Unified fluid circuit assembly for a clinical hematology instrument

• US 5,788,927 A
• Filed: 07/30/1996
• Issued: 08/04/1998
• Est. Priority Date: 07/30/1996
• Status: Expired due to Term

• Current Assignee: Siemens Healthcare Diagnostics Incorporated (Siemens AG)
• Original Assignee: Bayer Corporation (Bayer AG)
• Inventors: Mawhirt, James, Cremins, John, Carlucci, Joseph, Farrell, Gregory A., Behringer, Bruce E.
• Primary Examiner(s): Le, Long V.
• Application Number:
  US08/688,517
• Time in Patent Office: 735 Days
• Field of Search: 422/63, 422/58, 422/67, 422/68.1, 422/81, 422/73, 422/82.01, 422/82.02, 422/82.05, 422/99, 422/100, 422/103, 436/43, 436/54, 436/164, 436/165, 436/174, 436/180
• US Class Current: 422/63
• CPC Class Codes: G01N 15/14 Optical investigation techniques, e.g. flow cytometry
• CPC Class Codes: G01N 35/1097 characterised by the valves valves in general F16K
• CPC Class Codes: Y10T 436/11 Automated chemical analysis
• CPC Class Codes: Y10T 436/25 including sample preparation
• CPC Class Codes: Y10T 436/2575 Volumetric liquid transfer

Abstract

A unified fluid cell circuit assembly for an analytical instrument, such as a clinical hematology, immunoassy or chemistry or a flow cytometry instrument. The assembly includes a unified fluid circuit, a shear valve, a fluid pump assembly, and a plurality of solenoid valves. The unified fluid circuit is made of a plurality of acrylic plates which have formed in the various plate surfaces chamber cavities, pneumatic, hydraulic and vent line, and valve cavities. The plates, when secured together, form a plurality of reaction chambers, a plurality of control valves and various lines as a network for controlling the flow and mixing of aliquots of a sample and fluids (rinse, reagents, etc.) to perform the reactions for analyzing the sample. The fluid pump assembly is connected to the unified flow circuit and has a plurality of diaphragm pumps which pump precise volumes of fluids. The solenoid valves provide the pressure and vacuum to operate the pumps and to provide a sample into the shear valve to form sample aliquots, and to mix the various aliquots with the reagents and diluents to form the reaction mixtures.

Claims

1. A unified fluid circuit assembly for use in an analytical instrument comprising:

a unified fluid circuit comprising a plurality of acrylic plates secured together into a unified circuit, each of the plurality of acrylic plates having a thickness and said plurality of plates having therein;

a plurality of reaction chambers, each chamber having a predetermined size, at least one inlet, and an outlet;

a first plurality of sample inlet passages corresponding to a first number of sample aliquots;

a second plurality of fluid inlet passages corresponding to a second number of fluids;

a third plurality of outlet passages;

a plurality of vent passages;

a network of diaphragm valves and pneumatic lines connecting said sample inlet passages, fluid inlet passages, reaction chamber inlets and outlets, vent passages, and outlet passages, each of said diaphragm valves having an open state and a closed state in response to an application of one of pressure and vacuum, wherein the network is operable to control the flow of selected ones of said sample aliquots and selected ones of said second number of fluids through said unified fluid circuit to form reaction mixtures in selected ones of said plurality of reaction chambers;

a shear valve mounted on said unified fluid circuit having a sample input and a plurality of sample aliquot outputs, said shear valve having a position operable to couple said sample aliquot outputs to the first plurality of sample inlet passages;

a fluid pump assembly comprising

a plurality of diaphragm pumps, each diaphragm pump having a pump chamber having a first transition state for filling the pump chamber with a precise amount of a fluid and a second transition state for expelling said precise amount from said pump chamber, said plurality of pump chambers having a respective plurality of outlet passages respectively connected to said second plurality of inlet passages, each diaphragm pump having a valve and a pneumatic line to control the transition state of the pump chamber by application of one of a pressure and a vacuum; and

a plurality of solenoid air valves coupled to the network and to the pneumatic lines of said fluid pump assembly, said solenoid air valves being selectively operable to provide pressure and vacuum to selected ones of said pneumatic lines thereby to control the flow of sample aliquots and fluids through said unified fluid circuit.

2. The assembly of claim 1 wherein the unified fluid circuit further comprises an aperture in at least one of said acrylic plates proximate to one of the plurality of reaction chambers, a heating element in said aperture thermally coupled to said one reaction chamber to heat said reaction chamber and its contents, said heating element being spaced from the other of said reaction chambers so as not to heat said other reaction chambers.

3. The assembly of claim 2 wherein said heating element further comprises a foil resistance heating element and a temperature sensor having an output corresponding to the temperature of the one reaction chamber.

4. The assembly of claim 3 wherein the temperature sensor is one of a thermocouple and a thermistor probe.

5. The assembly of claim 2 wherein the one reaction chamber further comprises at least one portion which is a thin acrylic wall having a thickness of less than 1.0 mm in thermal contact with said heating element.

6. The assembly of claim 1 wherein the unified fluid circuit further comprises a first area, said first area having therein at least one of said plurality of reaction chambers, said assembly further comprising a calorimeter including:

a light source having a light beam output directed into said one reaction chamber;

an optical filter having a wavelength selective passband output corresponding to a color; and

a light detector responsive to the output of the optical filter and having an electrical output signal corresponding to an intensity of the color of said light beam after having passed through said one reaction chamber.

