WO2007054220A1

WO2007054220A1 - Methods and devices for surface modification of micro-structured substrates

Info

Publication number: WO2007054220A1
Application number: PCT/EP2006/010425
Authority: WO
Inventors: Christian Schmidt; Leander Dittmann
Original assignee: Christian Schmidt; Leander Dittmann
Priority date: 2005-11-09
Filing date: 2006-10-30
Publication date: 2007-05-18

Abstract

This invention relates to methods and devices for the production of surface modified micro-structured substrates and their application in natural sciences and technology, in particular in analysis and detection systems. The method of manufacturing a substrate (1) having a stucture (3), preferably a hole or cavity or channel, in said substrate (1) comprises the steps: modifying said surface of said substrate so as to alter the surface properties (2) of said substrate; introducing a structure (3) in a region of said substrate (1) by a method which alters the surface properties of said substrate within said region (4) but not outside of said region.

Description

Methods and devices for surface modification of micro-structured substrates

Field of the Invention

This invention relates to methods and devices for the production of surface modified micro-structured substrates and their application in natural sciences and technology, in particular in analysis and detection systems.

Background hi many biological applications local differences in surface properties of e.g. analysis chips are required for proper function. Examples are changes/patterns in hydrophobicity to define wettable spots for droplet formation on substrates or substrate surfaces covered by inert molecules to avoid unspecific adsorptions. Many methods exist for such surface patterning, e.g. lithography or molecular self assembly. However, many of these methods require their own proper steps in the substrate processing chain. Combining these surface modifying methods with methods used to structure (e.g. forming holes or cavities) substrates on a micrometer scale and below, requirements for proper alignment and quality become exceedingly difficult to achieve and expensive. This adds to the cost and complexity of the substrate processing, yet it cannot be ensured that the desired substrate quality can be achieved.

Accordingly, it was an object of the present invention to provide for a method manufacturing a substrate having a structure that is in a precisely defined alignment with local differences in surface properties of this substrate. Moreover, it has been an object of the present invention to provide for such method that is easy to perform and reproducible and requires neither a complicated sequence of design steps nor very precise adjustments to achieve highly precise alignment between the structure(s) and patterned/modified surface region(s). hi fact, one important objective has been the possible use of one and the same device and possibly method to introduce a structure as well as to (re-)modify the substrate surface. This objective has been extended to the point of fusing the structure introducing step and surface (re-)modification step into one single step. It was furthermore an object of the invention to provide for a method allowing the controlled modification of surface regions, wherein the geometrical features and amount of modification can be easily controlled and influenced. It was furthermore an object of the invention to provide for such a method that is economical to perform and less costly than methods according to the prior art.

Invention

a) definitions

The term "introducing a structure", as used herein, is meant to refer to a process whereby in a surface of said substrate, a local feature is introduced confined to a defined region which feature is distinguishable from its surroundings, for example by microscopy, and is typically based on locally confined geometric changes such as removal or remodelling of the substrate. In a preferred embodiment, this feature may be a hole or a cavity or a channel in said substrate. As used herein, the term "cavity" is meant to signify a structure which can be described as a recess within the structure without actually extending through the substrate. In contrast thereto, this is the characteristic of a "hole" which essentially extends from one side of the substrate to another side of the substrate. As used herein, the term "channel" and "hole" are used synonymously, with a "channel" usually referring to a hole structure that may be slightly more extended (i.e. having a higher aspect ratio) than a normal "hole", in that it may extend from one side of the substrate for a substantial length within the substrate, and only thereafter stretch to the other side of the substrate, if at all. The term "aspect ratio" is meant to characterise the ratio between the depth and diameter of a hole/channel. Holes having a high aspect ratio are holes having a small diameter compared to their depth or height. As used herein, in one embodiment "channels" are holes having a high aspect ratio. In contrast to these trans-substrate-channels, sometimes reference is also made to structures as being "channels" which are cavities that extend along a surface of the substrate without actually stretching through the substrate i.e. without stretching from one surface to another opposite surface. Because of the typical size of the structure that is being introduced in a substrate according to the present invention, such typical size being a diameter (or the length of the smallest spatial extension if more rectangular) in the range of from 0.01 μm to 500 μm, this structure-"introducing" step is also sometimes referred to as "micromachining a structure".

