EP1366088A1 - Phosphorhaltige polymere für optischen signalwandler - Google Patents
Phosphorhaltige polymere für optischen signalwandlerInfo
- Publication number
- EP1366088A1 EP1366088A1 EP02704708A EP02704708A EP1366088A1 EP 1366088 A1 EP1366088 A1 EP 1366088A1 EP 02704708 A EP02704708 A EP 02704708A EP 02704708 A EP02704708 A EP 02704708A EP 1366088 A1 EP1366088 A1 EP 1366088A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- polymer
- groups
- different
- functional groups
- phosphorus
- 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.)
- Withdrawn
Links
Classifications
-
- G—PHYSICS
- G02—OPTICS
- G02B—OPTICAL ELEMENTS, SYSTEMS OR APPARATUS
- G02B6/00—Light guides; Structural details of arrangements comprising light guides and other optical elements, e.g. couplings
- G02B6/10—Light guides; Structural details of arrangements comprising light guides and other optical elements, e.g. couplings of the optical waveguide type
- G02B6/12—Light guides; Structural details of arrangements comprising light guides and other optical elements, e.g. couplings of the optical waveguide type of the integrated circuit kind
- G02B6/122—Basic optical elements, e.g. light-guiding paths
- G02B6/1221—Basic optical elements, e.g. light-guiding paths made from organic materials
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F230/00—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and containing phosphorus, selenium, tellurium or a metal
- C08F230/02—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and containing phosphorus, selenium, tellurium or a metal containing phosphorus
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F251/00—Macromolecular compounds obtained by polymerising monomers on to polysaccharides or derivatives thereof
- C08F251/02—Macromolecular compounds obtained by polymerising monomers on to polysaccharides or derivatives thereof on to cellulose or derivatives thereof
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F275/00—Macromolecular compounds obtained by polymerising monomers on to polymers of monomers containing phosphorus, selenium, tellurium or a metal as defined in group C08F30/00
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F8/00—Chemical modification by after-treatment
- C08F8/40—Introducing phosphorus atoms or phosphorus-containing groups
-
- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09D—COATING COMPOSITIONS, e.g. PAINTS, VARNISHES OR LACQUERS; FILLING PASTES; CHEMICAL PAINT OR INK REMOVERS; INKS; CORRECTING FLUIDS; WOODSTAINS; PASTES OR SOLIDS FOR COLOURING OR PRINTING; USE OF MATERIALS THEREFOR
- C09D151/00—Coating compositions based on graft polymers in which the grafted component is obtained by reactions only involving carbon-to-carbon unsaturated bonds; Coating compositions based on derivatives of such polymers
- C09D151/003—Coating compositions based on graft polymers in which the grafted component is obtained by reactions only involving carbon-to-carbon unsaturated bonds; Coating compositions based on derivatives of such polymers grafted on to macromolecular compounds obtained by reactions only involving unsaturated carbon-to-carbon bonds
-
- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09D—COATING COMPOSITIONS, e.g. PAINTS, VARNISHES OR LACQUERS; FILLING PASTES; CHEMICAL PAINT OR INK REMOVERS; INKS; CORRECTING FLUIDS; WOODSTAINS; PASTES OR SOLIDS FOR COLOURING OR PRINTING; USE OF MATERIALS THEREFOR
- C09D151/00—Coating compositions based on graft polymers in which the grafted component is obtained by reactions only involving carbon-to-carbon unsaturated bonds; Coating compositions based on derivatives of such polymers
- C09D151/02—Coating compositions based on graft polymers in which the grafted component is obtained by reactions only involving carbon-to-carbon unsaturated bonds; Coating compositions based on derivatives of such polymers grafted on to polysaccharides
-
- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09D—COATING COMPOSITIONS, e.g. PAINTS, VARNISHES OR LACQUERS; FILLING PASTES; CHEMICAL PAINT OR INK REMOVERS; INKS; CORRECTING FLUIDS; WOODSTAINS; PASTES OR SOLIDS FOR COLOURING OR PRINTING; USE OF MATERIALS THEREFOR
- C09D153/00—Coating compositions based on block copolymers containing at least one sequence of a polymer obtained by reactions only involving carbon-to-carbon unsaturated bonds; Coating compositions based on derivatives of such polymers
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T428/00—Stock material or miscellaneous articles
- Y10T428/29—Coated or structually defined flake, particle, cell, strand, strand portion, rod, filament, macroscopic fiber or mass thereof
Definitions
- the invention relates to a phosphorus-containing polymer for coating dielectric materials, a process for its production and its use, and an optical signal converter with a coating of the polymer and its use.
- Dielectric materials are coated with multifunctional polymers for bio- and chemofunctionalization, i.e. H. with the aim of chemical and / or biochemical ((bio-) chemical) recognition elements, such as. B. receptors, antibodies, DNA, etc., can be immobilized on their surface.
- Such coated dielectric materials e.g. B. coated optical waveguides are used as signal transducers (transducers), such as those used in sensors for bio or chemical sensors.
- bio or chemical sensors Devices that can detect an analyte qualitatively or quantitatively with the aid of a signal converter and a detection reaction are referred to as bio or chemical sensors.
