WO2006077038A1 - Procede d'encapsulage de molecules detecteurs par une membrane semi-permeable - Google Patents

Procede d'encapsulage de molecules detecteurs par une membrane semi-permeable Download PDF

Info

Publication number
WO2006077038A1
WO2006077038A1 PCT/EP2006/000165 EP2006000165W WO2006077038A1 WO 2006077038 A1 WO2006077038 A1 WO 2006077038A1 EP 2006000165 W EP2006000165 W EP 2006000165W WO 2006077038 A1 WO2006077038 A1 WO 2006077038A1
Authority
WO
WIPO (PCT)
Prior art keywords
membrane
matrix material
molecules
sensor molecules
semipermeable membrane
Prior art date
Application number
PCT/EP2006/000165
Other languages
German (de)
English (en)
Inventor
Károly Nagy
Thomas Freese
Andreas Greiner
Phillip Hanefeld
Joachim H. Wendorff
Original Assignee
Ehrfeld Mikrotechnik Bts Gmbh
Philipps-Universität Marburg
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 Ehrfeld Mikrotechnik Bts Gmbh, Philipps-Universität Marburg filed Critical Ehrfeld Mikrotechnik Bts Gmbh
Publication of WO2006077038A1 publication Critical patent/WO2006077038A1/fr

Links

Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
    • G01N33/5436—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals with ligand physically entrapped within the solid phase
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/66—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving blood sugars, e.g. galactose

