Assay apparatuses, methods and reagents

• US 20070231217A1
• Filed: 12/21/2006
• Published: 10/04/2007
• Est. Priority Date: 12/21/2005
• Status: Active Grant

• Current Assignee: Meso Scale Technologies, LLC
• Original Assignee: Meso Scale Technologies, LLC
• Inventors: Jeffrey-Coker, Bandele, Glezer, Eli, Clinton, Charles, Stevens, Carl, Sigal, George, Kumar, Sudeep, Vock, Michael, Kovacs, Sandor
• Granted Patent: US 10,302,649 B2
• Time in Patent Office: Days
• US Class Current: 422/119
• CPC Class Codes: B01L 3/50255 Multi-well filtration
• CPC Class Codes: B01L 3/5085 for multiple samples, e.g. microtitration plates
• CPC Class Codes: B67B 7/24 Hole-piercing devices
• CPC Class Codes: G01N 2035/0405 manipulating closing or opening means, e.g. stoppers, screw caps, lids or covers
• CPC Class Codes: G01N 2035/0425 Stacks, magazines or elevators for plates
• CPC Class Codes: G01N 2035/1025 Fluid level sensing
• CPC Class Codes: G01N 21/6452 Individual samples arranged in a regular 2D-array, e.g. multiwell plates
• CPC Class Codes: G01N 21/66 electrically excited, e.g. electroluminescence
• CPC Class Codes: G01N 33/5302 Apparatus specially adapted for immunological test procedures
• CPC Class Codes: G01N 33/582 with fluorescent label
• CPC Class Codes: G01N 35/028 having reaction cells in the form of microtitration plates
• CPC Class Codes: G01N 35/1002 Reagent dispensers
• CPC Class Codes: G01N 35/1011 Control of the position or alignment of the transfer device
• CPC Class Codes: G01N 35/1079 with means for piercing stoppers or septums
• CPC Class Codes: G01N 35/1081 characterised by the means for relatively moving the transfer device and the containers in an horizontal plane G01N35/1011 takes precedence
• CPC Class Codes: G01N 35/109 with two horizontal degrees of freedom
• CPC Class Codes: Y10T 83/9314 Pointed perforators

Abstract

We describe apparatuses, systems, method, reagents, and kits for conducting assays as well as process for their preparation. They are particularly well suited for conducting automated sampling, sample preparation, and analysis in a multi-well plate assay format. For example, they may be used for automated analysis of particulates in air and/or liquid samples derived therefrom in environmental monitoring.

Claims

1. An apparatus for measuring a signal from wells of sealed multi-well assay plates, the apparatus comprising:

(a) a seal removal tool for removing seals from wells of said multi-well plates and

(b) a detection system for measuring said signal from wells of said multi-well plate.

2. The apparatus of claim 1, wherein said seal removal tool comprises a piercing probe with a seal piercing tip.

3. The apparatus of claim 2, wherein said piercing probe comprises:

a piercing section with external surfaces that taper to a vertex so as to form said piercing tip at one end of a piercing direction and

a seal displacement section, arranged adjacent to said piercing section along said piercing direction, with a cross-sectional shape, perpendicular to said piercing direction, that substantially conforms to, but is undersized relative to, the well openings of said individual wells.

4. The apparatus of claim 3, wherein said cross-sectional shape is a circle.

5. The apparatus of claim 3, wherein said cross-sectional shape is a square or a rounded square.

6. The apparatus of claim 3, wherein said piercing section is pyramidal.

7. The apparatus of claim 3, wherein said piercing section is conical.

8. The apparatus of claim 3, wherein said piercing section has exposed edges that extend in a radial direction from said tip.

9. The apparatus of claim 3, wherein said piercing probe is spring loaded such that the maximal downward force, along said piercing direction, of the piston on a plate seal is defined by the spring constant of a spring.

10. The apparatus of claim 3, wherein said piercing probe further comprises a plate stop section adjacent to said seal displacement section that defines the maximum distance of travel of said piercing probe into said wells.

11. The apparatus of claim 3 further comprising a pipetting probe.

12. The apparatus of claim 11, wherein

said piercing probe has a through-hole parallel to said piercing direction and off-set from said piercing tip and

said pipetting probe is movably located in said through-hole such that it can be withdrawn into said piercing probe during seal removal operations and extended from said piercing probe during pipetting operations.

13. The apparatus of claim 12, wherein movement of said piercing probe and pipetting probe are controlled independently.

14. The apparatus of claim 12, wherein

said piercing probe further comprises a plate stop section adjacent to said seal displacement section that defines the maximum distance of travel of said piercing probe into said wells and

said pipetting probe is coupled to said piercing probe by a spring with a spring constant chosen such that

(i) when fully withdrawn from said well, said pipetting probe does not extend from said piercing probe,

(ii) translation of said pipetting probe toward a well results in the cotranslation of said piercing probe and allows for the delivery of sufficient force to remove a seal on said well, and

(iii) continued translation past the maximal distance of travel of said piercing probe results in compression of the spring and extension of said pipetting probe from said piercing probe into said well.

15. The apparatus of claim 1, wherein said seal removal tool is selected from the group consisting of a coring tool, a peeling tool and a cap removal tool.

18. The apparatus of claim 1, wherein said detection system is a light imaging system.

19. A method of detecting a signal from wells of a multi-well plate using the apparatus of any one of claims 1-15 and 18, the method comprising:

(a) removing a seal from a well of a multi-well plate and

(b) detecting said signal from said well.

20. A method of detecting a signal from wells of a multi-well plate using the apparatus of any one of claims 2-15 and 18, the method comprising:

(a) piercing a seal on a well of a multi-well plate and

(b) detecting said signal from said well.

21. The method of claim 20, wherein said piercing comprises

cutting said seal into sections and

folding said sections against the internal walls of said well.

22. The method of claim 21 further comprising one or more of:

pipetting a sample into said well,

pipetting an assay reagent into said well,

washing said well,

illuminating said well, or

applying an electrical potential to said well.

23. The method of claim 22 further comprising repeating said method on one or more additional wells of said plate.

16-17. -17. (canceled)

24-52. -52. (canceled)