EP1868716A1 - Monolithische funktionalisierbare materialien - Google Patents
Monolithische funktionalisierbare materialienInfo
- Publication number
- EP1868716A1 EP1868716A1 EP06726165A EP06726165A EP1868716A1 EP 1868716 A1 EP1868716 A1 EP 1868716A1 EP 06726165 A EP06726165 A EP 06726165A EP 06726165 A EP06726165 A EP 06726165A EP 1868716 A1 EP1868716 A1 EP 1868716A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- maleic anhydride
- monolithic
- composition
- reaction
- base composition
- 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- Withdrawn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
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- 239000000203 mixture Substances 0.000 claims abstract description 89
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- 238000007348 radical reaction Methods 0.000 claims abstract description 3
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- 230000006870 function Effects 0.000 claims description 20
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- 150000001875 compounds Chemical class 0.000 claims description 16
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 16
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- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 claims description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 6
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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
- B01J19/24—Stationary reactors without moving elements inside
- B01J19/248—Reactors comprising multiple separated flow channels
- B01J19/2485—Monolithic reactors
-
- 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
- B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
- B01J20/22—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof comprising organic material
- B01J20/26—Synthetic macromolecular 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
- B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
- B01J20/22—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof comprising organic material
- B01J20/26—Synthetic macromolecular compounds
- B01J20/261—Synthetic macromolecular compounds obtained by reactions only involving carbon to carbon unsaturated bonds
-
- 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
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- B01J31/003—Catalysts comprising hydrides, coordination complexes or organic compounds containing enzymes
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- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F222/00—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by a carboxyl radical and containing at least one other carboxyl radical in the molecule; Salts, anhydrides, esters, amides, imides, or nitriles thereof
- C08F222/04—Anhydrides, e.g. cyclic anhydrides
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- G01N2030/528—Monolithic sorbent material
Definitions
- the present invention relates to the field of porous monolithic organic materials.
- the invention also relates to the various processes for preparing these materials. These monolithic materials have certain advantages over more traditional macroporous materials, particularly related to the absence of interstitial spaces in the packed state.
- a general method for the elaboration of monolithic and porous organic materials in the elements that one wishes inside a simple cavity (column, capillary), or a microsystem (channels, tanks, chambers, points of derivation) is based on the in situ thermal, photochemical or radiochemical polymerization of monomers dissolved in a pore-forming solvent mixture.
- the object of the present invention is to propose, on the one hand, novel monolithic materials that can be tailored to their function, after adjustment of the porosity-permeability characteristics and, on the other hand, processes for the preparation of these monolithic materials, characterized by a simplified implementation.
- the subject of the invention is polymeric monolithic materials comprising maleic anhydride functional groups that can be functionalized.
- the invention relates to a method for preparing functionalizable monolithic materials, said method comprising a prior step of treating the surface of the walls which serve as support for said monolithic materials, characterized in that it consists of a thermal, photochemical or radiochemical radical polymerization reaction of a composition comprising a base composition comprising: maleic anhydride as base monomer, known for its electron-accepting character favorable to the formation of charge-transfer complexes with monomers having an electron donor character, combined with ethylenic comonomers of electron donor nature and / or other ethylenic monomers of electron donor or acceptor nature;
- a mixture of pore-forming solvents said base composition optionally being supplemented with a photoinitiator or a thermal initiator.
- the invention relates to compositions based on maleic anhydride, comonomers and / or other monomers and pore-forming solvents used for the production of monolithic materials according to the invention.
- the invention relates to monolithic materials in which the maleic anhydride functions are functionalized by reaction with nucleophilic compounds.
- the properties resulting from this functionalization are extremely varied: hydrophilic / hydrophobic balance adjustable, presence of positive or negative electrical charges, various functional organic groups, optionally optically active, specific substrates, artificial or enzymatic catalytic sites, etc.
- This diversity of accessible properties makes it possible to adjust the functional properties of porous materials as a phase for hydrophobic interaction chromatography, affinity chromatography, ion chromatography, electrochromatography, capillary electrophoresis, as a reactor, as a support for the absorption and analysis of compounds. as a sensor within a detection device.
