Remotely programmable matrices with memories

• US 6,372,428 B1
• Filed: 06/16/1998
• Issued: 04/16/2002
• Est. Priority Date: 04/25/1995
• Status: Expired due to Term

• Current Assignee: Irori Technologies Incorporated
• Original Assignee: Discovery Partners International, Inc. (Infinity Pharmaceuticals, Inc.)
• Inventors: David, Gary S., Senyei, Andrew E., Nova, Michael P.
• Primary Examiner(s): ZITOMER, STEPHANIE W
• Application Number:
  US09/098,122
• Time in Patent Office: 1,400 Days
• Field of Search: 435/6, 435/7.1, 435/287.1, 435/287.2, 435/288.1, 435/288.3, 435/288.4, 435/288.7, 436/501, 536/24.3
• US Class Current: 435/6.1
• 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 2219/00295 the reactor vessels having pervious side walls
• CPC Class Codes: B01J 2219/00299 Generally cylindrical reactor vessels
• CPC Class Codes: B01J 2219/00308 interchangeably mounted in racks or blocks
• CPC Class Codes: B01J 2219/00333 Closures attached to the reactor vessels
• CPC Class Codes: B01J 2219/00344 Caps
• CPC Class Codes: B01J 2219/00461 Beads and reaction vessel together
• CPC Class Codes: B01J 2219/00463 Directed sorting
• CPC Class Codes: B01J 2219/005 Beads
• CPC Class Codes: B01J 2219/00502 Particles of irregular geometry
• CPC Class Codes: B01J 2219/0054 Means for coding or tagging the apparatus or the reagents
• CPC Class Codes: B01J 2219/00542 Alphanumeric characters
• CPC Class Codes: B01J 2219/00547 Bar codes
• CPC Class Codes: B01J 2219/00549 2-dimensional
• CPC Class Codes: B01J 2219/00551 3-dimensional
• CPC Class Codes: B01J 2219/0056 Raised or sunken areas
• CPC Class Codes: B01J 2219/00563 Magnetic means
• CPC Class Codes: B01J 2219/00567 Transponder chips
• CPC Class Codes: B01J 2219/00569 EEPROM memory devices
• CPC Class Codes: B01J 2219/00585 Parallel processes
• CPC Class Codes: B01J 2219/0059 : Sequential processes
• CPC Class Codes: B01J 2219/00592 : Split-and-pool, mix-and-divide processes
• CPC Class Codes: B01J 2219/00596 : Solid-phase processes
• CPC Class Codes: B01J 2219/00689 : using computers
• CPC Class Codes: B01J 2219/00695 : Synthesis control routines, e.g. using computer programs
• CPC Class Codes: B01J 2219/0072 : Organic compounds
• CPC Class Codes: B01J 2219/00722 : Nucleotides
• CPC Class Codes: B01J 2219/00725 : Peptides
• CPC Class Codes: B01L 2300/0609 : Holders integrated in container to position an object
• CPC Class Codes: B82Y 10/00 : Nanotechnology for information processing, storage or transmission, e.g. quantum computing or single electron logic
• CPC Class Codes: C07K 1/00 : General methods for the preparation of peptides , i.e. processes for the organic chemical preparation of peptides or proteins of any length
• CPC Class Codes: C07K 1/04 : on carriers C07K1/003, C07K1/006 take precedence
• CPC Class Codes: C07K 1/047 : Simultaneous synthesis of different peptide species; Peptide libraries
• CPC Class Codes: C40B 40/06 : Libraries containing nucleotides or polynucleotides, or derivatives thereof
• CPC Class Codes: C40B 40/10 : Libraries containing peptides or polypeptides, or derivatives thereof
• CPC Class Codes: C40B 60/14 : for creating libraries
• CPC Class Codes: C40B 70/00 : Tags or labels specially adapted for combinatorial chemistry or libraries, e.g. fluorescent tags or bar codes
• CPC Class Codes: G01N 15/149 : specially adapted for sorting particles, e.g. by their size or optical properties
• CPC Class Codes: G01N 2035/00782 : reprogrammmable code
• CPC Class Codes: G01N 35/00732 : Identification of carriers, materials or components in automatic analysers
• CPC Class Codes: G01N 35/00871 : Communications between instruments or with remote terminals
• CPC Class Codes: G11C 13/0014 : comprising cells based on organic memory material
• CPC Class Codes: G11C 13/0019 : comprising bio-molecules
• CPC Class Codes: G11C 13/025 : using fullerenes, e.g. C60, or nanotubes, e.g. carbon or silicon nanotubes

