Integrated nucleic acid diagnostic device
AssigneeAffymetrix, Inc.
InventorsRolfe C. Anderson, Robert J. Lipshutz, Richard P. Rava, Stephen P. A. Fodor
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Abstract
The present invention provides a miniaturized integrated nucleic acid diagnostic device and system. The device of the invention is generally capable of performing one or more sample acquisition and preparation operations, in combination with one or more sample analysis operations. For example, the device can integrate several or all of the operations involved in sample acquisition and storage, sample preparation and sample analysis, within a single integrated unit. The device is useful in a variety of applications, and most notably, nucleic acid based diagnostic applications and de novo sequencing applications.
Claims91
A miniature fluidic system, comprising:
- a body having at least two discrete reaction chambers, each of said reaction chambers comprising at least one vent port, and wherein each of said reaction chambers is fluidly connected to a common chamber or channel;
- a pneumatic system for selectively applying a pressure differential between said common channel or chamber and at least a selected one of said at least two discrete chambers, whereby said pressure differential directs a fluid sample in said body between said common channel or chamber and said at least one selected chamber.
The system of claim 81, wherein said pneumatic system is further capable of applying a pressure differential to said diaphragm valve to deflect said diaphragm valve.
The system of claim 20, wherein said temperature controller comprises a thermoelectric temperature controller.
The system of claim 20, wherein said temperature controller comprises a resistive heater.
The system of claim 22, wherein said resistive heating element is a NiCr/polyimide/copper laminate heating element.
The system of claim 24, wherein said temperature sensor is a thermocouple.
The system of claim 25, wherein said temperature sensor is a resistance thermometer.
A miniature fluidic system, comprising:
- a body having at least first and second chambers disposed therein, each of said at least first and second chambers having a fluid inlet and being in fluid connection, and at least one of said at least first and second chamber being a hybridization chamber for analyzing a component of a fluid sample, said hybridization chamber including a polymer array, said polymer array including a plurality of different polymer sequences coupled to a surface of a single substrate, each of said plurality of different polymer sequences being coupled to said surface in a different, known location;
- a sample inlet, fluidly connected to at least one of said first and second chambers, for introducing a fluid sample into said system;
- a fluid transport system for moving a fluid sample from said at least first chamber to said at least second chamber.
A miniature fluidic system, comprising:
- a body having at least two distinct chambers disposed therein, each of said at least two chambers being fluidly connected to at least one other of said at least two chambers;
- a sample inlet, fluidly connected to at least one of said at least two chambers, for introducing a fluid sample into said at least one chamber;
- a fluid transport system for moving a fluid sample from at least a first chamber of said at least two chambers to at least a second chamber of said at least two chambers;
- and
- a separation channel for separating a component of said fluid sample, said separation channel being fluidly connected to at least one of said chambers and including at least first and second electrodes in electrical contact with opposite ends of said separation channel for applying a voltage across said separation channel.
A miniature fluidic system, comprising:
- a body having at least two chambers disposed therein, at least one of said at least two chambers being an in vitro transcription reaction chamber, said in vitro transcription reaction chamber having an effective amount of an RNA polymerase and four different nucleoside triphosphates, disposed therein;
- a sample inlet, fluidly connected to at least one of said at least two chambers, for introducing a fluid sample into said at least one chamber;
- and
- a fluid transport system for moving a fluid sample from at least a first of said at least two chambers to at least a second chamber of said at least two chambers.
A miniature fluidic system, comprising:
- a body having at least two chambers disposed therein, at least one of said at least two chambers being a cell lysis chamber, for lysing cells in said fluid sample, said cell lysis chamber comprising a cell lysis system;
- a sample inlet, fluidly connected to at least one of said at least two chambers, for introducing a fluid sample into said at least one chamber;
- and
- a fluid transport system for moving a fluid sample from at least a first of said at least two chambers to at least a second chamber of said at least two chambers.
A miniature fluidic system, comprising:
- a body having at least two chambers disposed therein, at least one of said at least two chambers being a nucleic acid purification chamber, for separating nucleic acids in said fluid sample from other contaminants in said fluid sample;
- a sample inlet, fluidly connected to at least one of said at least two chambers, for introducing a fluid sample into said at least one chamber;
- and
- a fluid transport system for moving said separated nucleic acids from said nucleic acid chamber to said at least a second chamber of said at least two chambers.
A miniature fluidic system, comprising:
- a body having at least a first chamber fluidly connected to a second chamber by a fluid passage;
- a sample inlet, fluidly connected to said first chamber, for introducing a fluid sample into said system;
- a differential pressure delivery system for maintaining said first chamber at a first pressure and said second chamber at a second pressure, said first pressure being greater than ambient pressure and said second pressure being greater than said first pressure, whereby when said second chamber is brought to ambient pressure, said first pressure forces a liquid sample in said first chamber into said second chamber.
A miniature fluidic system, comprising:
- a body having at least a first chamber fluidly connected to a second chamber;
- a sample inlet, fluidly connected to said first chamber, for introducing a fluid sample into said at first chamber;
- a differential pressure delivery source for maintaining said first chamber at a first pressure and said second chamber at a second pressure, said second pressure being less than ambient pressure and said first pressure being less than said second pressure, whereby when said first chamber is brought to ambient pressure, said second pressure draws a liquid sample in said first chamber into said second chamber.
A method of directing a fluid sample in a miniature fluidic system, comprising:
- providing a microfabricated device having at least first and second chambers disposed therein, wherein each of said at least first and second chambers is in fluid connection with a common chamber or channel, has at least first and second controllable valves disposed across said fluid connection, respectively, and includes at least one vent;
- applying a positive pressure to said common chamber or channel;
- selectively opening said at least first controllable valve, whereby said positive pressure forces said fluid sample from said common chamber or channel into said first chamber.
A method of mixing at least two discrete fluid components in a microfabricated fluidic system, comprising:
- providing a microfabricated channel having a vent disposed at an intermediate location in said channel, said vent having a gas permeable fluid barrier disposed across said vent;
- introducing said at least two discrete fluid components into said channel separated by a gas bubble;
- flowing said at least two fluid components past said vent, whereby said bubble exits said vent, allowing said at least two fluid components to mix.
A method of repeatedly measuring a known volume of a fluid in a miniature fluidic system, comprising:
- providing a microfabricated device having at least first and second chambers disposed therein, wherein said at least first and second chambers are in fluid connection, each comprise at least one vent port, and wherein at least one of said chambers is a volumetric chamber having a known volume;
- filling said volumetric chamber with said fluid to create a first aliquot of said fluid;
- transporting said first aliquot of said fluid to said at least second chamber;
- and
- repeating said filling and transporting steps.
Dependencies are inferred from the claim text.