- Identified detection element examples include the binding of ligands to complexes, the complexation of ions, the binding of ligands to (biological) receptors, membrane receptors or ion channels, from antigens or haptens to antibodies, from substrates to enzymes, from DNA or RNA to certain proteins, the hybridization of DNA / RNA / PNA or the
- Analytes can be: ions, proteins, natural or artificial antigens or haptens, hormones, cytokines, mono- and oligosaccharides, metabolic products, or other biochemical markers that are used in diagnostics, enzyme substrates, DNA, RNA, PNA, potential active substances, drugs , Cells, viruses.
- recognition elements are:
- bio or chemical sensors can be used in environmental analysis, the
- Food sector, human and veterinary diagnostics and plant protection are used to determine analytes qualitatively and / or quantitatively.
- the specificity of the recognition reaction makes it possible to analyze analytes in complex samples such as B. ambient air, polluted water or body fluids without or only with little prior purification to determine qualitatively or quantitatively.
- bio or chemical sensors can also be used in (bio) chemical research and drug discovery to investigate the interaction between two different substances (e.g. between proteins, DNA, RNA, or biologically active substances and proteins, DNA, RNA etc.).
- the integration of the recognition reaction with the signal converter into a bio or chemical sensor can take place by immobilizing the recognition element or the analyte on the surface of the signal converter.
- the recognition reaction i.e. H. binding or reaction of the analyte with the
- the optical properties of the medium change directly on the surface of the signal converter (e.g. change in the optical refractive index, absorption, fluorescence, phosphorescence, luminescence etc.), which is converted by the signal converter into a measurement signal.
- Optical waveguides are a class of signal converters that can be used to detect the change in the optical properties of a medium that borders a waveguiding layer, typically a dielectric. If light is transported as a guided mode in the wave-guiding layer, the light field at the medium / waveguide interface does not drop abruptly, but rather sounds at it
- Waveguide adjacent so-called detection medium exponentially.
- This exponentially falling light field is called evanescent field.
- the refractive index of which differs as much as possible from that of the adjacent medium decay lengths of the evanescent field (intensity drops to the value 1 / e) of ⁇ 200 nm are achieved.
- Do the optical properties of the medium bordering the waveguide change e.g.
- the waveguide detection medium interface must be stable.
- the detection elements must be immobilized within the range of the evanescent field of the waveguide. • Under the reaction conditions of the recognition reaction, the
- Immobilization of the detection element must be stable.
- the surface of waveguides can be used in many different ways
- Detection elements are immobilized. This can e.g. B. happen by physisorption of the detection elements on the signal converter surface. Clerc and Lukosz 7 describe the physisorption of avidin on SiO 2 -TiO 2 waveguide surfaces.
- biotinylated antibodies can be immobilized on the avidin layers applied in this way.
- a disadvantage of this immobilization method of recognition elements on waveguide surfaces is the instability of the physisorbed avidin layer. A change in the reaction conditions, such as. B. temperature changes, pH changes, addition of detergents etc., can lead to desorption of the avidin layer and thus also of the antibody.
- the detection elements can also be covalently bound to the surface of a waveguide.
- Bifunctional silanes which form a covalent bond with the waveguide surface, represent one possibility 8 .
- the recognition elements such as. B. proteins or DNA 9 , covalently bound.
- These bifunctional silanes are very reactive and the covalent bond to the waveguide surface has to be carried out under absolutely dry reaction conditions to avoid hydrolysis of the reactive silane.
- the binding of the detection elements via these silanes to the waveguide surfaces is stable under acidic, neutral and slightly basic conditions. At pH values above 9, however, hydrolysis of the silane can occur, which can lead to desorption of the detection elements from the surface.
- Another disadvantage of this immobilization method is the relatively high non-specific adsorption of proteins such as. B. albumin to the functionalized waveguide surfaces 10 .
- the non-specific binding to these waveguide surfaces can be reduced by blocking agents such as e.g. B. polyethylene glycols 11 are bound to the surface.
- hydrophilic polymers such as. B. polyacrylamides, dextrans, polyethylene glycols etc.
- these polymers have the task of minimizing the non-specific binding of proteins etc. to the surface.
- the recognition elements are then covalently bound to these polymers in a further step.
- the problem with this surface functionalization is that several steps have to be carried out to immobilize the detection elements on the surface and the instability of the silane bond to the waveguide surfaces at pH> 9.
- the detection elements can also be bound to polymers which are applied directly to the waveguide layers without prior silanization.
- Charged copolymers based on polylysine and polyethylene glycol electrostatically adsorb onto some metal oxide surfaces 13 , such as TiO 2 , Si 0j4 Ti 0 ⁇ 6 O 2 and Nb 2 O 5 . With the help of optical waveguides it could be shown that this
- Polymers are derivatized with photoactivatable groups either 14 or are incubated together with photo crosslinkers 15 '16, may be applied by photoreaction directly to the waveguide surface and networked together.
- polymers have a low ui-specific adsorption of proteins and are stable over a wide range of reaction conditions.
- the recognition elements can either be bound during the photoreaction or after the photoreaction.
- polymers are used which, in addition to the photoreactive groups, also carry functional groups which enable covalent immobilization of the recognition elements.
- the photoreactive compounds must either be applied to the surface by spotter or spin coating and then concentrated or dried there. This can result in partial dewetting of the waveguide surface, which results in incomplete coverage.
- U.S. Patent 4,904,634 1S describes an active material that can be used as an adsorbent.
