DE10124988A1 - Dispensing arrangement and method for dispensing a solution to be dispensed using the dispensing arrangement - Google Patents

Abstract

A dispensing arrangement has a substrate. The substrate has an upper surface and a lower surface. Furthermore, 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 substrate is electrically contacted in such a way that an electrical potential can be generated between the predetermined area and the dispensing device. The electrical potential generated between the predetermined area and the dispensing device enables the direction of the dispensing of the solution to be dispensed to be controlled towards the predetermined area.

Description

The invention relates to a dispensing arrangement and a Method for dispensing a solution to be dispensed using the dispensing arrangement

Bio / chemo arrays miniaturized on substrates serve this purpose Detection of certain molecules in solutions to be examined. The sensors are in large numbers on a semiconductor substrate, z. B. a silicon chip that certain electronic Provides functions, realizable or even on one Glass, plastic, or other substrate Substrate material. The high degree of parallelization enables the simultaneous parallel execution of a series various investigations, e.g. B. Investigations on that Presence of different substances (i.e. to be detected Molecules) in a given liquid to be examined. This property gives rise to such sensor Array chips with corresponding evaluation system diverse Applications, for example in medical diagnostics, in in the pharmaceutical industry for example for high-throughput Patterning procedure ("High Throughput Screening" (HTS)), in in the chemical industry, in food analysis, and in environmental and food technology.

The basic principle of many known sensors is that so-called catcher molecules, for example using microdispensing techniques, are first applied to a substrate made of a suitable material and immobilized in various ways. Fig. 7, such a substrate 700 schematically shows with n positions 701, on 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. If 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 capture 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 complementarity, or at least sufficient, for hybridization of the two nucleic acid strands with one another between the two Requires molecules.

However, other combinations between catcher molecules on the substrate 700 and molecules to be detected in the liquid to be examined are also possible. For example, 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 other proteins or peptides that bind the capture peptide or capture protein. Of great importance for the pharmaceutical industry is the use of low molecular weight (ie less than about 1,700 g / mol 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 possibly Low-molecular compounds present in a liquid to be examined.

To prove the bond between the on the Carrier molecule applied and the in the to investigating liquid present, to be detected It is known to be an optical detection method or molecule to use an electronic verification procedure.

In a known optical method to the in the investigating solution specific molecules present Fluorescent label ("label") bound to the Exposure to, for example, UV light for lighting can be stimulated. As a rule, this bond is one chemically covalent bond. Now the substrate after the Bringing into contact with the liquid to be examined and after a further rinsing step in which to  Examining liquid present, but not bound molecules are removed, exposed to light, so can be based on knowledge of the location of each Catcher molecules are determined at which positions of the Specific binding has occurred and to which positions no specific binding took place Has. Due to the exact knowledge of the used Catcher molecules can indicate the existence or the absence Existence of certain molecules to be detected in the to examining liquid can be closed.

The optical detection method points in comparison to one known electrical detection methods, in particular the Downside to being a relatively complicated and expensive one optical system must be used for evaluation. This complicates z. B. the use of such an optical Verification procedure in a doctor's office.

It is also known for the detection of the binding that has occurred electrical detection method. Examples of one such electrical detection methods are from [1], [2], [3], [4], [5], [6], [7] and [8] are known.

With both optical and electrical Detection methods are predisposed to capture molecules Areas of a substrate immobilized. Usually done this immobilization by applying one of these Solution containing capture molecules by means of dispensing technology on the specified area of the substrate. The one in this Capture molecules present can then be dissolved using the respond to each predetermined area of the substrate to be immobilized on this. With optical Proof is often the given area  any more discrete from other areas on the substrate Area on the substrate, the nature of which is often identical is with that of the rest of the substrate. With electrical The specified range is often a verification method exposed electrode on the surface of the substrate or an electrode that is coated with another material, e.g. B. with the Material of the rest of the substrate surrounding the electrode, is covered.

