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WO2008068678A1 - Dispositif biotechnologique comportant un moyen d'actionnement pour modifier la mobilité de biomolécules présélectionnées - Google Patents

Dispositif biotechnologique comportant un moyen d'actionnement pour modifier la mobilité de biomolécules présélectionnées Download PDF

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Publication number
WO2008068678A1
WO2008068678A1 PCT/IB2007/054838 IB2007054838W WO2008068678A1 WO 2008068678 A1 WO2008068678 A1 WO 2008068678A1 IB 2007054838 W IB2007054838 W IB 2007054838W WO 2008068678 A1 WO2008068678 A1 WO 2008068678A1
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Prior art keywords
permeation layer
actuation means
present
changing
ratio
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PCT/IB2007/054838
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English (en)
Inventor
Ralph Kurt
Murray Fulton Gillies
Roel Penterman
Stefano Cattaneo
Dirk Jan Broer
Emiel Peeters
Original Assignee
Koninklijke Philips Electronics N. V.
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 Koninklijke Philips Electronics N. V. filed Critical Koninklijke Philips Electronics N. V.
Priority to EP07849282A priority Critical patent/EP2092338A1/fr
Priority to JP2009538839A priority patent/JP2010511490A/ja
Publication of WO2008068678A1 publication Critical patent/WO2008068678A1/fr

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    • 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
    • G01N33/54366—Apparatus specially adapted for solid-phase testing
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/001—Enzyme electrodes
    • C12Q1/002—Electrode membranes
    • 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
    • G01N33/54306—Solid-phase reaction mechanisms

Definitions

  • BIOTECHNOLOGICAL DEVICE INCLUDING AN ACTUATION MEANS FOR CHANGING THE MOBILITY OF PRESELECTED BIOMOLECULES
  • the detection usually occurs in such a way that the fluid to be analyzed is provided on a substrate material, which contains capture sites for the target molecules which are subject to detection.
  • a capture site may comprise a corresponding DNA-strand in case the target molecule is also a DNA-strand or an antibody in the case of a protein assay.
  • the target molecules in the fluid will then bind specifically to the capture site and remain there even after the fluid is removed.
  • the target molecule contains a label and in this way may be detected.
  • the label could be a fluorescent label or a magnetic label depending on the detection means, i.e., the type of bio-sensor, optical or magnetic sensor.
  • the permeation layer provides capture sites for the immobilization of nucleic acids (or other preselected biomolecules or target molecules).
  • nucleic acids or other preselected biomolecules or target molecules.
  • the main function of the permeation layer is to separate the captured target molecules from the highly reactive electrochemical environment generated immediately at the electrode surface.
  • the layer also allows ions and gasses arising from electrochemical reactions at the electrodes to gradually diffuse into the biological solution.
  • the permeation layers which are known in the art are passive hydrogels, i.e., hydrogels that are in wet conditions insensitive to external stimuli. Furthermore, due to the uniform swelling and/or porosity of the permeation layer, the preselected biomolecules or target molecules will in many cases also enter the permeation layer uniformly, i.e., also at positions where no capture sites are present. It is therefore an object of the present invention to provide a device, which is able of at least partially overcoming some of the above-mentioned drawbacks and helps increasing the specif ⁇ ty and the effectivity of the analysis. This object is solved by a composite according to claim 1 of the present invention. Accordingly, a biotechnological device is provided, comprising at least one permeation layer and at least one actuation means which is capable of
  • biotechnological device is to be understood in its widest sense and includes especially one or more of the following devices: - devices for the detection of one or more preselected biomolecules in a fluid sample, especially devices for the detection of biomolecules in aqueous solution. devices for the controlled release of a compound, especially for drug release. - devices for performing amplification reactions such as PCR
  • artificial scaffolds for tissue engineering and (stem) cell therapies including devices for the release of molecules such as growth factors, cytokines etc. to stimulate growth or proliferation of cells and devices which pump nutrients towards cells or accelerate degradation of the scaffold on command.
  • biomolecules as well as “target molecules”, “capture sites” “drugs” according to the present invention are to be understood in the widest sense and especially include and/or mean the product(s) of an amplification reaction, including both target and signal amplification); purified samples, such as purified genomic DNA, RNA, proteins, etc.; raw samples (bacteria, virus, genomic DNA, etc.); biological molecular compounds such as, but not limited to, nucleic acids and related compounds (e.g. DNAs, RNAs, oligonucleotides or analogs thereof, PCR products, genomic DNA, bacterial artificial chromosomes, plasmids and the like), proteins and related compounds (e.g.
