WO2002094442A1 - Systeme de distribution sur puce biocapteur et procede pour la distribution d'une solution a distribuer par utilisation de ce systeme de distribution sur une puce biocapteur - Google Patents

Systeme de distribution sur puce biocapteur et procede pour la distribution d'une solution a distribuer par utilisation de ce systeme de distribution sur une puce biocapteur Download PDF

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Publication number
WO2002094442A1
WO2002094442A1 PCT/DE2002/001562 DE0201562W WO02094442A1 WO 2002094442 A1 WO2002094442 A1 WO 2002094442A1 DE 0201562 W DE0201562 W DE 0201562W WO 02094442 A1 WO02094442 A1 WO 02094442A1
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Prior art keywords
substrate
dispensed
solution
biosensor chip
dispensing
Prior art date
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PCT/DE2002/001562
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German (de)
English (en)
Inventor
Roland Thewes
Eugen Unger
Original Assignee
Infineon Technologies Ag
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Publication date
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Priority to EP02740301A priority Critical patent/EP1392437A1/fr
Publication of WO2002094442A1 publication Critical patent/WO2002094442A1/fr

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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/02—Burettes; Pipettes
    • B01L3/0241—Drop counters; Drop formers
    • B01L3/0268—Drop counters; Drop formers using pulse dispensing or spraying, eg. inkjet type, piezo actuated ejection of droplets from capillaries
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J19/0046—Sequential or parallel reactions, e.g. for the synthesis of polypeptides or polynucleotides; Apparatus and devices for combinatorial chemistry or for making molecular arrays
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/508—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above
    • B01L3/5088—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above confining liquids at a location by surface tension, e.g. virtual wells on plates, wires
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B82—NANOTECHNOLOGY
    • B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
    • B82Y30/00—Nanotechnology for materials or surface science, e.g. nanocomposites
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00277—Apparatus
    • B01J2219/00351—Means for dispensing and evacuation of reagents
    • B01J2219/00364—Pipettes
    • B01J2219/00371—Pipettes comprising electrodes
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00277—Apparatus
    • B01J2219/00497—Features relating to the solid phase supports
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
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    • B01J2219/00527—Sheets
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    • B01J2219/00585—Parallel processes
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    • B01J2219/00603—Making arrays on substantially continuous surfaces
    • B01J2219/00605—Making arrays on substantially continuous surfaces the compounds being directly bound or immobilised to solid supports
    • B—PERFORMING OPERATIONS; TRANSPORTING
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    • B01J2219/00603—Making arrays on substantially continuous surfaces
    • B01J2219/00605—Making arrays on substantially continuous surfaces the compounds being directly bound or immobilised to solid supports
    • B01J2219/0061—The surface being organic
    • B—PERFORMING OPERATIONS; TRANSPORTING
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    • B01J2219/00583—Features relative to the processes being carried out
    • B01J2219/00603—Making arrays on substantially continuous surfaces
    • B01J2219/00605—Making arrays on substantially continuous surfaces the compounds being directly bound or immobilised to solid supports
    • B01J2219/00612—Making arrays on substantially continuous surfaces the compounds being directly bound or immobilised to solid supports the surface being inorganic
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583—Features relative to the processes being carried out
    • B01J2219/00603—Making arrays on substantially continuous surfaces
    • B01J2219/00605—Making arrays on substantially continuous surfaces the compounds being directly bound or immobilised to solid supports
    • B01J2219/00614—Delimitation of the attachment areas
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583—Features relative to the processes being carried out
    • B01J2219/00603—Making arrays on substantially continuous surfaces
    • B01J2219/00605—Making arrays on substantially continuous surfaces the compounds being directly bound or immobilised to solid supports
    • B01J2219/00614—Delimitation of the attachment areas
    • B01J2219/00621—Delimitation of the attachment areas by physical means, e.g. trenches, raised areas
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583—Features relative to the processes being carried out
    • B01J2219/00603—Making arrays on substantially continuous surfaces
    • B01J2219/00605—Making arrays on substantially continuous surfaces the compounds being directly bound or immobilised to solid supports
    • B01J2219/00623—Immobilisation or binding
    • B01J2219/00626—Covalent
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583—Features relative to the processes being carried out
    • B01J2219/00603—Making arrays on substantially continuous surfaces
    • B01J2219/00653—Making arrays on substantially continuous surfaces the compounds being bound to electrodes embedded in or on the solid supports
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583—Features relative to the processes being carried out
    • B01J2219/00603—Making arrays on substantially continuous surfaces
    • B01J2219/00659—Two-dimensional arrays
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
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    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
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    • B01J2219/00583—Features relative to the processes being carried out
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    • B01J2219/00677—Ex-situ synthesis followed by deposition on the substrate
    • B—PERFORMING OPERATIONS; TRANSPORTING
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    • B01J2219/00709—Type of synthesis
    • B01J2219/00713—Electrochemical synthesis
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
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    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00718—Type of compounds synthesised
    • B01J2219/0072—Organic compounds
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
    • B01L2400/0415—Moving fluids with specific forces or mechanical means specific forces electrical forces, e.g. electrokinetic
    • C—CHEMISTRY; METALLURGY
    • C40—COMBINATORIAL TECHNOLOGY
    • C40B—COMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES
    • C40B60/00—Apparatus specially adapted for use in combinatorial chemistry or with libraries
    • C40B60/14—Apparatus specially adapted for use in combinatorial chemistry or with libraries for creating libraries

