SAMPLE PROCESSING APPARATUS AND METHODS

• US 20140113278A1
• Filed: 10/22/2012
• Published: 04/24/2014
• Est. Priority Date: 10/22/2012
• Status: Active Grant

• Current Assignee: QIAGEN Gaithersburg, Inc. (Qiagen NV)
• Original Assignee: QIAGEN Gaithersburg, Inc. (Qiagen NV)
• Inventors: THOMAS, BRADLEY SCOTT, CUI, BOWEN, EDENS, CARL THEODORE, LEONARD, ANDREW, JUNGHEIM, BERT, RAMACHANDRAN, SUGANTHI, TROXEL, JASON
• Granted Patent: US 9,260,763 B2
• Time in Patent Office: Days
• US Class Current: 435/5
• CPC Class Codes: B01L 2200/142 Preventing evaporation
• CPC Class Codes: B01L 2300/047 Additional chamber, reservoir
• CPC Class Codes: B01L 2300/0829 Multi-well plates; Microtitration plates
• CPC Class Codes: B01L 3/5021 Test tubes specially adapted for centrifugation purposes centrifuges B04B5/04
• CPC Class Codes: B01L 3/50853 with covers or lids
• CPC Class Codes: B01L 3/50855 using modular assemblies of strips or of individual wells
• CPC Class Codes: B01L 9/06 Test-tube stands; Test-tube holders
• CPC Class Codes: C12Q 1/70 involving virus or bacteriophage immunoassay for viruses G01N33/56983
• CPC Class Codes: G01N 1/34 Purifying; Cleaning processes or apparatus for extracting or separating nucleic acids from biological samples C12N15/1003
• CPC Class Codes: G01N 1/38 Diluting, dispersing or mixing samples
• CPC Class Codes: G01N 1/44 Sample treatment involving radiation, e.g. heat
• CPC Class Codes: G01N 2035/00495 Centrifuges
• CPC Class Codes: G01N 2035/00524 Mixing by agitating sample carrier
• CPC Class Codes: G01N 2035/0412 Block or rack elements with a single row of samples
• CPC Class Codes: G01N 2035/0418 Plate elements with several rows of samples
• CPC Class Codes: G01N 2333/025 Papovaviridae, e.g. papillomavirus, polyomavirus, SV40, BK virus, JC virus
• CPC Class Codes: G01N 35/0099 comprising robots or similar manipulators robots per se B25J
• CPC Class Codes: G01N 35/026 having blocks or racks of reaction cells or cuvettes
• CPC Class Codes: Y10T 436/25375 Liberation or purification of sample or separation of material from a sample [e.g., filtering, centrifuging, etc.]

Abstract

An automated process for converting samples includes: receiving tube strips having a number of sample tubes and samples therein, transferring multiple tube strips to a tube strip holder, dispensing sample conversion buffer into each tube, shaking the tube strip holder a first time, centrifuging the tube strip holder, removing a liquid supernatant from each tube, simultaneously inspecting the contents of each tube, dispensing a specimen transport medium and a denaturation reagent into each tube, shaking the tube strip holder a second time, heating the tube strip holder for a first length of time, shaking the tube strip holder a third time, heating the tube strip holder for a second length of time, shaking the tube strip holder a fourth time, and transferring at least a portion of each sample to a respective well on an output plate.

Claims

1. An automated process for converting biological samples into an output format suitable for further analysis, the process comprising:

receiving a plurality of tube strips in one or more tube strip racks, each tube strip having a plurality of sample tubes with a respective sample in each tube;

transferring a group of tube strips from the one or more tube strip racks to a tube strip holder, the tube strip holder having plurality of wells configured to each hold at least one tube strip;

dispensing a sample conversion buffer into each sample tube in the group of tube strips;

shaking the tube strip holder a first time to simultaneously mix the contents of each sample tube in the tube strip holder;

centrifuging the tube strip holder to simultaneously centrifuge the contents of each sample tube in the tube strip holder;

removing a liquid supernatant from each sample tube in the tube strip holder;

moving the tube strip holder to an inspection station;

simultaneously inspecting the contents of each tube in the tube strip holder to determine whether a pellet has formed in each tube in the tube strip holder;

dispensing a specimen transport medium and a denaturation reagent into each tube in the tube strip holder;

shaking the tube strip holder a second time to simultaneously mix the contents of each sample tube in the tube strip holder;

heating the tube strip holder for a first length of time to simultaneously incubate the contents of each sample tube in the tube strip holder;

shaking the tube strip holder a third time to simultaneously mix the contents of each sample tube in the tube strip holder;

heating the tube strip holder for a second length of time to simultaneously incubate the contents of each sample tube in the tube strip holder;

shaking the tube strip holder a fourth time to simultaneously mix the contents of each sample tube in the tube strip holder; and

transferring at least a portion of each sample to a respective well on an output plate.

