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

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 reaction vessels, wherein each of the reaction vessels has a volume between about 10 attoliters and about 50 picoliters;
• a sealer constructed and positioned to apply a sealing component to the surface of the assay consumable;
• a sample loader configured to load an assay sample into at least a portion of the plurality of reaction vessels of the assay consumable;
• a bead loader comprising a magnetic field generator positioned adjacent to the assay consumable and configured to create relative motion between a plurality of magnetic beads and the reaction vessels;
• and
• an imaging system configured to acquire an image of at least a portion of the reaction vessels 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.

An apparatus for inserting beads into reaction vessels 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 reaction vessels, wherein each of the reaction vessels has a volume between about 10 attoliters and about 50 picoliters;
• a bead loader configured to insert individual beads into individual reaction vessels, such that each reaction vessel containing a bead will contain no more than one bead;
• and
• a controller configured to automatically operate the bead loader to insert individual beads into individual reaction vessels.

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 reaction vessels, wherein each of the reaction vessels has a volume between about 10 attoliters and about 50 picoliters;
• a sealer constructed and positioned to apply a sealing component to the surface of the assay consumable;
• 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 reaction vessels, such that a plurality of reaction vessels into which assay sample is loaded contain either zero or a single analyte molecule or particle;
• an imaging system configured to acquire an image of at least a portion of the reaction vessels of the assay consumable containing assay sample;
• a detector configured to interrogate at least a portion of the reaction vessels containing assay sample and determine a fraction of the plurality of reaction vessels interrogated that contain an analyte molecule or particle;
• and
• a computer implemented system configured to 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;
• wherein the sealer, the sample loader, and the imaging system are arranged to be positioned about the assay consumable when the assay consumable is coupled to the assay consumable handler, and wherein the apparatus is capable of providing rotational relative motion between the assay consumable and the sealer, the sample loader, and the imaging system.

An apparatus for inserting beads into a plurality of reaction vessels on an assay consumable, comprising:

• an assay consumable handler configured to be operatively coupled to the assay consumable, wherein the assay consumable comprises a surface comprising the plurality of the reaction vessels, wherein each of the reaction vessels has a volume between about 10 attoliters and about 50 picoliters;
• a bead applicator configured to apply a plurality of magnetic beads to the surface of the assay consumable or place a plurality of magnetic beads in close proximity to the surface;
• a bead loader comprising a magnetic field generator positioned adjacent to the assay consumable and configured to create relative motion between the magnetic beads and the reaction vessels;
• and
• a controller configured to automatically operate the bead loader to create relative motion between the magnetic beads and the reaction vessels and insert beads into the reaction vessels.