- This material consists of a metal oxide V-hydroxide surface and a chemically bonded monolayer of a phosphorus-containing organic material.
- the phosphorus-containing organic material is specified there as follows:
- the organic material has 1-2 phosphorus-containing groups.
- the phosphorus-containing groups have the general formula RR'PO (OH) or RR'PO (OH), where R consists of one to 30 carbon-containing groups and R 'consists either of hydrogen or from one to 30 carbon-containing groups.
- R or R ' can also be an organic radical from the group of long- or short-chain aliphatic hydrocarbons, aromatic hydrocarbons, carboxylic acids, aldehydes, ketones, amines, amides, tioamides,
- R or R ' can also have a functional group at a position in the molecule which is distant from the phosphorus-containing group.
- the functional group can be a carboxyl, glucose, cyano, cyanate, isocyanate, thiocyanate, phenyl, diphenyl, tertiary butyl, sulfonic acid, benzyl sulfone, halogen, nitrate, phosphate, phosphinate, phosphinite , Phosphonate, hydroxymethylamide,
- Alkoxymethylamide benzophenone, azide, triazene, acylphosphane, quaternary ammonium group or combinations of these groups.
- R or R ' can also carry a cation exchange group, such as -HSO 3 , -N (CH 3 ) 3 C1, -COONa, -NH 2 and -CN.
- R can also be an oligomer composed of 2-4 monomers and one
- Coupling element for biological material such as enzymes, antibodies, cells, yeasts, proteins, microbes, pharmaceuticals, vaccines. • Coating of piezo crystals. • Coatings for the passivation of biological implants (bones etc.).
- Detection elements must be immobilized within the range of the evanescent field of the waveguide. • The immobilization of the recognition elements must be stable under the reaction conditions of the recognition reaction.
- the invention relates to a phosphorus-containing polymer, suitable for coating dielectric surfaces of the general formulas I or II,
- F for functional groups which are present in addition to A are the same or different and are bonded directly or indirectly to P,
- nl for a number from 1 to about 1000
- n2 for a number from 1 to about 100
- ol for a number from 0 to about 1000
- o2 stands for a number from 1 to about 1000.
- the polymer according to the invention is suitable for coating dielectric materials, in particular dielectric waveguide surfaces.
- the thickness of the coating is usually between 0.5 and 700 nm, preferably between 0.5 and 200 nm, in particular between 0.5 and 10 nm.
- the second object of the invention is a method for producing a polymer according to the invention by copolymerization of
- (C) optionally a monomer containing a segment U or a plurality of monomers containing the same or different, identical or different segments U.
- the third subject of the invention is a further process for producing a polymer according to the invention
- step (iii) optionally converting part of the functional groups to the same or different segments U, wherein step (iii) can be carried out after, before or together with step (ii), and wherein in steps (ii) and (iii) not all functional groups are reacted and the unreacted functional groups form the functional groups F of the polymer , The can not in the
- Steps (ii) and (iii) implemented functional groups are partially or completely converted to functional groups F using one or more identical or different crosslinkers.
- the fourth object of the invention is the use of an inventive
- Polymers for coating dielectric materials, in particular dielectric waveguides can be used to coat dielectric materials, in particular dielectric waveguides, from TiO 2 , TajOj, ZrO 2 , HfO 2 or Al 2 O 3 , preferably from TiO 2 or be used.
- the fifth object of the invention is an optical signal converter with a coated dielectric waveguide, the coating of which consists of a polymer according to the invention.
- the sixth object of the invention is the use of an optical signal converter according to the invention for immobilizing chemical and / or biochemical recognition elements.
- the phosphorus-containing polymer according to the invention contains various functional groups or segments in order to meet the requirements mentioned for the waveguide coating:
- the polymer component P is the polymer component P.
- the phosphorus-containing groups A of the polymer which ensure stable binding of the polymer to the surface of the waveguide.
- mEq milliequivalents
- the functional groups F of the polymer by means of which recognition elements can be immobilized directly or with the aid of a crosslinker, covalently, coordinatively or via another chemical bond to the polymer and thus to the surface of the bio- or chemosensor.
- the segments U which suppress the non-specific binding of proteins etc. to the polymer and thus to the waveguide. U may be absent in the polymer if the non-specific binding is already suppressed by the polymer component.
- the polymers according to the invention can be linear, branched or crosslinked and an average molecular weight of 1,000 to 10,000,000 g / mol, preferably 2,100 to 1,000,000 g / mol, particularly preferably 5,000 to 500,000 g / mol, is extremely preferred
- the determination of the molecular weight can, for. B. done by vapor pressure osmosis or light scattering.
- the polymer components P can be constructed randomly or in blocks.
- these are hydrophilic polymers, in the context of the teaching according to the invention a hydrophilic polymer is understood to mean a polymer which can be wetted or swelled with water or aqueous solutions. Examples include: • Polyvinyl alcohols, polyvinylamine, polyallylamine, polyethyleneimine, polyacrylates, polyacrylamides, imides of polymaleic anhydride-alt-methyl vinyl ether or derivatives thereof. • Linear polyethylene glycols, polypropylene glycols or derivatives thereof.
- polyureas • polyureas, polyurethanes, polyesters, polycarbonates, polyhydroxycarboxylic acids or derivatives thereof, which consist of hydrophilic diols / polyols and / or
- Diamines / polyamines are built up.