The following explains how to dispense a Solution containing capture molecules to be immobilized by means of known dispensing technology to a given one Area of a substrate is ideally applied.

In FIGS. 3A and 3B, 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 that pass through the predetermined area 301 the large guide projections 304 is formed.

Fig. 3A and 3B show the case that the guide projections 304 are formed relatively large so that they are able, the dispensed volume of the solution to completely receive the 303rd Fig. 3A shows a drop of solution 303 which is being dispensed from the nozzle 302nd Fig. 3B shows the result after dispensing the solution from the nozzle 303 302nd It should be noted that the solution 303 in FIG. 3B completely wets the predetermined area 301 , which represents the ideal case.

In FIGS. 3C and 3D, a substrate 300 , a predefined area 301 of the substrate 300 , a dispensing device 302 (here a nozzle), a solution 303 to be dispensed, small guide projections 305 , and a cavity 306 that pass through the predefined area 301 the small guide projections 304 is formed.

Fig. 3C and 3D show the case that smaller guide projections 305 are provided than that shown in FIGS. 3A and 3B. Figure 3C shows the drop of solution 303 as it is being dispensed from nozzle 302 . FIG. 3D shows the case after dispensing the drop of solution 303 from the nozzle 302 such that this drop is now above the predetermined range between the guide projections 305 , but the volume of the drop of solution 303 in FIG. 3D is due to 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 completely, ie uniformly, wetted by the drop of the solution 303 , which represents the ideal case.

However, such an ideal case cannot usually be realized with conventional chip arrangements with sensor electrodes. FIG. 8A 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 formed by the large guide projections 803 Cavity 806 . Fig. 8B shows a substrate 800, a predetermined region 801 on the substrate 800, a to be dispensed solution 802, small guide projections 805, an enclosed during dispensing air bladder 804 between the solution 802 and the predetermined area 801, and formed by the small guide protrusions 805 Cavity 806 .

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 can not contact any catcher molecules to be immobilized in the solution 802 . Thus, not to immobilized capture molecules on that region of the predetermined range 801, which is below the air bladder 804 is immobilized while, be immobilized to be immobilized capture molecules in the solution 802 on the area of the predetermined range 801 that contacts the solution 802 directly.

Thus, incomplete wetting of the predetermined area 801 with the solution 802 leads to the undesirable state that after the immobilization phase, a partial area of the predetermined area 801 has immobilized capture molecules, while another partial area of the predetermined area 801 has no immobilized capture molecules. In the later detection method, such an uneven immobilization of capture molecules on the predetermined area 801 could lead to undesired measurement artifacts.

Another disadvantage with such dispensing methods in the state The technique is that because of the small volume that be used in such dispensing procedures that Dispense itself in terms of what you want Dispensing location is often very imprecise. As above explained, such dispensing procedures are in the prior art Technology often with very small volumes, for example with volume in the nanoliter range. The volume of the too dispensing solution is therefore often experienced per se its weight, a weight that is about as big as the force due to drag such a volume experienced during dispensing. After exiting to Example, a nozzle in such a dispensing process can before dispensing the volume of the dispensed Solution due to this air resistance to the side of the Target trajectory of this volume between the nozzle and the Migrate substrate, which is the exact placement of the volume of the solution to be dispensed at a specific location of the Substrate difficult.

The invention is therefore based on the problem of spatial Accuracy with which a volume of the solution to be dispensed can be dispensed onto a substrate to improve.

This problem is solved with a dispensing arrangement with the Features solved according to the independent claim.

A dispensing arrangement has a substrate. The substrate has an upper surface and a lower surface. Furthermore, the dispensing arrangement has a Dispensing device for receiving a dispense Solution. The dispensing device is at a distance arranged above the upper surface of the substrate  such that the solution to be dispensed is above a predetermined area of the upper surface of the substrate can be dispensed. The substrate is electrical contacted in such a way that between the specified range and the dispensing device generates an electrical potential can be. That between the given range and the Dispensing device generated electrical potential allows the direction of dispensing the to dispensing solution controlled to the specified area can be.

