Automated analyzer with reagent agitating device

• US 5,637,275 A
• Filed: 06/02/1995
• Issued: 06/10/1997
• Est. Priority Date: 03/04/1991
• Status: Expired due to Term

• Current Assignee: Siemens Healthcare Diagnostics Incorporated (Siemens AG)
• Original Assignee: Chiron Corporation (Bayer AG)
• Inventors: Whitesel, Mary B., Mann, Raymond A., Polaniec, James P., Woyansky, George J., Pabst, Stefan R., Klingshirn, Frank C., Lewis, Scott C., Carey, Glen A.
• Primary Examiner(s): Le, Long V.
• Application Number:
  US08/459,398
• Time in Patent Office: 739 Days
• Field of Search: 422/63-67, 422/100, 422/103, 422/104, 422/81, 436/43, 436/47, 436/48, 436/49, 436/54, 366/214, 366/218
• US Class Current: 422/64
• CPC Class Codes: B01L 2300/0854 Double walls
• CPC Class Codes: B01L 3/508 rigid containers not provided for above
• CPC Class Codes: G01N 2035/00386 using fluid heat transfer medium
• CPC Class Codes: G01N 2035/00396 where the fluid is a liquid
• CPC Class Codes: G01N 2035/00524 Mixing by agitating sample carrier
• CPC Class Codes: G01N 2035/00752 bar codes
• CPC Class Codes: G01N 2035/0441 for samples
• CPC Class Codes: G01N 2035/0443 for reagents
• CPC Class Codes: G01N 2035/0465 Loading or unloading the conveyor
• CPC Class Codes: G01N 2035/0484 Belt or chain
• CPC Class Codes: G01N 2035/0486 Gearing, cams
• CPC Class Codes: G01N 2035/1025 Fluid level sensing
• CPC Class Codes: G01N 21/76 Chemiluminescence; Bioluminescence
• CPC Class Codes: G01N 35/0098 involving analyte bound to insoluble magnetic carrier, e.g. using magnetic separation magnetic particles used in immunoassays G01N33/54326; magnetic separation in general B03C
• CPC Class Codes: G01N 35/021 having a flexible chain, e.g. "cartridge belt", conveyor for reaction cells or cuvettes
• CPC Class Codes: G01N 35/025 having a carousel or turntable for reaction cells or cuvettes
• CPC Class Codes: G01N 35/1002 Reagent dispensers
• CPC Class Codes: G01N 35/1065 Multiple transfer devices
• CPC Class Codes: Y02A 90/10 Information and communication technologies [ICT] supporting adaptation to climate change, e.g. for weather forecasting or climate simulation
• CPC Class Codes: Y10S 215/01 Fins
• CPC Class Codes: Y10S 215/03 : Medical
• CPC Class Codes: Y10S 215/08 : Mixing
• CPC Class Codes: Y10T 436/11 : Automated chemical analysis
• CPC Class Codes: Y10T 436/113332 : with conveyance of sample along a test line in a container or rack
• CPC Class Codes: Y10T 436/114165 : with step of insertion or removal from test line
• CPC Class Codes: Y10T 436/114998 : with treatment or replacement of aspirator element [e.g., cleaning, etc.]
• CPC Class Codes: Y10T 436/119163 : with aspirator of claimed structure
• CPC Class Codes: Y10T 436/25 : including sample preparation
• CPC Class Codes: Y10T 436/2575 : Volumetric liquid transfer

Abstract

An analyzer for performing automated assay testing. The analyzer includes a storage and conveyor system for conveying cuvettes to an incubation or processing conveyor, a storage and selection system for test sample containers, a storage and selection system for reagent containers, sample and reagent aspirating and dispensing probes, a separation system for separating bound from unbound tracer or labeled reagent, a detection system and date collection/processing system. All of the subunits of the machine are controlled by a central processing unit to coordinate the activity of all of the subunits of the analyzer. The analyzer is specifically suited for performing heterogeneous binding assay protocols, particularly immunoassays.

Claims

1. Apparatus for depositing sample and reagent into each of a plurality of cuvettes conveyed along an event path in an automated analyzer to assay a test sample, said analyzer having an event conveyor for conveying said plurality of cuvettes serially along said event path, said apparatus for depositing including a vertical sample dispense axis and a vertical reagent dispense axis which is spaced from and downstream of said sample dispense axis, said apparatus comprising:

(a) sample transport and selection means for supporting a plurality of sample containers, each container containing a different liquid sample to be analyzed and for selectively positioning any one of said sample containers at a vertical sample aspirating axis which is spaced from said sample dispense axis,

(b) sample probe transport means for supporting a sample probe for selective vertical movement between an upper position and a lower dispense and aspirating positioned horizontal movement between said sample aspirating axis and said sample dispense axis for aspirating a volume of sample from a sample container at said sample aspiration axis and depositing said volume of sample into a cuvette at said sample dispense axis,

(c) reagent transport and selection means for supporting a plurality of reagent containers, each reagent container containing a different reagent and for selectively positioning any one of said reagent containers at a vertical reagent aspirating axis which is spaced from said reagent dispense axis,

