[go: up one dir, main page]

WO2002018945A2 - Puce d'analyse - Google Patents

Puce d'analyse Download PDF

Info

Publication number
WO2002018945A2
WO2002018945A2 PCT/EP2001/009286 EP0109286W WO0218945A2 WO 2002018945 A2 WO2002018945 A2 WO 2002018945A2 EP 0109286 W EP0109286 W EP 0109286W WO 0218945 A2 WO0218945 A2 WO 0218945A2
Authority
WO
WIPO (PCT)
Prior art keywords
molecules
code
analysis chip
immobilized
type
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/EP2001/009286
Other languages
German (de)
English (en)
Other versions
WO2002018945A3 (fr
Inventor
Ralph Müller
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Sygnis Pharma AG
Original Assignee
BASF Lynx Bioscience AG
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by BASF Lynx Bioscience AG filed Critical BASF Lynx Bioscience AG
Priority to AU2002212136A priority Critical patent/AU2002212136A1/en
Publication of WO2002018945A2 publication Critical patent/WO2002018945A2/fr
Publication of WO2002018945A3 publication Critical patent/WO2002018945A3/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J19/0046—Sequential or parallel reactions, e.g. for the synthesis of polypeptides or polynucleotides; Apparatus and devices for combinatorial chemistry or for making molecular arrays
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00277—Apparatus
    • B01J2219/00497—Features relating to the solid phase supports
    • B01J2219/00527—Sheets
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00277—Apparatus
    • B01J2219/00497—Features relating to the solid phase supports
    • B01J2219/00527—Sheets
    • B01J2219/00529—DNA chips
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00277—Apparatus
    • B01J2219/0054—Means for coding or tagging the apparatus or the reagents
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00277—Apparatus
    • B01J2219/0054—Means for coding or tagging the apparatus or the reagents
    • B01J2219/00542—Alphanumeric characters
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00277—Apparatus
    • B01J2219/0054—Means for coding or tagging the apparatus or the reagents
    • B01J2219/00547—Bar codes
    • B01J2219/00549—2-dimensional
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583—Features relative to the processes being carried out
    • B01J2219/00603—Making arrays on substantially continuous surfaces
    • B01J2219/00605—Making arrays on substantially continuous surfaces the compounds being directly bound or immobilised to solid supports
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583—Features relative to the processes being carried out
    • B01J2219/00603—Making arrays on substantially continuous surfaces
    • B01J2219/00605—Making arrays on substantially continuous surfaces the compounds being directly bound or immobilised to solid supports
    • B01J2219/00608—DNA chips
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583—Features relative to the processes being carried out
    • B01J2219/00603—Making arrays on substantially continuous surfaces
    • B01J2219/00605—Making arrays on substantially continuous surfaces the compounds being directly bound or immobilised to solid supports
    • B01J2219/0061—The surface being organic
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583—Features relative to the processes being carried out
    • B01J2219/00603—Making arrays on substantially continuous surfaces
    • B01J2219/00605—Making arrays on substantially continuous surfaces the compounds being directly bound or immobilised to solid supports
    • B01J2219/00612—Making arrays on substantially continuous surfaces the compounds being directly bound or immobilised to solid supports the surface being inorganic
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583—Features relative to the processes being carried out
    • B01J2219/00603—Making arrays on substantially continuous surfaces
    • B01J2219/00659—Two-dimensional arrays
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/0068—Means for controlling the apparatus of the process
    • B01J2219/00702—Processes involving means for analysing and characterising the products
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00718—Type of compounds synthesised
    • B01J2219/0072—Organic compounds
    • B01J2219/00722—Nucleotides
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00718—Type of compounds synthesised
    • B01J2219/0072—Organic compounds
    • B01J2219/00725—Peptides
    • C—CHEMISTRY; METALLURGY
    • C40—COMBINATORIAL TECHNOLOGY
    • C40B—COMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES
    • C40B40/00—Libraries per se, e.g. arrays, mixtures
    • C40B40/04—Libraries containing only organic compounds
    • C40B40/06—Libraries containing nucleotides or polynucleotides, or derivatives thereof
    • C—CHEMISTRY; METALLURGY
    • C40—COMBINATORIAL TECHNOLOGY
    • C40B—COMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES
    • C40B40/00—Libraries per se, e.g. arrays, mixtures
    • C40B40/04—Libraries containing only organic compounds
    • C40B40/10—Libraries containing peptides or polypeptides, or derivatives thereof
    • C—CHEMISTRY; METALLURGY
    • C40—COMBINATORIAL TECHNOLOGY
    • C40B—COMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES
    • C40B70/00—Tags or labels specially adapted for combinatorial chemistry or libraries, e.g. fluorescent tags or bar codes

