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WO2006000275A1 - Procede de fabrication de puces a adn a partir de substrats poreux - Google Patents

Procede de fabrication de puces a adn a partir de substrats poreux Download PDF

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Publication number
WO2006000275A1
WO2006000275A1 PCT/EP2005/005056 EP2005005056W WO2006000275A1 WO 2006000275 A1 WO2006000275 A1 WO 2006000275A1 EP 2005005056 W EP2005005056 W EP 2005005056W WO 2006000275 A1 WO2006000275 A1 WO 2006000275A1
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WO
WIPO (PCT)
Prior art keywords
rod
porous substrate
shaped
pores
mask
Prior art date
Application number
PCT/EP2005/005056
Other languages
German (de)
English (en)
Inventor
Stephan Dertinger
Thomas Haneder
Alfred Martin
Original Assignee
Infineon Technologies 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 Infineon Technologies Ag filed Critical Infineon Technologies Ag
Publication of WO2006000275A1 publication Critical patent/WO2006000275A1/fr

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    • 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
    • B01J2219/00351—Means for dispensing and evacuation of reagents
    • B01J2219/00373—Hollow needles
    • B01J2219/00376—Hollow needles in multiple or parallel arrangements
    • 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
    • B01J2219/00351—Means for dispensing and evacuation of reagents
    • B01J2219/00427—Means for dispensing and evacuation of reagents using masks
    • 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
    • B01J2219/00513—Essentially linear supports
    • B01J2219/0052—Essentially linear supports in the shape of elongated tubes
    • 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
    • B01J2219/00513—Essentially linear supports
    • B01J2219/0052—Essentially linear supports in the shape of elongated tubes
    • B01J2219/00522—Essentially linear supports in the shape of elongated tubes in a multiple parallel arrangement
    • 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
    • B01J2219/00583—Features relative to the processes being carried out
    • B01J2219/00603—Making arrays on substantially continuous surfaces
    • B01J2219/00664—Three-dimensional arrays
    • B01J2219/00666—One-dimensional arrays within three-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
    • B01J2219/00583—Features relative to the processes being carried out
    • B01J2219/00603—Making arrays on substantially continuous surfaces
    • B01J2219/00673—Slice 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
    • B01J2219/00583—Features relative to the processes being carried out
    • B01J2219/00603—Making arrays on substantially continuous surfaces
    • B01J2219/00677—Ex-situ synthesis followed by deposition on the substrate
    • 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
    • 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
    • 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
    • C40B60/00—Apparatus specially adapted for use in combinatorial chemistry or with libraries
    • C40B60/14—Apparatus specially adapted for use in combinatorial chemistry or with libraries for creating libraries