- the invention thus relates to the various uses of functionalized monolithic materials for analytical microsystems.
- the subject of the invention is a polymeric monolithic material with functional groups characterized in that these are maleic anhydride units.
- the various applications most often require the elaboration of porous monolithic phases of optimal functional and fluidic characteristics.
- the experiment shows that the microstructure and the porosity of the monoliths are very dependent on the composition of the precursor reaction mixture (nature and quantity of the monomers, nature and composition of the pore-forming mixture) as well as the conditions of the elaboration (temperature, nature and kinetics priming reactions, duration of heat treatment, photochemical or radiochemical).
- the invention relates to a process for preparing functionalizable monolithic materials, said method comprising a preliminary step of treating the surface of the walls which serve as support for said monolithic materials, characterized in that it consists in a radical thermal, photochemical or radiochemical polymerization reaction of a composition comprising a base composition comprising: maleic anhydride as a base monomer, combined with ethylenic comonomers of electron-donating nature and / or other ethylenic monomers of donor or electron acceptor character;
- a mixture of pore-forming solvents said base composition optionally being supplemented with a photoinitiator or a thermal initiator.
- the monolithic materials have been developed in bodies or hollow objects of various sizes and shapes, having a cavity delimited by surfaces made of various materials, hereinafter referred to as "container objects". Examples of such container objects are:
- container objects are more particularly adapted to the elaboration of monolithic materials by photopolymerization when the cavity is delimited on one of its surfaces by a material transparent to UV-visible radiation.
- the elaboration of the monolithic materials is feasible by thermal or radiochemical polymerization.
- the monolithic materials preparation method includes a thermal polymerization reaction of a composition A comprising, in addition to the base composition, a thermal initiator, said reaction being conducted at a temperature of 40 to 90 0 C for a period of between 1 to 6 hours.
- the process for preparing monolithic materials comprises a photochemical polymerization reaction of a composition B comprising, in addition to the base composition, a photoinitiator.
- the choice of the nature and quantity of the initiator introduced into the formulation, the spectral range used and the power of the light source is of great importance for obtaining the desired morphological and fluidic characteristics.
- the formulation of the monomers and solvents with a photoinitiator is degassed for 5 min under nitrogen.
- the container objects are then filled with the solution and placed under a source of ultraviolet radiation of varying intensity (0.01 to 100 mW / cm 2 ) for an optimized time (depending on the support and the application). In general, this time varies from 1 minute to about 60 minutes.
- the monolith is then washed with an inert organic solvent for a time corresponding to about 100 column volumes.
- Inert organic solvents suitable for washing monoliths are for example an alkane or a mixture of C 8 to C 8 alkanes, toluene, tetrahydrofuran, ethyl acetate.
- a photoinitiator of the polymerization without the use of photoinitiator added to the base composition: this is a specific characteristic of mixtures of maleic anhydride and electro-donor monomers such as vinyl ethers; the formation of an absorbent charge transfer complex in the near UV would be at the origin of this behavior.
- These formulations can be polymerized under UV according to the same procedure as that described above but without the addition of photoinitiator.
- the polymerization time varies between 20 minutes and about 2:30.
- the monolith is then washed with an inert organic solvent for a time corresponding to about 100 column volumes.
- the process for preparing monolithic materials comprises a polymerization reaction under ionizing radiation, in particular under an electron beam (radiochemical priming), of the base composition.
- Container objects filled with precursors are irradiated without initiator, with doses ranging between 10 and 1000 kGy at various dose rates: from 0.01 to 100 kGy / s.
- the monolith is then washed with an inert organic solvent for a time corresponding to about 100 column volumes.
- the preliminary surface treatment of the walls of the location where it is desired to make the monolith is an essential element for obtaining a satisfactory anchoring of the monoliths and it is produced by grafting these surfaces with nucleophilic compounds.
- nucleophiles such as the amine functions of the aminopropyltrimethoxysilane (gamma-APS) group attached to the surface of glass or silica substrates, or the amino functions introduced to the surface of substrates made of polymeric materials, especially those used in analytical microsystems, for example the lithographable resin SU-8 after treatment with ammonia or an organic amine compound.