- the hydrophilic diols / polyols can be polyethylene glycols, polypropylene glycols etc.
- the diamines / polyamines can be Jeffamines, polyethyleneimines, polyvinylamines, polyallylamines, polyethyleneimines etc. Polysaccharides such as cellulose, starch, agarose, dextran, chitosan,
- Hyaloronic acid or derivatives thereof especially hydroxyalkyl derivatives or acid half esters.
- Polypeptides or derivatives thereof which are made up of one or more different amino acids, such as.
- Branched polyols based on glycidol such as. B. in the patent application EP 0 116 978 and WO 00/37532, both of which are referred to in this regard and the content of which is hereby incorporated into this application, or derivatives thereof.
- Preferred are polyols based on glycidol with a degree of polymerization of 1 to 300, a polydispersity less than 1.7, a content of branched units, based on the totality of all monomer units and determined by 13 C-NMR spectroscopy, of 10 to 33 mol%.
- a stable anchoring of the polymer on the waveguide surface is achieved by several phosphorus-containing groups which are bonded directly or via a spacer S to a carbon atom of the polymer component.
- the groups A preferably satisfy the formula
- group or groups Y is selected from the following phosphorus-containing radicals:
- the polymer preferably contains one or more of the following groups Y: -O (R'O) PO 2 H, -P (RO) O 2 H, -N (CH 2 -P (R'O) O 2 H) 2 , in particular -N (CH 2 -P (R'O) O 2 H) 2 , where R 'is preferably -H.
- the spacer S is coupled directly to a C atom of the polymer and carries p the same or different phosphorus-containing radicals Y.
- the following spacers (group (s) Y are also indicated) are preferred according to the invention:
- the polymer according to the invention contains phosphorus-containing groups A in the form of a spacer S which carries one to six identical or different phosphorus-containing radicals.
- Functional groups F for immobilizing recognition elements F stands for functional groups which are bonded directly to a carbon atom of the polymer and covalently, coordinatively or via another chemical bond to the polymer and thus to the surface via the recognition elements or with the aid of a crosslinker of the bio or chemical sensor can be immobilized.
- the detection elements can be directly coupled before the waveguide is coated with the polymer or afterwards.
- Typical functional groups for covalently immobilizing recognition elements are e.g.
- the recognition elements can also be coordinatively immobilized on the polymer.
- Typical groups for this are, for example: iminodiacetic acid, nitrilotriacetic acid.
- biochemical recognition reactions can be used to immobilize recognition elements on the polymer.
- the following groups can be bound to the polymer: StrepTag 24 , digoxin, digoxigenin, biotin, thiobiotin, fluorescein, dinitrophenol, streptavidin, avidin, etc.
- the polymer according to the invention contains functional groups F with crosslinkers which can be bound to the polymer before or after the coating of the waveguide.
- crosslinkers can be linear, branched or crosslinked molecules, oligomers or polymers with a molecular weight or average molecular weight of 50 to 50,000 which carry two or more identical or different functional groups, or other commercial crosslinkers.
- Preferred crosslinkers can generally be expressed using the formula
- Pl can be: • Linear or branched alkyl or aryl radicals with 1-10 C atoms. • Linear polyethylene glycols, polypropylene glycols, copolymers of these polymers or derivatives thereof.
- Polysaccharides such as cellulose, starch, agarose, dextran, chitosan, hyaloronic acid or derivatives thereof.
- Polypeptides or derivatives thereof which are made up of one or more different amino acids, such as.
- Polyserine Polyglycine, polyseringlycerin etc.
- Branched polyols or oligools based on glycidol such as. B. in the patent application EP 0 116 978 and WO 00/37532, both of which are referred to in this regard and the content of which is hereby incorporated into this application, or derivatives thereof.
- Preferred are polyols based on glycidol with a degree of polymerization of 1 to 300, a poly-dispersity less than 1.7, a content of branched units, based on the totality of all monomer units and determined by 13 C-NMR spectroscopy, of 10 to 33 mol%.
- FI are functional groups that allow coupling of the crosslinker to the functional groups F of the polymer.
- F2 are functional groups to which recognition elements can be bound via a covalent, coordinative or other chemical bond.
- FI and F2 can be the same or different functional groups. Examples of groups FI and F2 are the following functional groups:
- a preferred crosslinker of the Fonnel Pl (Fl) m (F2) n is ethylene glycol bisuccinimidyl succinate.
- the polymer can have segments U which suppress the non-specific binding of proteins etc. to the polymer and thus to the waveguide. These segments are covalently attached to the polymer unit P and can preferably be hydrophilic linear, branched or crosslinked oligomers or polymers with a preferred molecular weight or average molecular weight of 100 to
- Oligo- or polysaccharides such as cellulose, starch, agarose, dextran, chitosan, hyaloronic acid or derivatives thereof.
- Oligo- or polypeptides or derivatives thereof which are made up of one or more different amino acids, such as. B. polylysine, polyphenylalanine lysine, polyglutamate, polymethylglutamate glutamate, polyphenyl-ala inglutamate, polyserine, polyglycine, polyseringlycerol etc. Branched polyols or oligools based on glycidol, such as. B. in the patent application EP 0 116 978 and WO 00/37532, both of which are referred to in this regard and the content of which is hereby incorporated into this application, or derivatives thereof.
