WO1998058293A2 - Procede et dispositif d'immobilisation de macromolecules - Google Patents

Procede et dispositif d'immobilisation de macromolecules Download PDF

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Publication number
WO1998058293A2
WO1998058293A2 PCT/EP1998/003657 EP9803657W WO9858293A2 WO 1998058293 A2 WO1998058293 A2 WO 1998058293A2 EP 9803657 W EP9803657 W EP 9803657W WO 9858293 A2 WO9858293 A2 WO 9858293A2
Authority
WO
WIPO (PCT)
Prior art keywords
light
solid phase
immobilization
biomacromolecules
field
Prior art date
Application number
PCT/EP1998/003657
Other languages
German (de)
English (en)
Other versions
WO1998058293A3 (fr
Inventor
Holger Breter
Winfried Jentsch
Original Assignee
Biotools - Institut Für Computerintegriertes Bioengineering Gmbh
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 Biotools - Institut Für Computerintegriertes Bioengineering Gmbh filed Critical Biotools - Institut Für Computerintegriertes Bioengineering Gmbh
Priority to AU85387/98A priority Critical patent/AU8538798A/en
Publication of WO1998058293A2 publication Critical patent/WO1998058293A2/fr
Publication of WO1998058293A3 publication Critical patent/WO1998058293A3/fr

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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
    • B82—NANOTECHNOLOGY
    • B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
    • B82Y30/00—Nanotechnology for materials or surface science, e.g. nanocomposites
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K17/00—Carrier-bound or immobilised peptides; Preparation thereof
    • C07K17/14—Peptides being immobilised on, or in, an inorganic carrier
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N11/00—Carrier-bound or immobilised enzymes; Carrier-bound or immobilised microbial cells; Preparation thereof
    • C12N11/14—Enzymes or microbial cells immobilised on or in an inorganic carrier
    • 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
    • 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
    • B01J2219/0043—Means for dispensing and evacuation of reagents using masks for direct application of reagents, e.g. through openings in a shutter
    • 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
    • B01J2219/00585—Parallel processes
    • 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
    • B01J2219/00596—Solid-phase processes
    • 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
    • B01J2219/00612—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
    • B01J2219/00605—Making arrays on substantially continuous surfaces the compounds being directly bound or immobilised to solid supports
    • B01J2219/00614—Delimitation of the attachment areas
    • B01J2219/00621—Delimitation of the attachment areas by physical means, e.g. trenches, raised areas
    • 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
    • B01J2219/00709—Type of synthesis
    • B01J2219/00711—Light-directed synthesis
    • 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 invention relates to a method and a device for immobilizing macromolecules according to the preambles of claims 1 and 19, 20, 21 and 22.
  • Immobilization methods of biomacromolecules on solid phases using light energy to release reactive functional groups are known.
  • DE 34 35 744 AI describes carrier materials for use in immune determinations which have photo-activatable molecules covalently bound on their surface. So-called heterobifunctional or homobifunctional compounds are used here to produce these carrier materials.
  • the compounds also referred to as bridging agents are covalently bound to the solid phase with a functional group, while the second functional group can be coupled to corresponding biomacromolecules by photoactivation.
  • Balls, microtiter plates or tubes made of plastic are used as carrier materials.
  • Plastic surfaces of these moldings or containers are made with the bridging agents such as Lomant's reagent II, N-succinimidyl-6- (4'-azido-2 '-nitrophenylamino) hexanoate treated.
  • Lomant's Reagent II forms a covalent bond with the plastic surface.
  • the second functional group can react with antigens, allergens or antibodies, as is provided here.
  • the carriers described here are not suitable for miniaturized immobilization of biomacromolecules.
  • the invention has for its object to enable light-induced addressable immobilizations of biomacromolecules on extremely small surface elements.
  • the method according to the invention enables biomacromolecules with suitable functional groups to be immobilized on a solid support on the smallest surface elements. For reasons of maintaining native molecular structures, it is important that the immobilization reactions can take place in the liquid phase.
  • biomacromolecules immobilized according to the invention on extremely small surface elements (nanoscale), it is possible to carry out a large number of bioassays such as immunoassays, hybridization assays or Liegand receptor binding assays in an effective manner.
  • the energy supply for the photoactivation of the photoactivatable functional groups of the carrier takes place using methods of scanning probe and optical near-field microscopy. With the local light irradiation that can be achieved in the near field area, it is possible to create extremely miniaturized immobilization areas by directly addressing the areas of the surface of the solid phase intended for molecular immobilization. By means of the method according to the invention, it is possible to achieve packing densities for the discrete planar arrangement that have not yet been achieved for the immobilized biomacromolecules.
  • Fig. 2 is a schematic representation of a die in plan view
  • Fig. 3 is a schematic representation of an immobilization device
  • Fig. 4 is a schematic representation of a
  • FIGS. 6-9 a schematic representation of the production of extremely miniaturized surface elements.
  • a near field light source 6 is directed to an immobilization area 9.
  • the immobilization area 9 is formed by a light exit cone 8, the dimensions of which are in turn defined by an aperture 7.
  • the near-field light source 6 is in a liquid phase 4, in which the biomacromolecules to be immobilized are contained in solution.
  • a photoactivatable layer is located on a solid phase 1, the photoactivatable functional groups 3 thereof are directed into the liquid phase 4.
  • Near-field light source 6, liquid phase 4 including the biomacromolecules to be immobilized and the solid phase 1 are arranged in a translucent flow cell, not shown here.
  • This device consists of a transparent plate 22 on which a layer 23 with photoactivatable functional groups is applied in a manner known per se.
  • the transparent plate 22 has continuous hollow channels 24.
  • a die 20 which can be put on and taken off is arranged on the layer 23.
  • This die 20, which is shown in plan view in FIG. 2, has continuous cavities 21.
  • the arrangement pattern of the cavities 21, the die 20, the channels 24 and the plate 22 are identical.
  • the diameter of the channels 24 is very much smaller than the diameter of the cavities 21.
  • the continuous cavities 21 are introduced into a silicon substrate with a thickness of 400-500 ⁇ m using an etching process.
  • the dissolved biomacromolecules to be immobilized are filled into the cavities 21 in a programmed manner.
  • the solution 26 is filled in via a cannula 25.
  • the air is pressed out of the cavities 21 through the channels 24 during filling.
  • the irradiation with light of a certain wavelength and a certain intensity takes place from the lower side of the transparent plate 22.
  • the functional groups of layer 23 activated in this way react with corresponding functional groups of the biomacromolecules in solution 26.
  • the die 20 is then covered with a glass plate from above and tipped over.
  • the plate 22 with the biomacromolecules 27 immobilized thereon, as shown in FIG. 5, is lifted off the matrix 20.
  • a further coated plate 22 with continuous channels 24 is placed on the die 20, turned over, and further solution 26 of biomacromolecules 27 is placed in the continuous cavities 21.
  • the immobilization is repeated on a new plate 22.
  • FIGS. 6 to 9 show the schematic sequence for producing very small three-dimensional elements.
  • a photoresist 12 is applied to a glass substrate 11.
  • a silicon layer 13 with a certain thickness is then evaporated on the photoresist 12.
  • a second photoresist 14 is applied to the silicon layer 13.
  • the photoresist 14 is exposed through a mask 15 with a predetermined pattern and with a specific resolution. Alternatively, this pattern can also be generated by means of an electron beam 16.
  • the corresponding pattern according to FIG. 8 is formed on the surface of the silicon layer 13.
  • the surface is now etched, for example by plasma etching.
  • the spaces 17 to the photoresist 12 are etched.