- FIG. 1 The effect of an increase in the duration of the polymerization on the permeability of the monoliths is presented in the appended FIG.
- the graph shows the influence of polymerization time on the loss of charge induced by the presence of UV-polymerized maleic anhydride monolith in a front capillary (points A) and after the modification of the maleic anhydride units with n-hexylamine (points B).
- the polymerization of precursor mixtures of monoliths containing maleic anhydride under an electron beam was carried out with doses of 10 kGy to 500 kGy and with various dose rates: from 0.01 kGy / s to 100 kGy / s and observed the formation of monoliths with an increase in the induced charge loss as a function of the applied dose.
- FIG. 2 shows scanning electron micrographs showing the morphology of maleic anhydride-based monoliths in capillaries of different diameters (inner diameter, upper lmm, low internal diameter 75 ⁇ m, polymerized under UV radiation) before modification (FIG. 2a, diameter 1 mm) and after modification (FIG.
- the invention relates to compositions based on maleic anhydride, comonomers and / or other monomers and pore-forming solvents used for the production of monolithic materials according to the invention.
- the process for producing monolithic materials uses a base composition comprising: maleic anhydride as basic monomer, combined with ethylenic comonomers of electron donor nature and / or other ethylenic monomers of donor or electron acceptor character;
- a mixture of pore-forming solvents said base composition being optionally or non-added with a thermal initiator or a photoinitiator.
- the process for producing monolithic materials uses a composition A comprising, in addition to the base composition, a thermal initiator.
- the molar content of maleic anhydride, evaluated relative to the number of moles of polymerizable functions in the monomer mixture is between 0.1 and 0.5, preferably between 0.2 and 0.5, while monomer ratio: pore-forming solvents is between 10-90% and 40-60% by weight; the thermal initiator is present at a level of between 0.05 and 5% by weight.
- the process for producing monolithic materials uses a composition B comprising, in addition to the base composition, a photoinitiator.
- the molar content of maleic anhydride, evaluated relative to the number of moles of polymerizable functions in the monomer mixture is between 0.1 and 0.5, preferably between 0.2 and 0.5, while monomer ratio: pore-forming solvents is between 10-90% and 40-60% by weight and the photoinitiator is present at a concentration of between 0.2 and 5% by weight.
- the comonomers used in these compositions are selected from the group: styrene and mono or multifunctional styrenic derivatives, mono- or multifunctional vinyl ethers (cyclohexyl vinyl ether, 1,4-bis (hydroxymethyl) cyclohexane divinyl ether), N-derivatives vinyl (N-vinyl pyrrolidone, N-vinyl carbazole), mono- or multifunctional acrylic and methacrylic esters (butyl acrylate, methyl methacrylate, hexanediol diacrylate, tripropylene glycol diacrylate), amides mono- or multifunctional acrylic and methacrylic, N-alkyl or N-aryl maleimides mono- and multifunctional.
- styrene and mono or multifunctional styrenic derivatives mono- or multifunctional vinyl ethers (cyclohexyl vinyl ether, 1,4-bis (hydroxymethyl) cyclohexane divinyl ether),
- the pore-forming solvent mixture used in the compositions of the invention comprises at least two solvents selected preferably from the group: pentane, hexane, cyclohexane, petroleum ether, toluene, dioxane, tetrahydrofuran, dichloromethane, ethyl acetate, alcohols.
- the thermal initiator is selected from the group: azobis-isobutyronitrile, hydrochloride 2,2-azobis (2-amidinopropane), 2,2-azobis (isobutyramide) dihydrate, benzoyl peroxide, dipropylperoxodicarbonate.
- One of the basic formulations for forming a maleic anhydride gel with a vinyl ether contains maleic anhydride (MA) combined with triethylene glycol divinyl ether (DVE3) or divinyl ether of bis (hydroxymethyl) -1,4 cyclohexane (CHVE) with a molar ratio of maleic and vinyl unsaturations of 1: 1 in a mixture of solvents: ethyl acetate cyclohexane (50-50% by weight).