Definitions

  • the invention relates to an analysis chip on which different types of molecules are immobilized in the respectively assigned spatial areas.
  • samples containing DNA or RNA molecules are being analyzed qualitatively or quantitatively using suitable DNA arrays.
  • suitable DNA arrays the binding or hybridization of the DNA molecules obtained to suitable DNA fragments, so-called targets, immobilized on the array is detected.
  • DNA arrays which are also called biochips. These are usually produced from microtiter plates that contain solutions with suitable DNA fragments in the wells.
  • the wells are small wells with a volume per well of, for example, 20 ⁇ l.
  • Each well contains a known, specially synthesized DNA fragment.
  • To build a DNA array e.g. 220 pl solution from a well to a precisely defined position on e.g. pipetted on a slide. This is done by so-called spotting robots. The pipetted DNA fragments are then immobilized on the slide or chip or target carrier.
  • the sample to be analyzed is then placed on the target carrier or the DNA array.
  • the sample contains radioactive or colored DNA or RNA molecules.
  • Hybridization takes place in a special hybridization chamber at a suitable temperature.
  • Non-hybridized or non-specifically bound DNA or RNA from the sample to be examined is removed by rinsing.
  • hybridized DNA or RNA molecules are detected according to their labeling in a reader.
  • Fluorescence signals can result from fluorescence labeling of the sample or target or by intercalators. Energy transfer or mechanisms of fluorescence quenching between sample and target can also be used.
  • the object of the invention is to increase the security of analysis and evaluation when using arrays and DNA chips. This object is achieved by the inventions according to the independent claims. Advantageous developments of the inventions are characterized in the subclaims.
  • an analysis chip is used on which different types of molecules are immobilized in the respectively assigned spatial areas.
  • these are DNA arrays.
  • the immobilized molecules are then, for example, gene segments or oligonucleotides that uniquely identify a gene.
  • it can also be antibody, protein, allergen arrays etc. or non-peptide chemical substance libraries.
  • the analysis chips are usually used to detect binding reactions. However, the detection of an enzymatic activity is also possible.
  • the spatial area assigned to a type of molecule is usually a rectangle or a circle, as it arises in spotting processes.
  • the area can also be distributed linearly or according to a predetermined scheme over the entire analysis chip in order to compensate for or find irregularities in the hybridization and to generate a redundancy of the hybridization reaction which increases the reliability of the marker analysis.
  • an associated code is formed on the analysis chip in an associated spatial area for each type of molecule, the code indicating what type of molecules is immobilized in the respective area.
  • each type of molecule is assigned a spatial area in which these molecules are immobilized.
  • a code is assigned to each type of molecule.
  • Each code in turn has a spatial area on the analysis chip in which it is formed. This associated spatial area can be identical to the spatial area in which the molecules are immobilized. However, it can also be adjacent to this spatial area or assigned to the immobilization area according to a fixed scheme.
  • the code can be read out at the same time and thus it can be determined which type of molecules the sample has bound to. It is then no longer necessary to provide array-specific information about the type and arrangement of the molecules on a supplementary sheet or in accompanying software. This prevents confusion between different types of molecules. This significantly increases safety in handling, evaluation and diagnosis.
  • the code is formed by the arrangement of the molecules themselves in the associated spatial area. In this way, the reaction result and the code can be read out in just one step.
  • each spatial area on the analysis chip assigned to a predetermined type of molecules is divided into a plurality of spots, and in that the code is a binary code which is generated by immobilizing molecules in some of these spots are and not in the remaining spots.
  • the binary code can be encoded, for example, in that an immobilized spot has a 1 and a free spot has a zero. speaks, or vice versa.
  • a database which is generally accessible on the Internet, explains how the individual codes are assigned to the immobilized types of molecules.
