Apparatus, systems and method for assaying biological materials using an annular format

• US 6,518,056 B2
• Filed: 04/27/1999
• Issued: 02/11/2003
• Est. Priority Date: 04/27/1999
• Status: Expired due to Fees

• Current Assignee: Agilent Technologies, Inc.
• Original Assignee: Agilent Technologies, Inc.
• Inventors: Schleifer, Arthur, Schembri, Carol T.
• Primary Examiner(s): Siew, Jeffrey
• Application Number:
  US09/302,011
• Publication Number:
  US 20020064774A1
• Time in Patent Office: 1,386 Days
• Field of Search: 435/5, 435/6, 435/7.1, 435/7.2, 435/91.2, 435/287.2, 536/22.1, 536/23.1, 536/24.3, 536/24.31, 536/24.32, 536/24.33
• US Class Current: 435/287.2
• CPC Class Codes: B01J 19/0046 Sequential or parallel reactions, e.g. for the synthesis of polypeptides or polynucleotides; Apparatus and devices for combinatorial chemistry or for making molecular arrays synthesis methods per se C40B50/00
• CPC Class Codes: B01J 2219/00378 Piezoelectric or ink jet dispensers
• CPC Class Codes: B01J 2219/00421 using centrifugation
• CPC Class Codes: B01J 2219/00536 in the shape of disks
• CPC Class Codes: B01J 2219/00585 Parallel processes
• CPC Class Codes: B01J 2219/0059 Sequential processes
• CPC Class Codes: B01J 2219/00596 Solid-phase processes
• CPC Class Codes: B01J 2219/00605 the compounds being directly bound or immobilised to solid supports
• CPC Class Codes: B01J 2219/0061 The surface being organic
• CPC Class Codes: B01J 2219/00612 the surface being inorganic
• CPC Class Codes: B01J 2219/00626 Covalent
• CPC Class Codes: B01J 2219/00637 by coating it with another layer
• CPC Class Codes: B01J 2219/00659 Two-dimensional arrays
• CPC Class Codes: B01J 2219/00675 In-situ synthesis on the substrate
• CPC Class Codes: B01J 2219/00689 using computers
• CPC Class Codes: B01J 2219/00702 Processes involving means for analysing and characterising the products
• CPC Class Codes: B01J 2219/00722 Nucleotides
• CPC Class Codes: B01L 3/5085 for multiple samples, e.g. microtitration plates
• CPC Class Codes: B82Y 30/00 Nanotechnology for materials or surface science, e.g. nanocomposites
• CPC Class Codes: C12Q 1/6832 Enhancement of hybridisation reaction
• CPC Class Codes: C12Q 1/6837 : using probe arrays or probe chips C12Q1/6874 takes precedence
• CPC Class Codes: C12Q 2523/32 : Centrifugation
• CPC Class Codes: C40B 40/06 : Libraries containing nucleotides or polynucleotides, or derivatives thereof
• CPC Class Codes: C40B 50/14 : Solid phase synthesis, i.e. wherein one or more library building blocks are bound to a solid support during library creation; Particular methods of cleavage from the solid support
• CPC Class Codes: C40B 60/14 : for creating libraries
• CPC Class Codes: G01N 1/2813 : Producing thin layers of samples on a substrate, e.g. smearing, spinning-on G01N1/30 takes precedence
• CPC Class Codes: G01N 2035/00158 : Elements containing microarrays, i.e. "biochip"
• CPC Class Codes: G01N 2035/00504 : combined with carousels
• CPC Class Codes: G01N 33/54366 : Apparatus specially adapted for solid-phase testing
• CPC Class Codes: G01N 35/00069 : whereby the sample substrate is of the bio-disk type, i.e. having the format of an optical disk
• CPC Class Codes: G01N 35/025 : having a carousel or turntable for reaction cells or cuvettes
• CPC Class Codes: G01N 35/1083 : with one horizontal degree of freedom

Abstract

An apparatus, systems and methods use an r, θ format for the manufacture and analysis of biological materials. The apparatus is an array of biological material in an annular region on a substrate. The apparatus is formed with a system for synthesizing arrays that includes a spinner assembly for rotating the substrate during the synthesis of the biological material thereon. The apparatus is hybridized with complementary biological material using a system for hybridizing that includes a spinner assembly to spin the apparatus after the complementary biological material is added. The hybridized apparatus is optically interrogated with a system for interrogation that includes a light source, optics, and a scanning assembly that holds and rotates the apparatus so that the light source can remain stationary. The method of assaying biological materials uses the systems for synthesizing, hybridizing and optically interrogating the apparatus in accordance with the invention.

Claims

1. An apparatus for assaying biological materials comprising:

a substrate having a surface, an outer edge and a center; and

a plurality of discrete features bound to the surface of the substrate in an annular pattern, the plurality of discrete features comprising a first biological material, wherein the annular pattern is a spiral pattern having one end adjacent to the outer edge of the substrate and an opposite end adjacent to the center of the substrate.

2. The apparatus of claim 1, wherein the substrate has a circular shape.

4. The apparatus of claim 1, wherein the plurality of discrete features further comprises:

a second biological material chemically associated with the first biological material; and

a signal producing system chemically associated with the plurality of discrete features.

