Support for analyte determination methods and method for producing the support

• US 20040175734A1
• Filed: 12/05/2003
• Published: 09/09/2004
• Est. Priority Date: 08/28/1998
• Status: Abandoned Application

• Current Assignee: Febit Ferrarius Biotechnology GmbH
• Original Assignee: Febit Ferrarius Biotechnology GmbH
• Inventors: Miller, Manfred, Lindner, Hans, Stahler, Cord F., Stahler, Peer F., Stahler, Fritz
• Application Number:
  US10/727,566
• Publication Number:
  US 20040175734A1
• Time in Patent Office: Days
• US Class Current: 435/6
• 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 19/0093 Microreactors, e.g. miniaturised or microfabricated reactors laboratory containers with capillary fluid transport in microfabricated channels or chambers B01L3/5027
• CPC Class Codes: B01J 2219/00317 Microwell devices, i.e. having large numbers of wells
• CPC Class Codes: B01J 2219/00432 Photolithographic masks
• CPC Class Codes: B01J 2219/00436 Maskless processes
• CPC Class Codes: B01J 2219/00439 using micromirror arrays
• CPC Class Codes: B01J 2219/00441 using lasers
• CPC Class Codes: B01J 2219/00448 using microlens arrays
• CPC Class Codes: B01J 2219/00479 Means for mixing reactants or products in the reaction vessels
• CPC Class Codes: B01J 2219/00497 Features relating to the solid phase supports
• CPC Class Codes: B01J 2219/00511 Walls of reactor vessels
• CPC Class Codes: B01J 2219/00529 DNA chips
• 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 2219/00603 Making arrays on substantially continuous surfaces
• CPC Class Codes: B01J 2219/00605 the compounds being directly bound or immobilised to solid supports
• CPC Class Codes: B01J 2219/00608 DNA chips
• CPC Class Codes: B01J 2219/0061 The surface being organic
• CPC Class Codes: B01J 2219/00612 the surface being inorganic
• CPC Class Codes: B01J 2219/00621 : by physical means, e.g. trenches, raised areas
• CPC Class Codes: B01J 2219/00637 : by coating it with another layer
• CPC Class Codes: B01J 2219/00648 : by the use of solid beads
• 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 2219/00704 : integrated with the reactor apparatus
• CPC Class Codes: B01J 2219/00711 : Light-directed synthesis
• CPC Class Codes: B01J 2219/00722 : Nucleotides
• CPC Class Codes: B01J 2219/00725 : Peptides
• CPC Class Codes: B01L 2300/0654 : Lenses; Optical fibres
• CPC Class Codes: B01L 2300/069 : Absorbents; Gels to retain a fluid
• CPC Class Codes: B01L 2300/0816 : Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2300/0864 : comprising only one inlet and multiple receiving wells, e.g. for separation, splitting
• CPC Class Codes: B01L 3/502715 : characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
• 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: C12N 15/10 : Processes for the isolation, preparation or purification of DNA or RNA chemical preparation of DNA or RNA C07H21/00; preparation of non-structural polynucleotides from microorganisms or with enzymes C12P19/34
• CPC Class Codes: C12P 19/34 : Polynucleotides, e.g. nucleic acids, oligoribonucleotides
• 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 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: G01N 21/253 : for batch operation, i.e. multisample apparatus analytical automats G01N35/00
• CPC Class Codes: G01N 21/6454 : using an integrated detector array
• CPC Class Codes: G01N 33/551 : the carrier being inorganic
• CPC Class Codes: G03F 7/70216 : Mask projection systems
• CPC Class Codes: Y10S 435/97 : Test strip or test slide
• CPC Class Codes: Y10S 435/973 : Simultaneous determination of more than one analyte

Abstract

A method for producing a support for determining analytes. The method comprises the steps of (a) providing a support comprising at least one channel, comprising a conduit having an intake and an outlet for passing fluid from the intake to the outlet, in the support body, (b) passing liquid with building blocks for synthesizing polymeric receptors through the channel or channels of the support body, (c) site- and/or time-specifically immobilizing the receptor building blocks in each case on predetermined positions in the channel or channels by illumination and (d) repeating steps (b) and (c) until the required receptors have been synthesized in each case on the predetermined positions.

Claims

1. A method for producing a support for determining analytes, comprising the steps of

(a) providing a support body comprising at least one channel,

(b) passing liquid with building blocks for synthesizing polymeric receptors through the channel or channels of the support body,

(c) site- or/and time-specifically immobilizing the receptor building blocks in each case on predetermined positions in the channel or channels and

(d) repeating steps (b) and (c) until the required receptors have been synthesized in each case on the predetermined positions.

2. The method as claimed in claim 1, characterized in that a support which comprises defined area regions with, in each case, identical receptor species is produced.

3. The method as claimed in claim 1 or 2, characterized in that the channels are arranged on at least one support surface.

4. The method as claimed in any of claims 1 to 3, characterized in that the support comprises a large number of channels which are preferably arranged parallel to one another.