2. The automated process of claim 1, wherein the sample comprises a cervical sample and the portion of each sample transferred to a respective well on the output plate is converted for further analysis to determine the presence of human papillomavirus.

3. The automated process of claim 1, further comprising:

receiving a plurality of individual sample vials in a sample vial rack, each sample vial having a respective specimen therein; and

wherein the respective sample in each tube is provided by transferring an aliquot of each specimen to a respective tube.

4. The automated process of claim 3, wherein the aliquot comprises a 4 milliliter aliquot.

5. The automated process of claim 1, further comprising providing the tube strip holder and the output plate on a sliding plate rack for simultaneous installation or removal.

6. The automated process of claim 1, wherein the sample conversion buffer dispensed into each sample tube comprises 400 microliters of sample conversion buffer.

7. The automated process of claim 1, wherein the sample conversion buffer is dispensed into each sample tube before or after transferring the group of tube strips to the tube strip holder.

8. The automated process of claim 1, wherein shaking the tube strip holder a first time comprises shaking the tube strip holder for 30 seconds at 800 rpm on a 3 millimeter orbit.

9. The automated process of claim 1, wherein centrifuging the tube strip holder comprises centrifuging the tube strip holder for 15 minutes at 2,900 gravities.

10. The automated process of claim 1, further comprising simultaneously inspecting the contents of each tube in the tube strip holder, after centrifuging and before removing the liquid supernatant, to determine whether a pellet has formed in each tube.

11. The automated process of claim 1, wherein removing the liquid supernatant comprises:

separately removing each tube strip from the tube strip holder;

rotating each removed tube strip from a vertical orientation to a rotated orientation to decant the liquid supernatant;

returning each removed tube strip to the vertical orientation; and

returning each tube strip to the tube strip holder.

12. The automated process of claim 11, wherein rotating each removed tube strip to decant the liquid supernatant comprises one of:

rotating the removed tube strip in a first direction from the vertical orientation to a rotated orientation of 150°

from the vertical orientation, holding the removed tube strip at 150°

for one second, and rotating the removed tube strip opposite the first direction to return the removed tube strip to the vertical orientation;

or

rotating the removed tube strip in a first direction from the vertical orientation to a rotated orientation of 210°

from the vertical orientation, holding the removed tube strip at 210°

for 0.5 to 1 second, and continuing to rotate the removed tube strip in the first direction to return the removed tube strip to the vertical orientation.

13. The automated process of claim 11, further comprising blotting each removed tube strip on an absorbent material before returning each removed tube strip to the vertical orientation.

14. The automated process of claim 1, wherein the specimen transport medium comprises 100 microliters of specimen transport medium

15. The automated process of claim 1, wherein the denaturation reagent comprises 50 microliters of denaturation reagent.

16. The automated process of claim 1, further comprising sealing each tube in the tube strip holder before shaking the tube strip holder a second time or heating the tube strip holder for a first length of time.

17. The automated process of claim 16, wherein sealing each tube comprises covering each tube in the tube strip holder with a single cover having an individual seal for each tube in the tube strip holder.

18. The automated process of claim 1, wherein shaking the tube strip holder a second time comprises shaking the tube strip holder for 2 minutes at 1250 rpm on a 3 millimeter orbit at room temperature.

19. The automated process of claim 1, wherein heating the tube strip holder for a first length of time comprises heating the tube strip holder at 65°

Celsius.

20. The automated process of claim 19, wherein the first length of time is 15 minutes.

21. The automated process of claim 1, wherein shaking the tube strip holder a third time comprises shaking the tube strip holder for 30 seconds at 1250 rpm on a 3 millimeter orbit.

22. The automated process of claim 1, wherein shaking the tube strip holder a third time comprises simultaneously heating the tube strip holder and shaking the tube strip holder.

23. The automated process of claim 22, wherein the simultaneous heating is at 65°

Celsius.

24. The automated process of claim 1, wherein heating the tube strip holder for a second length of time comprises heating the tube strip holder at 65°

Celsius.

25. The automated process of claim 24, wherein the second length of time is 30 minutes.

26. The automated process of claim 1, wherein shaking the tube strip holder a fourth time comprises shaking the tube strip holder for 10 seconds at 1250 rpm on a 3 millimeter orbit.

27. The automated process of claim 1, wherein shaking the tube strip holder a fourth time comprises simultaneously heating the tube strip holder and shaking the tube strip holder.

28. The automated process of claim 27, wherein the simultaneous heating is at 65°

Celsius.

29. The automated process of claim 1, wherein transferring at least a portion of each sample to a respective well on an output plate comprises transferring a 75 microliter portion.

30. The automated process of claim 1, wherein the tube strip holder has one separate well for each tube strip.