Definitions

  • a method for encapsulating sensor molecules wherein the sensor molecules are introduced into a matrix material, then this is divided into defined units, these units are coated with a semi-permeable membrane, then dissolved or degraded the matrix material and selectively removed by the semipermeable membrane and against a fluid medium is exchanged so that the sensor molecules are freely movable within the volume enclosed by the membrane.
  • biomolecules and whole cells plays an important role in many applications of modern biotechnology and medical diagnostics.
  • the general goal is to immobilize the biomolecules (or cells) and to study their specific function under different conditions or to detect their presence.
  • the full functionality of the biomolecules can generally be studied in a freely mobile state, in solution, or the presence in the bound state can be detected and investigated.
  • Another prerequisite for modern technology is the parallel examination of numerous samples, such as e.g. through high-throughput screening.
  • This requirement is met by assigning the different molecules to specific positions in an array. The presence of a particular molecule is then determined by changing the properties of the site (e.g., fluorescence) where the molecules were selectively bound. The identification is thus solved by the localization of the changes in the array.
  • immobilization methods include the inclusion of biomolecules in a semipermeable membrane, according to Biosens. Bioelectron. 8 (1993) page 443, the microencapsulation in polymer microcapsules according to Meth. Enzymol. 44 (1976) page 169 or in hydrogels according to Meth. Enzymol. 135 (1987) page 30.
  • the disadvantage of these methods is that in many cases desorption or leaching of the biomolecules occurs, that it is unsuitable for many biomolecules, that immediate or delayed denaturation can occur, and finally, that the function required free movement in volume can not be adequately secured, see Analyst 121 (1996) 29R.
  • Another method is the incorporation of biomolecules in an inorganic matrix, prepared according to sol-gel method and characterized by a porous structure.
  • the disadvantage of this method is that often the function of the biomolecules is adversely affected by changes in their conformation in the pores, by strong interactions with the pore walls and / or by a hindered rotation in the pores, and that not all biomolecules are accessible, according to Analytica Chimica Acta 461 (2000) pages 1-36.
  • the object of the present invention was therefore to provide a method for the immobilization of biomolecules, which does not have the above disadvantages and further ensures a rapid interaction with the analyte.
  • the method according to the invention does not have the aforementioned disadvantages and thus a simple possibility of encapsulation of sensor molecules, which allows reactions of the entrapped biomolecules with other molecules in freely movable state and makes the positioning of the microcompartments possible. Therefore, the method is particularly suitable, for example, for the production of microarrays.
  • the present invention thus relates to a method for encapsulating sensor molecules, characterized in that the sensor molecules are introduced into a matrix material, this is then divided into defined units, these units are coated with a semipermeable membrane, then dissolved or degraded the matrix material and selectively is removed by the semipermeable membrane and exchanged for a fluid medium, so that the sensor molecules are freely movable within the volume enclosed by the membrane.
  • Sensor molecules in the sense of the invention are all molecules which change in their chemical or physical properties measurably when they come into contact with small molecules that can diffuse through the membrane.
  • the sensor molecules are preferably biomolecules, such as, for example, proteins, peptides, enzymes or amino acids.
  • sensor molecules such as Pfla ⁇ zenlektine and polysaccharides.
  • sensor molecules such as fluorescently labeled Concanavalin A and dextran, which are used for the detection of glucose by fluorescence resonance energy transfer (FRET).
  • FRET fluorescence resonance energy transfer
  • matrix materials are preferably polymers which do not render the stored sensor molecules nonfunctional and which can be removed from the system by methods such as washing out or temperature treatment through the membrane and which can be processed well by the methods described.
  • a matrix material is used, which can be brought from the liquid form into a solid form.
  • This is preferably porous silicate or other inorganic matrix or hydrogel or low molecular weight polymer, e.g. For example, polyethylene glycol (PEG).
  • PEG polyethylene glycol
  • a material which is swellable is particularly preferred.
  • the sensor molecules to be immobilized are added to the preferably present in liquid form matrix material and preferably solidified.
  • the division into defined units is preferably carried out in the solid state.
  • the solid matrix material including the sensor molecules, is preferably prepared by cutting and / or milling, or in liquid units, preferably by atomizing into defined units, i. brought into the desired shape and size.
  • matrix material and sensor molecule are processed below the melting point of the matrix material in the solid state and brought into the desired shape. It is also possible that matrix material and sensor molecule is processed above the melting point in a liquid state and brought into the desired shape.
  • matrix material and sensor molecule are processed in the presence of solvents in a liquid state and brought into the desired shape.
  • solvents particularly suitable for this purpose are hydrogels or low molecular weight polymers such as, for example, poly (ethylene glycol) (PEG).