  • polypeptides especially means and/or includes the diffusion rate in the parts of the at least one permeation layer affected by the actuation means and/or the average electrophoretic mobility of the preselected biomolecules inside the parts of the at least one permeation layer affected by the actuation means.
  • the transport of biological particles to the capture site is increased and/or influenced by using an electrical field generated by either the same electrodes used for actuating the permeation layer and/or separate electrodes meant specifically for generating an electrical field directed towards the capture site.
  • the transport will be accelerated by charging an electrode near the capture site with a positive voltage.
  • the polarity of charge is dependent on the pH and this should therefore according to a further embodiment of the present invention be taken into account when choosing the polarity of the voltage required for accelerating transport.
  • the dielectrophoretic effect is used to improve the transport of even non-charged bio- particles (e.g. cells).
  • This embodiment is particularly useful when an electric dipole can be induced on the bio-particle.
  • after capturing the frequency of the applied voltage is changed to repel non-specifically bonded bio-particles. This has been shown for a wide range of applications within the present invention to further lower the background signal.
  • distance in connection with mobility in the sense of the present invention especially means and/or includes the average distance from the surface of the permeation layer - especially in the parts of the at least one permeation layer affected by the actuation means - to the capture sites/probes.
  • This distance is according to the present invention especially meant as a macroscopic dimension and is measured in a straight line although the shortest "travel distance" for a molecule flowing from said surface towards said capture sites/probes might be significantly larger in a nanoporous, mesoporous or network like structure.
  • capture site in the sense of the present invention is especially a certain area within the device where one or more (usually identical) capture probes are located.
  • capture probes in the sense of the present invention especially mean and/or include molecules (or assemblies of molecules) which are able to interact specifically with the preselected biomolecules.
  • each of the capture site(s) may comprise only one capture probe (e.g. in case the capture probe is an antibody or a cell) or a high number of capture probes (e.g. in case the capture probe is a DNA-strand).
  • the type of capture probe may vary from site to site on the array.
  • the flow of preselected biomolecules to the capture sites can be increased while in other areas of the . mobility . , , permeation layer the ratio ⁇ p ⁇ is kept constant or even reduced.
  • the design of the device can be made more compact - In many applications of the present invention, a better control over the fluid comprising the preselected biomolecules can be obtained.
  • the present invention provides in one embodiment a device for analyzing one or more samples, especially fluid samples for the presence, amount or identity of one or more preselected biomolecules (which are in this context to be called target molecules) of interest in the samples.
  • the target molecule(s) and the capture site(s) and probe(s) may be, but not limited to, the product(s) of an amplification reaction, including both target and signal amplification; purified samples, such as purified genomic DNA, RNA, proteins, etc.; raw samples (bacteria, virus, genomic DNA, etc.); biological molecular compounds such as, but not limited to, nucleic acids and related compounds (e.g. DNAs, RNAs, oligonucleotides or analogs thereof, PCR products, genomic DNA, bacterial artificial chromosomes, plasmids and the like), proteins and related compounds (e.g.
  • polypeptides polypeptides, peptides, monoclonal or polyclonal antibodies, soluble or bound receptors, transcription factors, and the like), antigens, ligands, haptens, carbohydrates and related compounds (e.g. polysaccharides, oligosaccharides and the like), cellular fragments such as membrane fragments, cellular organelles, intact cells, bacteria, viruses, protozoa, and the like.
  • the actuation e.g. polysaccharides, oligosaccharides and the like
  • cellular fragments such as membrane fragments, cellular organelles, intact cells, bacteria, viruses, protozoa, and the like.
  • means is capable of changing the ratio ⁇ p ⁇ of the preselected biomolecules in at
  • means is capable of changing the ratio ⁇ p ⁇ of the preselected biomolecules in at
  • At least one actuation means is capable or increasing the ratio ⁇ p ⁇ or
  • the actuation means will according to a further embodiment of the present invention be associated with at least one of the capture site(s), which helps to direct the preselected biomolecules to the capture site(s).
  • actuation means is capable of increasing the ratio ⁇ p ⁇ of the preselected
  • biomolecules in at least selected parts of the permeation layer by a factor of >2, preferably by a factor of >5 and most preferred by a factor of >10 (in wet conditions).