(d) reagent probe transport means for supporting a reagent aspirating and dispensing probe for selective vertical movement between an upper position and a lower aspirating and dispense position and for horizontal movement between said reagent dispense axis and said reagent aspirating axis, and

(e) control means including a central processing means operatively connected to said sample transport and selection means, said sample probe transport means, said reagent transport and selection means, and said reagent probe transport means, for aspirating a volume of a specified test sample from a selectively positioned sample container at said sample aspirating axis and dispensing said specific test sample into a cuvette at said sample dispense axis, for aspirating a volume of a specific reagent which corresponds with said specific test sample at said reagent aspirating axis from a selectively positioned reagent container and dispensing said specific reagent into a cuvette which contains said specific sample when the cuvette is located at said reagent dispense axis

wherein said reagent transport and selection means comprises;

(a) a fixed supporting base,

(b) a reagent tray which is mounted on said base for rotation about a primary vertical axis of rotation, wherein said reagent containers include a first set of containers and a second set of containers, each container of said first set of containers adapted to contain a solid phase reagent which includes paramagnetic particles which requires agitation to maintain homogeneity, said first set of reagent containers being located in a first circle which is concentric with said primary vertical axis of rotation and, wherein said second set of reagent containers are mounted on said tray in a second circle which is concentric with said primary vertical axis of rotation, each of said second containers being adjacent to and paired with a corresponding first reagent container and adapted to contain a tracer reagent that is used in conjunction with a paired solid phase reagent for a particular sample test, each of said first set of reagent containers being mounted on said tray for rotation about a respective one of a plurality of secondary vertical axes along said circle,

(c) first drive means including a first electric motor for rotating said tray about said primary vertical axis of rotation, and

(d) second drive means including a reversible second electric motor for rotating each of said first set of reagent containers about said respective secondary axis of rotation for agitating the reagent in said containers, and wherein said control means controls operation of said first electric motor for selectively positioning any one of said reagent containers to said reagent aspirating axis;

wherein said second drive means comprises;

(a) a holder for each of said first set of reagent containers which is mounted for rotation about a respective one of said secondary vertical axes on said tray,

(b) a satellite gear for each of said first set of reagent containers, each of said satellite gears being fixed to its respective container and concentric with the respective secondary vertical axis of the container,

(c) a sun gear which is concentric with said primary vertical axis of rotation and is in driving engagement with each of said satellite gears so that rotation of said sun gear about said primary vertical axis causes each of said satellite gears to rotate about said respective secondary vertical axis, and

(d) a drive coupling for operatively connecting said second electric motor to said sun gear.

2. In an analyzer as recited in claim 1, wherein said sample transport and selection means comprises:

(a) a fixed supporting base,

(b) a tray which is mounted on said base for rotation about a vertical axis of rotation, said sample containers being supported on said tray in a circle which is concentric with said axis of rotation and which intersects said sample aspirating axis, and

(c) drive means including an electric motor for rotating said tray about said axis of rotation, said motor being controlled by said control means for selectively positioning any one of said sample containers at said sample aspirating axis.

3. In an analyzer as recited in claim 2, wherein said sample aspirating axis is a first aspirating axis, said sample probe transport means is capable of aspirating a volume of sample at a second vertical aspirating axis, said tray is an inner tray, said sample containers are inner sample containers, said drive means is a first drive means and said sample transport and selection system further comprises:

(a) an outer ring-shaped tray which surrounds said inner tray and is mounted for rotation about said axis of rotation independently of said inner tray,

(b) a plurality of outer sample containers which are supported on said outer tray in a circle which is concentric with said axis of rotation, each of said containers containing a specific sample for analysis, and

(c) second drive means including a second electric motor for rotating said outer tray about said axis of rotation independently of said inner tray, said second electric motor being operatively connected to said control means so that any one of said outer sample containers is selectively positioned to said second aspirating axis for aspiration of a volume of sample by said sample probe using said sample probe transport means from an outer sample container which is positioned at said second aspirating axis.

4. In an analyzer as recited in claim 1, wherein said sample probe transport means comprises:

(a) a fixed supporting base,

(b) a carriage which is mounted on said supporting base for horizontal movement between said sample dispense axis and said sample aspirating axis,

(c) first drive means for selectively controlling the horizontal movement of said carriage,

(d) a probe supporting assembly which supports said sample probe and which is mounted on said carriage for vertical movement, and

(e) second drive means for selectively controlling the vertical movement of said probe supporting assembly.

5. In an analyzer as recited in claim 4, wherein said first drive means includes a first electric motor, said second drive means includes a second electric motor and said control means includes a central processing unit which is operatively connected to said first and second electric motors.

6. In an analyzer as recited in claim 5, wherein each of said electric motors is a reversible stepper motor, said first motor being fixed relative to said supporting base, and said second motor being fixed relative to said carriage and movable with said carriage.