  • matrix material and sensor molecules can likewise be produced by means of conventional methods, for example by screen or mask printing, injection molding methods, embossing methods and / or stamping methods.
  • screen or mask printing for example by screen or mask printing, injection molding methods, embossing methods and / or stamping methods.
  • Matrix material and sensor molecules are preferably arranged in a grid (microarray).
  • the units containing the matrix material and the biomolecules are preferably coated in a subsequent step with a semipermeable membrane which prevents the washing out of the molecules to be immobilized.
  • thermoplastic polymers such as preferably polystyrene, polyurethane, polyurea, polycarbonates,
  • Polycarbonates polylactides, polyglycolides, polysulfones, polyethersulfones, polyesters, polyamides, polyesteramides, polyvinyl chloride, polynorbornene, polyethylene, polypropylene, polybutadiene, polysiloxanes, polyanhydrides, polyacrylates, polymethacrylates, polyethers, polylactide, and / or polycaprolactone, elastic polymers and crosslinked Polymers and especially by gas phase producible polymers, such as Parylene, are used. Furthermore, it can also be prepared from dissolved polymers (for example poly (venyl alcohol)), e.g.
  • aqueous lattices or suspensions of water-insoluble polymers created semipermeable membrane can be used.
  • Also possible is the use of blends, random copolymers, graft or block copolymers, dendrimers and / or highly branched polymers.
  • Also preferred as semipermeable layers is poly (p-xylylene).
  • Matrix material and sensor molecules can also be coated on one side or on all sides with a semipermeable membrane
  • the coating with a semipermeable membrane is preferably carried out
  • polymerization of [2.2] para-cyclophane followed by vapor deposition of the formed 1,4-quinodimethane to form a film of poly-p-xylylene (PPX) is preferred.
  • the permeability of the semipermeable membrane can be adjusted via the layer thickness, via the use of multilayers, via a subsequent grafting or another chemical type of modification. It is also possible to adjust the permeability of the semipermeable membrane via the use of block copolymers, via the use of polyelectrolytes and / or via the use of polymer blends.
  • the matrix material is washed out of the chambers, liquefied or swollen.
  • the chambers can be filled with the desired solution.
  • Particularly suitable as the solution are water, physiological buffer systems, organic solvents such as alcohols, saline solutions (e.g., isotonic saline), isotonic glycerol solutions, serum replacement, plasma substitutes, glucose solutions, nutrient media, and / or supercritical carbon dioxide.
  • analytes can be detected by applying specific reactions and using appropriate analytical methods.
  • the invention also relates to the use of the encapsulated sensor molecules produced by the process according to the invention, e.g. labeled or unlabelled plant lectins / metalloproteins preferably fluorescently labeled concanavalin A and polysaccharides such as dextran, dextran 40, 60 or 70 for the detection of analytes, particularly preferably for the detection of glucose by fluorescence resonance energy transfer (FRET).
  • labeled or unlabelled plant lectins / metalloproteins preferably fluorescently labeled concanavalin A and polysaccharides such as dextran, dextran 40, 60 or 70 for the detection of analytes, particularly preferably for the detection of glucose by fluorescence resonance energy transfer (FRET).
  • FRET fluorescence resonance energy transfer
  • the detections can be carried out in vitro or in vivo.
  • Fig. 1 is a schematic representation of the concept of the method according to the invention.
  • FIG. 5 Schematic representation of the coating of sensor molecules + matrix material with a semipermeable membrane.
  • FIG. 6 Alternative coating methods: application of sensor molecules + matrix material to a holder coated with semipermeable membrane or foil.
  • Fig. 1 shows a schematic representation of the concept of erf ⁇ ndungswashen method.
  • a mixture of the solution with sensor molecules (1) and the solid dissolvable matrix material (2) or a solution of the matrix material is first prepared (FIG. 1a).
  • the sample solution (3) is then added e.g. solidified by freeze-drying.
  • the solid samples (4) may e.g. with an extruder (5) and by cutting the extruded mass produced (Fig. Ib) and coated with a semi-permeable membrane with an adjustable cut-off (6) (Fig. Ic).
  • the matrix material is then washed out (FIG. Id).
  • the samples (sensor molecules + matrix material) are placed in a suitable solution (7), wherein the molecules of the matrix material diffuse into the washing solution (8) through the semipermeable membrane (6). After several washes, the capsule is free of matrix material (9) and the sensor molecules remain trapped.
  • matrix materials with other properties are also conceivable.
  • Fig. 2 shows an example for the preparation of the sample (4) shows (sensor matrix material molecules +) ⁇ at low temperatures and positioning on a support (10).
  • This manufacturing method should be used at temperatures lower than the melting point of the sample.
  • the solid sample Substance is pressed out with an extruder (5) and cut with a knife, a laser or a waterjet cut (11).
  • the dimensions of the samples (4) are limited by the exit opening and the feed of the extruder (5).
  • By moving the holder (10), the desired arrangement of the samples (4) can be achieved.
  • the thus positioned samples are coated with a semipermeable membrane (12).
  • the application of the semipermeable membrane is carried out by spin-coating, coating with a film or preferably by vapor deposition (see Figures 5 and 6).
  • the permeability of the membrane envelope is adjusted by the thickness or structure of the membrane so that the molecules 'of the Mairixm ⁇ erialsliurchBiffunlliererrkö ⁇ rie ⁇ ", but not the to be immobilized' molecules.