Abstract

Combinations, called matrices with memories, of matrix materials with remotely addressable or remotely programmable recording devices that contain at least one data storage unit are provided. The matrix materials are those that are used in as supports in solid phase chemical and biochemical syntheses, immunoassays and hybridization reactions. The data storage units are non-volatile antifuse memories or volatile memories, such as EEPROMS, DRAMS or flash memory. By virtue of this combination, molecules and biological particles, such as phage and viral particles and cells, that are in proximity or in physical contact with the matrix combination can be labeled by programming the memory with identifying information and can be identified by retrieving the stored information. Combinations of matrix materials, memories, and linked molecules and biological materials are also provided. The combinations have a multiplicity of applications, including combinatorial chemistry, isolation and purification of target macromolecules, capture and detection of macromolecules for analytical purposes, selective removal of contaminants, enzymatic catalysis, cell sorting, drug delivery, chemical modification and other uses. Methods for electronically tagging molecules, biological particles and matrix support materials, immunoassays, receptor binding assays, and other methods are also provided.

Claims

1. A combination of a matrix with memory, comprising:

(A) a memory device having encoded information stored therein; and

(B) a matrix material, wherein;

the device is less than about 20 mm³ in size;

the matrix material is either comprised of particles of a size such that at least one dimension is no more than about 100 mm or the matrix material is in the form of a container used for chemical syntheses.

2. The combination of claim 1, wherein the matrix comprises a plurality of particles and the combination further comprises the plurality of particles linked to or proximate to the memory device.

28. The combination of claim 1, wherein:

the memory device further comprises a plurality of memory address locations; and

each of the memory address locations is uniquely addressable for storing the encoded information.

29. The combination of claim 1, wherein the memory device further comprises an antenna for receiving transmitted electromagnetic radiation.

30. The combination of claim 1, wherein the memory device further comprises a shell that encloses the memory device.

31. The combination of claim 1, wherein the memory device is encased in the matrix material.

32. The combination of claim 1, wherein the memory device comprises an optical storage medium for retaining the encoded information in the form of a plurality of optically readable holes or pits formed in the optical storage medium.

3. A solid phase matrix support for use in assays in which a ligand reacts with an anti-ligand therefor, comprising:

(A) a combination of a matrix with memory, comprising;

(i) a memory device having encoded information stored therein; and

(ii) a matrix material, wherein;

the matrix material is either comprised of particles of a size such that at least one dimension is no more than 100 mm or the matrix material is in the form of a container selected from the group consisting of vials, test tubes, culture dishes, vessels of a volume of about 100 ml or less, and microtiter plates or is in the form of a continuous surface that encases the memory device; and

at least a portion of the surface of the matrix is adapted for linking the anti-ligand or ligand; and

(B) a molecule selected from a ligand or receptor, wherein the ligand or receptor is linked directly or indirectly to the surface of the matrix adapted for linking.

4. The matrix support of claim 3, wherein the matrix comprises material selected from the group consisting of polystyrene, polycarbonate, polypropylene, nylon, glass, dextran, chitin, sand, pumice, Teflon®

, agarose, polysaccharides, dendrimers, buckyballs, polyacrylamide, silicon and rubber.

5. The matrix support of claim 3, wherein the ligand and anti-ligand comprise an antigen and antibody.

6. An assay for detecting a ligand or anti-ligand, comprising:

(A) providing the solid support of claim 3, wherein the encoded information includes information that identifies the molecule;

(B) contacting the solid phase matrix with a sample containing a ligand or anti-ligand that specifically reacts with the linked molecule;

(C) adding a label reagent to the sample, wherein the label reagent specifically binds to the ligand or anti-ligand that has bound to the linked molecule, and analyzing the solid phase matrix to detect the presence of the label indicative of binding of the ligand or anti-ligand to the molecule that is bound to the support; and

(D) reading the information in each memory device to identify the linked molecule.

7. The method of claim 6, wherein a plurality of combination of matrices with memories, each with a different bound molecule are contacted with the sample.

8. The method of claim 6, wherein the identifying information is pre-encoded in the memory device.

9. The method of claim 6, wherein the encoded information is stored by remotely programming the memory device.

10. The matrix support of claim 3, wherein the memory device is remotely programmable.

11. The method of claim 6, wherein the label is selected from among a radiolabel, fluorescent label, luminophore label and enzyme label.

12. The method of claim 6, wherein the matrix comprises material selected from the group consisting of polystyrene, polycarbonate, polypropylene, nylon, glass, dextran, chitin, sand, pumice, Teflon®

, agarose, polysaccharides, dendrimers, buckyballs, polyacrylamide, silicon and rubber.

13. The method of claim 6, wherein the assay is an immunoassay and the ligand is an antigen, and the anti-ligand is an antibody.

14. The method of claim 6, wherein the molecule that is bound to the support is a receptor, and the sample contains ligands therefor.

15. The method of claim 6, wherein the molecule that is bound to the support is a ligand, and the sample contains anti-ligands therefor.

