Temperature-controlled incubator having a receptacle mixing mechanism

• US 8,337,753 B2
• Filed: 10/19/2007
• Issued: 12/25/2012
• Est. Priority Date: 05/01/1998
• Status: Expired due to Term

• Current Assignee: Gen-Probe Incorporated (Hologic Incorporated)
• Original Assignee: Gen-Probe Incorporated (Hologic Incorporated)
• Inventors: Ammann, Kelly G., Schneider, Robert E., Smith, Robert J.
• Primary Examiner(s): Gordon, Brian R
• Application Number:
  US11/875,285
• Publication Number:
  US 20080063573A1
• Time in Patent Office: 1,894 Days
• Field of Search: 422 63- 65, 422/68.1, 422/307, 236/2, 237/14, 366144-147, 366208-240
• US Class Current: 422/64
• CPC Class Codes: B01L 2200/147 Employing temperature sensors
• CPC Class Codes: B01L 2300/1822 using Peltier elements
• CPC Class Codes: B01L 2300/1827 using resistive heater
• CPC Class Codes: B01L 7/52 with provision for submitting samples to a predetermined sequence of different temperatures, e.g. for treating nucleic acid samples amplification or hybridisation processes per se C12Q1/68; controlling sequential reactions for synthesis B01J19/0046
• CPC Class Codes: B01L 7/5255 by moving sample containers
• CPC Class Codes: G01N 2035/00356 Holding samples at elevated temperature (incubation)
• CPC Class Codes: G01N 2035/00524 Mixing by agitating sample carrier
• CPC Class Codes: G01N 2035/0437 Cleaning cuvettes or reaction vessels
• CPC Class Codes: G01N 2035/0455 Coaxial carousels
• CPC Class Codes: G01N 2035/103 using disposable tips
• 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 35/0099 comprising robots or similar manipulators robots per se B25J
• 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 436/115831 Condition or time responsive
• 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 automated analyzer for performing multiple diagnostic assays simultaneously includes multiple stations, or modules, in which discrete aspects of the assay are performed on fluid samples contained in reaction receptacles. The analyzer includes stations for automatically preparing a specimen sample, incubating the sample at prescribed temperatures for prescribed periods, performing an analyte isolation procedure, and ascertaining the presence of a target analyte. An automated receptacle transporting system moves the reaction receptacles from one station to the next. The analyzer further includes devices for carrying a plurality of specimen tubes and disposable pipette tips in a machine-accessible manner, a device for agitating containers of target capture reagents comprising suspensions of solid support material and for presenting the containers for machine access thereto, and a device for holding containers of reagents in a temperature controlled environment and presenting the containers for machine access thereto. A method for performing an automated diagnostic assay includes an automated process for isolating and amplifying a target analyte. The process is performed by automatically moving each of a plurality of reaction receptacles containing a solid support material and a fluid sample between stations for incubating the contents of the reaction receptacle and for separating the target analyte bound to the solid support from the fluid sample. An amplification reagent is added to the separated analyte after the analyte separation step and before a final incubation step.

Claims

1. An incubator for receiving at least one reaction receptacle and maintaining the contents of the reaction receptacle in a temperature controlled environment, said incubator comprising:

a housing defining an incubation chamber therein;

a heat source in thermal communication with said incubation chamber;

a receptacle carrier carousel rotatably disposed within said housing and comprising a plurality of receptacle holding stations arranged circumferentially thereabout, each receptacle holding station being configured to carry a reaction receptacle therein and to permit the reaction receptacle carried thereby to more horizontally within said receptacle holding station with respect to said receptacle carrier carousel; and

a receptacle mixing mechanism positioned adjacent to said receptacle carrier carousel, wherein said receptacle carrier carrousel is configured to sequentially place a reaction receptacle carried in each receptacle holding station in an operative position with respect to said receptacle mixing mechanism by rotation of said receptacle carrier carousel, and wherein said receptacle mixing mechanism is constructed and arranged to engage a reaction receptacle placed in an operative position with respect to said receptacle mixing mechanism by said receptacle carrier carousel and to agitate the engaged reaction receptacle by moving the reaction receptacle with respect to the receptacle carrier carousel and within the receptacle holding station in a generally horizontal, reciprocating path.

2. The incubator of claim 1, further comprising a home sensor coupled to said receptacle mixing mechanism and constructed and arranged to determine when a portion of the receptacle mixing mechanism is in a predefined home position to engage or disengage a reaction receptacle disposed in the operative position with respect to said receptacle mixing mechanism.

3. The incubator of claim 1, wherein said receptacle mixing mechanism comprises:

a motor;

a shaft operatively coupled to said motor, at least a portion of said shaft extending into said incubation chamber; and

a disk mounted on the portion of said shaft disposed within said incubation chamber, said disk mounted in such a manner that the plane of the disk is disposed at an acute angle with respect to the longitudinal axis of said shaft.

