Method for agitating the contents of a reaction receptacle within a temperature-controlled environment

• US 8,318,500 B2
• Filed: 10/19/2007
• Issued: 11/27/2012
• 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:
  US11/875,306
• Publication Number:
  US 20090067280A1
• Time in Patent Office: 1,866 Days
• Field of Search: 422 63- 64, 422/68.1, 436/43, 436/45, 436/49, 436/54, 436/174, 436/180, 436/47, 366144-147, 366/151.2
• US Class Current: 436/54
• CPC Class Codes: B01F 29/10 with receptacles rotated about two different axes, e.g. receptacles having planetary motion
• CPC Class Codes: B01F 29/30 Mixing the contents of individual packages or containers, e.g. by rotating tins or bottles
• CPC Class Codes: B01F 29/322 of two or more containers supported for simultaneous mixing, e.g. for bottles in crates
• CPC Class Codes: B01F 29/40354 arranged for planetary motion
• 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: B01L 9/06 Test-tube stands; Test-tube holders
• CPC Class Codes: B03C 1/282 with associated accumulation indicator, e.g. Hall sensor
• CPC Class Codes: B03C 1/288 disposed at the outer circumference of a recipient
• CPC Class Codes: B03C 1/30 Combinations with other devices, not otherwise provided for
• CPC Class Codes: B03C 2201/26 for use in medical applications
• CPC Class Codes: C12Q 1/6813 Hybridisation assays
• CPC Class Codes: C12Q 1/6832 Enhancement of hybridisation reaction
• CPC Class Codes: C12Q 1/6834 Enzymatic or biochemical coupling of nucleic acids to a solid phase
• CPC Class Codes: C12Q 2537/10 the purpose or use of
• 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: G01N 35/025 : having a carousel or turntable for reaction cells or cuvettes
• CPC Class Codes: G01N 35/1065 : Multiple transfer devices
• CPC Class Codes: Y10T 156/1105 : Delaminating process responsive to feed or shape at delamination
• CPC Class Codes: Y10T 156/1906 : Delaminating means responsive to feed or shape at delamination
• CPC Class Codes: Y10T 29/53657 : to apply or remove a resilient article [e.g., tube, sleeve, etc.]
• CPC Class Codes: Y10T 29/53683 : Spreading parts apart or separating them from face to face engagement
• CPC Class Codes: Y10T 29/53843 : Tube, sleeve, or ferrule inserting or removing
• CPC Class Codes: Y10T 436/11 : Automated chemical analysis
• CPC Class Codes: Y10T 436/111666 : Utilizing a centrifuge or compartmented rotor
• CPC Class Codes: Y10T 436/113332 : with conveyance of sample along a test line in a container or rack
• 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 436/2575 : 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. A method for agitating the contents of a reaction receptacle within a temperature-controlled environment, said method comprising the automated steps of:

placing a plurality of reaction receptacles within a temperature-controlled incubator;

moving the reaction receptacles in a circular path within the incubator on a receptacle carrier located within said incubator;

while moving the reaction receptacles in the circular path within the incubator, moving one of said reaction receptacles into a position at which it will engage with a mixing mechanism disposed within said incubator along the circular path; and

agitating only the reaction receptacle engaged with said mixing mechanism to thereby agitate the contents of said reaction receptacle by moving the reaction receptacle on the receptacle carrier in a generally horizontal, reciprocating path of motion.

2. The method of claim 1, wherein said reaction receptacle is moved at a predetermined frequency for a predetermined period of time.

3. The method of claim 1, further comprising, before moving one of said reaction receptacles into the position at which it will engage with said mixing mechanism, determining if said mixing mechanism is in a predetermined position able to become engaged or disengaged with said reaction receptacle.

4. The method of claim 3, wherein said mixing mechanism includes a motorized shaft, and wherein said determining step is performed with a sensor comprising a pin extending radially with respect to said motorized shaft and an optical switch adapted to detect the periodic presence of said pin as the pin rotates about the axis of said motorized shaft.

5. The method of claim 1, further comprising the automated step of dispensing reaction materials into said reaction receptacle while said reaction receptacle is disposed within said incubator.

6. The method of claim 5, wherein said dispensing step comprises pipetting reaction materials into the reaction receptacle through a hole formed in said incubator.

7. The method of claim 5, further comprising the automated step of moving said reaction receptacle between a first location within said incubator at which said dispensing step is performed and a second location within said incubator at which said agitating step is performed.

8. The method of claim 1, wherein said receptacle carrier comprises a rotatable carousel located within said incubator.

9. The method of claim 5, wherein the reaction materials dispensed into said reaction receptacle include amplification reagents.

10. The method of claim 9, further comprising the step of performing an amplification procedure within said incubator after dispensing the amplification reagents into said reaction receptacle.

11. The method of claim 10, wherein the temperature within said incubator does not vary by more than about 0.1°

C. during the amplification procedure.

12. The method of claim 1, wherein:

said reaction receptacle includes a manipulating structure and said mixing mechanism includes a motorized shaft and a skewed disk attached to a portion of said shaft located within said incubator;

said step of moving one of said reaction receptacles into the position at which it will engage with said mixing mechanism comprises engaging said skewed disk with said manipulating structure; and

said agitating step comprises rotating said shaft and said skewed disk such that said skewed disk imparts a reciprocating motion to said reaction receptacle.

13. The method of claim 12, wherein said mixing mechanism further includes a damper operatively coupled to said motorized shaft.

14. The method of claim 13, wherein said damper comprises a viscous harmonic damper.

15. The method of claim 1, wherein the reaction receptacle is placed within said incubator through a receptacle access opening formed in said incubator, and wherein said incubator includes a closure mechanism constructed and arranged to be movable between a closed position preventing access to said incubator through said receptacle access opening and an open position permitting access to said incubator through said receptacle access opening.

16. The method of claim 1, further comprising the step of adjusting the temperature of the contents of said reaction receptacle to approximate the temperature of said incubator prior to placing said reaction receptacle into said incubator.

17. The method of claim 1, wherein said reaction receptacle comprises a plurality of integrally connected receptacle vessels.