WO2001029549A2

WO2001029549A2 - Method for producing electric conductive structures in the nanometric range and their use as an impedimetric sensor

Info

Publication number: WO2001029549A2
Application number: PCT/EP2000/009784
Authority: WO
Inventors: Frank Katzenberg
Original assignee: Fraunhofer Gesellschaft zur Förderung der angewandten Forschung e.V.
Priority date: 1999-10-19
Filing date: 2000-10-06
Publication date: 2001-04-26
Also published as: DE19950378B4; DE19950378A1; WO2001029549A3; EP1222453A2

Abstract

The invention relates to a method for producing electric conductive structures in the nanometric range and to their use in an impedimetric biochemical sensor. The invention is characterised in that, using a dielectric surface substrate, having a surface topography consisting of a plurality of angular contours which run largely parallel to one another and which project above the surface of the surface substrate, an oblique shadowing which deposits electrically conductive material on the surface substrate is carried out in such a way, that said electrically conductive material settles in preference on the angular contours.

Description

Process for the production of electrical conductor structures in the nanometer range and their use as an impedimetric sensor

Technical field

The invention relates to a method for producing electrical conductor structures in the nanometer range, i.e. electrically conductive wires, the diameter of which typically range from 1 nm to 500 nm.

State of the art

The motivation for the production of such nanowires arises from the search for improved solutions for sensors, in particular biochemical sensors, with the aid of which impedance measurements can be used to demonstrate molecular binding events, for example the hybridization of a DNA with special oligonucleotides or the binding of antibodies to antigens.

Typically, electrodes applied to a carrier substrate and configured in an interdigital electrode arrangement are suitable for this purpose. The selectively acting detector substances, for example oligonucleotides or antigens, are applied between the electrodes and bound to the substrate. As will be shown below, they form an interaction layer in the form of a dielectric, the dielectric change of which represents the measured variable of the biochemical sensor to be detected. In the presence of antibodies, for example, binding reactions with the corresponding antigens occur, as a result of which the dielectric behavior of the interaction layer between the electrodes changes. In order to detect the dielectric change within the interaction layer as sensitively as possible, the electrical field lines of the electrical field between the electrodes should run largely within the interaction layer. This is the case if the ratio of the electrode spacing to the layer thickness of the dielectric is close to or less than 1. However, this requirement leads to technical problems in the design of such electrode structures, especially since the layer thickness of the Interaction layer usually designed as a monolayer is only a few 10 nm - this corresponds approximately to the length of the oligonucleotides or antigens oriented perpendicular to the substrate surface. The electrode spacing should be of the same or even a smaller dimension in order to achieve the desired sensitivity of the biochemical sensor.

There are a number of electrical methods for the detection of molecular binding events, both based on the potentiometric (see Bergfeld, et. Al., Biosen. & Bioelectron. 6, (1991), page 55), capacitive (Swietlow, Electroanalysis 4 (1992) , Page 921) and the impedimetric principle. Furthermore, measurement arrangements have also been implemented in which a thin interaction layer has been applied as a gate between the drain and source electrodes of a field-effect transistor. All known electrical detection methods, however, have in common that their detection capability is not particularly sensitive to molecular binding events, especially since their electrode arrangements have distances that are much larger than the order of magnitude of the molecular species to be detected, which is immobilized as a dielectric interaction layer between the electrodes. In order to increase the detection sensitivity of such biochemical sensors, the known relationships have led to reducing the electrode spacings (see DE 196 10 115 A1, EP 0 701 691 B1 and K. Reimer, et al., Sens. & Actuat ., 46-47 (1995), p. 66). In the cases mentioned above, the electrode structure was produced by means of electron beam lithography, which is a very expensive method due to its sequential character. In addition, the main area of application of such sensors is biomedicine, and so the individual sensors are often disposable products that represent a cost factor that should not be underestimated due to the high throughput. It is important to look for more economical solutions with such biochemical sensors.

In a contribution by Kasapbasioglu et al., Sens. & Actuat. 13-14 (1993) p. 749 it is proposed to use so-called metal islands for the detection of biochemically relevant substances to be used in fractal form, which are introduced between two spaced electrodes in order to concentrate the electrical field between the electrodes in the vicinity of the interaction layer. Disadvantages, however, are the undefined and uncontrollably wide distribution of distances and sizes, as well as the partial percolation, which makes their use more difficult, which does not go beyond laboratory prototype use.

Presentation of the invention

The invention is based on the object of taking measures which serve to increase the sensitivity of impedimetrically operating biochemical sensors. In particular, it is important to significantly reduce the manufacturing outlay and the associated costs in the production of such sensors. At the same time, however, the detection sensitivity of such sensors should be increased if the interaction layer between the electrodes is as large as possible.

The solution to the problem on which the invention is based is specified in the independently formulated patent claims. Features which advantageously further develop the inventive concept are the subject matter of the subclaims and the description, in addition to the figures which represent particularly suitable exemplary embodiments.

