Automatic device for dispensing samples in liquid medium for use in chemical or biological reactions

• US 6,893,611 B1
• Filed: 03/19/1999
• Issued: 05/17/2005
• Est. Priority Date: 03/20/1998
• Status: Expired due to Fees

• Current Assignee: Fondation Jean Dausset
• Original Assignee: Fondation Jean Dausset-Ceph
• Inventors: Cohen, Patrick, Victor, Jean-Marc, Thomas, Gilles
• Primary Examiner(s): SNAY, JEFFREY R
• Application Number:
  US09/646,668
• Time in Patent Office: 2,251 Days
• Field of Search: 422/100, 422 62- 67, 436/180, 436/43, 141/237, 738/633.2, 738/64, 738/640.1, 738/641.1, 738/642.4, 738/642.5, 435/287.3
• US Class Current: 422/63
• CPC Class Codes: B01L 3/0268 using pulse dispensing or spraying, eg. inkjet type, piezo actuated ejection of droplets from capillaries
• CPC Class Codes: G01N 2035/00237 Handling microquantities of analyte, e.g. microvalves, capillary networks

Abstract

An automatic device for dispensing samples in liquid medium for use in chemical or biological reactions, including a first supply plate with N receptacles, a second supply plate with M receptacles, a removable plate for sample and a piezoelectric micropipette.

Claims

1. An automatic device for producing a plurality of reaction samples in liquid medium, wherein said device comprises:

a first supply plate, comprising N receptacles each intended to contain a first constituent, wherein said plate is a removable microplate;

a second supply plate, comprising M receptacles each intended to contain a second constituent, wherein said plate is a removable microplate;

a removable plate for samples, comprising a plurality of cavities arranged in the form of an array comprising at least N rows and at least M columns, wherein each cavity is configured to hold a volume on the order of at least ten nanoliters, wherein said cavities are intended to contain a mixture of constituents originating from said first and second supply plates;

a piezoelectric micropipette, wherein said micropipette is able to sample a predetermined amount of said first and/or second constituents and to deliver a volume on the order of a nanoliter, wherein said piezoelectric micropipette is capable of delivering at least one drop of said first and/or second constituents into each cavity of said removable plate for samples;

a means for displacing said piezoelectric micropipette along at least two perpendicular axes Y, Z so that said piezoelectric micropipette can sample a predetermined amount of said first and/or second constituents from each filled receptacle of said first and second supply plates; and

a means for relatively displacing the piezoelectric micropipette and the removable plate for samples.

2. The device of claim 1, further comprising a stepper or DC motor, wherein said stepper or DC motor is configured to advance said piezoelectric micropipette relative to said removable plate for samples.

3. The device according to claim 1, wherein said piezoelectric micropipette is able to count the number of drops said micropipette delivers and to deliver a predetermined number of drops.

4. The device according to claim 1, further comprising a refrigeration tray supporting said removable plate for samples.

5. The device according to claim 1, further comprising at least one optical system, wherein said optical system is in line with said removable plate for samples, and is configured to count the number of drops delivered with each discharge of said piezoelectric micropipette, and to transmit this number to a coordination device, and wherein the coordination device is configured to send an order for a second pass in line with a cavity or several cavities to the micropipette when a discrepancy is noted between the counted number of drops discharged and the designated theoretical number of drops.

6. The device according to claim 1, further comprising a second piezoelectric micropipette, wherein said second piezoelectric micropipette is identical to said piezoelectric micropipette and both said piezoelectric micropipette and said second piezoelectric micropipette are configured to operate alternately.

7. The device according to claim 1, further comprising an automatic washing station for said piezoelectric micropipette, wherein each washing station is configured to decontaminate said piezoelectric micropipette.

8. The device according to claim 7, wherein said washing station comprises a means for filling said piezoelectric micropipette with a water-immiscible carrier liquid and an optical means for verifying the proper filling of said piezoelectric micropipette.

9. The device according to claim 1, wherein said piezoelectric micropipette comprises two conducting parts separated by a nonconducting material, which are linked at the upper part to an electrical system, so that when the orifice of the piezoelectric micropipette comes into contact with a constituent of a receptacle of the first or of the second supply plate, it brings about closure of the electrical circuit formed by the two electrically linked conducting parts of said piezoelectric micropipette, which commands the stoppage of the vertical displacement of said piezoelectric micropipette.

10. The device according to claim 1, further comprising an automatic means for fitting a seal on said sample plate.

11. The device according to claim 1, further comprising an automatic system configured to remove and fit a cover on said first and second supply plates as well as on a filled sample plate.

12. The device according to claim 1, wherein said first and second supply plates are disposed along the X axis on either side of said removable plate for samples, wherein said plates are configured to be carried together by a movable bench along said X axis.

13. The device according to claim 1, wherein the arrays of said cavities of said removable plate for samples is a square array with N equal to M.