  • At least one actuation means is cap 1 able of decreasing ° the ratio " dT ⁇ is—tance of the
  • the actuation means will according to a further embodiment of the present invention be associated with those parts of the permeation layer which are not associated to one of the capture site(s). According to one embodiment of the present invention, at least one
  • actuation means is capable of decreasing the ratio ⁇ p ⁇ of the preselected
  • biomolecules in at least selected parts of the permeation layer by a factor of >2, preferably by a factor of >5 and most preferred by a factor of >10 (in wet conditions).
  • means is capable of changing the ratio ⁇ p ⁇ of the preselected biomolecules in at
  • the swelling of the permeation layer (or parts thereof), the ratio ⁇ p ⁇ can be set
  • the actuation means is capable of changing the swelling of selected parts of the permeation layer by a factor of >1.2 (in wet conditions), preferably by >2, more preferably >5 and most preferably >10 (in wet conditions). According to an embodiment of the present invention, the actuation
  • means is capable of changing the ratio ⁇ p ⁇ of the preselected biomolecules in at
  • the ratio ⁇ p ⁇ can be
  • the actuation means is capable of changing the permeability of selected parts of the permeation layer by a factor of >2, preferably >5 and most preferred >10 (in wet conditions).
  • permeability (commonly symbolized as K, or k) is especially to be understood as a measure of the ability of a porous material to transmit fluids.
  • Ki is the intrinsic permeability [L2]
  • C is a dimensionless constant that is related to the configuration of the flow-paths d is the average, or effective pore diameter [L].
  • the permeability can be measured either directly (e.g. using Darcy's law) or through estimation using empirically derived formulas.
  • Other units are the SI units cm 2 and m 2 .
  • the device comprises at least one capture site, whereby the actuation means is capable of
  • the average size of the at least one capture site is ⁇ lO ⁇ m and ⁇ lOOO ⁇ m, preferably >20 ⁇ m and ⁇ 500 ⁇ m and most preferred >50 ⁇ m and ⁇ 200 ⁇ m.
  • the device comprises >10, preferably >100 and most preferred ⁇ IOOO capture sites.
  • the device comprises at least one active layer part associated with every capture site, whereby the term "active layer part" means the part of the at least one permeation
  • the average ratio of the size of the active layer to the size of the associated capture site is >1 : 1 and ⁇ 10:l, preferably >1,5:1 and ⁇ 3:l.
  • the device comprises at least one transition region between the capture site(s) and/or active layer part(s), which are unaffected by the at least one actuation means.
  • the average diameter of the at least one transition region is >5 ⁇ m and ⁇ 5000 ⁇ m, preferably >10 ⁇ m and ⁇ lOOO ⁇ m, more preferably >20 ⁇ m and ⁇ 500 ⁇ m and most preferred >50 ⁇ m and ⁇ 200 ⁇ m.
  • the at least one permeation layer has an average thickness in wet state (but before changing the permeability and/or swelling of certain regions) in the range of >l- ⁇ 500 ⁇ m, preferably >5- ⁇ 200 ⁇ m, more preferably >10- ⁇ 100 ⁇ m.
  • the actuation in the range of >l- ⁇ 500 ⁇ m, preferably >5- ⁇ 200 ⁇ m, more preferably >10- ⁇ 100 ⁇ m.
  • means is capable of changing the ratio ⁇ p ⁇ of the preselected biomolecules in at
  • means is capable of changing the ratio ⁇ p ⁇ of the preselected biomolecules in at
  • At least selected parts of the permeation layer by changing at least one property/parameter out of the group comprising mobility, distance, permeability and swelling at least of parts of the permeation layer via a change in pH.
  • means is capable of changing the ratio ⁇ p ⁇ of the preselected biomolecules in at
  • the actuation means operates in a pH-range from >2 to ⁇ 12, preferably > 4 to ⁇ 9, more preferably from >5 to ⁇ 8, most preferably >6.5 to ⁇ 7.5 .
  • means is capable of changing the ratio ⁇ p ⁇ of the preselected biomolecules in at
  • means is capable of changing the ratio ⁇ p ⁇ of the preselected biomolecules in at
  • At least selected parts of the permeation layer by changing at least one property/parameter out of the group comprising mobility, distance, permeability and swelling at least of parts of the permeation layer electrically and/or electrochemically.
  • means is capable of changing the ratio ⁇ p ⁇ of the preselected biomolecules in at
  • the voltage applied is chosen so that no gas is generated, which will be for most applications around 2-3V. According to an embodiment of the present invention, the actuation
  • means is capable of changing the ratio ⁇ p ⁇ of the preselected biomolecules in at
  • At least selected parts of the permeation layer by changing at least one property/parameter out of the group comprising mobility, distance, permeability and swelling at least of parts of the permeation layer by electrolysis, i.e. by generating ions electrically or electrochemically.