16. The method of claim 7, wherein the bound molecules are receptors.

17. The method of claim 7, wherein the bound molecules are ligands.

18. The method of claim 7, that is a multianalyte immunoassay.

19. The method of claim 7, wherein the identifying information comprises physical or chemical characteristics of the linked molecule.

20. The method of claim 6, wherein the ligands and anti-ligands each comprise single-stranded nucleic acids.

21. The support of claim 3, wherein the linked molecules comprise nucleic acids.

22. The method of claim 6, wherein the linked molecules comprise proteins or peptides.

23. The support of claim 3, wherein the linked molecules comprise proteins or peptides.

24. A method for performing multiplexed solid phase assays, comprising:

(A) providing a plurality of the supports of claim 3, comprising a plurality of linked molecules;

(B) contacting the supports with a sample, containing a ligand or anti-ligand that specifically reacts with the linked molecule;

(C) adding label reagents to the sample, wherein the label reagents specifically bind to the ligands or anti-ligands that have bound to the linked molecules, and analyzing the solid phase matrices to detect the presence of the label indicative of binding of the ligand or anti-ligand to the molecules bound to each support; and

(D) reading the encoded information in each memory device to identify the linked molecule.

25. The method of claim 24, wherein:

the steps of contacting and adding label reagents are performed simultaneously.

26. The support matrix of claim 3, wherein the memory device includes a data storage unit having memory means for storing a plurality of data points and means for receiving a transmitted electromagnetic signal so that a write signal causes a stored data point corresponding to the data signal to be stored within the memory means.

27. The method of claim 6, wherein the memory device includes a data storage unit having memory means for storing a plurality of data points and means for receiving a transmitted electromagnetic signal so that a write signal causes a stored data point corresponding to the data signal to be stored within the memory means.

33. The matrix support of claim 3, wherein:

the memory device comprises a plurality of memory address locations; and

each of the memory address locations is uniquely addressable for storing the encoded information.

34. The matrix support of claim 3, wherein the memory device further comprises an antenna for receiving transmitted electromagnetic radiation.

35. The matrix support of claim 3, wherein the memory device further comprises a shell that encloses the memory device.

36. The matrix support of claim 3, wherein the memory device is encased in the matrix material.

37. The matrix support of claim 3, wherein the memory device comprises an optical storage medium for retaining the encoded information in the form of a plurality of optically readable holes or pits formed in the optical storage medium.

38. The method of claim 6, wherein:

the memory device comprises a plurality of memory address locations; and

each of the memory address locations is uniquely addressable for storing the encoded information.

39. The method of claim 6, wherein the memory device further comprises an antenna for receiving transmitted electromagnetic radiation.

40. The method of claim 6, wherein the memory device further comprises a shell that encloses the memory device.

41. The method of claim 6, wherein the memory device is encased in the matrix material.

42. The method of claim 6, wherein the memory device comprises an optical storage medium for retaining the encoded information in the form of a plurality of optically readable holes or pits formed in the optical storage medium.

43. A solid phase for use in assays for biomolecules, comprising:

(a) a particle and a transponder, wherein the transponder is located inside said particle or is attached to the surface of said particle, the transponder comprising a radio transmitter-receiver encoded with data, the data is transmitted to a receiver in response to a specific electromagnetic signal; and

(b) a member of a biomolecular binding pair attached to the surface of the particle, wherein the biomolecule specifically binds to the biomolecular binding pair member.

44. The particle of claim 43, wherein the surface of the particle is glass, latex or plastic.

45. The particle of claim 43, wherein the biomolecular binding pair is an antigen-antibody pair.

46. A method of detecting a member of a biomolecular binding pair in a sample, comprising the steps of:

(a) providing at least one solid phase particle, said particles having a transponder located inside or attached to each of said particles, the transponders having a memory element and an index number encoded on the memory elements creating at least one class of transponders, each class having a different index number;

(b) the solid particles having a first member of said biomolecular binding pair attached to a surface thereof;

(c) contacting the solid phase particles with a sample to cause a second member of the biomolecular binding pair to specifically bind to the first member attached to the solid phase particle;

(d) adding a label reagent to the sample, said label reagent specifically binds the second member of the biomolecular binding pair on the solid phase particle, and analyzing the solid phase particles to detect the presence of the label indicative of binding of the second member present in the sample to said first member; and

(e) decoding the index number encoded on the transponders using a scanner device to identify the class of the transponders to which the second member of the biomolecular binding pair is bound.

47. The method of claim 46, wherein the index number is encoded on the transponder memory element by the transponder manufacturer.

48. The method of claim 46, wherein the index number is encoded on the transponder memory element by the user with a scanner device.