The term "to alter the surface properties of said substrate", as used herein, is meant to denote a process by which the properties of a surface of said substrate are changed from a first state, prior to such modification, to a second state after such modification. The alteration may be a change in for example chemical affinity/reactivity towards a compound or group of compounds, a change in for example the behaviour of the surface towards solvents, or it may be a simple physical change in for example the surface roughness. Typical alterations of surface properties according to the present invention are changes in hydrophilicity/hydrophobicity of the surface of said substrate, or the blocking of the surface of said substrate by attaching proteins, such as serum albumin to said surface.

The term "sorption", as used herein, is meant to designate "adsorption" and/or "absorption" or a combination of both.

In the present invention, sometimes reference is made to "a compound or composition of compounds" which is applied to a substrate surface in a "modifying step". Such "compound or composition of compounds" is also herein sometimes synonymously referred to as "surface modifying material".

b) invention

The foregoing objectives are solved by a device and method of manufacturing a substrate having a structure, preferably a hole or cavity or channel, and with respect to this structure locally defined surface properties. The method according to the present invention comprises two processing steps, that are modifying said surface of said substrate so as to alter the surface properties of said substrate,, and introducing a structure, preferably a hole or cavity or channel, in a region in said substrate by a method which alters the surface properties of said substrate within said region, preferably in a predefined manner, but does not alter the surface properties of said substrate outside of said region. As an example, the substrate surface of a glass substrate was covered with a hydrophobic silane (e.g. 4-aminobutyldimethylmethoxysilane C7H19NOSi, n-decyldimethylchlorosilane C12H27ClSi) as a surface modifying material by surface exposure to a silane containing atmosphere at 200 °C (2 μl silane/1 1 air) and afterwards the substrate was subjected to a structure introducing step such as controlled electrical discharge or laser ablation. The structure formed (usually a hole) exhibited pure substrate material on its surface and, depending on the power content and duration of the introducing step, was surrounded by a surface region of remodified (i.e. pure) substrate material (the surface modifying material in this region was usually burned during the introducing step), whereas the further parts of the substrate surface surrounding this region had a hydrophobic silane as previously applied in the first step.

For situations where the requirements for structure formation and appropriate change of surface modification have no common parameter range, the following sequence of processing steps is preferred:

- introducing a structure, preferably a hole or cavity or channel in said substrate

- modifying said surface of said substrate entirely or in certain areas of interest so as to alter the surface properties of said substrate in these areas

- applying a method which remodifies the surface properties of said substrate inside the structure and/or within said region.

Preferably all three steps are performed without moving the substrate from or in the structure producing set-up, or the remodifying step uses a method automatically leading to a remodiflcation centered at the structure (even in case of misalignments) due to inherent physical properties of this method.

As an example of one embodiment of the present invention, the surface modification of said substrate is realized by application of a compound or of a composition of compounds to the surface, preferably in a layer, or by abrasion of said surface. Herein, preferably, said application occurs by sorption or covalent binding of said compound(s) to said surface, including processes such as immersion of said substrate in a solution or atmosphere containing fully or partly said compound or said composition of compounds, any other appropriate transfer technique, such as drop casting, spin coating, doctor blading, Langmuir Blodgett techniques, vapor deposition of said compound or composition of compounds on said substrate. Accordingly, this surface modification is either done on said surface in its entirety or partly on a defined area or several defined areas of the surface. Preferably, said defined area at least partially surrounds said region where said structure is introduced, or said defined area is adjacent to said region where said structure is introduced.