The dispensing arrangement according to the invention brings the Advantage that by applying an electrical potential between at least the predetermined area of the substrate and a volume of the dispensing device to be dispensed Solution actively in the direction of the target position, that is the predetermined area of the substrate, electrostatically is drawn. So the trajectory becomes one too small volume of the solution to be dispensed from the Dispensing device through between the given Area of the substrate and the dispensing device existing electrostatic field lines determined, whereby a lateral migration of the volume of the dispensed Solution outside of the intended trajectory of the volume of the solution to be dispensed and therefore the site-specific accuracy with which the volume of the to dispensing solution can be applied to the substrate can, is increased.

Furthermore, the active, electrostatic pulling of the volume of the solution to be dispensed for a particular one specified area reduces the risk that the Dispense between the volume of dispensed  Solution and the predetermined area of the substrate Air bubble is trapped. The volume of the too Dispensing solution becomes effective through the field lines between the dispensing device and the given one Area of the substrate drawn onto this, making the volume the solution to be dispensed to the specified area hugs closely, d. H. the predetermined area of the substrate completely and evenly wetted.

According to an embodiment of the invention Dispensing arrangement is the electrical contacting of the Set up the substrate so that the electrical potential can be applied to the entire surface of the substrate. In this Scenario exists between the entire top surface of the Substrate and the dispenser for control a volume of the solution to be dispensed from the nozzle to Potential determining substrate, and the predetermined Area of the substrate on which the solution to be dispensed should be dispensed, represents a mentally delimited Subdivision of the entire upper surface of the substrate. Accordingly, the specified area bears according to this Embodiment same electrostatic charge as that entire top surface of the substrate.

With a potential applied to the entire surface of the substrate are preferably two construction options of the substrate provided.

In the first option, the substrate itself consists of an electrically conductive material, and the electrical Contacting is direct electrical contacting between the substrate itself and one with the substrate coupled voltage source. Possible electrically conductive  Materials from which the substrate could be made for example polysilicon or different metals such as for example gold.

Since in this embodiment, the potential over the entire surface field lines can be applied to the substrate between the dispenser and the top surface of the substrate not only between the predetermined range of Substrate onto which the solution to be dispensed dispenses should be, and the dispensing device, but also between other areas on the top surface of the Substrate and the dispensing device. In this Case the flight path of the dispensed volume becomes too dispensing solution through the shortest field line to the determined upper surface of the substrate. At vertical dispenser aligned with the top surface this shortest field line is the field line that is perpendicular to the specified area on the top surface of the Substrate runs. For this reason, it is with one Embodiment important, the lateral position of the Dispensing device as precisely as possible above the predetermined area of the substrate to which the dispensing solution to be dispensed, too position so that the trajectory of the to be dispensed Solution defining field lines between the Dispensing device and the predetermined range of Substrate that field line from the majority of the field lines is the shortest.

In a second embodiment, in which the potential all over the top surface of the substrate is, the substrate consists of a non-electrical conductive material and electrical contacting  an indirect electrical contact between the Substrate and an electrically conductive, with a Voltage source coupled body. With this Embodiment is the volume of dispensed Solution not directly on the electrically conductive material, but on the non-electrically conductive material of the Dispensed substrate. A preferred, not electric Conductive material is silicon dioxide or silicon nitride. Preferred, electrically conductive materials from which the body coupled to the voltage source can include all metals with high electrical Conductivity. For example, aluminum, gold, platinum, Copper, tungsten or palladium as material for the electrical conductive body can be used.

According to an embodiment of the invention, this is electrically conductive, connected to a voltage source Bodies within the substrate between the top surface and the lower surface of the substrate.

The electrically conductive, with a voltage source connected body is according to another embodiment of the invention below the lower surface of the substrate arranged.