5. The apparatus of claim 4, wherein the second biological material is complementary to the first biological material.

6. The apparatus of claim 5, wherein the first biological material is an oligonucleotide probe and the second biological material is a target nucleotide sequence.

11. The apparatus of claim 1, further comprising a housing for holding the substrate and the plurality of discrete features bound to the substrate surface.

12. The apparatus of claim 11, wherein the housing comprises:

a plate having an outer edge, a first side and a second side opposite to the first side, the plate comprising;

a port extending from the first side to the second side of the plate,

a first recess in the first side coaxial with the port,

a second recess in the first side having an annular shape and being coaxial with the first recess,

a third recess in the first side having an annular shape and being coaxial with the second recess, the third recess for receiving the substrate, wherein the first recess and the second recess in the plate and the substrate define a chamber in the housing for receiving the second biological material and ancillary materials through the port, the plurality of discrete features being adjacent to a region in the chamber corresponding to the second recess and being visible from the first side of the plate; and

a recess extending radially from the outer edge of the plate inward being in communication with the second recess; and

a valve assembly in the radially extending recess, the valve assembly comprising an actuator, a biasing means and a cap, the cap being attached to the outer edge of the plate such that the radially extending recess forms a valve chamber inside the plate.

13. The apparatus of claim 12, wherein the port comprises a septum for allowing the second biological material and ancillary materials to pass into the chamber, the septum preventing the materials from exiting the chamber through the port.

14. The apparatus of claim 12, wherein the housing further comprises:

a second radially extending recess located diametrically opposite to said radially extending recess;

a second valve assembly similar to said valve assembly enclosed in the second radially extending recess;

a fourth recess in the second side of the plate having an annular shape; and

a ring frame attached to the second side of the plate, the ring frame enclosing the fourth recess, the fourth recess and the ring frame forming an annular cavity within the housing,

wherein said radially extending recess and the second radially extending recess intersect with the fourth recess and are in communication with the annular cavity, and

wherein at least one of said radially extending recess and the second radially extending recess is in communication with the exterior of the plate adjacent to the second side.

18. The apparatus of claim 11 wherein he substrate has a circular shape.

3. An apparatus for assaying biological materials comprising:

a substrate having a surface;

a plurality of discrete features bound to the surface of the substrate in an annular pattern, the plurality of discrete features comprising a first biological material; and

a housing for holding the substrate and the plurality of discrete features bound to the substrate surface, the housing comprising a valve assembly and a plate, the plate having an outer edge, a first side and a second side opposite to the first side, wherein the plate comprises;

a port extending from the first side to the second side of the plate,

a first recess in the first side coaxial with the port,

a second recess in the first side having an annular shape and being coaxial with the first recess,

a third recess in the first side having an annular shape and being coaxial with the second recess, the third recess for receiving the substrate, wherein the first recess and the second recess in the plate and the substrate define a chamber in the housing for receiving the second biological material and ancillary materials through the port, the plurality of discrete features being adjacent to a region in the chamber corresponding to the second recess and being visible from the first side of the plate; and

a recess extending radially from the outer edge of the plate inward being in communication with the second recess; and

wherein the valve assembly is located in the radially extending recess, the valve assembly comprising an actuator, a biasing means, and a cap, the cap being attached to the outer edge of the plate such that the radially extending recess forms a valve chamber inside the plate.

7. The apparatus of claim 3, wherein the annular pattern is a plurality of annular rings.

8. The apparatus of claim 7, wherein the plurality of annular rings are concentric annular rings of decreasing diameter from the outer edge of the substrate to the center.

9. The apparatus of claim 8, wherein the plurality of annular rings are segmented.

10. The apparatus of claim 3, wherein the annular pattern is a spiral pattern having one end adjacent to the outer edge of the substrate and an opposite end adjacent to the center of the substrate.

15. The apparatus of claim 3, wherein the port comprises a septum for allowing the second biological material and ancillary materials to pass into the chamber, the septum preventing the materials from exiting the chamber through the port.

16. The apparatus of claim 3, wherein the housing further comprises:

a second radially extending recess located diametrically opposite to said radially extending recess;

a second valve assembly similar to said valve assembly enclosed in the second radially extending recess;

a fourth recess in the second side of the plate having an annular shape; and

a ring frame attached to the second side of the plate, the ring frame enclosing the fourth recess, the fourth recess and the ring frame forming an annular cavity within the housing,

wherein said radially extending recess and the second radially extending recess intersect with the fourth recess and are in communication with the annular cavity, and

wherein at least one of said radially extending recess and the second radially extending recess is in communication with the exterior of the plate adjacent to the second side.

17. The apparatus of claim 3, wherein the substrate has a circular shape.

19. The apparatus of claim 3, wherein the plurality of discrete features further comprises:

a second biological material chemically associated with the first biological material; and

a signal producing system chemically associated with the plurality of discrete features.

20. The apparatus of claim 19, wherein the second biological material is complementary to the first biological material.

21. The apparatus of claim 20, wherein the first biological material is an oligonucleotide probe and the second biological material is a target nucleotide sequence.