Abstract

L'invention concerne un procédé et un dispositif d'immobilisation de macromolécules selon les termes des revendications 1 et 19, 20, 21 et 22. L'invention a pour objet de permettre l'immobilisation adressable et induite par lumière de biomacromolécules sur des éléments surfaces extrêmement petits. Pour ce faire, l'immobilisation des macromolécules sur une phase solide est réalisée par photoactivation de groupes fonctionnels correspondants de la phase solide et par liaison à cette phase solide de groupes réactifs des biomacromolécules en solution. La photoactivation de la réaction d'immobilisation est réalisée par miniaturisation de l'action de la lumière à la surface de la phase solide, une commande adressable de l'action de la lumière sur la surface étant effectuée d'après le modèle prédéterminé.
PCT/EP1998/003657 1997-06-18 1998-06-18 Procede et dispositif d'immobilisation de macromolecules WO1998058293A2 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU85387/98A AU8538798A (en) 1997-06-18 1998-06-18 Method and device for immobilizing macromolecules

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE19726634.7 1997-06-18
DE19726634A DE19726634A1 (de) 1997-06-18 1997-06-18 Verfahren und Vorrichtung zur Immobilisierung von Makromolekülen

Publications (2)

Publication Number Publication Date
WO1998058293A2 true WO1998058293A2 (fr) 1998-12-23
WO1998058293A3 WO1998058293A3 (fr) 1999-04-15