According to a further embodiment of the invention, the electrical contact created in such a way that electrical potential to just a single given Area of the substrate can be created. According to this Embodiment of the invention exist only between the predetermined area of the substrate and the Dispensing device field lines that create an electrical field symbolically represent that a volume of dispensed  Solution towards the substrate. To other areas of the Substrate that is not the specified area of the substrate are either no potential or a the volume of the dispensing solution created repulsive potential. There Field lines along which the solution to be dispensed for Substrate is attracted, only between the desired predetermined area of the substrate and the Dispenser exist, is according to this Embodiment of the invention the exact positioning the dispensing device above the predetermined range of the substrate is not as important as in the Embodiments of the invention in which the potential is applied to the entire surface of the substrate.

The substrate preferably consists of a non-electrical one conductive material and the specified area of the substrate is an electrode that is coupled to a voltage source is. According to such an embodiment of the invention the electrode, that is the predetermined area of the substrate, one of a plurality of electrodes on the top Surface of the substrate, relative to the position specific to the other electrodes on the surface of the substrate increasing the volume of the solution to be dispensed Potential can be applied.

According to a further embodiment of the invention the electrode not only above the surface of the substrate, but also below the top surface of the substrate be arranged. According to such an embodiment do not apply the solution to be dispensed directly to the electrode dispensed itself, but not on the electrical conductive material of the substrate.  

According to a particularly preferred embodiment of the Invention has the electrode covering the given area of the substrate represents gold. The use of gold not only enables high electrical conductivity, but also the immobilization of on the electrode applied capture molecules using a known gold Sulfur coupling.

In all of the previous exemplary embodiments, a suitable, not electrically conductive material Silicon dioxide or silicon nitride. Depending on the purpose however, other materials, e.g. B. polymeric Materials such as polyethylene, polypropylene, polyethylene Polypropylene block copolymers, polystyrene, aluminum oxide, Titanium oxide, as well as tantalum oxide can be used.

According to an embodiment of the invention Dispensing device a nozzle. The nozzle is preferably such set up that the solution to be dispensed in volume up can be dispensed to a nanoliter. To For example, microdispensing purposes are piezomicro nozzles prefers.

In another embodiment of the invention the dispensing device, for example a nozzle immobilizing capture molecules. In that the too dispensing solution to a given given Area of the substrate is dispensed, the in the too Dispensing solution contained capture molecules on the predefined area of the substrate applied in a site-specific manner, so that they can be immobilized on the substrate. This presupposes that the nature of the given Range is such that a chemical, i.e. H. covalent,  Binding between the capture molecule to be immobilized and yourself is possible. Immobilizing one in the too dispensing solution contained capture molecule depending on Structure of the substrate can therefore be either electrical conductive material or a non-electrically conductive Material.

According to a further embodiment of the invention one above the top surface of the substrate Dielectric layer arranged so that the Dielectric layer the top surface of the substrate as well, if any, on the top surface of the substrate arranged electrode covered. This may be the case electrode located on the surface of the substrate covered, but this is covered by one Dielectric layer protected from external influences. If one Dielectric layer on the top surface of the substrate is applied depends, for example, on how the immobilized to capture molecules should or like the electrical potential between the given area of the substrate and the Dispensing device of the dispensing arrangement are generated should.

Such a dielectric layer on the top surface of the substrate and, if present, on the upper surface electrode arranged on the substrate can be applied, can have silicon dioxide or silicon nitride.

According to a further embodiment of the invention on the upper surface or, if present, on the Dielectric layer to the side of the specified area arranged upwardly extending guide projections.  

Such guide projections have guide surfaces that follow lead inside to the given area. Such Guide tabs can be used to create the dispensing solution targeted above the given Collect area of the substrate. The effect of Leadership is particularly important in cases wear where the volume is misplaced dispensing solution laterally above the given Area of the substrate should be avoided. this could for example in the above-mentioned embodiment of FIG Case in which a potential is applied to the entire surface of the substrate can be created so that between the Dispensing device and the substrate several field lines Trajectory of a volume of the solution to be dispensed can influence. This could make it undesirable "Flow away" from the volume of the solution to be dispensed the specified area on the surface of the Substrate come. Such "flowing away" should therefore be avoided.