As an example (Figure 1), after producing a hole through the substrate (such as glass) by means of a controlled electrical discharge step, the substrate surface was covered with a hydrophobic silane (e.g. 4-aminobutyldimethylmethoxysilane C7H19NOSΪ, n- decyldimethylchlorosilane C12H27ClSi) by surface exposure to a silane containing atmosphere at 200 °C (2 μl silane/ 1 1 air) and afterwards the substrate was subjected to a structure introducing step so as to remodify the surface properties inside and surrounding the structure. Using, for example, a controlled dielectric breakdown as introducing step, has the advantage that a second application of such controlled dielectric breakdown (now as remodification step, parameters e.g. 10^Λ3 - 10^Λ4 V, 0.1 - 10 mm electrode distance, current limitation via 1 - 10 GOhm resistance, duration set by timer e.g. 1 - 1000 msec) focuses by itself in the afore produced structure. However, the parameters of this second "introducing" step are chosen so as to only remodify the surface in and around the structure instead of producing a new structure altogether. Controlling power, power dissipation and power duration of the dielectric breakdown allows to well define the spatial extension of the region around the structure where compounds that had been applied to the surface in the modifying step are desired to be removed. At the same time, such control allows to define the surface density of surface modifying material remaining after the remodification step in this region. Thus, as an example, hydrophobicity can be locally reduced by removing silane (that had been previously applied in a modifying step) to a certain amount depending on the parameters of the remodification step. Remodification parameters my be adjusted resulting in a density gradient of silane starting at the structure with low density (i.e. more hydrophilic region) and increasing density with increasing distance from structure up to the density reached at the edge of the remodified region corresponding to the most hydrophobic area, the hydrophobicity of which is defined by the surface modifying material (silane) of choice. It is to be noted that the density of the compound(s) applied in the modifying step, at the edge of the remodified region is the same as in the area outside of said region, i.e. it is the density in which the compound(s) had been applied in said modifying step. At various places the present invention refers to a "structure introducing step". Preferably, said structure introducing step(s) is (are) selected from the group of shot based methods, such as local laser ablation methods or electric discharge methods or dielectric breakdown or focused ion beam milling (FIB) methods, preferably controlled electric discharge methods or controlled dielectric breakdown methods. This introducing step alters the surface properties/structures of the substrate at the region intended to be structured or remodified to a certain amount which depends on the parameters chosen (e.g. applied energy). Varying these parameters allows for a controlled interpolation or separation between surface remodifϊcation (preferably at lower energy; see below) and surface structuring (micro-machining), both performed using one single device. If parameters for surface structuring and remodification share a common range, both processes are combined to one single process step.

In one embodiment of the method according to the present invention surface modification occurs before introducing a structure. Herein, preferably, said structure introducing removes any altered surface properties resulting from said surface modification step in the region where said structure is introduced, thereby effectively restoring surface properties that were present prior to the modifying step, or in addition thereto, also removing any contaminants from said region, such as dust particles etc., in those circumstances where such contaminants were present prior to the modifying step. This is particularly so in circumstances where the modified surface was not clean, e.g. caused by contamination with dust particles or adsorbed materials, hi these circumstances, the surface in said region improves by the structure introducing step, both in quality and cleanliness even when compared to the original, that is the surface prior to modification, hi another embodiment said surface modifying occurs after introducing said structure (i.e. first introducing step). In this embodiment, a second introducing step (also referred to as remodification) is thereafter performed in said region, at an energy particularly chosen to alter surface properties inside the structure and/or within the region surrounding the structure, such that no new structure is created but that said surface properties are locally modified (e.g. removed) in said region where said structure has been introduced and/or inside the structure itself. Preferably the second introducing step is performed in said region, at an energy chosen such that no new structure is created but that said surface properties altered by said modifying step in said region are remodified, e.g. removed in said region where said structure has been introduced, and/or in said structure itself. Typically, this energy is lower than was used for the first introducing step. For dielectric discharge, this energy is defined as the power of the dielectric discharge multiplied with its duration, for laser ablation it is the product of intensity and duration. Controlling both, power and duration of the remodifying step, at least two important properties of the resulting remodifϊed surface of the structure and its surrounding can be adjusted: (1) the higher power or duration, the larger the size of the region where the surface modifying material is removed or possibly transformed/reacted, and (2) controlling energy (e.g. voltage, current and duration for dielectric discharge, intensity for laser ablation) properly, a partial removal/transformation/reaction of surface modifying material can be achieved that allows to define precisely surface properties in that region such as hydrophobicity and binding affinities. In a preferred embodiment, surface properties are restored in said region by said second introducing step that were present prior to the modifying step. Preferably, said second introducing step occurs by a method, such as controlled dielectric breakdown (controlled high voltage discharge), which by itself centers remodification in and/or around said structure and which remodifies the surface in and/or around said structure.

Preferably the power, power dissipation and/or power duration used for the first and/or second introducing step is chosen such as to define the spatial extension of said region where altered surface properties are to be removed, and/or is chosen such as to define a surface density of said compound or composition of compounds applied by said modifying step and remaining after said introducing step(s) in said region.