The idea on which the invention is based is the sharp concentration of the electric field between two electrodes, within which the interaction layer required for the detection of biochemical substances, in which, for example, oligonucleotides or antigens are introduced, is provided. In order to limit the electrical field line course to the interaction layer as defined as possible, this is interspersed with so-called nanowires, these are miniaturized line wire sections with a typical line cross section of 1 to 500 nm and line lengths greater than 100 nm, which are preferably perpendicular to the electrical field lines running between the electrodes are arranged. This measure makes it possible to apply the electric field to the To concentrate the electrode gap and in particular on the surface of the nanowires, although the electrode spacing can be several micrometers, so that the electrode arrangement can be produced using customary, not cost-intensive methods.

The nanowires required for the functioning of such a biochemical sensor should also be able to be produced using a process-technically simple and inexpensive method. For this purpose, according to the invention, a method for producing related electrical conductor structures in the nanometer range is designed such that using a dielectric surface substrate having a surface topography, the surface topography of which has a large number of edge runs which run largely parallel to one another and which rise above the surface of the surface substrate, the surface substrate is electrically oblique shading acting on the conductive material is carried out in such a way that the electrically conductive material preferably settles on the edges.

Uniaxially oriented semicrystalline polymer thin films which are themselves embedded in an amorphous matrix can be used as particularly suitable surface substrate materials, the crystalline regions on the surface being raised above the amorphous regions and forming edges. Alternatively, it is also possible to transfer corresponding surface topologies to silicon or silicon oxide substrate surfaces by means of reactive ion etching.

In order to maintain the conductor structures in the desired dimensions, the edge pulls serve as the preferred location for metal material deposition, which occurs on the edge pulls as part of oblique shading. The oblique shading itself represents a deposition process, preferably an anisotropic vapor deposition process, in which the electrically conductive material to be deposited is directed obliquely to the surface of the surface substrate in its vapor phase, whereby it preferably settles on the raised edges. An electrical conductor structure obtained in this way, the applied, for example, to a thin polymer film, is now provided with the biochemical sensor substances and is introduced between two electrodes of a biochemical sensor in the form of a plurality of conductor structure layers of this type which are stacked one above the other.

The inventive use of nanowires between conventionally structured electrodes, the electrode spacing of which is several micrometers apart, leads to a near-surface concentration of the electric field and thus to a significantly higher sensitivity in the detection of molecular binding events in an interaction layer of molecular thickness. Due to the much larger active sensor surface, the sensitivity can exceed that of an electron beam lithographically structured electrode arrangement, although the manufacturing costs are significantly reduced.

Thus, a main aspect of the invention is the saving in carrying out biochemical examinations by the possibility of producing an inexpensive biochemical sensor in which an expensive nanostructuring of the electrode arrangement can be dispensed with.

Brief description of the invention

The invention is described below by way of example without limitation of the general inventive concept using exemplary embodiments with reference to the drawing. Show it:

1a, b top view and side view of an impedimetric biochemical sensor with nanowire structure,

Fig. 2 representation of a surface topology of a semi-crystalline

Polymer thin film, as well

Fig. 3 schematic diagram to explain the oblique shading. Description of an embodiment

1 a shows the top view of an impedance-acting biochemical sensor, which is essentially characterized in that two electrodes 1, 2 are arranged at a distance of a few μm, preferably on a carrier substrate 3 (see FIG. 1 b). Between the electrodes 1, 2 there is a conductor structure 4 consisting of a plurality of nanowires arranged parallel to one another, the arrangement of which can be seen in a detailed illustration in FIG. 1b.

The left electrode 1 is shown in FIG. 1 b and applied directly to the carrier substrate 3. In the space between the electrode 1 and the electrode 2, not shown, the nanowires 4 shown in cross section are each provided with an equidistant mutual distance. The longitudinal extension of the nanowires 4 is oriented perpendicular to the electrical field lines 5, the electrical field lines concentrating on the surface of the nanowires (see arrow representations). The cross section of the nanowires typically has sizes between 5 and 20 nm, their mutual distance is approximately the same order of magnitude, preferably between 5 and 30 nm. The surface of the carrier substrate 3 and the surface of the nanowires are with biochemical sensors 6 in the form of antigens or applied to oligonucleotides. The corresponding binding events take place on the antigens or oligonucleotides 6, on which, for example, certain DNA fragments hybridize.