The problem underlying the invention becomes according to the invention also with a method for dispensing a solution to be dispensed in a given area a substrate using the dispensing arrangement such as solved above.

In a method of dispensing one to be dispensed Solution on a given area of a substrate Use the dispensing arrangement as explained above the dispensing device and / or the substrate relative moved towards each other in such a way that after the movement has been completed Dispensing device above the specified range for Rest comes. An electrical potential is between the  predetermined area of the substrate and the Dispensing device created. The dispenser will for dispensing a volume of the solution to be dispensed causes. This is left between the dispensing device and the given area of the substrate Potential on the dispensed volume of the dispensed Solution act so that a volume of to be dispensed Solution controlled in the direction of the predetermined range becomes.

Embodiments of the invention are in the figures shown and are explained in more detail below.

Show it

Figure 1 is a schematic representation of an embodiment of the dispensing arrangement according to the invention, in which a potential can be applied to the entire surface of the substrate.

FIG. 2 shows an embodiment of the dispensing assembly of the invention can be applied to different areas of the substrate at the position-specifically different to the substrate Potentialien;

Fig. 3 is a schematic representation of various dispensing arrangements according to the prior art;

Fig. 4 is a schematic representation of an embodiment of the dispensing assembly according to the invention, in which a potential can be generated over the entire surface along the substrate by a substrate is located in the body;

Fig. 5 is an embodiment of the dispensing assembly according to the invention, in which a potential can be generated over the entire surface along the substrate by a substrate is located below the body;

Fig. 6 shows an embodiment of the dispensing assembly of the invention can be created in which different potentials at different predetermined regions of the substrate and in which a dielectric layer is applied above the upper surface of the substrate;

Fig. 7 is an addressable substrate having a plurality of predetermined areas in accordance with the prior art;

Fig. 8 is a schematic representation of an incomplete wetting a predetermined region of a substrate using a dispensing assembly according to the prior art.

Fig. 1, a substrate 100, predetermined regions 101 shows the substrate 100, a voltage source 102, a dispensing device 103 (here, a nozzle 103), one along which the attracted to be dispensed solution 104, the field lines 105 to be dispensed solution 104 to the substrate 100 out and a ground 106 .

In the exemplary embodiment shown in FIG. 1, 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. For this reason, there is an electrical potential between the upper surface of the substrate 100 with the predetermined areas 101 of the substrate 100 and the solution 104 to be dispensed, which is symbolically represented by the multiple field lines 105 . Since there is not only an electric field between the desired, here central, predetermined region 101 and the solution 104 to be dispensed, but also between the nozzle 103 and the upper surface, the surrounding regions of the substrate 100 and the other predetermined regions 101 of the substrate 100 , 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), an along which the attracted to be dispensed solution 203, the field lines 204 to be dispensed solution 203 to the substrate 200 out 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 .

The substrate 200 consists of a non-electrically conductive material, for example SiO ₂ , so that the predetermined regions 201 , 206 of the substrate 200 are 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 desired 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 . If a volume of to be dispensed solution 203 from the nozzle 202 out is between the predetermined area 201 of the substrate 200 and the nozzle 202 existing, attracting electric potential along the field lines 204 drawn this due to the to the predetermined area 201 of the substrate 200th In this case, the field lines 205 along which the solution 203 to be dispensed is repelled from the substrate 200 prevent the volume of the solution 203 to be dispensed from moving to other locations, for example to the predetermined areas 206 or to another location on the surface of the substrate 200 , is drawn. For this purpose, each predetermined region 201 , 206 of the substrate 200 should be individually coupled to a voltage source (not shown here). Accordingly, 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 regions 401 on the upper surface of the substrate 400, a voltage source 402, a dispensing device 403 (here a nozzle 403), a to be dispensed solution 404, the field lines 405 along which the to be dispensed solution 404 is attracted toward the substrate 400 , a body 406 made of electrically conductive material, an earth 407 and the shortest field line 408 between the nozzle 403 and the substrate 400 .