4. The incubator of claim 3, wherein said motor is mounted on an outer surface of said housing and said shaft extends from said motor through an opening formed in said housing and into said incubation chamber.

5. The incubator of claim 3, further comprising a damper coupled to said motor.

6. The incubator of claim 5, wherein said damper comprises a viscous harmonic damper attached to said motor.

7. The incubator of claim 3, further comprising a home sensor adapted to determine when the shaft is in a predefined rotational position to engage or disengage a reaction receptacle disposed in the operative position with respect to said receptacle mixing mechanism.

8. The incubator of claim 7, wherein said home sensor comprises a pin extending radially with respect to said shaft and a switch adapted to detect the presence of said pin.

9. The incubator of claim 8, wherein said switch comprises a slotted optical switch.

10. The incubator of claim 1, further comprising a heat sensor constructed and arranged to measure the temperature within said incubation chamber.

11. The incubator of claim 1, wherein said housing includes one or more openings formed therein to permit access to a reaction receptacle carried in said housing to allow fluid transfer to or from the reaction receptacle while the reaction receptacle is carried in said housing.

12. The incubator of claim 1, wherein said receptacle mixing mechanism is disposed at a position along the perimeter of said carousel and radially outwardly from the perimeter of said carousel.

13. The incubator of claim 1, wherein said housing includes a receptacle access opening formed therein and configured to allow movement of a reaction receptacle into or out of said housing through said receptacle access opening, and wherein said incubator further comprises a closure mechanism coupled to said housing in proximal relation to said receptacle access opening, said closure mechanism being constructed and arranged to be movable between a closed position preventing access to said housing through said access opening and an open position permitting access to said housing through said access opening.

14. The incubator of claim 13, further comprising:

a second receptacle access opening formed in said housing for allowing movement of a reaction receptacle into or out of said housing through said second receptacle access opening; and

a second closure mechanism operatively positioned with respect to said second receptacle access opening and movable between a closed position preventing access to said housing through said second access opening and an open position permitting access to said housing through said second access opening.

15. The incubator of claim 13, further comprising one or more sensors operatively positioned with respect to said closure mechanism and constructed and arranged to indicate whether said closure mechanism is in said closed position or in said open position.

16. A system for maintaining a reaction mixture in a temperature controlled environment, said system comprising:

at least one reaction receptacle adapted to contain a reaction mixture and including manipulating structure; and

an incubator for receiving said reaction receptacle, said incubator comprising;

a housing defining an incubation chamber therein;

a heat source in thermal communication with said incubation chamber;

a receptacle carrier carousel rotatably disposed within said housing and comprising a plurality of receptacle holding stations arranged circumferentially thereabout, each receptacle holding station being configured to carry a reaction receptacle therein and to permit the reaction receptacle carried thereby to move horizontally within said receptacle holding station with respect to said receptacle carrier carousel, said reaction receptacle being disposed in one of said receptacle holding stations; and

a receptacle mixing mechanism positioned adjacent to said receptacle carrier carousel, wherein said receptacle carrier carrousel is configured to sequentially place a reaction receptacle carried in each receptacle holding station in an operative position with respect to said receptacle mixing mechanism by rotation of said receptacle carrier carousel, and wherein said receptacle mixing mechanism is constructed and arranged to engage said manipulating structure of a reaction receptacle placed in an operative position with respect to said receptacle mixing mechanism by rotation of said receptacle carrier carousel and to agitate said engaged reaction receptacle by moving the reaction receptacle with respect to the receptacle carrier carousel and within the receptacle holding station in a generally horizontal, reciprocating path to thereby mix the reaction mixture contained within said reaction receptacle.

17. The system of claim 16, wherein said receptacle mixing mechanism comprises:

a motor;

a shaft operatively coupled to said motor, at least a portion of said shaft extending into said incubation chamber; and

a disk mounted on the portion of said shaft disposed within said incubation chamber, said disk mounted in such a manner that the plane of the disk is disposed at an acute angle with respect to the longitudinal axis of said shaft, said disk being adapted to engage said manipulating structure of said reaction receptacle such that rotation of said shaft and disk imparts a corresponding horizontal, reciprocating motion to said reaction receptacle.

18. The system of claim 17, further comprising a home sensor adapted to determine when said disk is in a predefined rotational position to engage or disengage said manipulating structure of said reaction receptacle disposed in the operative position with respect to said receptacle mixing mechanism.

19. The system of claim 16, wherein said reaction receptacle comprises a plurality of tubes operatively connected to each other, said manipulating structure projecting from one of said tubes.

20. The system of claim 17, wherein said manipulating structure comprises a lateral plate and a transverse piece attached to an end of said lateral plate and extending transversely with respect thereto, said transverse piece including a convex surface that is contacted by said receptacle mixing mechanism when said receptacle mixing mechanism is agitating said reaction receptacle.