- These segments can be missing in the polymer if the non-specific binding is already suppressed by the polymer component.
- the polymer of the invention can be prepared by, for.
- different monomers containing groups A, F and U can be copolymerized by methods known to the accomplished synthetic chemist. So the polymer z. B. by copolymerization of vinylphosphonic acid, polyethylene glycol methyl ether acrylate and acrylic acid.
- the detection element can then be bound before or after the polymer is applied to the waveguide surface. For this, the carboxylic acid groups are through
- polymers can be synthesized according to known methods which have identical or different functional groups F.
- the phosphorus-containing groups A and optionally segments U can then be introduced in further steps. It is ensured that only a certain part of groups F is implemented.
- the recognition elements can then be bound via the remaining groups F.
- the phosphorus-containing groups A can be generated by the reaction with polyphosphoric acid. Only part of the hydroxyl groups are converted.
- the detection element can then be bound before or after the polymer is applied to the waveguide surface. For this purpose, the hydroxyl groups are converted by, for. B. with
- Toluene sulfonic acid chloride activated and then reacted with nucleophilic functional groups of the recognition element, which leads to a covalent connection of the recognition element to the polymer.
- the polymer can e.g. B. can also be made from polymers that carry carboxylic acid groups or derivatives thereof.
- z. B. aminoethylphosphonic acid or H 2 N- (C 6 H 4 ) 2 -N (CH 2 PO 3 H 2 ) 2
- the phosphorus-containing groups A are introduced. Only some of the carboxylic acid groups are reacted.
- the detection element can then be bound before or after the polymer is applied to the waveguide surface.
- the carboxylic acid groups by reaction z. B. activated with carbodiimides and then implemented with nucleophilic functional groups of the recognition element, which leads to a covalent attachment of the recognition element to the polymer.
- amine-containing polymers such.
- the phosphorus-containing groups A can be introduced in this way. Only a part of the amine groups is implemented.
- the detection element can then be bound before or after the polymer is applied to the waveguide surface. To do this, the amine groups are through
- the phosphorus-containing groups A are preferably suitable for anchoring the polymer to waveguides made of materials such as TiO 2 , Ta ⁇ s, ZrO 2 , HfO 2 , Al 2 O 3 , SiO 2 (Si (Ti) O 2 ), In 2 O 3 / SnO 2 (ITO), aluminum silicates, Nb 2 O 5 , vanadium oxides, or mixtures of these materials.
- the waveguide materials can also be oxides or hydroxides of the following elements, which can form oxides or hydroxides: Sc, Y, Ti, Zr, Hf, V, Nb, Ta, Cr, Mo, W, Mn, Tc, Re, Fe, Ru , Os, Co, Rh, Ir, Ni, PD, Pt, Cu, Ag, Au, Zn, Cd, Hg, B, AI, Ga, In, Tl, Ge, Sn, Pb, As, Sb, Bi, Lanthanide , Actinides and mixtures thereof as well as mixtures from group Ha (Be, Mg, Ca, Sr, Ba, Ra) and Vlb (Se, Te, Po)).
- the polymer is applied to the waveguide surfaces from organic or aqueous solution. This can be done by incubation in the solution, dipping, spraying, spotting, spin coating or similar conventional methods. Typically, solutions between 0.001 and 1,000 g / 1, in particular between 0.1 and 10 g / 1, are used and the waveguide surfaces are coated at temperatures between 0 and 200 ° C., in particular between 20 and 30 ° C.
- the incubation time of the waveguide materials with the polymer solutions can be between 10 s and 48 h, typically between 10 min and 24 h. After the incubation, the waveguides are rinsed with organic solvents or aqueous solutions and, if necessary, further derivatized.
- Detection elements can be covalently, coordinatively or via another chemical bond to the functional groups directly or with the aid of a crosslinker
- the detection elements can be directly coupled before the waveguide is coated with the polymer or afterwards.
- the recognition elements can have their own functional groups such as carboxylic acid, carboxylic acid ester, carboxylic acid chloride, carboxylic acid anhydride, carbonic acid nitrophenyl ester, carboxylic acid N-hydroxysucinimide, carboxylic acid imidazolide, carbon acid pentafluorophenyl ester, hydroxy, toluenesulfonyl, trifluoromethylsulfonyl, epoxy, aldehyde, ketone, ß-dicarbonyl, isocyanate, thioisocyanate, nitrile, amine, aziridine, hydrazine, hydrazide, nitro, thiol, disulfide, thiosetamide, chloroacetamide, halogeno, iodoacetamide, halogeno,
- Proteins as recognition elements can e.g. B. can be immobilized on the polymer via their amino acid side chains. Especially amino acids such as B. lysines, cysteines, serines, tyrosines, histidines, glutamates, aspartates, which are located on the surface of a protein have functional groups in their side chains which can form a covalent bond with the functional groups of the polymer. Functional groups can also be generated in the recognition elements by derivatization (phosphorylation of tyrosines), oxidation (e.g. oxidation of diol units of glycosylated proteins to aldehyde groups), reduction (e.g. from disulfide bridges to thiols) or coupling of a crosslinker.