In the exemplary embodiment shown in FIG. 4, 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 . As already explained above for FIG. 1, it is therefore important that 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 .

As can be seen from the plus signs in FIG. 4, a potential can be generated over the entire surface of the upper surface of the substrate 400 by means of the body 406 introduced between the upper surface of the substrate 400 and the lower 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 to be dispensed solution 504, the field lines 505 along which the to be dispensed solution 504 is attracted towards the substrate 500 , a body of electrically conductive material 506 below the lower surface of the substrate 500 , an earth 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 correspondingly to FIG. 5.

Fig. 6 shows a substrate 600, a desired predetermined range 601 to which one is to be dispensed to be dispensed solution 603, a dispensing device 602, the field lines 604 along which is attracted to be dispensed solution 603 to the substrate 600 out 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 ground 607 and a dielectric layer 608 on the upper surface of the substrate 600 . The explanation of FIG. 2 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 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, as already explained for FIG. 2, 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 . In this regard, it can 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 of the substrate 600 can be separated 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.

FIGS. 7 and FIG. 8 have already been explained in the introductory part, in the light of the prior art.

The following references have been cited in this document:
[1] M. Paeschke et al., Electroanalysis 1996 , 7 , no. 1, p. 1-8
[2] R. Hintzsche et al., "Microbiosensors using electrodes made in Si-technology", in "Frontiers in Biosensorics I - Fundamental Aspects", FW Scheller et al. ed., 1997, Birkhauser Verlag Basel
[3] WO 93/22678
[4] DE 196 10 115 A1
[5] US Serial No 60/007840
[6] Peter Van Gerwen et al., Transducers '97, p. 907-910
[7] Christian Krause et al., Langmuir, vol. 12, no. 25, 1996 p. 6059-6064
[8] VM Mirsky, Biosensors & Bioelectronics 1997 , Vol. 12 No. 9-10, pp. 977-989

LIST OF REFERENCE NUMBERS

100

substratum

101

Specified areas

102

voltage source

103

Dispensing device (here a nozzle)

104

Solution to be dispensed

105

Field lines along which the solution to be dispensed

104

to the substrate

100

is attracted

106

grounding

107

Shortest field line between the nozzle

103

and the substrate

100

200

substratum

201

Positively charged, predetermined areas

202

Dispensing device (here a nozzle)

203

Solution to be dispensed

204

Field lines along which the solution to be dispensed

203

to the substrate

200

is attracted

205

Field lines along which the solution to be dispensed

203

from the substrate

200

is repelled

206

Negatively charged, predetermined areas

207

grounding

300

substratum

301

Specified areas

302

Dispensing device (here nozzle)

303

Solution to be dispensed

304

Great leadership

305

Small leadership leads

306

Cavity formed by the guide projections

400

substratum

401

Specified areas

402

voltage source

403

Dispensing device (here nozzle)

404

Solution to be dispensed

405

Field lines along which the solution to be dispensed

404

to the substrate

400

is attracted

406

Body made of electrically conductive material

407

grounding

408

Shortest field line between the nozzle

403

and the substrate

400

500

substratum

501

predetermined areas

502

voltage source

503

Dispensing device (here nozzle)

504

Solution to be dispensed

505

Field lines along which the solution to be dispensed

504

to the substrate

500

is attracted

506

Body made of electrically conductive material

507

grounding

508

Shortest field line between the nozzle

503

and the substrate

500

600

substratum

601

Positively charged, predefined area

602

Dispensing device (here a nozzle)

