Signal measuring system having a movable signal measuring device

• US 7,794,659 B2
• Filed: 03/10/2006
• Issued: 09/14/2010
• Est. Priority Date: 03/10/2005
• Status: Active Grant

• Current Assignee: Gen-Probe Incorporated (Hologic Incorporated)
• Original Assignee: Gen-Probe Incorporated (Hologic Incorporated)
• Inventors: Li, Haitao, Nguyen, Thanh N., Heinz, Robert E., Scalese, Robert F., Davis, Christopher B., Knight, Byron J., Macioszek, Jerzy A., Li, Florence F., Lair, Gary D.
• Primary Examiner(s): Warden; Jill
• Assistant Examiner(s): Sasaki; Shogo
• Application Number:
  US11/372,223
• Publication Number:
  US 20060210433A1
• Time in Patent Office: 1,649 Days
• Field of Search: 435/6, 435/287.2, 435/287.3, 435/288.7, 436/165, 422/52, 422 63- 67, 422 8205- 8211
• US Class Current: 422/82.05
• 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: C12Q 1/6813 Hybridisation assays
• CPC Class Codes: C12Q 1/6851 Quantitative amplification
• CPC Class Codes: C12Q 2537/165 Mathematical modelling, e.g. logarithm, ratio
• CPC Class Codes: G01N 2021/6419 Excitation at two or more wavelengths
• CPC Class Codes: G01N 2021/6421 Measuring at two or more wavelengths
• CPC Class Codes: G01N 2021/6432 Quenching
• CPC Class Codes: G01N 2021/6439 with indicators, stains, dyes, tags, labels, marks
• CPC Class Codes: G01N 2021/6441 with two or more labels
• CPC Class Codes: G01N 2035/00346 Heating or cooling arrangements
• 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 2035/0097 monitoring reactions as a function of time
• CPC Class Codes: G01N 2035/0441 for samples
• CPC Class Codes: G01N 2035/0443 for reagents
• CPC Class Codes: G01N 2035/0444 for cuvettes or reaction vessels
• CPC Class Codes: G01N 2035/0455 Coaxial carousels
• CPC Class Codes: G01N 2035/0491 Position sensing, encoding; closed-loop control
• CPC Class Codes: G01N 2035/103 using disposable tips
• CPC Class Codes: G01N 21/6428 Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes" in vivo A61B5/00; immunoassay G01N33/53
• CPC Class Codes: G01N 21/6454 : using an integrated detector array
• CPC Class Codes: G01N 21/76 : Chemiluminescence; Bioluminescence
• CPC Class Codes: G01N 2201/0415 : Carrusel, sequential
• CPC Class Codes: G01N 35/00693 : Calibration
• CPC Class Codes: G01N 35/0092 : Scheduling
• 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 35/026 : having blocks or racks of reaction cells or cuvettes
• CPC Class Codes: G01N 35/028 : having reaction cells in the form of microtitration plates
• CPC Class Codes: G01N 35/04 : Details of the conveyor system G01N35/021 - G01N35/028 take precedence
• CPC Class Codes: G01N 35/1002 : Reagent dispensers
• CPC Class Codes: Y10S 435/808 : Optical sensing apparatus
• CPC Class Codes: Y10S 435/809 : Incubators or racks or holders for culture plates or containers
• CPC Class Codes: Y10T 436/113332 : with conveyance of sample along a test line in a container or rack
• CPC Class Codes: Y10T 436/25 : including sample preparation

Abstract

An automated analyzer for performing multiple diagnostic assays simultaneously includes multiple stations in which discrete aspects of the assay are performed on fluid samples contained in reaction receptacles. The analyzer includes stations for automatically preparing a sample, incubating the sample, preforming an analyte isolation procedure, ascertaining the presence of a target analyte, and analyzing the amount of a target analyte. An automated receptacle transporting system moves the reaction receptacles from one station to the next. A method for performing an automated diagnostic assay includes an automated process for isolating and amplifying a target analyte, and, in one embodiment, a method for real-time monitoring of the amplification process.

Claims

1. An apparatus for measuring a signal emitted by the contents of each of a plurality of reaction receptacles comprising:

a moving reaction receptacle carrier including a plurality of reaction receptacle stations, each of said reaction receptacle stations adapted to carry two or more reaction receptacles;

a housing containing said reaction receptacles and said reaction receptacle carrier;

two or more signal measuring devices, each said signal measuring device is constructed and arranged to measure the amount of a different optical signal emitted by the contents of a reaction receptacle placed in operative proximity to each signal measuring device, each signal measuring device being positioned with respect to said reaction receptacle carrier such that reaction receptacles carried on said reaction receptacle carrier are successively moved into operative proximity to each signal measuring device as said reaction receptacle carrier moves the reaction receptacles; and