7. In an analyzer as recited in claim 6, wherein said first drive means comprises:

(a) a first horizontal lead screw which has a central longitudinal axis and which is drivenly connected to said first motor for rotation of said lead screw about said central longitudinal axis,

(b) a first threaded follower which is fixed to said carriage and which is mounted on said lead screw for movement along the axis of said lead screw so that said follower moves axially along said lead screw toward said aspirating axis when said lead screw is rotated in a first direction and toward said dispensing axis when the lead screw is rotated in a second direction, and wherein said second drive means comprises;

(1) a second vertical lead screw which has a central longitudinal axis and which is drivenly connected to said second motor for rotation of said second lead screw about the central longitudinal axis of said second lead screw,

(2) a second threaded follower which is fixed to said probe supporting assembly and which is mounted on said second lead screw for movement along the axis of said second lead screw so that said probe holding assembly moves downwardly along said second lead screw when said second lead screw is rotated in a first direction and upwardly along said second lead screw when said second lead screw is rotated in a second direction.

8. In an analyzer as recited in claim 1, wherein said analyzer comprises a wash station having a receptacle which has an open top and which is located along a vertical wash axis, said wash axis being located between said sample dispense axis and said sample aspirating axis, said sample probe transport means being controlled by said control means for positioning said sample probe at said wash axis and lowering said probe into said receptacle for a wash cycle after dispensing of sample into said cuvette by said sample probe.

9. In an analyzer as recited in claim 1, wherein each of said reagent containers includes a chamber for holding reagent and at least one fin which extends into said chamber for agitating said reagent as the container rotates about said respective secondary axis of rotation.

10. In an analyzer as recited in claim 1, wherein said second electric motor is reversible and each of said containers is rotated at times clockwise when viewed from the top and at other times counterclockwise when viewed from the top.

11. In an analyzer as recited in claim 10, wherein said second electric motor is a stepper motor and said electrical control means includes a central processing unit which controls speed, direction of rotation and acceleration of the stepper motor to produce a desired controlled turbulent motion of liquid in the reagent containers.

12. In an analyzer as recited in claim 1, wherein said reagent probe transport means comprises:

(a) a fixed supporting base,

(b) a carriage which is mounted on said supporting base for horizontal movement between said reagent dispense axis and said reagent aspirating axis,

(c) first drive means for selectively controlling the horizontal movement of said carriage,

(d) a probe supporting assembly which supports said reagent probe and which is mounted on said carriage for vertical movement, and

(e) second drive means for selectively controlling the vertical movement of said probe supporting assembly.

13. In an analyzer as recited in claim 12, wherein said first drive means includes a first electric motor, said second drive means includes a second electric motor and said control means includes a central processing unit which is operatively connected to said first and second electric motors.

14. In an analyzer as recited in claim 13, wherein each of said electric motors is a reversible stepper motor, said first motor being fixed relative to said supporting base, and said second motor being fixed relative to said carriage and movable with said carriage.

15. In an analyzer as recited in claim 14, wherein said first drive means comprises:

(a) a first horizontal lead screw which has a central longitudinal axis and which is drivenly connected to said first motor for rotation of said lead screw about said central longitudinal axis,

(b) a first threaded follower which is fixed to said carriage and which is mounted on said lead screw for movement along the axis of said lead screw so that said follower moves axially along said lead screw toward said aspirating axis when said lead screw is rotated in a first direction and toward said dispensing axis when the lead screw is rotated in a second direction, and wherein said second drive means comprises;

(1) a second vertical lead screw which has a central longitudinal axis and which is drivenly connected to said second motor for rotation of said second lead screw about the central longitudinal axis of said second lead screw,

(2) a second threaded follower which is fixed to said probe supporting assembly and which is mounted on said second lead screw for movement along the axis of said second lead screw so that said probe holding assembly moves downwardly along said second lead screw when said second lead screw is rotated in a first direction and upwardly along said second lead screw when said second lead screw is rotated in a second direction.

16. In an analyzer as recited in claim 13, wherein said control means comprises:

(a) first sensing means operatively connected to said central processing unit for monitoring the horizontal movement of said carriage and providing signals to said central processing unit which are indicative of a position of the carriage relative to the supporting base, and

(b) second sensing means operatively connected to said central processing unit for monitoring the vertical movement of said reagent probe supporting assembly and providing signals to said central processing unit which are indicative of a position of the reagent probe supporting assembly relative to the carriage.

17. In an analyzer as recited in claim 1, wherein each satellite gear has teeth on its outer periphery, wherein said sun gear is ring-shaped with teeth on its outer periphery for engaging the teeth of said satellite gears, wherein said second electric motor is located within said sun gear and has a drive shaft which extends along said primary axis, and wherein said drive coupling comprises:

(a) a hub gear which is fixed to the drive shaft of said second electric motor and which has a plurality of first driving protuberances which are located in a concentric circle about said primary axis, and

(b) a plurality of second driving protuberances on said sun gear which are located in a circle which is concentric about said primary axis and which are in driving engagement with said first driving protuberances.