- MA maleic anhydride
- DVE3 triethylene glycol divinyl ether
- CHVE divinyl ether of bis (hydroxymethyl) -1,4 cyclohexane
- FIG. 4 represents the influence of the composition in terms of weight content of monomers (maleic anhydride and equimolar vinyl diether in unsaturated functional groups) and of ethyl acetate in the precursor mixture of the monolith on the pressure loss per unit. of length for a flow rate of 1 ⁇ l / min after polymerization under UV radiation (3 min, internal diameter of the capillary 75 microns).
- formulations evaluated include as monomers maleic anhydride and hexanediol diacrylate, the molar ratio between the monomer molecules being 2: 1 while the weight ratio is 1: 1.15. These formulations make it possible to obtain another type of phase with a high content of maleic anhydride, a suitable permeability and a homogeneous morphology.
- AM BMA: DVE3: HDDA, the molar ratio between the monomer molecules being 2: 2: 1: 1 while the weight ratio is 1: 1.45: 1: 1.15;
- AM BMA: DVE3: TPGDA, the molar ratio between the monomer molecules being 2: 2: 1: 1 while the weight ratio is 1: 1.45: 1: 1.5;
- - AM BMA: CHVE: H DDA, the molar ratio between the monomer molecules being 2: 2: 1: 1 while the weight ratio is 1.17: 1.7: 1: 1.3;
- AM maleic anhydride
- BMA butyl methacrylate
- CHVE bishydroxymethyl-1,4-cyclohexane divinyl ether
- DVE3 triethylene glycol divinyl ether
- HDDA 1,6-hexanediol diacrylate
- TPGDA tripropylene diacrylate glycol
- the invention relates to monolithic materials in which the maleic anhydride functions are functionalized by reaction with nucleophilic compounds.
- the functionalization is carried out by addition of nucleophiles by infusion or in the form of an aqueous solution, organic, hydro-organic emulsion, mini or microemulsion.
- nucleophiles by infusion or in the form of an aqueous solution, organic, hydro-organic emulsion, mini or microemulsion.
- the chemical nature of these compounds can be very varied: simple organic compounds carrying at least one nucleophilic function (such as aliphatic or aromatic amines, alcohols, phenols, phosphines, and compounds with activated hydrogen), compounds with a hydrocarbon backbone more complex and / or carrying multiple chemical functions, neutral or ionic, oligomers and synthetic polymers, proteins, enzymes, antibodies, nucleic acids and so on.
- hydrophilic / hydrophobic balance adjustable presence: positive or negative electrical charges, functional organic groups, optionally optically active, specific substrates, recognition sites, artificial catalytic sites or enzymatic.
- the monoliths containing the maleic anhydride functional groups also have the advantage of possessing ionic functions of the carboxylate type, which are generated either by coupling with the functional nucleophile or by hydrolysis of all or the remainder of maleic anhydride functions. These ionized functions can be very useful for performing capillary electrochromatography, or for generating an electro-osmotic flow for the transport of solvents or solutions in microsystems.
- nucleophiles for example an active biological compound and polyethylene glycol which carries an amine function (peg-Nhb) to adjust the hydrophilic character of the functionalized porous material. Subsequent hydrolysis deactivates unreacted maleic anhydride functions.
- the functionalization is carried out dynamically, under mild conditions, by infusing through the column a solution of variable concentration between 0.5% and 50% (by weight ) amine in THF, toluene or acetonitrile (depending on the nature of the amine) for a period of between 1 h and 4 h.
- a solution of variable concentration between 0.5% and 50% (by weight ) amine in THF, toluene or acetonitrile (depending on the nature of the amine) for a period of between 1 h and 4 h.
- THF tris (hydroxymethyl) aminomethane
- trypsin The modification with trypsin is carried out dynamically for a time that varies from 1 h to 4 h depending on the chosen temperature, most often between 4 ° C and 25 ° C.
- the range of concentrations chosen for immobilization of trypsin was defined between 0.02 mg / ml up to 1 mg / ml trypsin in phosphate buffer depending on the volume of the reactor.