It is preferred that the power, power dissipation and/or power duration is chosen such as to produce within said region a density gradient of said compound or composition of compounds applied by said modifying step, wherein, preferably, said density gradient shows the lowest density in and/or nearest to said structure and a density increasing with distance from said structure, preferably up to density achieved by the modifying step, more preferably in a radial fashion around said structure.

In one embodiment, said modifying step occurs at the same time as said first introducing step and/or, if present, at the same time as said second introducing step, preferably by performing said introducing step(s) in a gaseous atmosphere of said compound or composition of compounds, or their precursor(s). Such precursors, upon activation by e.g. heat, undergo a reaction and form the desired compound(s) as surface modifying material. Structure formation and/or remodification in gaseous atmosphere allows for a chemical reaction initiated by the structure forming energy. For this, gas composition and pressure are controlled in such a way that (ionized) gas molecules interact with the substrate surface in a manner beneficial for the intended application, thus leading to a surface modification at the structure and its surrounding, the size of the latter depending on the energy content and density and composition of the gaseous atmosphere. This modification may also involve a deposition and can, in some aspects, be considered a strongly localized chemical vapor deposition.. This process can be complementary to the one already described. No special description will be made because all statements made in this application apply accordingly. However it must be noted that no prior surface modification, i.e. prior to the structure introducing step, is required to obtain patterned surfaces. Examples include electric discharges and laser ablation in an atmosphere containing precursors of the surface modification material that react upon activation, e.g. due to temperature increase, on the substrate surface. Having a nearly inert atmosphere containing additional oxygen (e.g. air), the modification/remodification process becomes an oxidation as used otherwise in this application.

In one embodiment, separation of the structure introducing step and the surface remodification step is done solely by time separation, that is after structure formation the substrate remains in the structure producing device where it is surface modified and thereafter subjected to a second introducing step by the device (which acts as a remodifying step only), now altering the surface in and around the structure produced before. Consequently, no re-placement and realignment of the substrate inside the device is required for this surface remodification.

One aspect of the method and device according to the present invention is based on the fact that if structure formation (in particular for structures fully traversing the substrate) and surface remodification are separated, electric discharge methods have inherent advantages for surface remodification in that they focus in and/or around the structures previously created. In electric insulators the path of DC and low frequency (up to several tens of kHz) electric discharges follows the route where materials are most easily ionized. Consequently, using DC or low frequency discharges for surface remodification in gaseous surroundings, the discharge path will follow the previously created structure even if the substrate is not precisely aligned between the electrodes. Tests showed that for DC discharges (usually 2 - 30 kV), the path went through the structure even if placed 2 - 5 mm off the electrode axis. This important feature of this invention allows also to remodify surfaces of substrates containing even the smallest substrate-passing structures made with any method. In other words, even for structures as small as 1 μm and less, the requirement for spatial adjustment within the remodifying setup (i.e. structure alignment with electrode axis) can be in the range of a few millimeters and consequently several orders of magnitude less critical as for established methods. Controlling the discharge parameters such as voltage, frequency and electrode distance and shape the set-up can be adjusted so as to have a spatial resolution of this remodifying step that adapts perfectly to the spacing between the structures on the substrate allowing to exclusively access single substrate structures if required.

Preferably, said structure has dimensions, preferably a diameter (or the length of the smallest spatial extension in case of a more rectangular structure), in the range of from 0.01 μm to 500 μm, preferably in the range of from 0.01 μm to 50 μm, more preferably 0.1 μm to 10 μm and even more preferably 0.3 μm to 5 μm.

In one embodiment, that frequently relates to patterning to reduce unspecific binding said region in which said structure is introduced has an area in the range of from 0.005 μm² to 10 mm², preferably 0.01 μm² to 1 mm², more preferably 0.1 μm² to 0.1 mm², and even more preferably 0.3 μm² to 0.02 mm².

The objects of the present invention are also solved by a device for performing the method according to the present invention comprising:

- means for modifying a surface of a substrate so as to alter the surface properties of said substrate, wherein, preferably, said means are means to deposit a compound or composition of compounds on said substrate,

- means for introducing a structure, preferably a hole or cavity or channel, in a region in said substrate by a method which does not alter the surface properties of said substrate outside of said region, but which, preferably, alters the surface properties of said substrate within said region.