- derivatization phosphorylation of tyrosines
- oxidation e.g. oxidation of diol units of glycosylated proteins to aldehyde groups
- reduction e.g. from disulfide bridges to
- the recognition elements can also be coordinated to the polymer.
- B. proteins such as enzymes, antibody fragments and receptors with special affinity sequences such.
- B. the 6xHistidine day 27 These affinity sequences have a high affinity and specificity for metal ion complexes such as. B. nickel nitrilotriacetic acid or copper iminodiacetic acid, which can be introduced as functional group F in the polymer.
- biochemical recognition reactions can also be used to immobilize recognition elements on the polymer.
- the very specific and high affinity binding of biotin to streptavidin 28 can be used to immobilize recognition elements on the polymer.
- the functional groups F of the polymer z.
- B. Streptavidin The
- the recognition element is then functionalized with biotin and can thus be bound to the polymer.
- the recognition element can be provided with a short amino acid sequence, the so-called StrepTag 24 , which also has a high specificity and affinity for streptavidin.
- IM high salt concentrations
- the presence of detergents in the reaction solution also does not lead to desorption of the polymer from the waveguide surface. Since the polymer is specifically bound to the waveguide surface via the phosphorus-containing groups, only a monolayer of polymer can be applied to the surface in the sense of chemiso ⁇ tion.
- the thickness of the polymer layers on the surface is therefore self-limiting and can be adjusted in a targeted manner using the average molecular weight and the chemical structure of the polymer. This can ensure that the detection elements are immobilized within the evanescent light field and thus in the sensitive detection area of the signal converter.
- the recognition elements are stably bound to the polymer via covalent, coordinative or other chemical bonds. Deso ⁇ tion of the detection elements from the polymer is avoided. Another effect of the very low non-specific interaction of the polymer with proteins and other organic molecules is the high activity of the immobilized recognition elements.
- the recognition elements are very specifically bound to the polymer, further non-specific interactions of the recognition elements with the polymer, which lead to a reduction in activity of the detection elements could not occur or only occur to a very small extent.
- the polymer can be applied to a wide variety of waveguide materials. Detection elements can then be immobilized on the polymer while maintaining their activity. The polymer thus acts as an interface to detection elements on signal converters such. B. immobilize waveguides.
- the polymer thus enables the integration of the detection reaction and signal converter into one sensor. Due to the flexible concept of the polymer, a wide variety of detection elements can be immobilized, so that the sensor can be used in environmental analysis, the food sector, human and veterinary diagnostics and crop protection to determine analytes qualitatively and / or quantitatively. Since the polymer prevents the non-specific binding of organic, inorganic compounds and macromolecules to the sensor surface, analytes in complex samples such as B. ambient air, polluted water or body fluids can be determined qualitatively or quantitatively without or only with little previous purification. In addition, the polymer can also be used in (bio) chemical research and drug discovery in order to investigate the interaction between two different substances in parallel or sequentially using a suitable signal converter. So z. B. the interaction of biologically active substances, such as. B. potential drugs with biomolecules such as proteins, membrane receptors, ion channels, DNA, RNA, etc. are examined.
- biologically active substances such as. B. potential drugs with biomolecules such
- Example 1 Polymer from phosphonate-functional copolymers.
- NMP N-methyl-2-pyrrolidone
- a solution of 2 mg / ml monoclonal mouse antibody against myobglobin in 10 mM sodium acetate buffer, adjusted to pH 5, was prepared and the waveguide surfaces were incubated therein for 2 hours. A surface concentration of antibody of 1.5 ng / mm 2 was obtained.
- Example 2 Polymer from phosphate esters of polyvinyl alcohol.
- Succinic anhydride was added to the solution and stirred at 21 ° C for 3 h.
- the solution in ethanol was adjusted to a concentration of 1 mg polymer per ml solution and the waveguide surfaces in this solution
- Example 3 Polymer made from imidized MA copolymers.
- Waveguide surfaces incubated in this solution for 18 h.
- the waveguides were then rinsed with ethanol and 10 mM NaOH.
- the surfaces were incubated in a 10 mg / ml solution of ethylene glycol bisuccinimidyl succinate in DMSO for 30 min and then rinsed with DMSO and ultrapure water.
- a solution of 2 mg / ml of monoclonal mouse antibodies against human chorionic gonadotropin in 10 mM sodium acetate buffer, adjusted to pH 5, was prepared and the waveguide surfaces were incubated therein for 2 hours.
- a surface concentration of antibody of 2.0 ng / mm 2 was obtained.
- Example 4 Polymer grafted with phosphonate-functional copolymers
- graft base (fatty acid-modified polyglycidol): A mixture of 28 g soybean oil fatty acid and 74 g epoxypropanol (glycidol) was heated to 140 ° C. for 1 h and then a mixture of 0.4 g within 6 h
- Phosphoric acid and 333.5 g epoxypropanol were added. The mixture was then stirred at 140 ° C for 16 h.
- Example 5 Polyglycidol, derivatized with maleic anhydride and imino-bis-methylenephosphonic acid.
- the mixture was heated to 80 ° C. for 15 minutes and 0.2 g of thiol-derivatized imido-bis-methylenephosphonic acid reagent and 0.3 g of triethylamine were added. After 15 minutes, 0.05 g of azoisobutyronitrile was added and stirring was continued for 4 hours at 80 ° C. and 1 hour at 100 ° C.
