said analysis region and a temperature sensor thermally coupled adjacent said analysis region for providing a temperature signal to a control unit, said thermal source responding to control signals as a function of signals from said temperature sensor to stabilize the temperature of said metal body structure, and

a replaceable reaction chamber cartridge for releasable insertion into said recess structure for connection in series between said heater chamber and said analysis region for modifying a constituent of interest in the sample of biological fluid to be analyzed.

2. The system of claim 1 wherein said thermal source is a thermoelectric unit that is physically coupled to a surface of said metal body structure and said temperature sensor is a thermistor embedded in said metal body structure adjacent said analysis region.

3. The system of claim 2 further includes heat sink structure spaced from said metal body structure, and wherein said thermoelectric unit has a hot face and a cold face, said cold face being thermally coupled to said metal body structure and said hot face being thermally coupled to said heat sink structure.

4. The system of claim 1 wherein said analysis region and said reaction chamber are connected in a series flow path, and said liquid flow means includes a positive displacement pump that is connected to said liquid flow path.

5. The system of claim 1 further includes a measuring system in sensing relation to said analysis region, said measuring system includes two electrode devices for measuring different constituents of interest in said sample, at least one of said electrode devices being an ion selective electrode device.

6. The system of claim 1 wherein said constituent of interest is urea, and further includes a measuring system in sensing relation to said analysis region, said measuring system includes an ammonium selective electrode, and said reaction chamber includes immobilized urease enzyme.

7. The system of claim 1 wherein said reaction chamber cartridge includes reaction chamber structure with an immobilized enzyme in said reaction chamber that is capable of converting the constituent of interest to a constituent detectable at said analysis region.

8. The system of claim 7 wherein said constituent of interest is glucose, and further includes a measuring system in sensing relation to said analysis region, said measuring system includes an oxygen sensing electrode, and said reaction chamber includes immobilized glucose oxidase.

9. The system of claim 1 wherein said reaction chamber cartridge includes structure defining inlet and outlet ports and seal structure coupled to said inlet and outlet port structures for sealing engagement with a flow path in said metal body structure.

10. The system of claim 9 wherein said reaction chamber is in the form of an elongated tube;

and said seal structure includes a seal member that includes a connector portion that receives an end of said tube, a seal portion, and a through passage between said connecter and seal portions of said seal member.

11. The system of claim 9 wherein said reaction chamber cartridge includes a metal temperature stabilizing cartridge body, said reaction chamber has a volume of less than about two hundred microliters and is in the form of an elongated tube that is disposed in coil form on said metal temperature stabilizing cartridge body;

glucose oxidase and urease enzymes are co-immobilized on the inner surface of said tube; and

said seal structure is carried by said temperature stabilizing cartridge body.

12. The system of claim 11 further includes means for biasing said temperature stabilizing cartridge body against said metal body structure, and wherein said temperature sensor is a thermistor embedded in said metal body structure adjacent said analysis region.

13. A replaceable cartridge assembly for use in an analysis cuvette for analyzing a biological fluid for a constituent of interest that includes flow path structure extending from a sample inlet port through structure defining an analysis region to an outlet port, a measuring system in sensing relation to said analysis region, and structure in said flow path structure defining a recess,

said replaceable cartridge assembly being adapted to be releasably inserted as a unit into said recess, said cartridge assembly including a metal temperature stabilizing cartridge body with a planar surface, spiral channel structure in said planar surface of said cartridge body, a tubular reaction chamber in spiral coil form releasably received in said channel structure, said reaction chamber structure having an immobilized enzyme in said reaction chamber that is capable of converting the constituent of interest to a constituent detectable by said measuring system, said reaction chamber structure including structure defining inlet and outlet ports and seal structure coupled to said inlet and outlet port structures for sealing engagement with a flow path in said analysis cuvette to permit replaceable insertion of said reaction chamber structure in series in a flow path in said analysis cuvette.

14. The cartridge assembly of claim 13 wherein said reaction chamber has a volume of less than about two hundred microliters and is in the form of an elongated tube that is disposed in coil form on said metal temperature stabilizing cartridge body;

and glucose oxidase and urease enzymes are co-immobilized on the inner surface of said tube.