  • redundancy of the hybridization reaction is obtained because there is more than one spot for each type of molecule.
  • Such a type of redundancy can be referred to as "internal" redundancy.
  • “External” redundancy is spoken of if more than one code is assigned to a molecular type, so that the code of the molecular type can still be recognized under certain circumstances if a spot does not provide a complete hybridization signal, for example due to technical shortcomings, although this was to be expected would.
  • the codes can be optimized for external redundancy with regard to fault tolerance. In the simplest case, this is achieved in that more bits are used per code, • would be needed as a minimum, about 4 are then both the 4-bit code instead of 3.
  • the code can be formed on the analysis chip independently of the immobilized molecules.
  • the code can then be generated using conventional means, such as a laser recorder such as the CD burner principle or a high-resolution printer.
  • the code can be arranged on the underside of the analysis chip.
  • the code on the underside of the analysis chip is first used in an area clearly assigned to the molecular spots, e.g. the same spatial position.
  • the analysis chip is then turned over and the hybridization signal, for example a fluorescence signal or radioactive radiation, is read out.
  • the examples focus on general fluorescence signals.
  • code and spots can be applied on the same carrier side, target spots and code being in the same spatial area and the target spot (s) being applied to the code area.
  • the code can be formed between the spots, for example in the gaps between circular spots. In such a case le only one spot needs to be set up for each type of molecule.
  • the code can be applied using common technical means, such as laser marking or microspotting (piezo, pin, imprint, etc.).
  • the code is preferably designed in the form of a two-dimensional barcode. This can be based on current standards, such as the type C symbol from the .One code from Axtel, Inc., Fountain Valley, CA 92708, USA, www.Axtel.com, which can encode 64 alphanumeric characters.
  • the code could then encode an alphanumeric string that represents the name of the immobilized type of molecule, for example the annotation of the gene as defined in a publicly accessible database. It was then no longer necessary to explain in a database that is generally accessible on the Internet, how the individual codes are assigned to the immobilized types of molecules. Sufficiently would in such a case, the simple indication of Code One Type C von Axtel- on the chip, associated with 'a reference to the database, see the sequences of the genes with the corresponding annotation.
  • a standardized array code could be stored for each global database entry (e.g. in the EMBL database), which allows the clear and reliable assignment of molecular types to all two-dimensional or multi-dimensional storage formats.
  • position marks can also be formed on the analysis chip. These can e.g. are formed by one of the areas with a plurality of spots, each spot carrying immobilized molecules, while in the areas with molecules which are used for the binding reaction, not all spots are occupied. Because on the latter a code is formed, which consists of occupied and unused spots.
  • the position marks could be characterized by the fact that all 25 spots are occupied and additionally serve as a basic pattern for the evaluation algorithm. In general, as few position marks as possible should be applied overall, since this does not take up too much spotting area.
  • a position mark already enables a precise spatial orientation of the analysis chip in a chip carrying a code according to the invention.
  • the codes can be selected in such a way that if the evaluation mask is shifted by one line or column, no more useful code is recognized. On the one hand, this increases security against incorrect reading in the event of displacements. On the other hand, it can also be recognized that there is a mask shift here.
  • the code can consist of a first part that describes the organism from which a gene comes, while a second part of the code names the gene itself. In this way, analysis chips can be set up that each carry all of the genes of humans or all of the genes of the mouse or another organism.
  • the hierarchical code can be from. consist of a first and a second part.
  • the first part of the hierarchical code can be arranged, for example, in the position marks, while the second part is arranged in the respective regions of the immobilized molecules.