- the reactor is then washed with phosphate buffer solution (PBS) and then with TRIS buffer to condition the column.
- PBS phosphate buffer solution
- the immobilization protocol is similar to that presented in the example of trypsin immobilization; the concentration of streptavidin is 0.01 mg / ml with a dwell time of 1 to 8 hours at room temperature.
- Functionalization with synthetic polymers terminal primary amine function
- the modification is performed by infusion of the monolith with a solution in the
- THF of a polymer having a primary amine end poly (N-isopropylacrylamide) or polyethylene glycol) and a tertiary amine such as triethylenediamine, for 1 h to 4 h, depending on the concentration of the solution of the functional polymer to graft, according to the degree of polymerization of the latter, and according to the concentration of tertiary amine.
- Monolithic materials based on maleic anhydride functionalized according to the invention have been characterized by several methods, as exemplified hereinafter.
- Monoliths functionalized with aliphatic amines and with polymers were characterized by infrared spectroscopy (IR) after washing and drying.
- IR infrared spectroscopy
- the analyzes were carried out in transmission mode after making a pellet of monolith powder before and after modification with KBr.
- Monoliths modified with specific interaction receptors were characterized by fluorescence at 532 nm of the streptavidin Cy3-excited label at 580 nm. A clear fluorescence of the samples modified with streptavidin and none on control monoliths is observed. Characterization by elemental nitrogen analysis
- Modified monoliths with various molecules have been characterized by elemental nitrogen analysis. Measurement of the pressure loss The structural modifications induced by the chemical functionalization are accompanied by limited modifications of the permeability of the monoliths. Clogging of the porous structure is avoided. Pressure measurements at different imposed solvent rates revealed limited increases in pressure drop. The results presented in Figure 1 illustrate the modified changes obtained after treatment with n-hexylamine. Hydrolysis of BAEE on trypsic reactors
- the enzymatic activity of monolithic phases functionalized with trypsin was measured by studying the kinetics of hydrolysis of the ethyl ester of N-benzoyl arginine (BAEE). Trypsic reactors prepared according to different protocols were fed with a substrate solution by means of a syringe pump and connected downstream to a circulation cell placed in a UV spectrometer. The efficiency of the hydrolysis was followed continuously by measuring the absorbance at 253 nm.
- Monoliths with high permeability prepared from certain maleic anhydride based formulations by thermal, photochemical or radiochemical polymerization, have been measured at low pressure (THF, toluene at constant pressure below 0). , 05 bar).
- THF toluene at constant pressure below 0.
- FIG. 6 shows the flow properties of toluene through a phase composed of AM / BMA / CHVE monomers polymerized under UV radiation for 1 h in a 1 mm column and unmodified (low pressure drop of 3 bar). on a column of 20 cm length and 75 ⁇ m internal diameter). Fluidic characterization at high pressure
- Maleic anhydride based monoliths of lower permeability prepared from certain maleic anhydride formulations by thermal, photochemical or radiochemical polymerization in capillaries with an internal diameter of between 75 ⁇ m and 1 mm, made the object of pressure drop measurements.
- the flow of a solvent is imposed by an HPLC pump (Waters) at a flow rate ranging from l ⁇ l / min to a few tens of ⁇ l / min or by a high pressure syringe (Harvard Instrumentation). Pressures of up to 150 bars were thus measured for THF flowing with a flow rate of 1 ⁇ l / min in a capillary length 20 cm and internal diameter 75 ⁇ m.
- FIG. 7 shows four monolithic phases with a high maleic anhydride content:
- FIG. 7a Mixture of AM / CHVE / BMA monomers, of which 28% of the polymerizable functions come from maleic anhydride, the porogen containing ethyl acetate ;
- 7b AM / CHVE / BMA monomer mixture, of which 28% of the polymerizable functions come from maleic anhydride, the porogen containing toluene;
- 7c Mixture of AM / CHVE monomers, 50% of the polymerizable functions are derived from maleic anhydride, the porogen containing ethyl acetate;
- Figure 7d Mixture of AM / DVE3 monomers, of which 50% of the polymerizable functions are derived from maleic anhydride, the porogen containing ethyl acetate.