Definitions

  • the invention relates to a biosensor chip dispensing arrangement and a method for dispensing a solution to be dispensed using the dispensing arrangement on a biosensor chip
  • Bio- / chemo-arrays miniaturized on substrates serve the detection of certain molecules in solutions to be examined.
  • the sensors are in large numbers on a semiconductor substrate, e.g. a silicon chip that certain electronic
  • the high degree of parallelization enables a number of different examinations to be carried out simultaneously, e.g. Examinations for the presence of different substances (i.e. molecules to be detected) in a given liquid to be examined.
  • This property results in a variety of applications for such sensor array chips with a corresponding evaluation system, for example in medical diagnostics, in the pharmaceutical industry, for example for high-throughput screening processes ("High Throughput Screening” (HTS)), in the chemical industry, in the Food analysis, as well as in environmental and food technology.
  • HTS High Throughput Screening
  • catcher molecules for example with
  • a substrate made of a suitable material Microdispensing techniques are applied and immobilized in various ways.
  • 7 schematically shows such a substrate 700 with n positions 701, on each of which different capture molecules are immobilized.
  • Such a substrate 700 is usually first brought into contact with the liquid to be examined at all positions for diagnosis (for example, to test a liquid to be examined for the presence of different molecules to be detected). Such contacting usually takes place by flooding the entire substrate 700 with the liquid to be examined.
  • the catcher molecules can bind to a molecule present in the liquid to be examined in a specific binding reaction according to the key-lock principle, according to which only those molecules in the liquid to be examined are bound by the catcher molecules for which the latter have a binding specificity, the molecule is specifically bound in the liquid to be examined by the capture molecules. If this is not the case, the molecule in the liquid to be examined is not bound by the capture molecule. Subsequent evaluation of the respective positions 701 of the substrate 700 then reveals whether a molecule or which molecule was present in the liquid to be examined.
  • Such substrates 700 are often used to detect nucleic acids in liquids to be examined. As described above, this takes place in that both the catcher molecule and the molecule to be detected in the liquid to be examined are both nucleic acids, ie DNA or RNA, with a specific binding being the complete or at least for hybridization of both nucleic acid strands requires sufficient complementarity between these two molecules.
  • nucleic acids can be used as capture molecules for peptides or proteins that bind specifically to nucleic acids. It is also known to use peptides or proteins as capture molecules for others
  • capture peptide or capture protein binding proteins or peptides are used.
  • low molecular weight chemical compounds as capture molecules for these low molecular weight binding proteins or peptides and vice versa, i.e. the use of proteins and peptides as capture molecules for low-molecular compounds which may be present in a liquid to be examined.
  • a fluorescent marking substance (“label”) is specifically bound to the molecules present in the solution to be examined, which can be excited to glow when exposed to, for example, UV light.
  • this bond is a chemically covalent bond.
  • the optical detection method has the particular disadvantage that a relatively complicated and expensive optical system must be used for the evaluation. This makes e.g. the use of such an optical detection method in a doctor's office.
  • capture molecules are immobilized on predetermined areas of a substrate.
  • this immobilization takes place by applying a solution containing these capture molecules to the predetermined area of the substrate by means of dispensing technology.
  • the capture molecules present in this solution can then react with the respective predetermined area of the substrate to be immobilized on this.
  • the predetermined area is often any area on the substrate which is discrete from other areas on the substrate, the nature of which is often identical to that of the rest of the substrate.
  • the predetermined area is often an exposed electrode on the surface of the substrate or an electrode which is coated with another material, for example with the material of the rest of the substrate surrounding the electrode.