  • the type of coding of the second part of the code in the respective areas and the type of coding of the first part of the code in the position marks should clearly differ from one another so that the position marks can still be recognized as such.
  • a second type of molecules can additionally be immobilized within a spatial area which is assigned to a first type of molecules.
  • the associated code can be tion of the molecules within one spatial region.
  • a further possibility of occupying slots several times can be achieved by designing the spots belonging to a type of molecule with a predetermined spatial pattern.
  • the spot for the individual types of target molecules can be in the form of an arrow, egg or eccentric, ie one Object that has a preferred direction that is oriented differently depending on the type of molecule.
  • Such patterns can be applied particularly easily when the target is transferred to the analysis chip by means of stamps which can also be rotated.
  • Spatial patterns can also be obtained, for example, by spotting a small circle and a large circle partially overlapping. In this case too, the spots belonging to a certain code can be recognized by the fact that they have the same spatial pattern.
  • a further efficient use of the space within an area can be achieved in that the distance between the spots of a first type of molecule within the one area and the distance between the spots of a second type of molecule within the same area differ.
  • the distance from spot to spot (pitch) can be 100 ⁇ m for the first type of molecule and 98 ⁇ m for the second type of molecule, in the manner of a vernier. Such a shift is easy to see. In this way, a specific pitch can be assigned to each type of molecule.
  • the spots of individual types of molecules can overlap, as can easily result from the different pitch.
  • the spot density can also be increased by a defined overlap of the spots.
  • the various possibilities of multiple use of an area mentioned above can all be combined with one another.
  • the security in the use of analysis chips can also be increased in that after reading out a detection reaction on the analysis chip, the result of the detection reaction is written on the analysis chip. In this way, information, such as a finding for medical purposes, is retained even if, for example, the DNA on the chip should degrade.
  • the analysis chip can then simply be given to the patient.
  • the analysis chip can also carry one of the types of coding mentioned.
  • the analysis result can be written to the analysis chip in a defined code form using customary means, for example by means of a laser, an ink jet or a laser printer. ckers, or other inscription-s * procedure.
  • the information should be readable as permanently as possible.
  • 1A shows the schematic structure of a preferred DNA array
  • FIG. 1B shows an evaluation of the DNA array according to FIG. 1A
  • 2A shows the schematic structure of an alternative DNA array
  • 2B shows the schematic structure of a further alternative DNA array
  • Fig. 5 is a schematic representation of an analysis chip on which the result of a detection reaction can be written.
  • FIG. 1A shows a DNA chip 10 with regions 12 arranged on a rectangular grid. Within each region 12 there is a grid of spots 14 on which oligonucleotides are immobilized. Position marks 16 are located at the outermost corners of the chip, which can be recognized by the fact that all spots 14 are occupied within their areas. Not all spots are occupied in one of the position marks 18, which can be recognized as a position mark due to its spatial position. Rather, this position marker 18 has a code for the word "human".
  • the DNA chip 10 is therefore a chip for a genetic test on humans.
  • the code in the position marker 18 can be built up, for example, by immobilizing dye molecules on individual spots in the simplest case, which corresponds to a set bit, while other spots are left free. In addition to dye molecules, double-stranded DNA molecules can also be immobilized, which are detected using intercalators.
  • an area 20 which has a code for the annotation of a first gene, for example "actin", ie here oligo- or polynucleotides are immobilized which are clearly representative of the gene which is present in humans encodes the protein ACTIN.
  • a code for a second gene has been generated by immobilizing the associated oligo / polynucleotides. In this way, one gene can be encoded in each area of the DNA array. If the genes are ambiguous, further information such as splice and mutation variants, polymorphisms, sequence areas and lengths, etc. can also be encoded.
