Apparatus and method for testing and continuously reading low-volume samples

• US 20040071599A1
• Filed: 03/21/2003
• Published: 04/15/2004
• Est. Priority Date: 03/22/2002
• Status: Active Grant

• Current Assignee: Marshfield Clinic Research Foundation, UT-Battelle LLC
• Original Assignee: Marshfield Clinic Research Foundation
• Inventors: Doktycz, Mitchel J., Weber, James L., Che, Jianhong, Fieweger, Kim M., Rusch, Terry L., Chudyk, Jon P., Hicks, J. Steven
• Granted Patent: US 7,232,547 B2
• Time in Patent Office: Days
• US Class Current: 422/99
• CPC Class Codes: B01L 2300/021 Identification, e.g. bar codes
• CPC Class Codes: B01L 2300/0812 Bands; Tapes
• CPC Class Codes: B01L 3/5085 for multiple samples, e.g. microtitration plates
• CPC Class Codes: G01N 35/00009 provided with a sample supporting tape, e.g. with absorbent zones
• CPC Class Codes: Y10T 436/143333 Saccharide [e.g., DNA, etc.]
• CPC Class Codes: Y10T 436/2575 Volumetric liquid transfer

Abstract

The present invention is directed to a well sampling tape (otherwise known as “microwell tape” or simply “tape”), a dispenser for dispensing small volumes of liquid into the wells formed in the tape and a detector for high-throughput sample reading of the liquid dispensed in the individual wells. The present invention is more specifically directed to a bioassay system incorporating the materials listed above.

Claims

1. A well sampling tape having a continuous length and containing a plurality of wells, the tape having at least one edge defined by a continuous row of indexing perforations.

2. The well sampling tape of claim 1 wherein each well of the plurality of wells comprises a base, a conically-shaped wall and an outer opening, wherein the base has a substantially planar shape, and wherein further the diameter of the base is less than the diameter of the opening.

3. The well sampling tape of claim 1 wherein each well of the plurality of wells has a volume ranging from 1 nanoliter to 1000 nanoliters.

4. The well sampling tape of claim 1 wherein each well of the plurality of wells has a volume ranging from 25 nanoliters to about 800 nanoliters.

5. A sample characterization system utilizing a microwell tape for analysis of samples, the microwell tape having a continuous length and containing a plurality of wells, the tape having at least one lateral edge defined by a continuous row of indexing perforations, the system comprising:

a. a drive mechanism adapted to automatically advance the microwell tape;

b. at least one dispenser for dispensing reagents into the wells of the microwell tape; and

c. sealing means for sealing the wells of the microwell tape.

6. The system of claim 5 further comprising a thermocycler.

7. The system of claim 5 further comprising a detector for analyzing the contents of the wells of the microwell tape, wherein the detector comprises means to advance the microwell tape through the detector.

8. The system of claim 5 further comprising an identification station for identifying each sample.

9. The system of claim 8 wherein the identification station is a bar code station.

10. The system of claim 5 wherein the microwell tape comprises a plurality of wells wherein each well has a sample volume ranging from 1 nanoliter to 1000 nanoliters.

11. The system of claim 5 wherein the microwell tape comprises a plurality of wells wherein each well has a sample volume no greater than about 500 nanoliters.

12. The system of claim 5 wherein the microwell tape comprises a plurality of wells wherein each well has a sample volume no greater than about 50 nanoliters.

13. The system of claim 5 wherein the dispenser comprises units consisting of the following:

an array of positive displacement heads for depositing sample aliquots in the wells of the microwell tape for analysis, a pin transfer system and a solenoid valve.

14. A system for automatically analyzing a large number of small-volume samples, comprising:

a. a microwell tape having a continuous length and containing a plurality of wells, the tape having first and second lateral edges defined by a continuous row of indexing perforations;

b. a drive mechanism adapted to move the microwell tape through the system;

c. a pipetter for transferring samples to the wells of the microwell tape. d. a dispenser for transferring a reagent to the well of the microwell tape;

e. sealing means for sealing the wells of the microwell tape;

f. a thermocycler; and

g. a detector for analyzing the contents of wells of the microwell tape.

15. The system of claim 14 wherein the drive mechanism comprises a pinned drive belt, the pinned drive belt being driven by a motor, wherein the pinned drive belt has pins regularly spaced along its length and wherein the pins are dimensioned and configured to matingly engage the indexing perforations of the microwell tape.

16. The system of claim 14 wherein the pipetter comprises a pin array comprising a plurality of pins, wherein the pipetter is further affixed to a transom such that the pipetter can move in an indexed manner to transfer samples to the microwell tape.

17. The system of claim 14 wherein the pipetter is a positive displacement pipetter.

18. The system of claim 14 wherein the pipetter is a passive displacement pipetter comprising a passive transfer pin array.

19. The system of claim 14 wherein the sealing means comprises sealing tape.

20. The system of claim 19 wherein the sealer tape is stored on a storage reel.

21. The system of claim 20 wherein the sealer tape is clear for reagent viewing or detecting.

22. The system of claim 14 wherein the sealing means comprises:

a. an indexing drum having cavities dimensioned to register with the wells of the microwell tape;

b. a wrap bar to position the sealing tape; and

c. a heat drum heated by a heating element to seal the sealing tape to the microwell tape.

23. The system of claim 14 wherein the dispenser comprises a solenoid valve adapted to dispense submicroliter volumes of reagents, wherein the dispenser is affixed to a transom for moving the dispenser in an indexed manner to transfer samples to the microwell tape.

24. The system of claim 14 wherein the sealing means comprises an indexing drum, a heat drum and sealer tape, wherein the heat drum is under tension and juxtaposed to the indexing drum and wherein the indexing drum has a plurality of cavities in register and dimensioned and configured to reflect profiles of the wells of the microwell tape.

25. The system of claim 14 wherein the detector comprises a detector head affixed to a transom such that the detector head is indexed to the microwell tape such that the detector head passes over the microwell tape.

26. The system of claim 14 adapted for use in detecting short tandem repeat polymorphisms (STRPs), SNPs and diallelic short insertion/deletion (indel) polymorphisms.

27. A drive mechanism for moving a continuous tape having indexing perforations, the mechanism comprising:

a. a motor;

b. a forward and rear belt drum, wherein one of the drums is engaged to the motor; and

c. at least one belt movably affixed to the forward and rear belt drum, the belt including a series of pins adapted to engage indexing perforations of the tape.

28. The drive mechanism of claim 27 further comprising at least one guide rail to position the belt on the forward and rear belt drum.

29. The drive mechanism of claim 27 further comprising a pinned belt drive to matingly engage with the indexing perforations of the microwell tape.