Definitions

  • the present invention relates to a method for the production of biochips from porous substrates, wherein the biological-chemical substances used in a corresponding assay as probes or capture molecules are first applied to the pore surfaces of a relatively long, rod-shaped, porous substrate, which subsequently into small finished Biochips is isolated.
  • the homogeneity of the individual chips can be improved and the production speed can be increased.
  • Porous substrates are due to their advantageous optical and fluid properties very well as a substrate for DNA and protein microarrays.
  • biochemical substances > 100
  • DNA, antibodies and proteins The biological substances are usually dissolved in a suitable buffer and applied spot by spot in a sequential process on the surface of the porous substrate by means of dispensing technique. Due to the sequential nature of this process is very time consuming. However, especially for high spot count arrays, it is desirable to parallelize the dispensing process.
  • the biological-chemical substance by various "spotting u such as reservoir needle, pin-and-ring or Piezobacter in which a biochemical substance such as a previously synthesized oligonucleotide as a microdroplets deposited locally on the substrate surface is, applied.
  • a biochemical substance such as a previously synthesized oligonucleotide as a microdroplets deposited locally on the substrate surface is, applied.
  • the spotting can be parallelized by the use of several such needles. However, this places higher demands on the logistics of the substances to be mocked.
  • Another problem is the homogeneity of the spots. For many needles, it can not be ensured that the amounts of liquid deposited are identical for all needles.
  • Another approach to achieving higher throughput is to use a miniaturized dispensing head that can deposit up to 384 spots simultaneously (see WO 01/62377).
  • Each dispensing nozzle is connected to a reservoir via a hose.
  • the technical effort for example, to align the substrate and Dispensierkopf plan-parallel to each other (minimizing the wedge error), however, is extremely high. In case of insufficient adjustment, no reproducible and homogeneous spots are available.
  • the present invention is therefore based on the object to enable a method which overcomes the above problems.
  • methods are provided, which are characterized in that the biological-chemical substances used in a corresponding assay as probes or catcher molecules are first applied to the pore surfaces of a rod-shaped porous substrate, which is then singulated into small, finished biochips. By doing so, the homogeneity of the individual biochips can be improved and the production speed can be increased.
  • a method of manufacturing a plurality of discrete biochips from a rod-shaped, porous substrate comprising the steps of: (i) providing a rod-shaped porous substrate having pores with a diameter in the range of between 1 ⁇ m and 100 microns and has a cross-sectional area which corresponds to the dimensions of a single biochip to be manufactured; (ii) coating the pore surfaces of the rod-shaped porous substrate with chemical molecules acting as catcher molecules, and (iii) slicing the rod-shaped porous substrate so as to obtain singulated, finished biochips having a thickness in the range of 100 to 1,000 ⁇ m.
  • the macroporous substrate used in step (i) preferably has a pore diameter of 1 ⁇ m to 50 ⁇ m, more preferably 1 to 20 ⁇ m.
  • the distance from the center of the pore to the center of the pore (pitch), ie, two adjacent or adjacent pores, is usually 1 to 100 ⁇ m, preferably 2 to 12 ⁇ m.
  • the pore density is usually in the range of 10 4 to 10 8 / cm 2 .
  • the length of the rod-shaped porous substrate is not subject to any specific limitation, but is usually in the range of about 1 cm to 30 cm for process reasons.
  • the cross-sectional area of the rod-shaped, porous substrate corresponds to the dimensions of a single biochip to be manufactured and is therefore usually 1 cm ⁇ 1 cm.
  • the pores may be in hexagonal or square arrangement. Further, the pores may be designed, for example, substantially round or elliptical.
  • the material of the rod-shaped porous substrate may in particular be selected from silica, alumina, glass or macroporous silicon, the latter being particularly preferred.
  • step (ii) the coating of the pore surfaces of the rod-shaped, porous substrate takes place with chemical-biological compounds or biomolecules acting as catcher molecules.
  • the site-specific attachment of such chemical-biological compounds or biomolecules to the pore surfaces is usually carried out by means of dispensing techniques, possibly assisted by pumping techniques.
  • a solution of biomolecules can be charged or filled by utilizing at least one needle or needle assembly into the pores of the substrate employed by utilizing the capillary force.
  • an excess of liquid may be charged through the pore opening with a needle or instrument having a multiplicity of such needles and liquids so that this pore fills with liquid through the capillary action.
  • the liquid can be removed by applying overpressure to the pore opening.
  • biomolecules which are coupled or bound site-specifically to the pore surfaces in step (ii) in particular DNA, RNA, PNA (in the case of nucleic acids and their chemical derivatives, eg single strands, triplex structures or combinations thereof can be present), saccharides, peptides , Proteins (eg antibodies, antigens, receptors), derivatives of combinatorial chemistry (eg organic molecules), cell components (eg organelles), cells, multicellular cells and cell aggregates. If the finished biochip is to be used in the context of an EIA or ELISA, in particular specific antibodies are used as biomolecules.