  • FIG. 1B shows the analysis chip according to FIG. 1A as it can be displayed on a screen after reading out by a fluorescence reader and evaluation. All areas 16, 18, 20, 22 are identified in their position and marked by rectangles. Areas 22 in which no hybridization signals could be recognized are crossed out. Areas 22 in which hybridization signals but no code could be recognized are e.g. marked with a crossed out full circle. Areas 20 in which a code was recognized are with the recognized code or the Em ⁇ or ⁇ S- ⁇ t-2 ⁇ a ⁇ gtoes-telmr ⁇ iElmatischen structure of an alternative DNA array 10, in which the code is independent of the molecules immobilized in spots 14 is formed in areas 24 of the DNA array 10 which lie in the gaps between the essentially circular spots 14.
  • FIG. 2B shows a preferred embodiment of a variant of the DNA array according to FIG. 2A, in which the oligonucleotides are immobilized directly above the two-dimensional bar code. Since a thin layer of oligo / polynucleotides is essentially transparent, the code can also be read through the DNA or proteins without difficulty.
  • the code is in the form of a two-dimensional bar code.
  • the type A symbol from Code One from Axtel, Inc., Fountain Valley, CA 92708, USA, www.Axtel.com is used as the standard for the code.
  • This standard allows the coding of 13 alphanumeric characters in 18 x 16 fields.
  • Type C symbol another variant, can encode 64 alphanumeric characters in 28 x 32 fields.
  • these codes are error-correcting, which further increases reading security.
  • the code size of symbol type A of 18 x 16 spots and the resulting small size of the code areas of approx. 100 ⁇ m edge length, on a single DNA chip of approx. 10 cm ⁇ 2 size the entire human genome with its almost 100,000 genes can be made available for a test.
  • Code One symbol type A is not used, but a simple binary code to designate the approximately 100,000 human genes, less than 20 bits are required. A range of 4x5 spots is therefore completely sufficient. To store the entire genome on a 10 cm A 2 chip, spot sizes of approx. 20 ⁇ m are sufficient.
  • FIG. 3A shows a possibility of forming the spots belonging to a type of molecule with a predetermined spatial pattern, here by an arrow 26 for a first gene, an arrow 28 for a second gene, etc.
  • 3B shows a further possibility of spatial coding.
  • two circles of essentially the same size are spotted side by side in different spatial arrangements, which results in spatial patterns 26 ', 28', etc. for different genes.
  • Fig. 3C shows the pattern of Fig. 3B when some of them are spotted on top of each other.
  • 3D shows a further possibility of spatial coding.
  • eccentrics with different spatial orientations are spotted essentially overlapping, which results in spatial patterns 26 ′′, 28 ′′, etc. for different genes.
  • the large circle in the middle contains immobilized molecules for all genes.
  • the distance (pitch) XI of the spots 30 of a first type of molecule within the area and the distance X2 of the spots 32 of a second type of molecule within the area differ slightly in two dimensions.
  • the distance XI can be 100 ⁇ m and the distance X2 can be 98 ⁇ m, in the manner of a vernier. Such a shift is easy to see.
  • a specific two-dimensional pitch can be assigned to each type of molecule. If only a few bits are set within a range, ie only a few spots are occupied for a code, the probability that two occupied spots overlap is relatively low.
  • a gene sorting algorithm can guarantee the greatest possible packing density with the highest level of detection reliability.
  • FIG. 5 shows a DNA array 34 onto which the result of the detection reaction can be written after reading out a detection reaction.
  • the DNA array 34 shows a section 36 in which the result can be written using conventional means.
  • the DNA array 34 shows a section 38 in which target molecules are immobilized. Which molecules are immobilized in the individual regions 40 of section 38 is indicated by a code which is represented by the spatial immobilization pattern. How the code is to be read is specified in a third section 42 on the DNA array 34. In the present case, it is stated that Code Alpha is used. Code Alpha can be explained elsewhere, for example on the Internet. 5 corresponds to FIG. IB.
  • the code can be stored in an associated spatial area on the surface of the chip or inside the chip, for example in an electronic memory chip, which can be read out via a contact field, like a telephone card.
  • all storage media can be used as long as they are in or on the chip itself, e.g. also a magnetic stripe on the chip.
  • Results of a detection reaction can also be written to such an electronic or other memory on or in the chip.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)