  • means is capable of changing the ratio ⁇ p ⁇ of the preselected biomolecules in at
  • the actuation by changing at least one property/parameter out of the group comprising mobility, distance, permeability and swelling at least of parts of the permeation layer by applying an electrical current.
  • means is capable of changing the ratio ⁇ p ⁇ of the preselected biomolecules in at
  • the actuation means is capable of changing at least one property/parameter out of the group comprising mobility, distance, permeability and swelling at least of parts of the permeation layer via a change in temperature.
  • the actuation means is capable of changing the permeability and/or swelling by a factor >1.2, preferably >2, more preferably >5 and most preferred >10 per 0.5 0 C.
  • means is capable of changing the ratio ⁇ p ⁇ of the preselected biomolecules in at
  • the actuation means is capable the changing at least one property/parameter out of the group comprising mobility, distance, permeability and swelling at least of parts of the permeation layer via a incident radiation.
  • the actuation means comprises at least one resistive heater element capable of changing the temperature locally in a predefined region of said permeation layer.
  • means is capable of changing the ratio ⁇ p ⁇ of the preselected biomolecules in at
  • the device according to the invention comprises at least one electrodes and/or at least one set of electrodes.
  • preselected biomolecules which may include actuating, accelerating or rejecting preselected biomolecules towards predefined locations by applying an electrical DC or AC field, i.e. by electrophoresis or dielectrophoresis.
  • the permeation layer is provided in close proximity to the at least one electrode and/or the at least one set of electrodes.
  • the actuation means is capable of changing one of the parameters including mobility, distance, permeability and/of swelling of the at least one permeation layer by inducing a phase transition resulting a micro phase separation with a continuous fluid/water phase in the permeation layer.
  • the actuation means is capable of changing one of the parameters including mobility, distance, permeability and/of swelling of the at least one permeation layer by inducing a LCST (lower critical solution temperature) phase transition in the permeation layer.
  • LCST lower critical solution temperature
  • the device comprises a hydrogel material, whereby preferably the permeation layer comprises a hydrogel material.
  • hydrogel in the sense of the present invention especially means that at least a part of the hydrogel material comprises polymers that in water form a water-swollen network and/or a network of polymer chains that are water- soluble.
  • the hydrogel material comprises in swollen state >50% water and/or solvent, more preferably >70% and most preferred >90%, whereby preferred solvents include organic solvents, preferably organic polar solvents and most preferred alkanols such as Ethanol, Methanol and/or (Iso-) Propanol.
  • the hydrogel material comprises a material selected out of the group comprising poly(meth)acrylic materials, subsituted vinyl materials or mixture thereof.
  • the hydrogel material comprises a poly(meth)acrylic material made out of the polymerization of at least one (meth)acrylic monomer and at least one polyfunctional (meth)acrylic monomer.
  • the (meth)acrylic monomer is chosen out of the group comprising (meth)acrylamide, (meth)acrylic acid, hydroxyethyl(meth)acrylate, ethoxyethoxyethyl(meth)acrylate or mixtures thereof.
  • the polyfunctional (meth)acrylic monomer is a bis-(meth)acryl and/or a tri-(meth)acryl and/or a tetra-(meth)acryl and/or a penta-(meth)acryl monomer.
  • the polyfunctional (meth)acrylic monomer is chosen out of the group comprising bis(meth)acrylamide, tripropyleneglycol di(meth)acrylates, pentaerythritol tri(meth)acrylate polyethyleneglycoldi(meth)acrylate, ethoxylated bisphenol-A- di(meth)acrylate , hexanedioldi(meth)acrylate or mixtures thereof.
  • the hydrogel material comprises an anionic poly(meth)acrylic material, preferably selected out of the group comprising (meth)acrylic acids, arylsulfonic acids, especially styrenesulfonic acid, itaconic acid, crotonic acid, sulfonamides or mixtures thereof, and/or a cationic poly(meth)acrylic material, preferably selected out of the group comprising vinyl pyridine, vinyl imidazole, aminoethyl (meth)acrylates or mixtures thereof, co -polymerized with at least one monomer selected out of the group neutral monomers, preferably selected out of the group vinyl acetate, hydroxyethyl (meth)acrylate (meth)acrylamide, ethoxyethoxyethyl(meth)acrylate or mixture thereof, or mixtures thereof.