  • oligonucleotides or DNA molecules to the substrate material can be via linker molecules according to the methods commonly used in the art, for example by treating the porous substrate material when using epoxy silanes as linker molecules by subsequent reaction of the terminal epoxy groups with terminal primary amino groups or thiol groups of oligonucleotides or DNA molecules which act as immobilized or fixed capture molecules for the target molecules present in the analyte of interest in corresponding analysis methods.
  • the oligonucleotides which can be used as catcher molecules can be synthesized using the synthesis strategy as described in Tet. Let. 22, 1981, pages 1859-1862.
  • the oligonucleotides can be derivatized during the preparation process either at the 5 or the 3-terminal position with terminal amino groups.
  • Another way of attaching such capture molecules to the inner wall surfaces of the pores can be carried out by first exposing the substrate to a chlorine source such as Cl 2 , SOCl 2 , COCl 2 or (COCl) 2 , optionally using a free radical initiator such as peroxides, azo compounds or Bu 3 SnH, and then with a corresponding nucleophilic compound, in particular with oligonucleotides or DNA molecules having terminal primary amino groups or thiol groups are reacted (see WO 00/33976).
  • a chlorine source such as Cl 2 , SOCl 2 , COCl 2 or (COCl) 2
  • a free radical initiator such as peroxides, azo compounds or Bu 3 SnH
  • step (iii) the then finished biochips are separated by sawing the rod-shaped, porous substrate so that individual, finished biochips having a thickness in the range from 100 to 1000 .mu.m, preferably 250 to 450 .mu.m are obtained.
  • the thus functionalized, rod-shaped, porous substrate can be placed on a sawing foil stretched in a sawing frame, such as, for example, a MylarO foil commonly used for such purposes, after which the Sawing out the individual chips from the rod-shaped substrate according to conventional techniques.
  • the slicing sawing has the consequence that advantageously no biological molecules are immobilized on the cut edges (top and bottom of the chips) in contrast to "spotted" porous substrates.
  • the sawing process should be compatible with the biological coating. This can be achieved, for example, by filling the pores before sawing with substances which do not attack the surface, can be washed out completely again from the pores after sawing by a solvent, but nevertheless in the sawing process, the surface in the pores before shegewasser and particles protects.
  • Suitable substances for this purpose are, for example, long-chain polyalkylene glycols, in particular polyethylene glycol (PEG) and polyvinyl alcohols.
  • the rod-shaped porous substrate having pores in the range of between 1 .mu.m and 100 .mu.m and a cross-sectional area of, for example, 1 cm x 1 cm, which corresponds to the later biochip dimensions, and a length of, for example, between 1 cm to 30 cm, in step (ii) are fluidly contacted by a fluidic mask at the two permeable end faces of the rod-shaped, porous substrate (see Figure 1).
  • the fluidic mask ensures that areas in array array are sealed against each other. Each area of the face can be covered with different substances.
  • the oligonucleotides provided as catcher molecules are then synthesized directly in the pores, whereby the synthesis takes place simultaneously in the pores of the entire rod and thus on many "chips.”
  • the rod-shaped, porous substrate is then separated again in slices, if only relatively small Spot densities are required, a large number of biochips can be made in parallel with this method, which improves both the cost and the homogeneity of the biochip.
  • the 5 rod-shaped, porous substrates can be connected directly to an oligosynthesizer (eg provided for phosphoramidite synthesis chemistry).
  • Another embodiment of the present invention provides for LO to locally prevent synthesis in the pores by occluding the pore, i. to close the pores locally and in a defined manner, so that no synthesis reagent can enter the pores. At the hidden place then no synthesis takes place.
  • the rod-shaped, porous substrate having pores L5 in the range of between 1 .mu.m and 100 .mu.m and a cross-sectional area of, for example, 1 cm x 1 cm, which corresponds to the later biochip dimensions, and a length of for example between 1 cm to 30 cm, in step (ii) are covered with a suitably configured mask. This -0 mask locally prevents chemical substances from entering the pores.
  • oligonucleotides by sequentially placing masks in locally different regions.
  • a corresponding surface-structured mask 25 made of elastomeric material can be brought into contact with the end face of the rod-shaped, macroporous substrate.
  • the mask may be made of a flexible plastic such as an elastomeric material compatible with synthetic chemistry (deprotecting agent, oxalic acid in water in the Case of phosphoroaraidite chemistry).
  • the elastomeric material is selected from polydialkylsiloxanes, polyurethanes, polyimides and crosslinked novolak resins. More preferably, the elastomeric material is polydimethylsiloxane (PDMS).
  • PDMS polydimethylsiloxane
  • PDMS has a low surface energy and is chemically inert.
  • PDMS is homogeneous, isotropic and optically transparent up to 300 nm.
  • the mask can contain holes (shadow mask) (see FIG. 2 a) or have a relief structure (stamp) (see FIG. 2 b), which respectively covers specific pores or pore areas.