5. The method as claimed in any of claims 1 to 4, characterized in that the receptors are selected from nucleic acids and nucleic acid analogs.

6. The method as claimed in claim 5, characterized in that the receptor building blocks are selected from nucleotides, oligonucleotides, nucleotide analogs and oligonucleotide analogs.

7. The method as claimed in any of claims 1 to 4, characterized in that the receptors are selected from polypeptides.

8. The method as claimed in claim 7, characterized in that the receptor building blocks are selected from amino acids and peptides.

9. The method as claimed in any of claims 1 to 7, characterized in that the site- or/and time-specific immobilization of the receptor building blocks takes place by illumination.

10. The method as claimed in claim 9, characterized in that the illumination takes place via a programmable light source matrix.

11. The method as claimed in any of claims 1 to 8, characterized in that the site- or/and time-specific immobilization of the receptor building blocks takes place by wetting with an activating fluid with controllable selection of the activated positions.

12. The method as claimed in any of claims 1 to 11, characterized in that the pattern of polymeric receptors is fixed by computer programming.

13. The method as claimed in any of claims 1 to 12, characterized in that the support is used for determining analytes in a sample.

32. The use of the method as claimed in any of claims 1 to 25, of the support as claimed in claim 26 or 27, of the reagent kit as claimed in claim 28 or of the apparatus as claimed in any of claims 29 to 31 for determining an analyte in a sample.

33. The use as claimed in claim 32 for the sequencing of nucleic acids.

34. The use as claimed in claim 33 for new sequencing or/and resequencing of complex genetic material such as, for example, individual genomes or synthetic nucleic acids.

35. The use as claimed in claim 32 for obtaining diagnostic information for individual patient management such as, for example, the individual effect of pharmaceuticals.

36. The use as claimed in claim 32 for analyzing the effect of pharmacological substances.

37. The use as claimed in claim 32 for setting up and analyzing substance libraries.

38. The use as claimed in claim 32 for comparing individuals in a population.

14. A method for integrated synthesis and analyte determination on a support, comprising the steps of:

(a) providing a support body,

(b) passing a liquid with, present therein, receptors or building blocks for synthesizing polymeric receptors over the support,

(c) site- or/and time-specifically immobilizing the receptors or receptor building blocks in each case on predetermined positions on the support,

(d) where appropriate repeating steps (b) and (c) until the required receptors have been synthesized in each case on the predetermined positions on the support,

(e) bringing the support into contact with a sample containing analytes and

(f) determining the analytes via their binding to the receptors immobilized on the support.

15. The method as claimed in claim 14, characterized in that the synthesis and analyte determination is carried out in an integrated apparatus, with the synthesis or/and the analyte determination process being monitored and controlled in any number of positions on the support.

16. The method as claimed in claim 15, characterized in that an integrated apparatus comprising a programmable light source matrix, a detector matrix, a support arranged between light source matrix and detector matrix, and means for supplying fluids into the support and for discharging fluids from the support is used.

17. The method as claimed in any of claims 14 to 16, characterized in that the analyte is removed again from the support after the determination.

18. The method as claimed in any of claims 14 to 17, characterized in that a plurality of synthesis/analyte determination cycles is carried out, with the receptors or a subsequent cycle being synthesized on the basis of the information from a preceding cycle.

19. The method as claimed in claim 18, characterized in that an extension of the receptors from the preceding cycle takes place for the subsequent cycle.

20. The method as claimed in claim 18, characterized in that a new support with receptors which are modified compared with the preceding cycle is synthesized for the subsequent cycle.

21. The method as claimed in claim 20, characterized in that the modification of the receptors comprises a change in the sequence or/and an exclusion of negative receptors from the preceding cycle.

22. The method as claimed in any of claims 14 to 21, characterized in that a planar support is used.

23. The method as claimed in any of claims 14 to 21, characterized in that a support with a large number of channels is used.

24. The method as claimed in any of claims 14 to 23, characterized in that a plurality of supports is used for a synthesis/analyte determination cycle.

25. The method as claimed in claim 24, characterized in that the plurality of supports is synthesized and analyzed in different detection apparatuses between which there are information technology links but which may be spatially separate from one another.

26. A support for determining analytes comprising a large number of channels, in particular capillary channels, a large number of different receptors being immobilized in the channels.

27. A support as claimed in claim 26, characterized in that it is optically transparent at least in the region of the reaction regions.

28. A reagent kit comprising a support as claimed in claim 26 or 27 and building blocks for synthesizing polymeric receptors on the support.

29. An apparatus for integrated synthesis and analyte determination on a support comprising a programmable light source matrix, a detector matrix, a support arranged between light source matrix and detector matrix, and means for supplying fluids into the support and for discharging fluids from the support.

30. An apparatus as claimed in claim 29 additionally comprising means for deprotection of reaction components on the support.

31. An apparatus as claimed in claim 29 or 30 additionally comprising electronic control means.