Abstract

L'invention concerne une puce d'analyse (10), par exemple un jeu ordonné d'échantillons d'ADN, sur laquelle sont immobilisées différents types de molécules respectivement dans différentes zones spatiales (14). Chaque type de molécules d'une zone spatiale (24) correspondante est associé à un code correspondant qui indique le type des molécules immobilisées dans la zone respective. Ce code peut être composé selon la disposition des molécules. Si, par exemple, dans une zone de 5x5 points seuls certains points sont occupés, on a un code binaire. En variante, le code (24) est représenté sur la puce quelles que soient les molécules immobilisées, par exemple, sous forme de code binaire bidimensionnel. L'utilisation du jeu ordonné d'échantillons d'ADN permet d'augmenter le degré de sécurité. En effet, lors de la lecture de la puce à l'aide du code respectif lui-même, on peut même déterminer quelle molécule cible a été liée et donc quelles molécules sont contenues dans l'échantillon sans avoir recours à des informations extérieures.
PCT/EP2001/009286 2000-08-30 2001-08-10 Puce d'analyse Ceased WO2002018945A2 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU2002212136A AU2002212136A1 (en) 2000-08-30 2001-08-10 Analysis chip

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE2000142797 DE10042797C2 (de) 2000-08-30 2000-08-30 Analysen-Chip
DE10042797.9 2000-08-30

Publications (2)

Publication Number Publication Date
WO2002018945A2 true WO2002018945A2 (fr) 2002-03-07
WO2002018945A3 WO2002018945A3 (fr) 2002-06-27

Family

ID=7654438

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2001/009286 Ceased WO2002018945A2 (fr) 2000-08-30 2001-08-10 Puce d'analyse

Country Status (3)

Country Link
AU (1) AU2002212136A1 (fr)
DE (1) DE10042797C2 (fr)
WO (1) WO2002018945A2 (fr)

Cited By (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1226866A3 (fr) * 2001-01-29 2003-12-10 Agilent Technologies, Inc. (a Delaware corporation) Production de matrices chimiques avec carte d'identification
EP1247570A3 (fr) * 2001-03-30 2003-12-17 Agilent Technologies, Inc. Lecture d'un array chimique
WO2005024695A3 (fr) * 2003-09-03 2005-11-03 Agilent Technologies Inc Procedes pour coder des informations non biologiques sur des microreseaux
EP1584372A3 (fr) * 2004-04-10 2005-11-16 Samsung Electronics Co., Ltd. Un micro-réseau avec d'information d'identification enregistrée sous forme d'un spot et et son procédé de préparation
WO2008096318A3 (fr) * 2007-02-09 2008-10-30 Koninkl Philips Electronics Nv Système d'identification
DE102009019476A1 (de) * 2009-05-04 2010-11-11 Biametrics Marken Und Rechte Gmbh Wiedererkennbarer Träger für optische Meßverfahren
WO2013013832A1 (fr) * 2011-07-27 2013-01-31 Scienion Ag Dispositif marqué
EP2933017A1 (fr) * 2014-04-17 2015-10-21 AyoxxA Biosystems GmbH Dispositif codé et procédé de codage et de décodage de zones de référence sur un substrat
WO2018144531A1 (fr) 2017-02-01 2018-08-09 Illumina, Inc. Système et procédé avec repères répondant à de multiples fréquences d'excitation
US11249025B2 (en) 2017-02-01 2022-02-15 Illumina, Inc. System and method with fiducials in non-rectilinear layouts
US11262307B2 (en) 2017-02-01 2022-03-01 Illumina, Inc. System and method with reflective fiducials for locating or registering locations receiving biological samples in successive cycles of fluorescent imaging
US11427868B2 (en) 2017-02-01 2022-08-30 Illumina, Inc. System and method with fiducials of non-closed shapes
US11835460B2 (en) 2017-02-01 2023-12-05 Illumina, Inc. System and method with fiducials having offset layouts

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20050135964A1 (en) * 2003-12-22 2005-06-23 Ulrich Sieben Carrier medium for analyzing a substance
WO2009091039A1 (fr) * 2008-01-16 2009-07-23 Nippon Telegraph And Telephone Corporation Dispositif de mesure à résonance plasmonique de surface, cellule d'échantillon, et procédé de mesure