  • FIGS. 3A and 3B are a substrate 300, a predetermined area 301 of the substrate 300, a dispensing device 302 (here a nozzle), a solution 303 to be dispensed, large guide projections 304, and a cavity 306, which is above the predetermined area 301 is formed by the large guide projections 304.
  • a dispensing device 302 here a nozzle
  • a solution 303 to be dispensed a solution 303 to be dispensed
  • large guide projections 304 large guide projections 304
  • a cavity 306 which is above the predetermined area 301 is formed by the large guide projections 304.
  • FIG. 3A and 3B show the case where the guide protrusions 304 are made relatively large so that they are able to completely absorb the dispensed volume of the solution 303.
  • Figure 3A shows a drop of solution 303 that is being dispensed from nozzle 302.
  • FIG. 3B shows the result after the solution 303 has been dispensed from the nozzle 302. It should be noted that the solution 303 in FIG.
  • FIG. 3A and 3B show the case that smaller guide protrusions 305 than that in Figs. 3A and 3B are provided.
  • Figure 3C shows the drop of solution 303 as it is being dispensed from nozzle 302.
  • 3D shows the case after dispensing the drop of solution 303 from the nozzle 302 such that this drop is now between the guide projections 305 above the predetermined range, but the volume of the drop of solution 303 in FIG. 3D is due of the small guide protrusions 305 cannot be fully received by them. For this reason, the drop of solution 303 extends upward beyond the guide protrusions 305, the surface tension of the solution 303 tending to maintain a generally spherical shape of the drop of the solution 303 above the predetermined area 301. It should be noted that the predetermined area 301 shown in Fig. 3D is complete, i.e. is evenly wetted by the drop of solution 303, which is the ideal case.
  • Fig. A shows a substrate 800, a predetermined area 801 on the substrate 800, a solution 802 to be dispensed, large guide projections 803, an air bubble 804 enclosed during the dispensing between the solution 802 and the predetermined area 801, and by the 8B shows a substrate 800, a predetermined area 801 on the substrate 800, a solution 802 to be dispensed, small guide projections 805, an air bubble 804 enclosed during the dispensing between the solution 802 and the predetermined area 801, and cavity 806 formed by the small guide projections 805.
  • FIG. 8A corresponds to FIG. 3B, but an air bubble 804 is enclosed between the solution 802 and the predetermined 801 during the dispensing. Since the dispensing often takes place with very small volumes in the applications described above (for example with volumes in the nanoliter range), the air bubble 804 cannot move upwards in order to be discharged into the atmosphere surrounding the solution 802. For this reason, the air bubble 804 below the solution 802 remains in contact with the predetermined area 801, so that this area of the predetermined area 801 cannot contact any catcher molecules to be immobilized in the solution 802. Thus, none are to be immobilized
  • Capture molecules are immobilized on that area of the predetermined area 801 that lies below the air bubble 804, while capture molecules to be immobilized on the area of the predetermined area 801 that directly contacts the solution 802 are immobilized in the solution 802.
  • this volume can move to the side of the desired trajectory of this volume between the nozzle and the substrate, which means the exact placement of the volume of the dispensing solution on a specific location of the substrate difficult.
  • a biosensor chip dispenser arrangement has a substrate.
  • the substrate has an upper surface and a lower surface.
  • the dispensing arrangement has a dispensing device for receiving a solution to be dispensed.
  • the dispensing device is arranged at a distance above the upper surface of the substrate such that the solution to be dispensed can be dispensed above a predetermined area of the upper surface of the substrate, the predetermined area of the upper surface of the substrate being set up in such a way that catcher molecules are applied to it are immobilizable.
  • the substrate is electrically contacted such that an electrical potential can be generated between the predetermined area and the dispensing device.
  • the electrical potential generated between the predefined area and the dispensing device enables the direction of the dispensing of the solution to be dispensed to the predefined area to be controlled.
  • the biosensor chip dispensing arrangement according to the invention has the advantage that by applying an electrical Potential between at least the predetermined area of the substrate and the dispensing device, a volume of the solution to be dispensed is actively electrostatically drawn towards the target position, that is, the predetermined area of the substrate.