a signal measuring device transport mechanism located outside said housing and constructed and arranged to move said signal measuring devices with respect to said reaction receptacle carrier;

wherein at least a portion of each of said signal measuring devices is located outside said housing, and each said signal measuring device is configured to measure the amount of an optical signal emitted by the contents of a reaction receptacle through an opening formed in said housing;

wherein said reaction receptacle carrier is constructed and arranged to successively present said reaction receptacle stations in signal measuring positions in which one of the reaction receptacles carried in the reaction receptacle station is in operative proximity to one of said signal measuring devices, and said signal measuring device transport mechanism is constructed and arranged to move each said signal measuring device with respect to said reaction receptacle carrier to successively place each said signal measuring device into operative proximity to each of the reaction receptacles carried in the reaction receptacle station and moved into the signal measuring position corresponding to the signal measuring device.

2. The apparatus of claim 1, wherein each said signal measuring device is positioned below said reaction receptacle carrier.

3. The apparatus of claim 1 comprising four signal measuring devices.

4. The apparatus of claim 1, wherein each said signal measuring device comprises a fluorometer constructed and arranged to measure a fluorometric emission from the contents of a reaction receptacle, wherein each fluorometer measures a fluorometric emission having a different wavelength.

5. The apparatus of claim 4, wherein each fluorometer comprises:

an excitation component constructed and arranged to direct excitation energy at the reaction receptacle, wherein the excitation component of each fluorometer directs an excitation energy of a different wavelength at the reaction receptacle; and

a detection component constructed and arranged to detect the amount of emission energy from the contents of the reaction receptacle, wherein the detection component of each fluorometer detects emission energy of a different wavelength.

6. The apparatus of claim 1, wherein

(a) said reaction receptacle carrier comprises a generally circular carousel mounted so as to be rotatable about an axis of rotation with said reaction receptacle stations positioned around the periphery of said carousel, and each said reaction receptacle station comprising two or more reaction receptacles aligned in a radial orientation with respect to the axis of rotation of said carousel,

(b) rotation of said carousel successively presents said reaction receptacle stations in the signal measuring positions in which one of the radially-aligned reaction receptacles carried in said reaction receptacle station is in operative proximity to the signal measuring device corresponding to that signal measuring position, and

(c) said signal measuring device transport mechanism is constructed and arranged to move said signal measuring devices in generally radial directions with respect to the axis of rotation of said carousel to successively place said signal measuring device into operative proximity to each of the radially-aligned reaction receptacles carried in the reaction receptacle station moved into the signal measuring position.

7. The apparatus of claim 6, wherein said signal measuring device transport mechanism comprises:

a fixed plate oriented generally perpendicularly with respect to the axis of rotation of said carousel; and

a translating assembly operatively associated with each said signal measuring device, each translating assembly including a track mounted on said fixed plate in a generally radial orientation with respect to the axis of rotation of said carousel, each said signal measuring device being mounted on the associated translating assembly and movable along said track.

8. The apparatus of claim 7, further comprising a mounting bracket for mounting each said signal measuring device to said translating assembly, wherein each said translating assembly further includes a bearing element to which said mounting bracket is attached, said bearing element being constructed and arranged to translate along said track of said translating assembly.

9. The apparatus of claim 7, further comprising a sensor located at a predetermined position along each said track and constructed and arranged to detect the presence of said signal measuring device at said predetermined position along said track.

10. The apparatus of claim 7, said signal measuring device transport mechanism further comprising:

a cam disk rotatably mounted adjacent to said fixed plate, each said track of said translating assemblies being arranged generally radially with respect to an axis of rotation of said cam disk, said cam disk including a cam slot associated with each said translating assembly, each said cam slot being arranged on said cam disk so that the radial distance between said cam slot and the axis of rotation of said cam disk varies from one end of said cam slot to an opposite end of said cam slot;

a motor operatively coupled to said cam disk to effect powered rotation of said cam disk; and

an engagement pin operatively associated with each said signal measuring device and engaged with an associated cam slot such that powered rotation of said cam disk causes said engagement pin to traverse along said cam slot, thereby causing a change in radial position of the associated signal measuring device in accordance with the change in the radial distance between the axis of rotation of said cam disk and the portion of the associated cam slot with which the engagement pin is engaged.

11. The apparatus of claim 10, wherein each said cam slot includes positioning points along said cam slot, said positioning points being defined by each end of said cam slot and by one or more points along said cam slot at which the curvature of said cam slot changes, whereby when said engagement pin is engaged with said cam slot at a positioning point, said signal measurement device is positioned in operative proximity to one of the reaction receptacles carried in the reaction receptacle station.

12. The apparatus of claim 10 comprising four signal measuring devices, four translating assemblies, and four cam slots.

13. The apparatus of claim 1, wherein a portion of each said signal measuring device extends into said housing.