14. The device according to claim 13, wherein said arrays have a width of around 5 cm, and comprise 100 columns and 100 rows with cavities of width (d₁) equal to around 400 μ

m and of depth equal to around 400-500 μ

m, two successive cavities in one row being spaced apart by a distance (d₂) equal to around 150 μ

m.

15. The device according to claim 1, further comprising vessels, wherein said vessels comprise different constituents disposed in proximity to said removable plate for samples.

16. The device of claim 1, further comprising a stepper or DC motor, wherein said stepper or DC motor is configured to advance said removable plate for samples relative to said piezoelectric micropipette.

17. The device of claim 1, further comprising means for triggering discharge of the micropipette in such a way that the micropipette is able to deliver at least one drop of constituent into each cavity of the sample plate.

18. An automatic device for producing a plurality of reaction samples in liquid medium, wherein said device comprises:

a first supply plate, comprising N receptacles each intended to contain a first constituent, wherein said plate is a removable microplate;

a second supply plate, comprising M receptacles each intended to contain a second constituent, wherein said plate is a removable microplate;

a removable plate for samples, comprising a plurality of cavities arranged in the form of an array comprising at least N rows and at least M columns, wherein each cavity is configured to hold a volume on the order of at least ten nanoliters, wherein said cavities are intended to contain a mixture of constituents originating from said first and second supply plates;

a piezoelectric micropipette, wherein said micropipette is able to sample a predetermined amount of said first and/or second constituents and to deliver a volume on the order of a nanoliter, wherein said piezoelectric micropipette is capable of delivering at least one drop of said first and/or second constituents into each cavity of said removable plate for samples;

a means for displacing said piezoelectric micropipette along at least two perpendicular axes Y, Z so that said piezoelectric micropipette can sample a predetermined amount of said first and/or second constituents from each filled receptacle of said first and second supply plates;

a means for displacing the piezoelectric micropipette relative to the removable plate for samples; and

a refrigeration tray supporting said removable plate for samples.

19. An automatic device for producing a plurality of reaction samples in liquid medium, wherein said device comprises:

a first supply plate, comprising N receptacles each intended to contain a first constituent, wherein said plate is a removable microplate;

a second supply plate, comprising M receptacles each intended to contain a second constituent, wherein said plate is a removable microplate;

a removable plate for samples, comprising a plurality of cavities arranged in the form of an array comprising at least N rows and at least M columns, wherein each cavity is configured to hold a volume on the order of at least ten nanoliters, wherein said cavities are intended to contain a mixture of constituents originating from said first and second supply plates;

a piezoelectric micropipette, wherein said micropipette is able to sample a predetermined amount of said first and/or second constituents and to deliver a volume on the order of a nanoliter, wherein said piezoelectric micropipette is capable of delivering at least one drop of said first and/or second constituents into each cavity of said removable plate for samples;

a means for displacing said piezoelectric micropipette along at least two perpendicular axes Y, Z so that said piezoelectric micropipette can sample a predetermined amount of said first and/or second constituents from each filled receptacle of said first and second supply plates;

a means for displacing the piezoelectric micropipette relative to the removable plate for samples; and

at least one optical system, wherein said optical system is in line with said sample plate and is configured to count the number of drops delivered with each discharge of said piezoelectric micropipette, and to transmit this number to a coordination device, and wherein the coordination device is configured to send an order for a second pass in line with a cavity or several cavities to the micropipette when a discrepancy is noted between the counted number of drops discharged and the designated theoretical number of drops.

20. An automatic device for producing a plurality of reaction samples in liquid medium, wherein said device comprises:

a first supply plate, comprising N receptacles each intended to contain a first constituent, wherein said plate is a removable microplate;

a second supply plate, comprising M receptacles each intended to contain a second constituent, wherein said plate is a removable microplate;

a removable plate for samples, comprising a plurality of cavities arranged in the form of an array comprising at least N rows and at least M columns, wherein each cavity is configured to hold a volume on the order of at least ten nanoliters, wherein said cavities are intended to contain a mixture of constituents originating from said first and second supply plates;

a piezoelectric micropipette, wherein said micropipette is able to sample a predetermined amount of said first and/or second constituents and to deliver a volume on the order of a nanoliter, wherein said piezoelectric micropipette is capable of delivering at least one drop of said first and/or second constituents into each cavity of said removable plate for samples;

a means for displacing said piezoelectric micropipette along at least two perpendicular axes Y, Z so that said piezoelectric micropipette can sample a predetermined amount of said first and/or second constituents from each filled receptacle of said first and second supply plates; and

a means for displacing the piezoelectric micropipette relative to the removable plate for samples; and

an automatic washing station for each piezoelectric micropipette, wherein said washing station is configured to decontaminate said piezoelectric micropipette.