Family Cites Families (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ES2097925T3 (es) * 1991-09-18 1997-04-16 Affymax Tech Nv Metodo para sintetizar diversas colecciones de oligomeros.
US5736332A (en) * 1995-11-30 1998-04-07 Mandecki; Wlodek Method of determining the sequence of nucleic acids employing solid-phase particles carrying transponders
US6458530B1 (en) * 1996-04-04 2002-10-01 Affymetrix Inc. Selecting tag nucleic acids
US5935785A (en) * 1997-04-30 1999-08-10 Motorola, Inc. Binding assay methods
DE69916421T2 (de) * 1998-09-09 2005-03-24 Hitachi Software Engineering Co., Ltd., Yokohama Biochip und verfahren zur verwendung des biochips
CA2347125A1 (fr) * 1998-10-16 2000-04-27 Larry S. Millstein Procedes permettant de creer des reseaux a motifs de molecules de liaison d'analytes
US6215894B1 (en) * 1999-02-26 2001-04-10 General Scanning, Incorporated Automatic imaging and analysis of microarray biochips
JP3469504B2 (ja) * 1999-06-01 2003-11-25 日立ソフトウエアエンジニアリング株式会社 マイクロアレイチップ及びそのインデックス方法

Cited By (20)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1226866A3 (fr) * 2001-01-29 2003-12-10 Agilent Technologies, Inc. (a Delaware corporation) Production de matrices chimiques avec carte d'identification
EP1247570A3 (fr) * 2001-03-30 2003-12-17 Agilent Technologies, Inc. Lecture d'un array chimique
WO2005024695A3 (fr) * 2003-09-03 2005-11-03 Agilent Technologies Inc Procedes pour coder des informations non biologiques sur des microreseaux
EP1584372A3 (fr) * 2004-04-10 2005-11-16 Samsung Electronics Co., Ltd. Un micro-réseau avec d'information d'identification enregistrée sous forme d'un spot et et son procédé de préparation
CN100352942C (zh) * 2004-04-10 2007-12-05 三星电子株式会社 具有微阵列识别信息的微阵列及其生产方法和使用方法
WO2008096318A3 (fr) * 2007-02-09 2008-10-30 Koninkl Philips Electronics Nv Système d'identification
US10076755B2 (en) 2009-05-04 2018-09-18 Biametrics Gmbh Recognizable carrier for optical measurement methods
DE102009019476A1 (de) * 2009-05-04 2010-11-11 Biametrics Marken Und Rechte Gmbh Wiedererkennbarer Träger für optische Meßverfahren
WO2010127834A1 (fr) * 2009-05-04 2010-11-11 Biametrics Marken Und Rechte Gmbh Support reconnaissable pour procédés de mesure optiques
WO2013013832A1 (fr) * 2011-07-27 2013-01-31 Scienion Ag Dispositif marqué
US20140213483A1 (en) * 2011-07-27 2014-07-31 Uwe Radelof Labeled device
EP2933017A1 (fr) * 2014-04-17 2015-10-21 AyoxxA Biosystems GmbH Dispositif codé et procédé de codage et de décodage de zones de référence sur un substrat
WO2015158911A1 (fr) * 2014-04-17 2015-10-22 AyoxxA Biosystems GmbH Dispositif codé et procédé de codage et de décodage de zones de référence sur un substrat
WO2018144531A1 (fr) 2017-02-01 2018-08-09 Illumina, Inc. Système et procédé avec repères répondant à de multiples fréquences d'excitation
EP3576868A4 (fr) * 2017-02-01 2021-03-17 Illumina, Inc. Système et procédé avec repères répondant à de multiples fréquences d'excitation
US11249025B2 (en) 2017-02-01 2022-02-15 Illumina, Inc. System and method with fiducials in non-rectilinear layouts
US11262307B2 (en) 2017-02-01 2022-03-01 Illumina, Inc. System and method with reflective fiducials for locating or registering locations receiving biological samples in successive cycles of fluorescent imaging
US11427868B2 (en) 2017-02-01 2022-08-30 Illumina, Inc. System and method with fiducials of non-closed shapes
US11835460B2 (en) 2017-02-01 2023-12-05 Illumina, Inc. System and method with fiducials having offset layouts
US11896944B2 (en) 2017-02-01 2024-02-13 Illumina, Inc. System and method with fiducials responding to multiple excitation frequencies

Also Published As

Publication number Publication date
AU2002212136A1 (en) 2002-03-13
DE10042797A1 (de) 2002-03-28
WO2002018945A3 (fr) 2002-06-27
DE10042797C2 (de) 2003-12-04