- Example 6 Polymer made from acetoacetoxy- and phosphate ester-modified dextran.
- Example 7 Polymer made from phosphonate-functional polylysine.
- the solution was cooled in ethanol to a concentration of 1 mg of polymer per ml of solution and the waveguide surfaces were incubated in this solution for 2 h.
- the waveguides were then rinsed with ethanol and 10 mM NaOH.
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- Medicinal Chemistry (AREA)
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- Polymers & Plastics (AREA)
- Engineering & Computer Science (AREA)
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- Wood Science & Technology (AREA)
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- General Chemical & Material Sciences (AREA)
- Microelectronics & Electronic Packaging (AREA)
- General Physics & Mathematics (AREA)
- Optics & Photonics (AREA)
- Other Resins Obtained By Reactions Not Involving Carbon-To-Carbon Unsaturated Bonds (AREA)
- Apparatus Associated With Microorganisms And Enzymes (AREA)
- Paints Or Removers (AREA)
- Optical Integrated Circuits (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Polyamides (AREA)
- Compositions Of Macromolecular Compounds (AREA)
- Addition Polymer Or Copolymer, Post-Treatments, Or Chemical Modifications (AREA)
- Polymers With Sulfur, Phosphorus Or Metals In The Main Chain (AREA)
Abstract
Description
Claims
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
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DE10108483 | 2001-02-22 | ||
DE10108483A DE10108483A1 (de) | 2001-02-22 | 2001-02-22 | Phosphorhaltige Polymere für optischen Signalwandler |
PCT/EP2002/001399 WO2002068481A1 (de) | 2001-02-22 | 2002-02-11 | Phosphorhaltige polymere für optischen signalwandler |
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EP1366088A1 true EP1366088A1 (de) | 2003-12-03 |
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Family Applications (1)
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EP02704708A Withdrawn EP1366088A1 (de) | 2001-02-22 | 2002-02-11 | Phosphorhaltige polymere für optischen signalwandler |
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US (2) | US7101945B2 (de) |
EP (1) | EP1366088A1 (de) |
JP (1) | JP2004528414A (de) |
AU (1) | AU2002238547B2 (de) |
CA (1) | CA2438648C (de) |
DE (1) | DE10108483A1 (de) |
WO (1) | WO2002068481A1 (de) |
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US7998699B2 (en) | 2002-08-15 | 2011-08-16 | University Of South Florida | Early detection of pathogens in blood |
US7062118B2 (en) * | 2003-07-18 | 2006-06-13 | 3M Innovative Properties Company | Microring resonator and method for manufacturing |
JP4662932B2 (ja) | 2003-08-15 | 2011-03-30 | ユニバーシティー オブ サウス フロリダ | 試料からの病原体の捕獲およびアウリントリカルボン酸除去のための物質および方法 |
ATE483003T1 (de) * | 2005-12-21 | 2010-10-15 | Siemens Healthcare Diagnostics | Polyelektrolyt mono- und multischichten für optische signalwandler |
US9528939B2 (en) | 2006-03-10 | 2016-12-27 | Indx Lifecare, Inc. | Waveguide-based optical scanning systems |
US9976192B2 (en) | 2006-03-10 | 2018-05-22 | Ldip, Llc | Waveguide-based detection system with scanning light source |
US9423397B2 (en) | 2006-03-10 | 2016-08-23 | Indx Lifecare, Inc. | Waveguide-based detection system with scanning light source |
US8288157B2 (en) | 2007-09-12 | 2012-10-16 | Plc Diagnostics, Inc. | Waveguide-based optical scanning systems |
DE102008019928A1 (de) | 2008-04-21 | 2009-12-31 | Siemens Healthcare Diagnostics Gmbh | Polyelektrolyt-Monoschichten mit kovalenten Bindungsstellen für optische Signalwandler |
GB2461026B (en) | 2008-06-16 | 2011-03-09 | Plc Diagnostics Inc | System and method for nucleic acids sequencing by phased synthesis |
JP5757535B2 (ja) | 2009-04-29 | 2015-07-29 | ピーエルシー ダイアグノスティクス, インコーポレイテッド | 走査光源による導波管に基づく検出システム |
US20110225809A1 (en) * | 2010-03-17 | 2011-09-22 | Alan Francis Daher | Apparatus for removably attaching an item to a surface |
US10018566B2 (en) | 2014-02-28 | 2018-07-10 | Ldip, Llc | Partially encapsulated waveguide based sensing chips, systems and methods of use |
WO2016138427A1 (en) | 2015-02-27 | 2016-09-01 | Indx Lifecare, Inc. | Waveguide-based detection system with scanning light source |
Family Cites Families (22)
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JPS6014763B2 (ja) * | 1977-03-18 | 1985-04-16 | 日本合成化学工業株式会社 | ビニルアルコ−ル重合体リン酸エステルの製造法 |
US4204037A (en) | 1978-04-04 | 1980-05-20 | Nasa | Method and automated apparatus for detecting coliform organisms |