- the invention relates to the various uses of functionalized monolithic materials for analytical microsystems.
- the functionalized monolithic materials according to the invention are used:
- a chromatographic method selected from the group: affinity, hydrophobic interaction, ionic interaction, electrochromatography, capillary electrophoresis;
- EXAMPLE 1 Separation Reactor Obtained by Functionalization with N-Hexylamine Nanochromatographic liquid-type (nano-LC) analyzes were carried out to evaluate the chromatographic performance of the columns obtained from maleic anhydride monocrystals prepared in capillaries and functionalized. by reaction with alkylamines.
- the separation tests of the peptides contained in cytochrome C and ⁇ -galactosidase digestates were carried out by injecting 0.1 ⁇ l with 1 ⁇ l of digestate solution of concentration between 80 fmol / ⁇ l and 800 fmol / ⁇ l on columns with an internal diameter of 75 ⁇ m and a length of between 5 and 20 cm, with linear water-acetonitrile gradient elution.
- This column was then polymerized electron beam with a dose of 100 kGy and at a flow rate of 0.68 kGy / s through 25 kGy passages.
- the column was washed with THF for 1 h to 1 ⁇ l / min, then modified with a C6 amine in THF (10% by weight) for 2 h, washed by infusion of THF for 1 h and TRIS buffer for 1 h. .
- the column was stabilized by infusion of a water: acetonitrile mixture (50-50% by weight). The pressure under analysis did not exceed 49 bars for a column length of 20 cm. The feasibility of separating the main peptides has been demonstrated on 5 cm long columns containing a monolith functionalized with n-hexylamine.
- Example 2 Tryptic Digestion Reactor Tryptic digestion was performed on a column 8 cm long and 75 ⁇ m in internal diameter. The monolith was polymerized under UV radiation for 10 min, then washed for 1 h and modified with trypsin in PBS phosphate buffer at 0.01 mg / ml for 1 h at 4 ° C. The column was then washed with PBS buffer and then with TRIS buffer. The digestion of 20 pmol of Cytochrome C was carried out continuously with a flow rate of 3.5 ⁇ l / min on a capillary length 8 cm in diameter of 75 ⁇ m containing a trypsin functionalized maleic anhydride monolith. The MALDI TOF mass spectrum obtained from 50 .mu.l of digestate solution is presented in the appended FIG. 9. The exploitation of the data allows the identification of the protein with a recovery of 65% of the sequence.
- Example 3 Digestion Reactor
- the hydrolysis of the ethyl ester of N-benzoyl arginine (BAEE) was carried out on a column 10 cm long and 1 mm in internal diameter.
- the monolith was polymerized UV for 1 h, then washed with THF and modified with trypsin in PBS buffer at 0.01 mg / ml, infused for 4 h at 4 ° C.
- the column is then washed with PBS buffer and then with TRIS buffer.
- the hydrolysis of BAEE (0.25 mM) was carried out by dynamic perfusion with detection by UV spectrometry at 253 nm.
- the hydrolysis of the BAEE approaches 91% yield, when the residence time in the column is correctly chosen, as shown in the graph presented in the appended FIG.
- Example 4 Affinity Reactor Streptavidin was immobilized on monolithic phases based on maleic anhydride prepared by polymerization under UV radiation. Specific interaction was performed with a fluorophore carrying biotin. Coupling efficiency was demonstrated by fluorescence imaging of the biotinyl Cy5 marker.
- EXAMPLE 5 Heat Valve Porous phases were prepared in fluidic microsystems comprising channels passing through chambers of the same section and length 100 ⁇ m filled with monolith functionalized with poly (NIPAM) amino terminal function. The temperature of the chambers can be modified by means of heating resistors inserted into the structure of the microsystem.