  • the trajectory of a very small volume of the solution to be dispensed from the dispensing device is determined by the electrostatic field lines existing between the predetermined area of the substrate and the dispensing device, as a result of which the volume of the dispensed device migrates sideways
  • Solution outside the intended trajectory of the volume of the solution to be dispensed is reduced and therefore the location-specific accuracy with which the volume of the solution to be dispensed can be applied to the substrate is increased.
  • the active, electostatic drawing of the volume of the solution to be dispensed to a certain predetermined area reduces the risk that an air bubble is enclosed between the volume of the solution to be dispensed and the predetermined area of the substrate during dispensing.
  • the volume of the solution to be dispensed is effectively drawn onto it by the field lines between the dispensing device and the predetermined area of the substrate, so that the volume of the solution to be dispensed clings closely to the predetermined area, i.e. completely and evenly wets the predetermined area of the substrate.
  • the electrical contacting of the substrate is set up in such a way that the electrical potential is applied to the entire surface of the substrate can be.
  • there is a potential for controlling a volume of the solution to be dispensed from the nozzle to the substrate, and the predetermined area of the substrate to which the solution to be dispensed is to be dispensed represents a conceptually delimited subdivision of the entire upper surface of the substrate.
  • the predetermined area according to this exemplary embodiment carries the same electrostatic charge as the entire upper surface of the substrate.
  • two options are preferably provided with regard to the structure of the substrate.
  • the substrate itself consists of an electrically conductive material, and the electrical contact is a direct electrical contact between the substrate itself and a voltage source coupled to the substrate.
  • Possible electrically conductive materials from which the substrate could consist are, for example, polysilicon or different metals such as gold.
  • field lines between the dispensing device and the upper surface of the substrate come not only between the predetermined area of the substrate to which the solution to be dispensed is to be dispensed and the dispensing device, but also between other areas on the top surface of the substrate and the dispensing device.
  • the flight path of the dispensed volume of the solution to be dispensed is determined by the shortest field line to the upper surface of the substrate.
  • this shortest field line is the field line which runs perpendicular to the predetermined area on the upper surface of the substrate.
  • the lateral position of the dispensing device as precisely as possible above the predetermined area of the substrate to which the solution to be dispensed is to be dispensed, so that the field lines determining the trajectory of the solution to be dispensed between the dispensing device and the predetermined area of the substrate is that field line from the plurality of field lines that is the shortest.
  • the substrate in which the potential is applied to the entire surface of the upper surface of the substrate, the substrate consists of a non-electrically conductive material and the electrical contact is an indirect electrical contact between the substrate and an electrically conductive body coupled to a voltage source ,
  • the volume of the solution to be dispensed is not dispensed directly on the electrically conductive material, but rather on the non-electrically conductive material of the substrate.
  • a preferred, non-electrically conductive material is silicon dioxide or silicon nitride.
  • Preferred, electrically conductive materials from which the body coupled to the voltage source can be created include all metals with high electrical conductivity. For example, aluminum, gold, platinum, Copper, tungsten or palladium can be used as the material for the electrically conductive body.
  • this electrically conductive body connected to a voltage source is arranged within the substrate between the upper surface and the lower surface of the substrate.
  • the electrically conductive body connected to a voltage source is arranged below the lower surface of the substrate.
  • the electrical contacting is created in such a way that the electrical potential can be applied to only a single predetermined region of the substrate.