US4308079A (en) * | 1980-06-16 | 1981-12-29 | Martin Marietta Corporation | Durability of adhesively bonded aluminum structures and method for inhibiting the conversion of aluminum oxide to aluminum hydroxide |
US4815843A (en) * | 1985-05-29 | 1989-03-28 | Oerlikon-Buhrle Holding Ag | Optical sensor for selective detection of substances and/or for the detection of refractive index changes in gaseous, liquid, solid and porous samples |
US4678840A (en) * | 1986-02-24 | 1987-07-07 | Nalco Chemical Company | Phosphonic acid-containing polymer |
US4904634A (en) * | 1986-12-29 | 1990-02-27 | Aluminum Company Of America | Active material useful as adsorbent comprising metal oxide/hydroxide surfaces reacted with one or more phosphorous-containing materials having selected organic radicals attached thereto |
FR2619568B1 (fr) * | 1987-08-21 | 1989-07-07 | Centre Nat Rech Scient | Polymeres derives du polystyrene, leurs procedes de preparation et leurs applications pour l'analyse et la purification de molecules d'origine biologique |
GB2221466A (en) | 1988-03-09 | 1990-02-07 | Aluminum Co Of America | Biologically reactive particles with biological, therapeutic and chromatographic applications |
DE3910563A1 (de) * | 1989-04-01 | 1990-10-04 | Cassella Ag | Hydrophile, quellfaehige pfropfcopolymerisate, deren herstellung und verwendung |
IL93020A (en) * | 1990-01-09 | 1995-06-29 | Yeda Res & Dev | Biosensors comprising a lipid bilayer doped with ion channels anchored to a recording electrode by bridging molecules |
US5171264A (en) * | 1990-02-28 | 1992-12-15 | Massachusetts Institute Of Technology | Immobilized polyethylene oxide star molecules for bioapplications |
EP0538425B1 (de) * | 1991-04-26 | 1996-11-27 | Paul Scherrer Institut | Verfahren und vorrichtung zur bestimmung einer messgrösse mittels eines integriert-optischen sensormoduls |
DE4227019A1 (de) * | 1992-08-14 | 1994-02-17 | Geckeler Kurt E Priv Doz Dr | Herstellung und Modifikation von Materialien auf der Basis von Amino- oder Amidpolymeren |
CA2108705A1 (en) | 1992-11-06 | 1994-05-07 | Richard Barner | Biologically recognizing layers on new ti02 waveguide for biosensors |
US5919712A (en) * | 1993-05-18 | 1999-07-06 | University Of Utah Research Foundation | Apparatus and methods for multi-analyte homogeneous fluoro-immunoassays |
WO1995020151A2 (en) * | 1994-01-21 | 1995-07-27 | Fci-Fiberchem, Inc. | Reducing the effects of water vapor and liquid water on optical waveguide sensors (ows) and optical waveguide chemical sensors (owcs) |
KR970703527A (ko) | 1994-05-27 | 1997-07-03 | 발데그 베르너 | 감쇠 여기되는 발광의 검출법(Process for detecting evanescently excited luminescence) |
AU5763296A (en) | 1995-05-12 | 1996-11-29 | Novartis Ag | Sensor platform and method for the parallel detection of a plurality of analytes using evanescently excited luminescence |
DE19544559C1 (de) * | 1995-11-30 | 1997-07-03 | Knorr Bremse Systeme | Zweiteilige Bremsscheibe, insbesondere für Nutzfahrzeug-Scheibenbremsen |
EP0887645A1 (de) | 1997-06-23 | 1998-12-30 | C.S.E.M. Centre Suisse D'electronique Et De Microtechnique Sa | Verfahren und Gerät zur hochempfindlichen Detektion von Prionen, Prion-Liganden und anderen Biomolekülen |
DE19818360C2 (de) | 1998-04-24 | 2000-05-31 | Suisse Electronique Microtech | Dextranbeschichtete Oberfläche |
JP2000327386A (ja) * | 1999-05-14 | 2000-11-28 | Taiheiyo Cement Corp | セメント用分散剤及びこれを含む水硬性組成物 |
-
2001
- 2001-02-22 DE DE10108483A patent/DE10108483A1/de not_active Withdrawn
-
2002
- 2002-02-11 JP JP2002567990A patent/JP2004528414A/ja active Pending
- 2002-02-11 AU AU2002238547A patent/AU2002238547B2/en not_active Ceased
- 2002-02-11 CA CA2438648A patent/CA2438648C/en not_active Expired - Fee Related
- 2002-02-11 WO PCT/EP2002/001399 patent/WO2002068481A1/de active IP Right Grant
- 2002-02-11 EP EP02704708A patent/EP1366088A1/de not_active Withdrawn
- 2002-02-20 US US10/081,628 patent/US7101945B2/en not_active Expired - Fee Related
-
2006
- 2006-08-21 US US11/507,329 patent/US7517705B2/en not_active Expired - Fee Related
Non-Patent Citations (1)
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See references of WO02068481A1 * |
Also Published As
Publication number | Publication date |
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AU2002238547B2 (en) | 2007-07-12 |
US20020114604A1 (en) | 2002-08-22 |
US20060287453A1 (en) | 2006-12-21 |
US7101945B2 (en) | 2006-09-05 |
DE10108483A1 (de) | 2002-09-05 |
CA2438648A1 (en) | 2002-09-06 |
WO2002068481A1 (de) | 2002-09-06 |
CA2438648C (en) | 2011-04-05 |
US7517705B2 (en) | 2009-04-14 |
JP2004528414A (ja) | 2004-09-16 |
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