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- Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Analytical Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Polymers & Plastics (AREA)
- Engineering & Computer Science (AREA)
- Materials Engineering (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- General Physics & Mathematics (AREA)
- Immunology (AREA)
- Pathology (AREA)
- Physics & Mathematics (AREA)
- Addition Polymer Or Copolymer, Post-Treatments, Or Chemical Modifications (AREA)
- Polymerisation Methods In General (AREA)
- Compositions Of Macromolecular Compounds (AREA)
- Manufacture Of Porous Articles, And Recovery And Treatment Of Waste Products (AREA)
- Solid-Sorbent Or Filter-Aiding Compositions (AREA)
- Catalysts (AREA)
- Other Resins Obtained By Reactions Not Involving Carbon-To-Carbon Unsaturated Bonds (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
FR0503529A FR2884253B1 (fr) | 2005-04-08 | 2005-04-08 | Materiaux monolithiques fonctionnalisables |
PCT/FR2006/000716 WO2006108943A1 (fr) | 2005-04-08 | 2006-03-31 | Materiaux monolithiques fonctionnalisables |
Publications (1)
Publication Number | Publication Date |
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EP1868716A1 true EP1868716A1 (de) | 2007-12-26 |
Family
ID=35266943
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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EP06726165A Withdrawn EP1868716A1 (de) | 2005-04-08 | 2006-03-31 | Monolithische funktionalisierbare materialien |
Country Status (8)
Country | Link |
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US (1) | US20080182918A1 (de) |
EP (1) | EP1868716A1 (de) |
JP (1) | JP2008539281A (de) |
KR (1) | KR101013317B1 (de) |
CN (1) | CN101171075B (de) |
CA (1) | CA2604089C (de) |
FR (1) | FR2884253B1 (de) |
WO (1) | WO2006108943A1 (de) |
Families Citing this family (5)
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EP2217646B1 (de) | 2007-11-09 | 2013-01-23 | 3M Innovative Properties Company | Poröse polymerharze |
US10625470B2 (en) * | 2016-09-28 | 2020-04-21 | Ada Foundation | 3D printing of composition-controlled copolymers |
CN108129660B (zh) * | 2016-12-01 | 2020-05-19 | 中国科学院大连化学物理研究所 | 一种有机整体材料及其制备和应用 |
BE1025524B1 (nl) * | 2017-09-04 | 2019-04-05 | PharmaFluidics N.V. | Chemische reactoren |
WO2024051811A1 (zh) * | 2022-09-09 | 2024-03-14 | 中国石油化工股份有限公司 | 可回收聚合物气凝胶、蓄冷相变复合材料及制法和应用 |
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GB821229A (en) * | 1955-12-13 | 1959-10-07 | Ionics | Method of manufacturing electrically conductive membranes |
US4468330A (en) * | 1981-04-27 | 1984-08-28 | Sekisui Kagaku Kogyo Kabushiki Kaisha | Filler for liquid chromatography useful for separating a hemoglobin variant in blood |
JPH0717688B2 (ja) * | 1988-03-30 | 1995-03-01 | 日本合成ゴム株式会社 | 高架橋ポリマー粒子およびその製造方法 |
JPH0214207A (ja) * | 1988-06-30 | 1990-01-18 | Kyowa Gas Chem Ind Co Ltd | 離型性の改良された注型成形品の製造法 |
US5474780A (en) * | 1990-04-27 | 1995-12-12 | Allergan, Inc. | Monolithic maleic anhydride drug delivery systems |
WO1994009063A1 (en) * | 1992-10-21 | 1994-04-28 | Cornell Research Foundation, Inc. | Pore-size selective modification of porous materials |
US5653875A (en) * | 1994-02-04 | 1997-08-05 | Supelco, Inc. | Nucleophilic bodies bonded to siloxane and use thereof for separations from sample matrices |
US5883144A (en) * | 1994-09-19 | 1999-03-16 | Sentinel Products Corp. | Silane-grafted materials for solid and foam applications |