7. The assembly of claim 6 wherein said first area of said unified fluid circuit has a reduced dimension corresponding to the thickness of two of said plurality of acrylic plates, and said light source and optical filter are mounted on opposite sides of said two plates.

8. The assembly of claim 1 wherein the unified fluid circuit further comprises a sample inlet and a sample passageway, a conductivity sensor disposed in said sample passageway, wherein the shear valve is interposed in said sample passageway between said sample inlet and said conductivity sensor, and the conductivity sensor having an output having a first state corresponding to the absence of a conductive sample in the sample passageway, and a second state corresponding to the presence of a conductive sample in the sample passage way.

9. The assembly of claim 8 wherein the unified fluid circuit further comprises a sample bypass line and the conductivity sensor second state further comprises an output signal having a first value corresponding to a valid conductive sample in the shear valve and a second value corresponding to an invalid conductive sample in the shear valve, wherein the network operates in response to the output signal first value by passing the sample in said sample passageway to selected ones of the reaction chambers and in response to the output signal second value by passing the sample in said sample passageway to the bypass line.

10. The assembly of claim 1 wherein the instrument is a clinical hematology instrument for analyzing a blood sample, further comprising a peroxidase reaction assembly mounted on the unified fluid circuit, said peroxidase reaction assembly comprising a metal reaction chamber and a heater for said reaction chamber, the metal reaction chamber having a first inlet for a reaction mixture including a first reagent and a blood sample aliquot, a second inlet for a second reagent, a third inlet for a third reagent, and a fourth inlet for a rinse fluid, wherein the peroxidase reaction assembly is coupled to the unified fluid circuit network so that the first inlet is coupled to a first one of said first plurality of blood sample aliquot passages, the second inlet is coupled to one of the plurality of said second plurality of inlet passages, the third inlet is coupled to a second one of the second plurality of inlet passages, the fourth inlet is coupled to a third one of the second plurality of inlet passages.

11. The assembly of claim 1 wherein the unified fluid circuit further comprises a first area, said first area having therein at least one of said plurality of reaction chambers, said assembly further comprising a cavity liner disposed within said one reaction chamber, said liner having an outer boundary smaller than said one reaction chamber;

and

a heating element disposed between said outer boundary of said cavity liner and said one reaction chamber surface, said heating element being in thermal contact with said cavity liner, wherein the cavity liner can absorb a greater thermal load than the acrylic plates.

12. The assembly of claim 11 wherein the heating element further comprises a wire heating element wound around the cavity liner and insulated from the acrylic plates.

13. The assembly of claim 1 wherein the network of diaphragm valves further comprises a plurality of dome valves.

14. The assembly of claim 1 wherein the unified fluid circuit further comprises a fourth plurality of outputs, wherein the network further comprises a subnetwork of lines and valves operable to connect each of the reaction chamber outlet to one of said fourth plurality of outputs.

15. The assembly of claim 14, wherein the fourth plurality of outputs further comprise at least one of a bypass outlet line and a flow cell input line.

16. The assembly of claim 14, wherein the fourth plurality of outputs further comprise at least one flow cell input line, the unified fluid circuit further comprises a vacuum storage cavity, and wherein the network further comprises a subnetwork of valves and lines operable to produce a first pressure state in said vacuum storage cavity, and a second pressure state in said vacuum storage cavity, the first state having a reduced pressure, wherein the transition from the first state to the second stated operates to draw a volume of fluid out of a selected reaction chamber into said flow cell input line.

17. The assembly of claim 1 wherein the shear valve further comprises a subnetwork of valves and lines operable to prevent filling at least one of said plurality of aliquot loops with a sample input, and wherein said fluid pump assembly is operable not to operate the at least one diaphragm pump corresponding to said at least one aliquot loop in response to said at least one aliquot loop not being filled with said sample input.

18. The apparatus of claim 1 wherein the unified fluid circuit further comprises a sample inlet and a sample passageway, and an electrochemical sensor disposed in said passageway, the electrochemical sensor having an output signal indicative of an electrochemical characteristic of a fluid in the passageway.

19. The apparatus of claim 18 wherein the electrochemical characteristic is pH.

20. The apparatus of claim 18 wherein the electrochemical characteristic is conductivity.

21. The apparatus of claim 18 wherein the sample is a blood sample.

22. The assembly of claim 1 further comprising a reaction assembly mounted on the unified fluid circuit, said reaction assembly comprising a metal reaction chamber and a heater for said reaction chamber, the metal reaction chamber having a first inlet for a reaction mixture comprising a sample aliquot and a reagent, at least a second inlet for a fluid to be added to the reaction mixture, wherein the metal reaction chamber is coupled to the unified fluid circuit network so that the first inlet is coupled to a first one of said plurality of sample aliquot passages, and the second inlet is coupled to one of the plurality of said second plurality of inlet passages.

23. The assembly of claim 22 wherein the heater further comprises a controller operable to heat a reaction mixture in the metal reaction chamber at a rate of up to 4°

C. per second to a temperature in the range of from 35°

C. to 70°

C.