Ensuring sample adequacy using turbidity light scattering techniques

• US 8,877,507 B2
• Filed: 10/09/2009
• Issued: 11/04/2014
• Est. Priority Date: 04/06/2007
• Status: Active Grant

• Current Assignee: Electrolux Home Care Products Incorporated (AB Electrolux), Becton, Dickinson & Co
• Original Assignee: QIAGEN Gaithersburg, Inc. (Qiagen NV)
• Inventors: Xia, Jiulin, Mantefuel, Richard L., Edens, Carl Theodore, Miller, Jonathan Matthew, Allen, Nadia P.
• Primary Examiner(s): Gakh, Yelena G
• Assistant Examiner(s): Adams, Michelle
• Application Number:
  US12/588,305
• Publication Number:
  US 20100205139A1
• Time in Patent Office: 1,852 Days
• Field of Search: None
• US Class Current: 436/43
• CPC Class Codes: B01L 2200/025 Align devices or objects to ensure defined positions relative to each other
• CPC Class Codes: B01L 2300/0829 Multi-well plates; Microtitration plates
• CPC Class Codes: B01L 9/06 Test-tube stands; Test-tube holders
• CPC Class Codes: G01N 15/075 by optical means
• CPC Class Codes: G01N 2035/00524 Mixing by agitating sample carrier
• CPC Class Codes: G01N 2035/00534 Mixing by a special element, e.g. stirrer
• CPC Class Codes: G01N 21/51 inside a container, e.g. in an ampoule G01N21/53 takes precedence
• CPC Class Codes: G01N 35/00594 Quality control, including calibration or testing of components of the analyser
• CPC Class Codes: G01N 35/0099 comprising robots or similar manipulators robots per se B25J
• CPC Class Codes: Y10T 436/11 Automated chemical analysis

Abstract

An automated method for assuring sample adequacy. The method includes providing a sample in a testing container, activating an illumination source to pass an illumination beam through the testing container and into the sample, and detecting an intensity of an emitted beam. The emitted beam includes at least a portion of the illumination beam that has been scattered by the sample. The method also includes generating a sample turbidity measurement based on the intensity of the emitted beam, and determining, based on the sample turbidity measurement, an adequacy of the sample to provide accurate results in a primary test.

Claims

1. An automated method for assuring sample adequacy, the method comprising:

providing a sample in a testing container;

activating an illumination source to pass an illumination beam through the testing container and into the sample, wherein the illumination beam travels upwards in a vertical direction as it passes through the testing container;

detecting an intensity of an emitted beam, the emitted beam comprising at least a portion of the illumination beam that has been scattered by the sample;

generating a reference beam by transmitting a portion of the illumination beam that is between the illumination source and the testing container along a reference beam path located below and outside the testing container;

measuring an intensity of the reference beam using a reference detector;

generating a sample turbidity measurement based on the intensity of the emitted beam; and

determining, based on the sample turbidity measurement, an adequacy of the sample to provide accurate results in a primary test of the sample;

conducting the primary test of the sample to obtain a primary test result;

evaluating the primary test result to determine whether the primary test result is a negative primary test result; and

reporting the negative primary test result only if the sample was determined to be adequate to provide accurate results in the primary test of the sample;

wherein the testing container is one of a plurality of testing containers in a tube unit, the tube unit comprising a frame extending horizontally along a longitudinal axis with the plurality of testing containers connected to the frame and arranged in a line along the longitudinal axis, and wherein each one of the plurality of testing containers extends downward in the vertical direction below the frame; and

wherein the emitted beam is detected by a sample detector positioned along a vertical extent of the testing container, wherein the sample detector is positioned at the end of an emitted beam path, and wherein the emitted beam path extends in a plane that is perpendicular to the vertical direction and is oriented at a non-perpendicular angle with respect to the longitudinal axis, to thereby reduce the likelihood that the emitted beam will pass through a scratched portion of the testing container.

2. The automated method for assuring sample adequacy of claim 1, wherein determining the adequacy of the sample comprises comparing the sample turbidity measurement with one or more predetermined criteria.

3. The automated method for assuring sample adequacy of claim 1, wherein the sample turbidity measurement correlates to the number of proteins, nucleic acids, cells or viruses in the sample.

4. The automated method for assuring sample adequacy of claim 1, wherein the sample turbidity measurement comprises an estimation of a number of cells in the sample, and determining the adequacy of the sample comprises comparing the estimation of the number of cells in the sample to a minimum number of cells.

5. The automated method for assuring sample adequacy of claim 1, further comprising storing one or more sample adequacy results and analyzing the one or more stored sample adequacy results to identify at least one of;

sample gathering errors, sample handling errors, sample processing errors, sample adequacy measurement errors, sample adequacy measurement calibration requirements, or a combination of the preceding.

6. The automated method for assuring sample adequacy of claim 1, further comprising providing an indicator of the adequacy of the sample to an operator.

7. The automated method for assuring sample adequacy of claim 6, further comprising allowing a decision maker to determine whether an inadequate sample should be tested if the sample was determined not to be adequate.

8. The automated method for assuring sample adequacy of claim 1, wherein conducting the primary test is performed after determining the adequacy of the sample.

9. The automated method for assuring sample adequacy of claim 1, wherein the sample comprises a human cervical sample and the primary test is a Human Papillomavirus screening test.

10. The automated method for assuring sample adequacy of claim 1, further comprising controlling the illumination source to regulate an intensity of the illumination beam based on the intensity of the reference beam.

11. The automated method for assuring sample adequacy of claim 1, further comprising using the reference beam to determine whether an intensity of the illumination beam is within an acceptable intensity range.

12. The automated method for assuring sample adequacy of claim 1, further comprising homogenizing the sample prior to or while detecting the intensity of the emitted beam.

13. The automated method for assuring sample adequacy of claim 12, wherein homogenizing the sample comprises mixing the sample using an orbital agitator, a linear agitator, a mixer comprising a paddle, a robotic arm that moves the testing container in a fashion that homogenizes the sample, aspiration by a pipettor, or dispensing by a pipettor.

14. The automated method for assuring sample adequacy of claim 1, wherein the illumination beam comprises monochromatic light.

15. The automated method for assuring sample adequacy of claim 1, wherein the emitted beam passes through a protected portion of the testing container.

16. The automated method for assuring sample adequacy of claim 15, wherein the testing container comprises a cylindrical tube, the illumination beam passes through an end of the cylindrical tube, and the emitted beam passes through a side of the cylindrical tube.

17. The automated method for assuring sample adequacy of claim 1, wherein detecting the intensity of the emitted beam comprises measuring the emitted beam at multiple detector angles and algorithmically combining the measurements at multiple detector angles to yield a single turbidity reading.