  • a microarray With various specific samples such a microarray can be produced.
  • the holder 10 is coated with a semipermeable membrane or any film prior to placing the samples (see Fig. 6a), the samples are placed on the membrane and also coated from above with a membrane. As a result, the samples are enclosed in a thin membrane structure (13) without a holder.
  • the sample can also be processed in liquid form, as shown in FIG. 3.
  • the molten sample is collected in a die head (14), e.g. InkJet filled, and held there in liquid form (temperature> melting point). So the sample can be sprayed onto a holder. On the cold holder, the liquid sample is cooled and transferred to the solid state, wherein the solvent also partially evaporated.
  • the sample can be placed on the fixture in a desired pitch and amount.
  • the solid samples are then coated with a semipermeable membrane. As described in Fig. 2 (see also Fig. 6a), the samples can also be applied to a membrane-coated holder whereby, after coating with a cover membrane, the samples are enclosed in a clean membrane structure (13).
  • a polymer strand in viscoelastic form could be applied to a fixture and cut into small pieces after cooling. The samples are then positioned in an array.
  • a layer (15) of desired thickness from the sample substance in solid or molten state to a suitable surface (16).
  • the layer can be cut into small pieces in the solid state.
  • the sample pieces (4) can then be applied to a holder (10) in the desired grid, where they are coated with a semipermeable membrane (12). Similar to FIG. 2 and 3 (see also Fig. 6a), the inclusion of the samples in a pure membrane structure (13) is also possible here.
  • the resulting pattern (array) can then also be further coated.
  • the dimensions of the samples are determined by the application. When applying for microarrays they are in the micrometer range, whereas in biotechnological applications -wo_die amount of biomolecules .ein mentionen a _wichtige_Rolle_spieJt_ (eg, _B ..._ e ⁇ ⁇ ⁇ i? -Beta u ng of enzymes) the dimensions of the samples can be in the centimeter range.
  • the individual working steps of the coating are shown in FIG. 5a.
  • the samples (4) lying on the holder (10) are preferably coated with a semipermeable membrane by vapor deposition. Coating with plastics from solution or melt, coating with a film, spin coating, laser welding or similar conventional methods of encapsulation are also applicable.
  • the molecules (18) preferably polymers, such as [2.2] ⁇ ara-cyclophane escape from a source (17).
  • these reactive molecules spontaneously polymerize to form a membrane (12).
  • a film of poly-p-xylylene (PPX) can be generated.
  • the permeability of the membrane can be adjusted. If the adhesion of the membrane to the surface of the support (matrix structure) is stable (not dissipated by solvent), and a thickness of the membrane meeting the requirements of the material penetration has been achieved, the incorporation of the samples is completed.
  • Stable adhesion can be achieved by selecting a suitable material for the support, or by functionalizing or treating the surface of the support.
  • the membrane can be pulled off the support together with the samples and turned over (Figure 5b), exposing the bottom surface.
  • the exposed surface of the sample-membrane structure can then also be coated (FIG. 5c).
  • the samples (4) can be cut out of the flat membrane ( Figure 5d) and incorporated into a desired structure.
  • FIG. 6 shows an alternative procedure to the method in FIG. 5.
  • the holder (10) is first coated with a membrane (12).
  • This membrane may alternatively have identical or different properties than the membrane that ensures the semipermeability and functionality of the concept.
  • the samples are coated and coated with a semi-permeable membrane, as described in Fig. 5. After removal from the support, the samples are in a free membrane structure (Figure 6c).
  • the samples may also be coated in a floating state by vapor deposition ( Figure 7).
  • the samples (4) are placed on a vibrating table (19) (e.g., vibrator, loudspeaker) and constantly pushed upwards. Due to the statistical orientation, they are coated with the membrane on each side.
  • a vibrating table (19) e.g., vibrator, loudspeaker
  • FIG. 8 Various shapes of individual samples can be made by screen / mask printing ( Figure 8).
  • the mask (20) is placed on a holder (10) and the sample mass lubricated in the mask. After removal of the mask, the sample remains on the holder.
  • Fig. 9 demonstrates the preparation of 3D samples. With a suitable mold (21) it is possible to produce any 3D shapes at lower temperatures. The solid samples can then be coated with the method in FIG. 7 with a semipermeable membrane.
  • the viscous solution was gently de-watered in a desiccator until the mixture solidified.
  • the shaping of the matrix mixture was carried out by three different methods:
  • the matrix mixture in a template with the hole dimensions of 8 mm x 8 mm x 1 mm was formed in a press at 35 0 C for 10 minutes. Subsequently, the resulting solids were cooled to -78 ° C, removed from the template and coated at room temperature with PPX.
  • the matrix mixture was extruded at a flow temperature of 35 0 C and an ejection temperature of 15 0 C. When cooled to 15 ° C., the matrix mixture showed good stiffness and was immediately cut with a blade into pieces of defined dimensions.
  • the pallet thus obtained had a diameter of 1 mm and a thickness of about 50 - 100 microns.
  • the pallets were applied to a previously prepared PPX film and coated with PPX at room temperature. In a final process, the matrix material was liquefied at 35 ° C and applied to a pre-coated PPX glass surface in a defined amount. After solidification at room temperature, it was coated with PPX.
  • the applied PPX layers had a thickness of 1.6 ⁇ m and 2.4 ⁇ m.
  • Vibrating table e.g., speaker