Similar Documents

Publication Publication Date Title
DE10042797C2 (de) Analysen-Chip
DE69839373T2 (de) Auf die Verwendung von nukleaseresistenten Fragmenten basierende Verfahren und Kits, die für Nukleinsäuretests mit hohem Durchsatz geeignet sind
DE60125312T2 (de) Mikroarray
DE69431719T2 (de) Hybridisierung und sequenzierung von nukleinsäuren
DE19740263C2 (de) Kachelungsverfahren zum Bauen eines chemischen Arrays
DE69333650T2 (de) Neue anordnungn von oligonukleotiden und ihr nutzen zum sortieren, isolieren, sequenzieren und manipulieren von nukleinsäuren
DE69430207T2 (de) Mikrofabriziertes poröses durchflussgerät
US6869763B1 (en) Microarray chip and method for indexing the same
DE69916421T2 (de) Biochip und verfahren zur verwendung des biochips
DE112014007175B4 (de) Substrat zur Verwendung bei der Analyse einer Nucleinsäure, Durchflusszelle zur Verwendung bei der Analyse einer Nucleinsäure und Nucleinsäure-Analysenvorrichtung
EP1007741A1 (fr) Procede de marquage de substances solides, liquides ou gazeuses
DE10037687A1 (de) Verfahren zur Herstellung von Oligonucleotid-Arrays und zur Durchführung von Hybridisierungs-Assays sowie Anlagen zur Durchführung dieser Verfahren
DE10137864B4 (de) Substanzträger mit Markierung
EP1260592A1 (fr) Biopuce
EP1397216B1 (fr) Procede de synthese et de transfert paralleles de molecules sur un substrat
WO2001056691A2 (fr) Procede et dispositif pour effectuer la synthese et l'analyse d'ensembles d'oligomeres, lies a un support, notamment de paires d'amorces pour la pcr, ainsi que supports comportant ces oligomeres
EP1234056B1 (fr) Determination dynamique d'analytes en utilisant une puce localisee sur une surface interne
DE60307760T2 (de) Chemische Arrays mit Verbindungsschicht
WO2022128610A1 (fr) Procédé et appareil pour attribuer un réactif spécifique à un espace de réaction
EP1000918B1 (fr) Procédé de vérification de la synthèse de molécules organiques en chimie combinatoire
DE69719312T2 (de) Verfahren und vorrichtung zur behandlung durch komplexierung eines wässrigen milieus
WO2002057013A2 (fr) Puce d'analyse a plusieurs niveaux fonctionnels destinee a la localisation par electrofocalisation
DE3921099A1 (de) Maschinenlesbarer datentraeger
WO2002004111A2 (fr) Puce a base de polymeres
WO2001040510A2 (fr) Sequençage dynamique par hybridation

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A2

Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BY BZ CA CH CN CO CR CU CZ DE DK DM DZ EC EE ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NO NZ PL PT RO RU SD SE SG SI SK SL TJ TM TR TT TZ UA UG US UZ VN YU ZA ZW

AL Designated countries for regional patents

Kind code of ref document: A2

Designated state(s): GH GM KE LS MW MZ SD SL SZ TZ UG ZW AM AZ BY KG KZ MD RU TJ TM AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE TR BF BJ CF CG CI CM GA GN GQ GW ML MR NE SN TD TG

121 Ep: the epo has been informed by wipo that ep was designated in this application
AK Designated states

Kind code of ref document: A3

Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BY BZ CA CH CN CO CR CU CZ DE DK DM DZ EC EE ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NO NZ PL PT RO RU SD SE SG SI SK SL TJ TM TR TT TZ UA UG US UZ VN YU ZA ZW

AL Designated countries for regional patents

Kind code of ref document: A3

Designated state(s): GH GM KE LS MW MZ SD SL SZ TZ UG ZW AM AZ BY KG KZ MD RU TJ TM AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE TR BF BJ CF CG CI CM GA GN GQ GW ML MR NE SN TD TG

DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
REG Reference to national code

Ref country code: DE

Ref legal event code: 8642

122 Ep: pct application non-entry in european phase
NENP Non-entry into the national phase

Ref country code: JP