Bioarray chip reaction apparatus and its manufacture
AssigneeAffymetrix, Inc.
InventorsDonald M. Besemer, Virginia W. Goss, James L. Winkler
Life of this patent
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Abstract
A body 300 having a cavity 310 for mounting a substrate 120 fabricated with probe sequences at known locations according to the methods disclosed in U.S. Pat. No. 5,143,854 and PCT WO 92/10092 or others, is provided. The cavity includes inlets 350 and 360 for introducing selected fluids into the cavity to contact the probes. Accordingly, a commercially feasible device for use in high throughput assay systems is provided.
Claims87
A method of making probe-chips comprising the steps of:
- forming a plurality of probe arrays on a substrate;
- separating said substrate into a plurality of chips, each of said chips comprising at least one probe array thereon;
- and
- mating at least one of said chips to a package, said package comprising a reaction chamber, said reaction chamber comprising inlets for flowing fluid therein, said at least one probe array in fluid communication with said reaction chamber.
An apparatus for packaging a substrate, said apparatus comprising:
- a substrate having a first surface and a second surface, said first surface comprising a probe array;
- a body having a mounting surface with a fluid cavity, said second surface attached to said cavity;
- and
- a cover attached to said mounting surface for sealing said cavity.
An apparatus for packaging a substrate, said apparatus comprising:
- a substrate having a first surface and a second surface, said first surface comprising a probe array and said second surface being an outer periphery of said first surface;
- a body having a mounting surface, an upper surface, and a cavity bounded by said mounting surface and said upper surface, said second surface being attached to said cavity and said first surface being within said cavity;
- and
- a cover attached to said mounting surface for defining an upper boundary to said cavity;
- wherein said cavity comprises a diffuser and a concentrator, said diffuser and said concentrator permitting laminar fluid flow through said cavity.
An apparatus for mixing a fluid, the apparatus comprising:
- a first substrate comprising a first inner surface functionalized with a microarray of reactive moieties;
- a substantially parallel second substrate also comprising a second inner surface, wherein said first and second inner surfaces bound a closed chamber there between, said chamber adapted to retain a quantity of fluid so that the fluid is in contact with both surfaces;
- at least one bubble disposed within said chamber;
- and
- means for moving the chamber so that the bubble moves relative to the fluid to effect mixing of the fluid.
An apparatus for mixing a fluid, the apparatus comprising:
- a first substrate comprising a first inner surface functionalized with a microarray of reactive moieties;
- a substantially parallel second substrate also comprising a second inner surface, wherein said first and second inner surfaces bound a closed chamber there between, said chamber adapted to retain a quantity of fluid so that the fluid is in contact with both surfaces;
- at least one bubble disposed within said chamber, wherein said bubble is a magnetic particle;
- and
- means for moving the bubble relative to the fluid to effect mixing of the fluid.
An apparatus for mixing a fluid, comprising:
- a first substrate and a second substrate having inner surfaces that define a closed chamber therebetween, said chamber adapted to retain a quantity of fluid so that the fluid is in contact with both inner surfaces;
- means for creating bubbles in the fluid within the apparatus, whereby each bubble displaces the fluid resulting in mixing;
- and
- means for moving a bubble in the fluid.
An apparatus for mixing a fluid, comprising:
- a first substrate and a substantially parallel second substrate having inner surfaces that define a closed chamber therebetween, said chamber adapted to retain a quantity of fluid so that the fluid is in contact with both inner surfaces;
- means for providing bubbles in the fluid within the apparatus, whereby each said bubble displaces the fluid resulting in mixing;
- and
- means for moving a bubble in the fluid.
An apparatus for mixing a fluid, comprising:
- a first substrate and a second substrate having inner surfaces that define a closed chamber therebetween, said chamber adapted to retain a quantity of fluid so that the fluid is in contact with both inner surfaces;
- and
- means for creating bubbles in the fluid at selected locations within the apparatus, whereby each bubble displaces the fluid resulting in mixing;
- and wherein at least one of said inner surfaces is functionalized with reactive moieties.
A method comprising:
- providing a first substrate and a second substrate having inner surfaces that define a closed chamber therebetween, said chamber adapted to retain a quantity of fluid so that the fluid is in contact with both inner surfaces, and wherein at least one of said inner surfaces is functionalized with polynucleotides, polypeptides, or polysaccharides;
- introducing a fluid containing a plurality of components into the closed chamber so as to provide a quantity of fluid therein in contact with both inner surfaces;
- providing a bubble in the fluid;
- and
- moving a bubble within the fluid to result in mixing.
A method of 66, wherein the at least one of said inner surfaces is functionalized with polypeptides.
A method comprising:
- providing a first substrate and a second substrate having inner surfaces that define a closed chamber therebetween, said chamber adapted to retain a quantity of fluid so that the fluid is in contact with both inner surfaces, and wherein at least-one of said inner surfaces is functionalized with an array of RNA or DNA probes;
- introducing a fluid sample containing DNA or RNA into the closed chamber so as to provide a quantity of fluid therein in contact with both inner surfaces;
- providing a bubble in the fluid;
- moving a bubble within the fluid to result in mixing;
- after hybridization is complete, removing the sample from the apparatus;
- and
- analyzing the functionalized inner surface for DNA or RNA that has hybridized.
A method comprising:
- providing a first substrate and a second substrate having inner surfaces that define a closed chamber therebetween, said chamber adapted to retain a quantity of fluid so that the fluid is in contact with both inner surfaces, and wherein at least one of said inner surfaces is functionalized with an immobilized biological polymer;
- introducing a fluid containing a plurality of components into the closed chamber so as to provide a quantity of fluid therein in contact with both inner surfaces;
- providing a bubble in the fluid;
- and
- moving a bubble within the fluid to result in mixing.
A method for mixing a film of fluid, comprising:
- providing a first substrate and a substantially parallel second substrate having inner surfaces that define a closed chamber therebetween, said chamber adapted to retain a quantity of fluid so that the fluid is in contact with both inner surfaces;
- introducing a fluid containing a plurality of components into the closed chamber so as to provide a film of fluid therein;
- and
- nucleating a bubble within the film of fluid, whereby, as the bubble is nucleated and dispelled, the fluid is displaced resulting in mixing.
An apparatus for mixing a fluid, comprising:
- a first substrate and a second substrate having inner surfaces that define a closed chamber therebetween, said chamber adapted to retain a quantity of fluid so that the fluid is in contact with both inner surfaces;
- means for nucleating bubbles in the fluid comprising discrete sources for creating individual bubbles at selected locations within the apparatus, whereby, as each bubble is nucleated and dispelled, the fluid is displaced resulting in mixing;
- and
- means for moving a bubble in the fluid.
Dependencies are inferred from the claim text.