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Immunology (AREA)
  • Engineering & Computer Science (AREA)
  • Hematology (AREA)
  • Molecular Biology (AREA)
  • Biomedical Technology (AREA)
  • Chemical & Material Sciences (AREA)
  • Urology & Nephrology (AREA)
  • Biotechnology (AREA)
  • Biochemistry (AREA)
  • Cell Biology (AREA)
  • Food Science & Technology (AREA)
  • Medicinal Chemistry (AREA)
  • Physics & Mathematics (AREA)
  • Analytical Chemistry (AREA)
  • Microbiology (AREA)
  • General Health & Medical Sciences (AREA)
  • General Physics & Mathematics (AREA)
  • Pathology (AREA)
  • Diabetes (AREA)
  • Investigating, Analyzing Materials By Fluorescence Or Luminescence (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)

Abstract

L'invention concerne un procédé d'encapsulage de molécules détecteurs. Les molécules détecteurs sont introduites dans une matière matrice puis cette dernière est divisée en unités définies. Ces unités sont recouvertes d'une membrane semi-perméable puis la matière matrice est dissoute ou décomposée et sélectivement éloignée par la membrane semi-perméable et échangée contre un agent fluide de telle façon que les molécules détecteurs se meuvent librement dans le volume entouré par la membrane mais sont immobilisées dans la membrane.
PCT/EP2006/000165 2005-01-18 2006-01-11 Procede d'encapsulage de molecules detecteurs par une membrane semi-permeable WO2006077038A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE200510002483 DE102005002483A1 (de) 2005-01-18 2005-01-18 Verfahren zum Einkapseln von Sensormolekülen mit einer semipermeablen Membran
DE102005002483.1 2005-01-18

Publications (1)

Publication Number Publication Date
WO2006077038A1 true WO2006077038A1 (fr) 2006-07-27

Family

ID=36128447

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2006/000165 WO2006077038A1 (fr) 2005-01-18 2006-01-11 Procede d'encapsulage de molecules detecteurs par une membrane semi-permeable

Country Status (2)

Country Link
DE (1) DE102005002483A1 (fr)
WO (1) WO2006077038A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111440331A (zh) * 2020-03-20 2020-07-24 华南农业大学 一种壳聚糖基细胞靶向粘附控释水凝胶及其制备方法和应用

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20020182658A1 (en) * 2001-04-11 2002-12-05 Motorola, Inc. Sensor device and methods for manufacture

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA1245984A (fr) * 1983-09-01 1988-12-06 Damon Biotech, Inc. Micro-encapsulation poly-ionique
US4933185A (en) * 1986-09-24 1990-06-12 Massachusetts Institute Of Technology System for controlled release of biologically active compounds
US5084350A (en) * 1990-02-16 1992-01-28 The Royal Institution For The Advance Of Learning (Mcgill University) Method for encapsulating biologically active material including cells
GB0311664D0 (en) * 2003-05-21 2003-06-25 Univ Manchester Polymeric hollow nanospheres