By introducing the nanowires 4 between the electrodes 1, 2, the electric field 5 that is formed between the electrodes 1, 2 is concentrated on the area of the interaction layer 7, which is expressed by the strongly curved field lines 5 within the interaction layer 7. In this way, the electric field 5 is concentrated in the immediate vicinity of the sensor surface, which at the same time also results in a significant increase in sensitivity in the detection of molecular binding events within the interaction layer 7. In order to produce equidistant nanowires aligned parallel to one another, the natural surface topology of uniaxially oriented semicrystalline polymers is advantageously used (see here FIG. 2). Such polymer thin films consist of nanocrystals, which are embedded in an amorphous matrix. The dimensions of such crystals parallel to the molecular chain direction typically range from 5 to 25 nm. In parallel, the crystals can be up to a few micrometers in size. On the surface of polymers, the crystals are raised compared to the amorphous regions, the transition between the crystalline and the amorphous region being characterized by a more or less sharp-edged transition, see FIG. 2, in which a melt-spun polymer thin film is shown. The protrusion of the polymer crystals from the amorphous regions is understandable by the diffusion of individual macromolecules during crystallization from the amorphous phase in the direction of the denser packed crystal that forms. In addition, in the case of melt-spun, uniaxially oriented polymer films, as shown in FIG. 2, cold stretching of the film occurs after the crystallization in the flow gradient, which causes the flowable, ie plastically deformable, amorphous areas to be constricted while maintaining the volume. Furthermore, in the case of the uniaxially oriented lamellar polymer structure, as is the case, for example, with polyethylenes, all the crystals lie almost parallel to one another on the surface.

Using such a polymer thin film, the desired nanowires can be produced by metallizing the surface topology in the course of oblique shading.

3 shows a schematic cross section through a polymer thin film 8, in the surface of which crystalline 9 and amorphous regions 10 are provided. The transition between a crystalline region 9 and an amorphous region 10 is characterized by a sharp edge line 11. By obliquely shading this nanoscopically ordered surface topology with the aid of evaporation at a certain angle of incidence to the substrate surface (see the arrows drawn obliquely to the substrate surface), only the crystal flanks of the edge strips 11 facing the evaporator source and the crystal surfaces are metallized. The vapor-deposited metal 12 decorates the crystals and forms elongated, wire-like metal geometries that extend longitudinally to the edges.

In a next step, electrode structures are applied in such a way that the electrode edges are aligned perpendicular to the molecular chain direction and thus parallel to the nanowires produced. Compared to the known solutions using island-shaped metal clusters, such a sensor structure has sharp spacing and size distributions with regard to the conductor structures provided between electrodes, which can be set by the physical history of the crystal. It is thus possible to set the surface topology as desired by specifically varying the crystallization temperature and the process temperature for producing the melt-spun polymer thin film.

A production of the oriented polymer thin films or oriented surfaces of solid polymers according to the “friction transfer” method (see also Katzenberg, et al., Sen'l Gakkaishi, J. Soc. Fiber Sei. & Techn. Japan, 53 (1997) p 549) is also conceivable.

Furthermore, the topology of the polymer thin films can be transferred by means of reactive ion etching into, for example, silicon or silicon oxide or ceramic substrates, on the surface of which nanowires can be applied by subsequent oblique shading. LIST OF REFERENCE NUMBERS

Electrodes carrier substrate nanowire, conductor structure electrical field lines antigens, oligonucleotides interaction layer polymer thin film crystalline area amorphous area edge pull metal deposition

Claims

claims

1. A method for producing an impedimetric sensor with an electrical conductor structure formed in the nanometer range, which is arranged between two electrodes of an electrode arrangement, characterized in that using a dielectric surface substrate having a surface topography, the surface topography of which has a large number of largely parallel to one another , has raised edges above the surface of the surface substrate, an oblique shading which acts on the surface substrate with electrically conductive material is carried out in such a way that the electrically conductive material preferably settles on the edges and in this way forms the electrical conductor structure, and that parallel to the edges Electrodes are applied in such a way that the electrical conductor structure is arranged between the electrodes.

2. The method according to claim 1, characterized in that the oblique shading is a deposition method, preferably an anisotropic vapor deposition method, in which the electrically conductive material is deposited obliquely to the surface of the surface substrate and perpendicular to the mutually parallel edges.

3. The method according to claim 1 or 2, characterized in that a semi-crystalline polymer thin film is used as the surface substrate.

4. The method according to claim 3, characterized in that the polymer thin film has nanocrystals which are embedded in an amorphous matrix, the crystalline regions on the surface of the amorphous regions being raised and forming edges.

5. The method according to claim 1 or 2, characterized in that the surface topology is obtained by means of reactive ion etching in Si or Si0 ₂ .

6. The method according to claim 1 or 2, characterized in that the surface topology is obtained by embossing a nanostructured tool, for example by nanoimprinting, in a polymer substrate.

7. The method according to any one of claims 1 to 6, characterized in that the electrical conductor structures are introduced between the electrodes such that a near-surface concentration of the electric field between the electrodes is brought about.

8. The method according to any one of claims 1 to 7, characterized in that the electrical conductor structure is arranged perpendicular to the electrical field lines running between the electrodes.

9. Use of the impedimetric sensor produced by a method according to one of claims 1 to 8, characterized in that it is used for impedance or capacitance measurement for the detection of biochemical reactions.

10. Use according to claim 9, characterized in that the impedimetric sensor is used for the detection of molecular binding events, preferably the hybridization of a DNA with oligonucleotides or bonds between antibodies to antigens.