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Application Number Title Priority Date Filing Date
PCT/EP1998/003657 WO1998058293A2 (fr) 1997-06-18 1998-06-18 Procede et dispositif d'immobilisation de macromolecules

Country Status (3)

Country Link
AU (1) AU8538798A (fr)
DE (1) DE19726634A1 (fr)
WO (1) WO1998058293A2 (fr)

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003023402A1 (fr) * 2001-09-12 2003-03-20 Sven Oscarsson Procede d'immobilisation et surfaces produites selon ce procede
WO2003033127A2 (fr) * 2001-10-19 2003-04-24 University Of Manchester Institute Of Science And Technology Procedes de modelisation d'une monocouche
WO2003053845A2 (fr) * 2001-10-26 2003-07-03 Penn State Research Foundation Nanolithographie par fonctionnalisation chimique
US7097974B1 (en) 1998-08-28 2006-08-29 Febit Biotech Gmbh Support for a method for determining an analyte and a method for producing the support
US7470540B2 (en) 2000-10-17 2008-12-30 Febit Ag Method and device for the integrated synthesis and analysis of analytes on a support

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0175973A1 (fr) * 1984-09-28 1986-04-02 ORPEGEN Medizinisch-Molekularbiologische Forschungsgesellschaft m.b.H Support pour l'utilisation dans des immunoessais
EP0419369A1 (fr) * 1989-09-22 1991-03-27 Sim (Societe D'investissement Dans La Microscopie) Sa Procédé de microlithographie en champ proche optique et dispositifs de microlithographie le mettant en oeuvre
WO1996033971A1 (fr) * 1995-04-25 1996-10-31 The Government Of The United States Of America, Represented By The Secretary Of The Navy Polymeres photoactivables destines a la production d'ensembles biomoleculaires a motifs

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0175973A1 (fr) * 1984-09-28 1986-04-02 ORPEGEN Medizinisch-Molekularbiologische Forschungsgesellschaft m.b.H Support pour l'utilisation dans des immunoessais
EP0419369A1 (fr) * 1989-09-22 1991-03-27 Sim (Societe D'investissement Dans La Microscopie) Sa Procédé de microlithographie en champ proche optique et dispositifs de microlithographie le mettant en oeuvre
WO1996033971A1 (fr) * 1995-04-25 1996-10-31 The Government Of The United States Of America, Represented By The Secretary Of The Navy Polymeres photoactivables destines a la production d'ensembles biomoleculaires a motifs

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
"UTILIZING OPTICAL LITHOGRAPHY IN THE SUB-MICRON DIMENSIONAL REGIME" IBM TECHNICAL DISCLOSURE BULLETIN, Bd. 33, Nr. 5, 1. Oktober 1990, Seite 187/188 XP000107428 *
KRAUSCH G ET AL: "Surface modification in the optical near field" MICROELECTRONIC ENGINEERING, Bd. 32, Nr. 1, September 1996, Seite 219-228 XP004013435 *
SIGRIST H ET AL: "SURFACE IMMOBILIZATION OF BIOMOLECULES BY LIGHT" OPTICAL ENGINEERING, Bd. 34, Nr. 8, 1. August 1995, Seiten 2339-2348, XP000518229 *

Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7097974B1 (en) 1998-08-28 2006-08-29 Febit Biotech Gmbh Support for a method for determining an analyte and a method for producing the support
US7737088B1 (en) 1998-08-28 2010-06-15 Febit Holding Gmbh Method and device for producing biochemical reaction supporting materials
US7470540B2 (en) 2000-10-17 2008-12-30 Febit Ag Method and device for the integrated synthesis and analysis of analytes on a support
US6835534B2 (en) 2000-10-27 2004-12-28 The Penn State Research Foundation Chemical functionalization nanolithography
WO2003023402A1 (fr) * 2001-09-12 2003-03-20 Sven Oscarsson Procede d'immobilisation et surfaces produites selon ce procede
WO2003033127A2 (fr) * 2001-10-19 2003-04-24 University Of Manchester Institute Of Science And Technology Procedes de modelisation d'une monocouche
WO2003033127A3 (fr) * 2001-10-19 2003-10-16 Univ Manchester Procedes de modelisation d'une monocouche
WO2003053845A2 (fr) * 2001-10-26 2003-07-03 Penn State Research Foundation Nanolithographie par fonctionnalisation chimique
WO2003053845A3 (fr) * 2001-10-26 2004-05-06 Penn State Res Found Nanolithographie par fonctionnalisation chimique

Also Published As

Publication number Publication date
AU8538798A (en) 1999-01-04
DE19726634A1 (de) 1998-12-24
WO1998058293A3 (fr) 1999-04-15

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