Systems, devices, and methods for ultra-sensitive detection of molecules or particles

• US 9,952,237 B2
• Filed: 02/25/2011
• Issued: 04/24/2018
• Est. Priority Date: 01/28/2011
• Status: Active Grant

• Current Assignee: Quanterix Corporation
• Original Assignee: Quanterix Corporation
• Inventors: Fournier, David, Campbell, Todd, Kan, Cheuk, Lawson, John, Rivnak, Andrew, Kagan, Michael, Duffy, David C.
• Primary Examiner(s): Nagpaul, Jyoti
• Application Number:
  US13/035,472
• Publication Number:
  US 20120196774A1
• Time in Patent Office: 2,615 Days
• Field of Search: 422 50, 422500
• CPC Class Codes: B01L 2200/0668 Trapping microscopic beads
• CPC Class Codes: B01L 2200/0689 Sealing
• CPC Class Codes: B01L 2300/0803 Disc shape
• CPC Class Codes: B01L 2400/043 magnetic forces
• CPC Class Codes: B01L 2400/086 using baffles or other fixed flow obstructions
• CPC Class Codes: B01L 3/502761 specially adapted for handling suspended solids or molecules independently from the bulk fluid flow, e.g. for trapping or sorting beads, for physically stretching molecules investigating characteristics of particles G01N15/00
• CPC Class Codes: B01L 3/5085 for multiple samples, e.g. microtitration plates
• CPC Class Codes: G01N 2035/00287 movable lid/cover for sample or reaction tubes
• CPC Class Codes: G01N 35/00029 provided with flat sample substrates, e.g. slides G01N35/028 takes precedence
• CPC Class Codes: G01N 35/0098 involving analyte bound to insoluble magnetic carrier, e.g. using magnetic separation magnetic particles used in immunoassays G01N33/54326; magnetic separation in general B03C
• CPC Class Codes: G01N 35/1065 Multiple transfer devices

Abstract

Described are systems, devices, and methods which related to various aspects of assays for detecting and/or determining a measure of the concentration of analyte molecules or particles in a sample fluid. In some cases, the systems employ an assay consumable comprising a plurality of assay sites. The systems, devices, and/or methods, in some cases, are automated. In some cases, the systems, devices, and/or methods relate to inserting a plurality of beads into assay sites, sealing assay sites, imaging assay sites, or the like.

Claims

1. An apparatus for performing an assay, comprising:

an assay consumable handler configured to be operatively coupled to an assay consumable having a surface comprising a plurality of assay sites, wherein the assay sites have a volume between about 10 attoliter and about 100 picoliter;

a sealer constructed and positioned to apply a sealing component to the surface of the assay consumable, wherein the sealing component is a sealing liquid;

a sample loader configured to load an assay sample into at least a portion of the plurality of assay sites of the assay consumable;

an imaging system configured to acquire an image of at least a portion of the assay sites of the assay consumable containing assay sample; and

a computer implemented control system configured to automatically operate the sealer and receive information from the imaging system related to the image.

2. The apparatus of claim 1, further comprising the assay consumable operatively coupled to the assay consumable handler.

3. The apparatus of claim 2, wherein the assay consumable contains the assay sample and the assay sample comprises an unknown concentration of an analyte molecule.

4. The apparatus of claim 3, wherein the computer implemented control system is configured to determine a measure of the unknown concentration of the analyte molecule in the assay sample.

5. The apparatus of claim 2, wherein the assay sites comprise a plurality of reaction vessels formed in the surface of the assay consumable.

6. The apparatus of claim 1, wherein the computer implemented control system is configured to automatically operate the sample loader.

7. The apparatus of claim 2, wherein the assay consumable comprises a plurality of fluidically isolated areas, each isolated area comprising a plurality of assay sites.

8. The apparatus of claim 7, wherein the plurality of fluidically isolated areas are situated on a disc.

9. The apparatus of claim 1, wherein the sealing liquid is substantially immiscible with a liquid contained in each assay site.