  • the substrate preferably consists of a non-electrically conductive material and the predetermined region of the substrate is an electrode which is coupled to a voltage source.
  • the electrode that is to say the predetermined region of the substrate, is one of a plurality of electrodes on the upper surface of the substrate, on the position-specific relative to the other electrodes on the surface of the substrate, the volume of which is to be dispensed Solution attracting potential can be created.
  • the electrode can be arranged not only above the surface of the substrate, but also below the upper surface of the substrate. According to such an embodiment, the solution to be dispensed is not dispensed directly onto the electrode itself, but rather onto the electrically non-conductive material of the substrate.
  • the electrode which represents the predetermined region of the substrate, has gold.
  • gold not only enables high electrical conductivity, but also the immobilization of capture molecules applied to the electrode by means of a known gold-sulfur coupling.
  • a suitable, non-electrically conductive material is silicon dioxide or silicon nitride.
  • silicon dioxide or silicon nitride.
  • other materials for example polymeric materials such as polyethylene, polypropylene, polyethylene-polypropylene block copolymers, polystyrene, aluminum oxide, titanium oxide, and tantalum oxide can be used.
  • the dispensing device is a nozzle.
  • the nozzle is preferably set up in such a way that the solution to be dispensed can be dispensed in volumes up to one nanoliter.
  • piezo micro nozzles are preferred.
  • the dispensing device for example a nozzle, contains capture molecules to be immobilized. Because the solution to be dispensed is dispensed onto a certain predetermined area of the substrate, the capture molecules contained in the solution to be dispensed are applied in a location-specific manner to the predetermined area of the substrate, so that they can be immobilized on the substrate.
  • a capture molecule contained in the solution to be dispensed can therefore be immobilized on either an electrically conductive material or a non-electrically conductive material.
  • a dielectric layer is arranged above the upper surface of the substrate, so that the dielectric layer covers the upper surface of the substrate and if present, covers the electrode located on the top surface of the substrate.
  • the electrode which may be located on the surface of the substrate is thereby covered, it is protected from external influences by such a dielectric layer. Whether a dielectric layer is applied to the upper surface of the substrate depends, for example, on how the capture molecules to be immobilized are to be immobilized or also how the electrical potential between the predetermined area of the substrate and the
  • Dispensing device of the dispensing arrangement is to be generated.
  • Such a dielectric layer which can be applied to the upper surface of the substrate and, if present, to the electrode arranged on the upper surface of the substrate, can have silicon dioxide or silicon nitride.
  • Dielectric layer arranged laterally upwardly extending guide projections.
  • Such guide projections have guide surfaces that lead inwards to the predetermined area.
  • Guide projections can be used to collect the solution to be dispensed in a targeted manner above the predetermined area of the substrate.
  • the effect of the guide projections is particularly important in those cases in which incorrect placement of the volume of the solution to be dispensed is to be avoided laterally above the predetermined area of the substrate. This could be the case, for example, in the embodiment of FIG Case in which a potential can be applied to the entire surface of the substrate, so that between the
  • Dispensing device and the substrate several field lines can influence the trajectory of a volume of the solution to be dispensed. This could lead to an undesired “flowing away” of the volume of the solution to be dispensed from the predetermined area on the surface of the substrate. Such "missing” should therefore be avoided.
  • the dispensing device and / or the substrate are moved relative to one another in such a way that, after the movement has been completed, the dispensing device is resting above the predetermined area comes.
  • the predetermined area of the substrate is set up in such a way that capture molecules can be immobilized on it.
  • the surface of the substrate in the predetermined area itself or an additional layer applied to the substrate in the predetermined area is set up in such a way that capture molecules can be immobilized on it.