15. The cartridge assembly of claim 13 wherein each said seal structure includes a connector portion that is connected to a said port structure, a seal portion that is adapted to seat in sealing relation on a port of said analysis cuvette recess, and a through passage between said connecter and seal portions of said seal structure.

16. A replaceable cartridge assembly for use in an analysis cuvette for analyzing a biological fluid for a constituent of interest that includes flow path structure extending from a sample inlet port through structure defining an analysis region to an outlet port, a measuring system in sensing relation to said analysis region, and structure in said flow path structure defining a recess,

said replaceable cartridge assembly being adapted to be releasably inserted as a unit into said recess, said cartridge assembly including

a metal temperature stabilizing cartridge body with a planar surface, spiral channel structure in said planar surface of said cartridge body for releasably receiving a tubular reaction chamber in spiral coil form,

an elongated tube disposed in spiral coil form in said spiral channel structure, said tube having inlet and outlet ports, seal members coupled to said inlet and outlet ports for sealing engagement with a flow path in said analysis cuvette to permit manual replaceable insertion of said cartridge assembly as a unit in series in said flow path in said analysis cuvette,

each said seal member including a connector portion that is connected to a said port, a seal portion that is adapted to seat in sealing relation on a port of said analysis cuvette recess, and an intermediate portion that defines a through passage between said connecter and seal portions of said seal member and

tab structure in said cartridge body for releasably receiving said intermediate portions of said seal members connected to said ports of said tubular reaction chamber.

17. A system for analyzing a biological fluid for a constituent of interest comprising analysis cuvette structure defining a sample inlet port, said analysis cuvette structure including metal track plate structure with an outwardly open flow path channel in a planar surface thereof that is coated with a thermally conductive, corrosion resistant dielectric material, and a transparent gasket member seated against said planar body surface, structure defining an analysis region, a measuring system in sensing relation to the analysis region, structure defining a recess, and passage structure defining a sample flow path between said inlet port structure and said recess and a sample flow path between said recess and said analysis region, and a replaceable cartridge assembly adapted to be releasably inserted as a unit into said recess, said cartridge assembly including a metal temperature stabilizing cartridge body with a planar surface, spiral channel structure in said planar surface of said cartridge body, a tubular reaction chamber in spiral coil form releasably received in said channel structure, said reaction chamber having an immobilized enzyme in said reaction chamber that is capable of converting the constituent of interest to a constituent detectable by the measuring system, and coupling structure for sealingly connecting said tubular reaction chamber to said passage structure when said replaceable cartridge assembly is in said recess.

18. The system of claim 17 and further including heat sink structure spaced from said metal track plate structure, a thermoelectric source physically coupled to said metal track plate structure and to said heat sink structure, a temperature sensor adjacent said analysis region, and a control unit responsive to said temperature sensor for operating said thermoelectric source to maintain the temperature of said metal track plate structure at about 30°

C.

19. The system of claim 18 further includes heat sink structure and wherein said thermal source is a thermoelectric unit that has a hot face and a cold face, said cold face being thermally coupled to said metal track plate structure and said hot face being thermally coupled to said heat sink structure, and said temperature sensor is a thermistor embedded in said metal track plate structure adjacent said analysis region.

20. The system of claim 19 wherein said measuring system includes two electrode devices for measuring different constituents of interest in said sample, at least one of said electrode devices being an ion selective electrode device.

21. The system of claim 20 wherein said reaction chamber structure has a volume of less than about two hundred microliters and is in the form of an elongated tube that is disposed in coil form in said channel structure;

glucose oxidase and urease enzymes are co-immobilized on the inner surface of said tube; and

said coupling structure is carried by said temperature stabilizing cartridge body.

22. The system of claim 21 further includes means for biasing said temperature stabilizing cartridge body against said metal track plate structure.

23. The system of claim 17 wherein said coupling structure includes a seal member with a connector portion that is connected to said reaction chamber structure, a seal portion that has an end surface projecting beyond the end of said replaceable cartridge assembly, said end surface being adapted to seat in sealing relation on a port of said recess, and a through passage between said connector and seal portions of said seal member.