603

Solution to be dispensed

604

Field lines along which the solution to be dispensed

603

to the substrate

600

is attracted

605

Field lines along which the solution to be dispensed

603

from the substrate

600

is repelled

606

Negatively charged, predetermined areas

607

grounding

608

Dielectric layer on the top surface of the substrate

600

700

Chip / substrate

701

predetermined areas

800

substratum

801

Specified area

802

Solution to be dispensed

803

Great leadership

804

Air bubble trapped during dispensing

805

Small leadership leads

806

Cavity formed by the guide projections

Claims (18)

1. Dispensing arrangement, with
a substrate having an upper surface and a lower surface; and
a dispensing device for receiving a solution to be dispensed, which 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,
wherein the substrate is electrically contacted such that an electrical potential can be generated between the predetermined area and the dispensing device, so that the direction of the dispensing of the solution to be dispensed can be controlled towards the predetermined area. 2. dispensing arrangement according to claim 1, in which the electrical contact is such that the electrical potential applied to the entire surface of the substrate can be. 3. dispensing arrangement according to claim 2, in which the substrate is made of an electrically conductive Material exists, and the electrical contacting one direct electrical contact between the substrate and is a voltage source coupled to the substrate. 4. dispensing arrangement according to claim 2, in which the substrate consists of a non-electrically conductive Material exists, and the electrical contacting one indirect electrical contact between the substrate  and an electrically conductive, with a voltage source coupled body. 5. Dispensing arrangement according to claim 4, wherein the body connected to a voltage source
within the substrate between the top surface and the bottom surface of the substrate; or
below the bottom surface of the substrate
is arranged. 6. dispensing arrangement according to claim 1, in which the electrical contact is such that the electrical potential to a single predetermined area of the substrate can be created. 7. dispensing arrangement according to claim 6, in which the substrate consists of a non-electrically conductive Material exists, and the predetermined area of the substrate is an electrode coupled to a voltage source is. 8. dispensing arrangement according to claim 7, wherein the electrode
on the top surface of the substrate; or
below the top surface of the substrate
is arranged. 9. dispensing arrangement according to claim 7 or 8, where the electrode is gold. 10. Dispensing arrangement according to one of claims 4, 5, 7, 8 or 9,  where the non-electrically conductive material Silicon dioxide, silicon nitride, polyethylene, polypropylene, Polyethylene-polypropylene block copolymers, polystyrene, Alumina, titanium oxide or tantalum oxide. 11. Dispensing arrangement according to one of the preceding Expectations, in which the dispensing device is a nozzle. 12. dispensing arrangement according to claim 11, in which the nozzle is set up such that the to dispensing solution in volumes up to 0.1 nl or less can be dispensed. 13. Dispensing arrangement according to one of the preceding Expectations, where the solution to be dispensed is on the given Contains capture molecules to be immobilized. 14. Dispensing arrangement according to one of the preceding Expectations, one above the top surface of the substrate Dielectric layer is arranged so that the Dielectric layer the top surface of the substrate as well, if any, on the top surface of the substrate arranged electrode covered. 15. dispensing arrangement according to claim 14, in which the dielectric layer is silicon dioxide or Has silicon nitride. 16. Dispensing arrangement according to one of the preceding Expectations,  on the top surface or, if present, on the dielectric layer to the side of the specified area arranged upwardly extending guide projections are. 17. A method for dispensing a solution to be dispensed onto a predetermined area of a substrate using the dispensing arrangement according to one of the preceding claims,
in which 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 comes to rest above the predetermined range;
in which an electrical potential is applied between the predetermined area and the dispensing device;
wherein the dispensing device is caused to dispense a volume of the solution to be dispensed; and
in which the potential existing between the dispensing device and the predetermined area is allowed to act on the dispensed volume of the solution to be dispensed, so that the volume of the solution to be dispensed is controlled in the direction of the predetermined area. 18. The method according to claim 17, in which the dispensing arrangement has a plurality of predetermined ones Has areas on the substrate to each alternating potentials are created.