  • An electrical potential is applied between the predetermined area of the substrate and the dispensing device.
  • Dispensing device is caused to dispense a volume of the solution to be dispensed.
  • the potential existing between the dispensing device and the predetermined area of the substrate is allowed to act on the dispensed volume of the solution to be dispensed, so that a volume of the solution to be dispensed is controlled in the direction of the predetermined area.
  • Fig.l is a schematic representation of a
  • Embodiment of the biosensor chip dispensing arrangement according to the invention in which a potential can be applied to the substrate over the entire surface;
  • FIG. 2 shows an embodiment of the biosensor chip dispensing arrangement according to the invention, in which different potentials to different areas of the substrate are specific to the position
  • Substrate can be created
  • Embodiment of the biosensor chip dispensing arrangement according to the invention in which a potential can be generated over the entire surface along the substrate by means of a body located in the substrate;
  • FIG. 5 shows an embodiment of the biosensor chip dispensing arrangement according to the invention, in which a
  • FIG. 6 shows an embodiment of the biosensor chip dispensing arrangement according to the invention, in which different potentials can be applied to different predetermined areas of the substrate and in which a dielectric layer is applied above the upper surface of the substrate;
  • FIG. 8 shows a schematic illustration of incomplete wetting of a predetermined area of a substrate using a dispensing arrangement according to the prior art.
  • FIG. 1 shows a substrate 100, predetermined areas 101 of the substrate 100, a voltage source 102, a
  • Dispensing device 103 (here a nozzle 103), a solution 104 to be dispensed, field lines 105 along which the solution 104 to be dispensed is drawn towards the substrate 100, and an earthing device 106.
  • the substrate 100 is made of an electrically conductive material, so that the substrate 100 is directly, ie directly, coupled to a voltage source 102 in order to generate an electrical potential on the entire surface of the substrate 100.
  • the substrate 100 has a plurality of predetermined regions 101, of which, viewed electrically, each predetermined region 101 is electrically separated from the surrounding upper surface of the substrate 100.
  • the solution 104 to be dispensed contained in the nozzle 103 is in electrical contact with the nozzle 103. Since the nozzle 103 is grounded due to the grounding 106, the solution 104 to be dispensed contained in the nozzle 103 is also grounded.
  • the nozzle 103 should be positioned directly above the desired, here the central, predetermined area 101 of the substrate 100, so that the dispensed volume of the solution 104 to be dispensed along the shortest field line, here the field line 107, to the desired predetermined area 101 of the substrate 100 can be controlled.
  • FIG. 2 shows a substrate 200, a positively charged, predetermined area 201 of the substrate 200, a dispensing device 202 (here a nozzle 202), a solution 203 to be dispensed, field lines 204, along which the solution 203 to be dispensed is drawn towards the substrate 200 field lines 205 along which the solution 203 to be dispensed is repelled from the substrate 200, a plurality of negatively charged predetermined regions 206 of the substrate 200, and an earth 207.
  • a dispensing device 202 here a nozzle 202
  • field lines 204 along which the solution 203 to be dispensed is drawn towards the substrate 200
  • field lines 205 along which the solution 203 to be dispensed is repelled from the substrate 200
  • an earth 207 an earth
  • the substrate 200 consists of a non-electrically conductive material, for example of SiO 2 , so that the predetermined regions 201, 206 of the substrate 200 are arranged and remain electrically insulated from one another. For this reason, different potentials can be applied to different predetermined areas 201, 206 of the substrate 200. In the embodiment shown in FIG. 2, it is desirable to dispense the solution 203 to be dispensed onto the predetermined area 201, wherein no solution 203 to be dispensed is to be dispensed onto the predetermined areas 206 of the substrate 200.
  • a position-specific potential is applied to a specific predetermined area of the substrate 200, here to the predetermined area 201, controlled by means of a computer and the individual couplings existing between the predetermined areas 201, 206 and the voltage source (not shown).