10. The apparatus of claim 1, wherein the surface is formed of cyclic olefin copolymer or cyclic olefin polymer and the sealing liquid is a fluorinated oil.

11. An apparatus for sealing a plurality of assay sites, comprising:

an assay consumable handler configured to be operatively coupled to an assay consumable having a surface comprising a plurality of assay sites, wherein the assay sites have a volume between about 10 attoliter and about 100 picoliter;

a sealer constructed and positioned to apply a sealing component to the surface of the assay consumable to form a plurality of sealed assay sites, wherein the contents of each sealed assay site is substantially isolated from the contents of each of the other plurality of sealed assay sites, wherein the sealing component is a sealing liquid; and

a controller configured to automatically operate the sealer to apply the sealing component to the plurality of assay sites.

12. The apparatus of claim 11, wherein the sealer, the sample loader, and the imaging system are positioned about the disc, and wherein the apparatus is capable of providing rotational relative motion between the disc and the sealer, the sample loader, and the imaging system.

13. The apparatus of claim 11, further comprising the assay consumable operatively coupled to the assay consumable handler.

14. The apparatus of claim 13, wherein the assay sites are sized and/or shaped to each contain only zero or one bead.

15. The apparatus of claim 11, wherein the plurality of assays sites are contained in a channel on the assay consumable.

16. The apparatus of claim 11, wherein the surface is formed of cyclic olefin copolymer or cyclic olefin polymer and the sealing liquid is a fluorinated oil.

17. An apparatus for inserting beads into assay sites on an assay consumable, comprising:

an assay consumable handler configured to be operatively coupled to an assay consumable having a surface comprising a plurality of assay sites, wherein the assay sites have a volume between about 10 attoliter and about 100 picoliters;

a bead loader configured to insert individual beads into individual assay sites, such that each assay site containing a bead will contain no more than one bead;

a sealer constructed and positioned to apply a sealing component to the surface of the assay consumable handler, wherein the sealing component is a sealing liquid; and

a controller configured to automatically operate the bead loader to insert individual beads into individual assay sites.

18. The apparatus of claim 17, further comprising the assay consumable operatively coupled to the assay consumable handler.

19. The apparatus of claim 17, wherein the apparatus is capable of fluidically isolating individual beads in individual assay sites.

20. The apparatus of claim 17, wherein the surface is formed of cyclic olefin copolymer or cyclic olefin polymer and the sealing liquid is a fluorinated oil.

21. An apparatus for performing an assay, comprising:

an assay consumable handler configured to be operatively coupled to an assay consumable having a surface comprising a plurality of assay sites, wherein the assay sites have a volume between about 10 attoliter and about 100 picoliter;

a sample loader configured to load an assay sample containing analyte molecules or particles having an unknown concentration to be measured into at least a portion of the plurality of assay sites, such that a plurality of assay sites into which assay sample is loaded contain either zero or a single analyte molecule or particle;

a sealer constructed and positioned to apply a sealing component to the surface of the assay consumable, wherein the sealing component is a sealing;

a detector configured to interrogate at least a portion of the assay sites containing assay sample and determine a fraction of the plurality of assay sites interrogated that contain an analyte molecule or particle; and

a computer implemented system configured receive information from the detector and from the information determine a measure of the unknown concentration of the analyte molecules or particles in the assay sample.

22. The apparatus of claim 21, further comprising the assay consumable operatively coupled to the assay consumable handler.

23. The apparatus of claim 21, wherein the computer implemented system is configured to determine the fraction of the at least a portion of the assay sites interrogated which contain zero or one analyte molecule or particle.

24. The apparatus of claim 23, wherein the measure of the unknown concentration of analyte molecules or particles in the assay sample is determined, at least in part, based on the fraction of the at least a portion of the assay sites interrogate which contain zero or one analyte molecule or particle.

25. The apparatus of claim 21, wherein the surface is formed of cyclic olefin copolymer or cyclic olefin polymer and the sealing liquid is a fluorinated oil.