49. The method of claim 46 wherein the label is a chromophore.

50. The method of claim 46 wherein the label is a fluorophore.

51. The method of claim 46, wherein the label is a chemiluminescent agent or a bioluminescent agent.

52. The method of claim 46, wherein an outer surface of the transponders is glass, plastic or latex.

53. The method of claim 46 wherein the index number comprises physical or chemical characteristics of the biomolecular binding pair member deposited on the solid phase.

54. The method of claim 46 wherein the index number comprises identifying characteristics of the sample.

55. A method of detecting at least two biomolecules in a sample, said biomolecules being a second member of a biomolecular binding pair, comprising the steps of:

(a) introducing into the sample at least two populations of solid phase particles, said particles having a transponder located inside or attached to each of said particles, each population of particle having a first member of a biomolecular binding pair attached to its surface, and the transponders in the first population being encoded with a different index number from the transponders of the second population, wherein, the first member on each population of particles specifically binds one of said second members present in said sample;

(b) contacting the solid phase with a label reagent that specifically binds to the second member of the biomolecular binding pair, and analyzing the particles to detect a label indicating binding of the second biomolecular binding pair member to the first biomolecular binding pair member; and

(c) decoding at least a portion of the transponders to determine the populations of the transponders to which the second member is bound.

56. A method of performing a multiplex solid phase assay for biomolecules in a sample, said biomolecules being a second member of a biomolecular binding pair comprising the steps of:

(a) providing multiple solid phases comprising particles, said particles having a transponder located inside or attached to each of said particles, the transponders having memory elements encoded with an index number creating two or more classes of transponders, each class having a different index number, each class of solid phase particles having a first biomolecular binding member immobilized on a surface thereof, wherein, the first member on each class of particles specifically binds one of said second members present ill said sample;

(b) contacting the solid phase particles with a sample to cause two or more different second members of a biomolecular binding pair in the sample to bind one of said first biomolecular binding pair member on the particles;

(c) contacting the solid phase particles with label reagents that specifically bind to the second member of the biomolecular binding pair;

(d) washing the solid phase particles to remove unbound sample components;

(e) analyzing the solid phase particles to detect the label, which indicates binding of the second biomolecular binding pair member to the first biomolecular binding pair member; and

(f) decoding the index number encoded on at least a portion of the transponders to identify the class of transponders to which a biomolecule is bound.

57. A method of detecting a member of a biomolecular binding pair in a sample comprising the steps of:

(a) providing at least one solid phase particle, said particles having a transponder located inside or attached to each of said particles, the transponders having memory elements and an index number encoded on the memory elements creating at least one class of transponders, each class having a different index number;

(b) the solid particles having a first member of said biomolecular binding pair attached to the surface of the solid phase particles;

(c) contacting the solid phase particles with a sample and a label reagent to cause a second member of the biomolecular binding pair present in said sample, and the label reagent to competitively bind to the first member attached to the solid phase particle;

(d) analyzing and detecting the presence of the label on the solid phase particle as an indirect determination of the presence of the second member in said sample;

(e) decoding the index number encoded on the transponders using a scanner device to identify the class of transponders to which the second member of the biomolecular binding pair is bound.

58. A method of detecting at least two biomolecules in a sample, said biomolecules being a second member of a biomolecular binding pair, comprising the steps of:

(a) providing at least two populations of solid phases comprising particles, said particles having a transponder located inside or attached to each of said particles, each population of particle having a first member of a biomolecular binding pair attached to its surface, and the transponders in the first population being encoded with a different index number than the transponders of the second population, wherein, the second members present in said sample competitively binds one of said first member on each population of the solid phase particles;

(b) contacting the solid phase particles with a sample and label reagents to cause the second members present in said sample, and the label reagents to competitively bind to one of said first member on the solid phase particles;

(c) analyzing the particles to detect a label to indirectly determine the presence of the second biomolecular binding pair member in the sample;

(d) decoding at least a portion of the transponders to determine the populations of the transponders.

59. A method of performing a multiplex solid phase assay for biomolecules in a sample, said biomolecules being a second member of a biomolecular binding pair, comprising the steps of:

(a) providing multiple solid phases comprising particles, said particles having a transponder located inside or attached to each of said particles, the transponders having memory elements encoded with an index number creating two or more classes of transponders, each class having a different index number, each class of solid phase particles having a first biomolecular binding member immobilized on a surface thereof, wherein, the second members present in said sample competitively bind to one of said first member on the multiple solid phase particles;

(b) contacting the solid phase particle with a sample and label reagents to cause the second members and the label reagents to competitively bind to one of said first member on the multiple solid phase particles;

(c) washing the solid phase to remove unbound sample components;

(d) analyzing the solid phase to detect the label, which indirectly indicates binding of the second biomolecular binding pair member to the first biomolecular binding pair member; and

(e) decoding the index number encoded on at least a portion of the transponders to identify the class of transponders to which a biomolecule is bound.