  • FIG. 4 shows a substrate 400, a plurality of predetermined areas 401 on the upper surface of the substrate 400, a voltage source 402, a dispensing device 403 (here a nozzle 403), a solution 404 to be dispensed, field lines 405, along which the solution 404 to be dispensed is attracted towards the substrate 400, a body 406 made of electrical conductive material, a ground 407 and the shortest field line 408 between the nozzle 403 and the substrate 400.
  • the substrate 400 consists of non-electrically conductive material and the predetermined regions 401 on the upper surface of the substrate 400 are to be understood as electrical regions of the upper surface of the substrate 400.
  • the nozzle 403 must be positioned exactly above the desired predetermined area of the substrate 400, that is to say above the predetermined area 401 central in FIG. 4, so that the Volume of the solution 404 to be dispensed can be controlled along the shortest field line 408 between the nozzle 403 and the substrate 400 to this desired predetermined area 401 of the substrate 400.
  • Body 406 a potential can be generated over the entire surface of the upper surface of the substrate 400.
  • the body 406 is directly coupled to a voltage source 402 and is preferably made of metals with a high conductivity, such as aluminum, copper, gold, platinum, tungsten or palladium.
  • FIG. 5 shows a substrate 500, a plurality of predetermined areas 501 on the upper surface of the substrate 500, a voltage source 502, a dispensing device 503 (here a nozzle 503), a solution 504 to be dispensed, field lines 505, along which the solution 504 to be dispensed is attracted toward the substrate 500, a body of electrically conductive material 506 below the lower surface of the Substrate 500, a ground 507 and a shortest field line 508 between the nozzle 503 and the substrate 500.
  • the body 506 shown in FIG. 5 is located under the lower surface of the substrate 500. Otherwise, the explanation for FIG. 4 applies accordingly to FIG. 5.
  • FIG. 6 shows a substrate 600, a desired predetermined area 601 to which a solution 603 to be dispensed is to be dispensed, a dispensing device 602, field lines 604, along which the solution 603 to be dispensed is drawn towards the substrate 600, field lines 605, along which the solution 603 to be dispensed is repelled from the substrate 600, a plurality of predetermined areas 606 to which the solution 603 to be dispensed is not to be dispensed, a grounding 607 and a dielectric layer 608 on the upper surface of the substrate 600.
  • the explanation of FIG applies accordingly to Fig. 6.
  • FIG. 6 differs from FIG. 2 in that a dielectric layer 608 is applied to the upper surface of the substrate 600. Accordingly, capture molecules which are contained in the solution 603 to be dispensed are not dispensed directly onto the predetermined area 601 (which is preferably an electrode in themselves), but rather are dispensed onto the dielectric layer 608 above the predetermined area 601.
  • the dielectric layer 608 could preferably consist of the same, non-electrically conductive material as the substrate 600.
  • a suitable, non-electrically conductive material for this purpose is silicon dioxide or silicon nitride.
  • the applied dielectric layer 608 can be provided to protect the predetermined areas 601, 606 of the substrate 600, so that catcher molecules contained in the solution 603 to be dispensed are not dispensed directly on the conductive material of the respective predetermined area 601, 606, but on the dielectric layer 608 above the respective predetermined area 601, 606.
  • the dielectric layer 608 may also be advantageous not to form the dielectric layer 608 flush with the material of the substrate 600, so that the dielectric layer 608 after the dispensing of different capture molecules on the respective predetermined areas 601 , 606 for further evaluation or detection can be separated from the substrate 600 with its predetermined areas 601, 606.
  • This has the advantage that the position specificity of the predetermined areas 601, 606 of the substrate 600 results in a corresponding position specificity of the solution 606 dispensed in each case on the dielectric layer 608.
  • Such a specific position transfer from the respective predefined areas 601, 606 of the substrate 600 to the dielectric layer 608 has the advantage that, using ever new dielectric layers 608, the dispensing arrangement, consisting of the substrate 600, the predefined areas 601, 606, the nozzle 602 and the grounding 607 can be used repeatedly.
  • dispensing device here a nozzle
  • dispensing device here a nozzle

