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US 9,156,010 B2Granted
Droplet-based assay system
AssigneeBio-Rad Laboratories, Inc.
InventorsBilly Wayne Colston, Jr., Benjamin Joseph Hindson, Kevin Dean Ness, Donald Arthur Masquelier, Fred Paul Milanovich, Douglas N. Modlin, Vincent Riot, Samuel Burd, Anthony Joseph Makarewicz, Jr., Phillip Belgrader
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Abstract
Systems, including apparatus and methods, for performing assays. These systems may involve separating sample components by partitioning them into droplets or other partitions, amplifying or otherwise reacting the components within the droplets, detecting the amplified components, or characteristics thereof, and/or analyzing the resulting data, among others.
Claims28
A system for sample analysis, comprising:
- a plurality of droplet generators that form a plurality of separate emulsions including droplets of partitioned samples, each droplet generator including a channel intersection at which one of the emulsions is formed from at least one carrier fluid stream and a sample stream, the samples being prepared as reaction mixtures for amplification of at least one nucleic acid target;
- containers defining cavities to hold the emulsions;
- a transport structure to transfer the emulsions from the droplet generators to the containers;
- a heating and cooling device to heat the emulsions in the cavities, with the emulsions held in an array, to induce nucleic acid amplification in droplets of the emulsions;
- a detection assembly to detect signals from intact droplets of the emulsions;
- a controller in communication with the detection assembly and programmed to estimate a presence, if any, of the nucleic acid target in the samples based on signals detected from the intact droplets;
- at least one pressure source that drives flow of the at least one carrier fluid stream and the sample stream to the channel intersection of each droplet generator;
- and
- a transport structure to transfer droplets of the emulsions from the containers to the detection assembly.
6 more elements
A system for sample analysis, comprising:
- a plurality of droplet generators that form a plurality of separate emulsions, each droplet generator including a carrier reservoir holding a carrier fluid, a sample reservoir holding a reaction mixture capable of amplification of a target, if present, in the reaction mixture, and an emulsion reservoir fluidically connected to the sample reservoir and the carrier reservoir, each droplet generator including a channel intersection at which one of the emulsions is formed from at least one carrier fluid stream received from the carrier reservoir and a sample stream received from the sample reservoir;
- at least one pressure source operatively connected to the droplet generators;
- containers defining cavities to hold the emulsions;
- a transport structure to transfer the emulsions from the emulsion reservoirs to the containers;
- a heating and cooling device to heat the emulsions in the containers, with the emulsions held in an array, to induce nucleic acid amplification in droplets of the emulsions;
- a detection assembly to detect signals from intact droplets of the emulsions;
- a transport structure to transfer droplets of the emulsions from the containers to the detection assembly;
- and
- a controller in communication with the detection assembly and programmed to determine a level of the target based on signals detected from intact droplets,
- wherein application of pressure to one or more of the reservoirs of each droplet generator with the pressure source drives flow of the at least one carrier fluid stream and the sample stream to the channel intersection of each droplet generator to form droplets of the reaction mixture disposed in the carrier fluid and to move the droplets in the carrier fluid to the emulsion reservoir.
7 more elements
Dependencies are inferred from the claim text.