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20020182658A1 (en) * 2001-04-11 2002-12-05 Motorola, Inc. Sensor device and methods for manufacture

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
PLASMA PARYLENE SYSTEMS: "Parylene Verfahren", INTERNET ARTICLE, 10 October 2004 (2004-10-10), XP002377740, Retrieved from the Internet <URL:http://web.archive.org/web/20041010082513/www.plasmaparylene.de/html/parylene_verfahren.html> *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111440331A (zh) * 2020-03-20 2020-07-24 华南农业大学 一种壳聚糖基细胞靶向粘附控释水凝胶及其制备方法和应用

Also Published As

Publication number Publication date
DE102005002483A1 (de) 2006-08-03

Similar Documents

Publication Publication Date Title
EP1064087B1 (fr) Production de nanogelules et de microgelules par auto-assemblage stratiforme de polyelectrolytes
DE3789114T2 (de) Einen dünnen film enthaltende ultrafiltrationsmembran.
DE1939066A1 (de) Mikrokapsel und Verfahren zu ihrer Herstellung
DE10344820B4 (de) Adsorptionsmembranen, Verfahren zur Herstellung derselben und Verwendung der Adsorptionsmembranen in Vorrichtungen
DE19812083A1 (de) Herstellung von Nano- und Mikrokapseln durch schichtweise Polyelektrolyt-Selbstassemblierung
WO2019219605A1 (fr) Procédé pour la fabrication d&#39;un insert pour culture de cellules comprenant au moins une membrane
DE10344819B4 (de) Adsorptionsmembranen, Verfahren zur Herstellung derselben und Vorrichtungen, welche die Adsorptionsmembranen umfassen
DE102012206042A1 (de) Verfahren und Vorrichtung zur gezielten Prozessführung in einem Mikrofluidik-Prozessor mit integrierten aktiven Elementen
EP2356215A1 (fr) Substrats permettant de sélectionner et d&#39;influencer spécifiquement le fonctionnement de cellules
WO2006077038A1 (fr) Procede d&#39;encapsulage de molecules detecteurs par une membrane semi-permeable
EP1490175A2 (fr) Dispositif a microreseau
DE4312970A1 (de) Mikrokapsel sowie Verfahren und Vorrichtung zu ihrer Herstellung
WO2002076608A2 (fr) Procede pour produire un jeu ordonne d&#39;echantillons pour detecter des constituants dans un echantillon biologique
EP2095876B1 (fr) Dispositif de recouvrement pour un porte-échantillons
EP3024567B1 (fr) Dispositif et procédé d&#39;encapsulation d&#39;un échantillon dans une capsule polymère
WO2017092859A1 (fr) Corps polymère microstructuré, microbioréacteur et procédés pour les réaliser
EP2322924A1 (fr) Protection contre des agents hydrophobes
DE102010022675B4 (de) Verfahren zur Herstellung einer Hydrogel-Mikrostruktur
EP0681834B1 (fr) Microcapsule, ainsi qu&#39;un procédé et un appareil pour la produire
DE102015200643B4 (de) Verfahren zur herstellung von neuronalen zellen enthaltenden strangförmigen kapseln und strangförmige kapseln
US20150315353A1 (en) Process for Producing Polymer Foams
DE102017123891B4 (de) Verfahren zum Bereitstellen eines kollagenbasierten Schichtmaterials und daraus hergestelltes biokompatibles Formteil
EP3536402A1 (fr) Chambre d&#39;essai
DE102006039588A1 (de) Substrat mit Lipidmembranen, Verfahren zur Erzeugung sowie Anordnung hierzu
DE102004061732A1 (de) Steuerbare Einrichtung aus mehreren Einzelspeicherzellen auf Hydrogelbasis

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application
NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 06706194

Country of ref document: EP

Kind code of ref document: A1

WWW Wipo information: withdrawn in national office

Ref document number: 6706194

Country of ref document: EP