  • an anionic poly(meth)acrylic material preferably selected out of the group comprising (meth)acrylic acids, arylsulfonic acids, especially st
  • the hydrogel material comprises a substituted vinyl material, preferably vinylcaprolactam and/or substituted vinylcaprolactam.
  • the crosslink density in the poly(meth)acrylic material is ⁇ O.OOOl and ⁇ O.l, preferably ⁇ O.OOl and ⁇ 0.05, or most preferably in the range >0.005 and ⁇ O.Ol.
  • crosslink density means or includes especially the following definition:
  • the crosslink density ⁇ x is
  • ⁇ x 0
  • the hydrogel material comprises a poly(meth)acrylic material co -polymerized with at least one monomer selected out of the group anionic monomers, preferably selected out of the group comprising arylsulfonic acids, especially styrenesulfonic acid, itaconic acid, crotonic acid or mixtures thereof, cationic polymers, preferably selected out of the group comprising vinyl pyridine, aminoethyl (meth)acrylates or mixture thereof, and neutral monomers, preferably selected out of the group vinyl acetate, hydroxy ethyl (meth)acrylate or mixture thereof, or mixtures thereof.
  • group anionic monomers preferably selected out of the group comprising arylsulfonic acids, especially styrenesulfonic acid, itaconic acid, crotonic acid or mixtures thereof
  • cationic polymers preferably selected out of the group comprising vinyl pyridine, aminoethyl (meth)acrylates or mixture thereof
  • neutral monomers preferably selected out
  • the hydrogel material is based on thermo-responsive monomers selected out of the group comprising N-isopropylamide , diethylacrylamide, carboxyisopropylacrylamide, hydroxymethylpropylmethacrylamide, acryloylalkylpiperazine.
  • the hydrogel material is functionalized with reactive side-groups such as amines or active esters, especially to perform in-situ 'cross-linking' of DNA or anti-bodies.
  • a composite, a method and/or device according to the present invention may be of use in a broad variety of systems and/or applications, amongst them one or more of the following: biosensors used for molecular diagnostics rapid and sensitive detection of proteins and nucleic acids in complex biological mixtures such as e.g. blood or saliva high throughput screening devices for chemistry, pharmaceuticals or molecular biology - testing devices e.g. for DNA or proteins e.g. in criminology, for on-site testing (in a hospital), for diagnostics in centralized laboratories or in scientific research tools for DNA or protein diagnostics for cardiology, infectious disease and oncology, food, and environmental diagnostics - tools for combinatorial chemistry tools for amplification of DNA, RNA or peptides analysis devices
  • Fig. 1 shows a very schematic cross-sectional partial view showing a device according to a first embodiment of the present invention with a plurality of capture sites covered by a permeation layer which swelling can be changed electrically
  • Fig. 2 shows the device of Fig. 1 after applying voltage
  • Fig. 3 shows a very schematic cross-sectional partial view showing a device according to a second embodiment of the present invention with a plurality of capture sites covered by a permeation layer which swelling can be changed electrically
  • Fig. 4 shows the device of Fig. 3 after applying voltage
  • Fig. 5 shows a very schematic cross-sectional partial view showing a device according to a third embodiment of the present invention with a plurality of capture sites each covered by a permeation layer whose swelling can be changed electrically Fig.
  • FIG. 6 shows the device of Fig. 5 after applying voltage
  • Fig. 7 shows a very schematic cross-sectional partial view showing a device according to a fourth embodiment of the present invention with a permeation layer comprising two different materials
  • Fig. 8 shows a very schematic cross-sectional partial view showing a device according to a fifth embodiment of the present invention with a permeation layer comprising two different materials
  • Fig. 1 shows a very schematic cross-sectional partial view showing a device 1 according to a first embodiment of the present invention with a plurality of capture sites covered by a permeation layer 20 which swelling can be changed electrically.
  • Fig. 1 is a partial view only and in most applications within the present invention much more capture sites and electrodes will be used.
  • the permeation layer 20 is provided on a substrate 50.
  • the device furthermore comprises a second substrate 60 which carries a counter-electrode to the electrodes 10a-e.
  • a bio liquid in most applications an aqueous solution
  • Fig. 2 shows the device of Fig. 1 after applying a voltage.
  • the components which are identical to Fig. 1 are not explicitly mentioned.