  • the substrate-inclined surface of the mask should have a flexible layer that is biocompatible and fluid-tight, which can be achieved, for example, with the use of PDMS as the mask material.
  • the layer must cover the surface in conformity, but must not close the holes.
  • Such a stamp or mold or mask made of elastomeric material having a relief structure for example, by Replica molds can be prepared by casting the liquid polymer precursor of an elastomer over a template (Master) with a correspondingly predetermined surface relief structure, as is known from soft lithography; See, for example, Xia et al., Angewandte Chemie, 1998, 110, pages 568 to 594.
  • a stamp mask with relief structure can be a kind of closed capillary structure or at least parts of channels or capillaries, the at least one inlet and after passing at least a pore, preferably a portion of pores, having an outlet.
  • the mask can be structured such that the channels formed are straight or meander-shaped and continuous or comb-shaped.
  • oligonucleotides provided as catcher molecules are then synthesized again directly in the now accessible pores, whereby the synthesis takes place simultaneously in the pores of the entire rod and thus on many "chips.” Subsequently, the rod-shaped porous substrate is again separated in slices.
  • a method of making a plurality of discrete biochips from a porous substrate comprising the steps of: (a) adjusting stacking a plurality of porous substrates in the range of 100 to 1000 microns to a rod-shaped macroporous substrate; (b) reversibly connecting the individual substrates by Annealing the rod-shaped macroporous substrate produced at a temperature in the range of 80 0 C to 200 0 C; (c) coating the pore surfaces of the rod-shaped porous substrate formed in step (b) with chemical-biological compounds functioning as catcher molecules, and (d) mechanically dicing the rod-shaped porous substrate such that finished biochips having a thickness in the range of 100 to 1,000 microns are obtained.
  • the substrates or individual chips used in step (a) preferably have a pore diameter of from 1 .mu.m to 50 .mu.m, more preferably from 1 to 20 .mu.m.
  • the distance from the center of the pore to the center of the pore (pitch), ie, two adjacent or adjacent pores, is usually 1 to 100 ⁇ m, preferably 2 to 12 ⁇ m.
  • the pore density is usually in the range of 10 4 to 10 8 / cm 2 .
  • the length of the rod-shaped porous substrate produced therefrom is not specifically limited, but is usually in the range of about 1 cm to 30 cm for process reasons.
  • the cross-sectional area of the individual substrates or chips, and thus also of the rod-shaped porous substrate, corresponds to the dimensions of a single biochip to be manufactured and is therefore usually 1 cm ⁇ 1 cm.
  • the pores may be in hexagonal or square arrangement. Further, the pores may be designed, for example, substantially round or elliptical.
  • the material may for example be selected from silica, alumina, glass or macroporous silicon.
  • steps (a) and (b) polished single chips are reversibly bonded to a bar.
  • the chips are stacked adjusted and connected by a tempering process.
  • the holding forces of the bond connection are low (only Hydrogen bonds, Van der Waals forces), so that the connection can be released again without mechanical damage.
  • the connection of the individual chips achieved by the annealing process must only fluidically seal to ensure that no liquid runs between the individual chips.
  • Fig. 1 shows schematically the contacting of a rod-shaped substrate used according to the invention with a fluidic mask, by which it is achieved that areas of the chip can be addressed separately fluidly.
  • Fig. 2 shows schematically the embodiment according to the invention, wherein the rod-shaped substrate is covered with a mask, 5 in order to achieve that the catcher molecule compounds get locally into the pores determined by the mask, wherein Fig. 2a, the provision of a mask with through holes (shadow mask ) and Fig. 2b show the provision of a stamp mask.
  • FIG. 1 shows how a rod-like porous substrate (10) with pores (11) used according to the invention is in fluidic contact with a fluidic mask (20) at its two end faces (12). Disposed on one of the fluidic masks (20) are separate supply lines (30) for individual, 5 determined pore areas, through which Different biomolecule solutions can be directed. Each region of the end face can be covered by the supply lines (30) with different substances or biomolecules. In addition, the fluidic mask ensures that regions in array arrangement are sealed against each other.
  • the oligonucleotides provided as catcher molecules can also be synthesized directly in the pores, whereby the synthesis takes place simultaneously in the pores of the entire rod and thus on many "chips.”
  • the rod-shaped, porous substrate is then separated again in slices.
  • the rod-shaped, porous substrate (10) via leads (30) to an oligo-synthesizer (not shown) are connected.
  • FIG. 2 a shows the arrangement of a shadow mask (50), while FIG. 2 b) shows the arrangement of a stamp mask with a relief structure (51) on a rod-shaped porous substrate (10) with pores (11) used in accordance with the invention.
  • a stamp mask with a relief structure (51) on a rod-shaped porous substrate (10) with pores (11) used in accordance with the invention depending on the mask pattern thereby locally pores or areas of pores are closed, so that no synthesis reagent or biomolecules (40) can get into these pores or, while other pores or areas of pores site-specific with the surface coating Biomolecules are provided. Subsequently, the rod-shaped, porous substrate is again separated by slices.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)