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Abstract

L'invention concerne un système de distribution comprenant un substrat (100) qui possède une surface supérieure et une surface inférieure. Le système de distribution selon l'invention comprend également un dispositif distributeur (103) contenant une solution à distribuer (104) et placé au-dessus de la surface supérieure du substrat (100) à une distance telle que la solution à distribuer (104) peut être distribuée au-dessus d'une zone prédéterminée (101) de la surface supérieure du substrat (100). A cet effet, le substrat est mis sous contact électrique de sorte qu'un potentiel électrique peut être généré entre la zone prédéterminée et le dispositif distributeur. Le potentiel électrique généré entre la zone prédéterminée et le dispositif distributeur permet de commander la direction dans laquelle la solution est distribuée vers la zone prédéterminée.
PCT/DE2002/001562 2001-05-22 2002-04-29 Systeme de distribution sur puce biocapteur et procede pour la distribution d'une solution a distribuer par utilisation de ce systeme de distribution sur une puce biocapteur WO2002094442A1 (fr)

Priority Applications (1)

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EP02740301A EP1392437A1 (fr) 2001-05-22 2002-04-29 Systeme de distribution sur puce biocapteur et procede pour la distribution d'une solution a distribuer par utilisation de ce systeme de distribution sur une puce biocapteur

Applications Claiming Priority (2)

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DE10124988.8 2001-05-22
DE2001124988 DE10124988A1 (de) 2001-05-22 2001-05-22 Dispensier-Anordnung und Verfahren zum Dispensieren einer zu dispensierenden Lösung unter Verwendung der Dispensier-Anordnung

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WO2002094442A1 true WO2002094442A1 (fr) 2002-11-28

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WO2003051517A2 (fr) * 2001-12-17 2003-06-26 Sunyx Surface Nanotechnologies Gmbh Surface hydrophobe pourvue d'une pluralite d'electrodes
WO2005039771A1 (fr) * 2003-10-23 2005-05-06 Scienion Ag Procedes et dispositifs pour le depot d'echantillons sur un substrat electriquement blinde
WO2005047696A1 (fr) * 2003-11-17 2005-05-26 Koninklijke Philips Electronics N.V. Système destiné à la manipulation d'une masse de fluide
EP1844852A1 (fr) * 2006-04-13 2007-10-17 Samsung Electronics Co., Ltd. Appareil et procédé d'impression d'une gouttelette biomoléculaire sur un substrat

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US5486337A (en) * 1994-02-18 1996-01-23 General Atomics Device for electrostatic manipulation of droplets
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US5486337A (en) * 1994-02-18 1996-01-23 General Atomics Device for electrostatic manipulation of droplets
US5846595A (en) * 1996-04-09 1998-12-08 Sarnoff Corporation Method of making pharmaceutical using electrostatic chuck
WO1999015876A1 (fr) * 1997-09-19 1999-04-01 Aclara Biosciences, Inc. Systeme et procede de transfert de liquides
FR2783179A1 (fr) * 1998-09-16 2000-03-17 Commissariat Energie Atomique Dispositif d'analyse chimique ou biologique comprenant une pluralite de sites d'analyse sur un support, et son procede de fabrication

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003051517A2 (fr) * 2001-12-17 2003-06-26 Sunyx Surface Nanotechnologies Gmbh Surface hydrophobe pourvue d'une pluralite d'electrodes
WO2003051517A3 (fr) * 2001-12-17 2004-01-22 Sunyx Surface Nanotechnologies Surface hydrophobe pourvue d'une pluralite d'electrodes
WO2005039771A1 (fr) * 2003-10-23 2005-05-06 Scienion Ag Procedes et dispositifs pour le depot d'echantillons sur un substrat electriquement blinde
US8614100B2 (en) 2003-10-23 2013-12-24 Scienion Ag Method and devices for depositing samples on an electrically shielded substrat
WO2005047696A1 (fr) * 2003-11-17 2005-05-26 Koninklijke Philips Electronics N.V. Système destiné à la manipulation d'une masse de fluide
EP1844852A1 (fr) * 2006-04-13 2007-10-17 Samsung Electronics Co., Ltd. Appareil et procédé d'impression d'une gouttelette biomoléculaire sur un substrat
US8470570B2 (en) 2006-04-13 2013-06-25 Samsung Electronics Co., Ltd. Apparatus and method for printing biomolecular droplet on substrate

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EP1392437A1 (fr) 2004-03-03

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