  • Fig. 2 is for explanatory reasons only and does not reflect the actual swelling in most applications. In many applications within the present invention, the amount of swelling is much larger than in Fig.2.
  • This swelling increases the speed with which the preselected biomolecules present in the bioliquid enter the permeation layer 20 and reach the capture sites 10a-e.
  • Fig. 3 shows a very schematic cross-sectional partial view showing a device 1 ' according to a second embodiment of the present invention with a plurality of capture sites covered by a permeation layer whose swelling can be changed electrically.
  • Fig. 3 the design of the device according to Fig. 3 is in some extent similar to that of Fig. 1 and therefore for the sake of brevity the components which are identical to Fig. 1 are not explicitly mentioned.
  • the device of Fig.3 differs from that of Fig. 1 in that that no opposite counter-electrode is present, rather on the substrate 50 first electrodes lOa-c and second electrodes 1 la-b are present. It should be noted that Fig. 3 is a partial view only and in most applications within the present invention much more electrodes will be used. However, only the first electrodes lOa-c have capture sites associated with them. It is also possible to have one shared common electrode. The size ratio of 11 and 10 should be approximately one.
  • Fig. 4 shows the device of Fig. 3 after applying voltage.
  • the first electrodes When applying voltage, the first electrodes will form the anodes and the second electrodes the cathodes (or vice versa, depending on the actual application). This will cause the permeation layer to swell in regions associated with the electrodes lOa-c and to shrink in regions associated with the electrodes 1 la-b.
  • the swelling - as discussed - increases the speed and amount of the preselected biomolecules present in the bioliquid which will then enter the permeation layer 20 and reach the capture sites lOa-c.
  • the preselected biomolecules will less likely enter the permeation layer 20 there, thus furthermore increasing the efficacy of the device for a large number of applications within the present invention.
  • Fig. 5 shows a very schematic cross-sectional partial view showing a device 1 " according to a third embodiment of the present invention with a plurality of capture sites 10a-e each covered by a permeation layer 20a-e whose swelling can be changed electrically.
  • This device has for some applications the advantage that a faster response can be achieved by reducing the dimensions of the hydrogel, as shown in Fig. 5. Furthermore an arrangement like this avoids internal stress and possible adhesion problems between the actuated and non-actuated areas of the hydrogel for a large number of applications within the present invention.
  • the device 1 " includes individually addressable electrodes According to an embodiment of the present invention (not shown in the Figs.) these electrodes and the other suitable components of the device are connected to a large area electronics platform such as amorphous silicon or low temperature polycrystalline silicon (LTPS) on glass or on plastic substrates.
  • amorphous silicon or low temperature polycrystalline silicon (LTPS) on glass or on plastic substrates.
  • Fig. 6 shows the device of Fig. 5 after applying voltage. It can be clearly seen, that - depending on the amount of voltage applied - the different permeation layers will also behave differently.
  • Fig. 7 shows a very schematic cross-sectional partial view showing a device 1 '" according to a fourth embodiment of the present invention with a permeation layer 20 comprising two different materials 22, 24. The device is shown partially only; the overall design of the device will be in analogy to Fig. 5. In accordance, also an electrode 10 and a substrate 50 are present. In Fig. 7, the permeation layer comprises a first material 22, which permeability may be changed when applying voltage and a second material 24, whose permeability does not change or changes only to a small extent.
  • the first material 22 is provided close to the capture site or the capture site is provided within the first material 22.
  • Fig. 8 shows an alternative to Fig. 7.
  • the first material 22 is spatially separated from the substrate .
  • the capture site is also provided within the first material 22.

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Abstract

La présente invention concerne un dispositif permettant d'analyser des échantillons y compris la mobilité, un moyen d'actionnement pour modifier le rapport des biomolécules présélectionnées dans l'échantillon à distance.
PCT/IB2007/054838 2006-12-04 2007-11-29 Dispositif biotechnologique comportant un moyen d'actionnement pour modifier la mobilité de biomolécules présélectionnées WO2008068678A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
EP07849282A EP2092338A1 (fr) 2006-12-04 2007-11-29 Dispositif biotechnologique comportant un moyen d'actionnement pour modifier la mobilité de biomolécules présélectionnées
JP2009538839A JP2010511490A (ja) 2006-12-04 2007-11-29 予め選択された生体分子の移動度を変化させる作動手段を有するバイオテクノロジー装置

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Application Number Priority Date Filing Date Title
EP06125328 2006-12-04
EP06125328.2 2006-12-04

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