Abstract

Procédé de fabrication de puces à ADN à partir de substrats poreux, selon lequel les substances biochimiques utilisées dans une analyse correspondante en tant que sondes ou molécules pièges sont d'abord déposées sur les surfaces des pores d'un substrat poreux, relativement long en forme de barre qui est ensuite divisé en petites puces à ADN finies. Le procédé selon la présente invention permet d'améliorer l'homogénéité des puces individuelles et d'augmenter la vitesse de fabrication.
PCT/EP2005/005056 2004-06-28 2005-05-10 Procede de fabrication de puces a adn a partir de substrats poreux WO2006000275A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE102004031167.6 2004-06-28
DE200410031167 DE102004031167A1 (de) 2004-06-28 2004-06-28 Verfahren zur Herstellung von Biochips aus porösen Substraten

Publications (1)

Publication Number Publication Date
WO2006000275A1 true WO2006000275A1 (fr) 2006-01-05

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Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1999003341A1 (fr) * 1997-07-16 1999-01-28 Don Stimpson Production parallele d'ensembles haute densite
WO1999013313A1 (fr) * 1997-09-11 1999-03-18 Genovations, Inc. Procede de production de reseaux a haute densite
WO1999055460A1 (fr) * 1998-04-27 1999-11-04 Corning Incorporated Reservoir capillaire etire pour imagerie
WO2002016651A2 (fr) * 2000-08-25 2002-02-28 Genospectra, Inc. Supports de sondes tridimensionnels
US20020086325A1 (en) * 2000-12-28 2002-07-04 Ebara Corporation Affinity detecting/analytical chip, method for production thereof, detection method and detection system using same
US20030124716A1 (en) * 2000-10-10 2003-07-03 Biotrove, Inc., A Delaware Corporation Apparatus for assay, synthesis and storage, and methods of manufacture, use, and manipulation thereof

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE10142691B4 (de) * 2001-08-31 2006-04-20 Infineon Technologies Ag Verfahren zum Nachweis biochemischer Reaktionen sowie eine Vorrichtung hierfür
DE10164800B4 (de) * 2001-11-02 2005-03-31 Infineon Technologies Ag Verfahren zur Herstellung eines elektronischen Bauelements mit mehreren übereinander gestapelten und miteinander kontaktierten Chips

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1999003341A1 (fr) * 1997-07-16 1999-01-28 Don Stimpson Production parallele d'ensembles haute densite
WO1999013313A1 (fr) * 1997-09-11 1999-03-18 Genovations, Inc. Procede de production de reseaux a haute densite
WO1999055460A1 (fr) * 1998-04-27 1999-11-04 Corning Incorporated Reservoir capillaire etire pour imagerie
WO2002016651A2 (fr) * 2000-08-25 2002-02-28 Genospectra, Inc. Supports de sondes tridimensionnels
US20030124716A1 (en) * 2000-10-10 2003-07-03 Biotrove, Inc., A Delaware Corporation Apparatus for assay, synthesis and storage, and methods of manufacture, use, and manipulation thereof
US20020086325A1 (en) * 2000-12-28 2002-07-04 Ebara Corporation Affinity detecting/analytical chip, method for production thereof, detection method and detection system using same

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