US5661221A (en) * | 1996-12-18 | 1997-08-26 | Colgate-Palmolive Company | Process for the preparation of cross-linked maleic anhydride copolymers |
US5929214A (en) * | 1997-02-28 | 1999-07-27 | Cornell Research Foundation, Inc. | Thermally responsive polymer monoliths |
US5865994A (en) * | 1997-03-13 | 1999-02-02 | Dionex Corporation | Bifunctional crown ether-based cation-exchange stationary phase for liquid chromatography |
DE19906984A1 (de) * | 1999-02-19 | 2000-08-31 | Bayer Ag | Vinylcyclohexan basierende Polymere |
DE60114009T2 (de) * | 2000-06-15 | 2006-06-22 | Isp Investments Inc., Wilmington | Kontinuierlicher lösungsmittelfreier prozess zur herstellung von copolymeren von maleinsäureanhydrid und c1-4? alkylvinylether |
AUPR143400A0 (en) * | 2000-11-13 | 2000-12-07 | Usf Filtration And Separations Group Inc. | Modified membranes |
DE60237251D1 (de) * | 2001-01-29 | 2010-09-23 | Tosoh Corp | Kationenaustauscher, Verfahren zu dessen Herstellung und dessen Verwendung |
GB0123232D0 (en) * | 2001-09-26 | 2001-11-21 | Smith & Nephew | Polymers |
US7060187B2 (en) * | 2001-11-26 | 2006-06-13 | Ge Healthcare Bio-Sciences Ab | Post-modification of a porous support |
AU2002353736B2 (en) * | 2001-11-26 | 2008-05-08 | Ge Healthcare Bio-Sciences Ab | Post-modification of a porous support |
US20040028901A1 (en) * | 2002-02-25 | 2004-02-12 | Rumpf Frederick H. | Compositions comprising continuous networks and monoliths |
KR100505361B1 (ko) * | 2002-06-03 | 2005-08-03 | 정원조 | 소결 무기 분말 프릿이 장착된 금속 튜빙/프릿 및 이를이용하여 제작하는 크로마토그래피 컬럼 |
US7491779B2 (en) * | 2002-06-05 | 2009-02-17 | Imperial College Of Science, Technology And Medicine | Polyvinyl ethers |
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JP4265181B2 (ja) * | 2002-09-11 | 2009-05-20 | 昭和電工株式会社 | 弱酸性陽イオン交換体の製造方法および陽イオンクロマトグラフィー用カラム |
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-
2005
- 2005-04-08 FR FR0503529A patent/FR2884253B1/fr not_active Expired - Fee Related
-
2006
- 2006-03-31 KR KR1020077022648A patent/KR101013317B1/ko not_active IP Right Cessation
- 2006-03-31 WO PCT/FR2006/000716 patent/WO2006108943A1/fr not_active Application Discontinuation
- 2006-03-31 CA CA2604089A patent/CA2604089C/fr not_active Expired - Fee Related
- 2006-03-31 US US11/910,964 patent/US20080182918A1/en not_active Abandoned
- 2006-03-31 EP EP06726165A patent/EP1868716A1/de not_active Withdrawn
- 2006-03-31 JP JP2008504799A patent/JP2008539281A/ja not_active Ceased
- 2006-03-31 CN CN2006800148290A patent/CN101171075B/zh not_active Expired - Fee Related
Non-Patent Citations (1)
Title |
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SCHULZ B ET AL: "Structure-release relations of physical polymer-biocide-combinations. Part 1: Influence of the polymer structure on the diffusive release of 3-methylpyrazole from monolithic systems", PHARMAZIE, DIE, GOVI VERLAG, ESCHBORN, DE, vol. 40, no. 8, 1 January 1985 (1985-01-01), pages 548 - 552, XP001539663, ISSN: 0031-7144 * |
Also Published As
Publication number | Publication date |
---|---|
US20080182918A1 (en) | 2008-07-31 |
CN101171075B (zh) | 2012-06-20 |
JP2008539281A (ja) | 2008-11-13 |
FR2884253B1 (fr) | 2007-06-22 |
CA2604089C (fr) | 2012-08-14 |
FR2884253A1 (fr) | 2006-10-13 |
CN101171075A (zh) | 2008-04-30 |
KR101013317B1 (ko) | 2011-02-09 |
CA2604089A1 (fr) | 2006-10-19 |
WO2006108943A1 (fr) | 2006-10-19 |
KR20080009070A (ko) | 2008-01-24 |
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