Preferably, the device according to the present invention further comprises:

- means for remodifying a surface of or in said structure and/or for remodifying a surface of or in said region surrounding the structure, wherein, preferably, said remodifying means are the same as said means for introducing a structure, which after introducing a structure in a first structure introducing step are adjusted, preferably by computer, so as to serve appropriately the purpose of surface remodification. In a preferred embodiment, said remodifying means are adjusted so as to not introduce a new structure, but to only remodify said surface of or in said structure, and/or for remodifiying a surface of or in said region. Preferably, all three steps are performed inside the device having the substrate and the means for structure formation and surface remodification spatially fixed during the entire process.

In a preferred embodiment said means for remodifying are means that center remodification by inherent physical properties of said structure or by inherent physical properties on said surface of said structure and/or of said region even when said substrate is slightly misaligned inside the device. Preferably, such means are means to generate controlled electric discharge(s), preferably under control of a computer, more preferably under control of a computer in conjunction with appropriate AD/DA conversion hardware and analog and digital control circuitry.

hi one embodiment said means for introducing a structure and surface remodification are means to generate a controlled dielectric breakdown (controlled electric discharge(s)), preferably comprising electrodes placed on opposite sides of said substrate, preferably under computer control, preferably in conjunction with appropriate AD/DA conversion hardware and analog and digital control circuitry, or said means for introducing a structure are a laser. The laser beam is usually focused at the substrate site where structure formation is initiated.

The present invention provides the basis for a substrate, preferably a dielectric substrate, having a structure (as defined above), preferably a hole or cavity or channel, in a region of said substrate (as defined above), produced by the method according to the present invention, characterized in that said region of said substrate has surface properties which are different to surface properties of said substrate outside of said region and wherein, preferably the extension, more preferably the radial extension of said region, may be below 1 micrometer and/or the region may possess a radially oriented density gradient of substrate surface modifying material, having the lowest density adjacent to the structure. In a preferred embodiment, the radial extension of said region from the rim of the structure (e.g. hole perimeter) to the outer region boundary can be exceedingly small, e.g. below the wavelength of light. Consequently, this enables the involvement/production of regions/structures not amenable to typical photolithography. Preferred substrate materials include glass, glass like materials such as quartz and siliconnitrid as well as many polymers such as polyoleofins and Teflon.

The present inventors have found that by combining structure-introducing steps that can be locally focussed and concentrated, together with surface modifying steps, allows for the production of substrates having structures such as holes in them, wherein local differences in surface properties can be precisely defined. Preferred structure-introducing steps according to the present invention are shot based methods such as electric discharge/dielectric breakdown and laser ablation methods, as for example disclosed in PCT/EP2005/003319, filed on March 30, 2005. The dielectric breakdown methods (DEB) disclosed in this application are explicitly referred to herein and incorporated herein by reference. Hence, whenever, the present application talks about dielectric breakdown methods, a method is implied as disclosed in PCT/EP2005/003319 in various embodiments. As stated before, electric discharge methods have been found to comprise the advantage of requiring only rather crude alignments if a remodification step is invoked.

Micromachining techniques and devices used to e.g. produce holes, channels and other (micro-)structures in substrates usually remove or at least strongly disturb, due to pre- and postprocessing steps (e.g. cleaning) and other requirements like photoresistive and/or metal coatings, most original surface properties or 'information'. Therefore, modification of such surfaces prior to the most conventional machining steps is not advised. However, specific surface properties of areas surrounding structures machined in substrates, to e.g. define regions surrounding such structures where aqueous solutions will adhere to, are often required. The present inventor has found an elegant solution to combine the two processes, that is surface structuring and modification, can be achieved with machining methods not disturbing globally the substrate surface properties. Such methods are e.g. shot methods such as local laser ablation or electric discharge/dielectric breakdown (PCT/EP2005/003319, filed on March 30, 2005). The invention consists of two main steps: (1) modification of the substrate surface area of interest (for simplicity often the entire surface) and (2) spatially localized micromachining. The order of these steps may be altered in specific embodiments (see also below). By definition, micromachining/structuring of the substrate usually exposes new, unmodified substrate material at the surface of the region where structuring takes place. The surface properties generated by such micromachining/structure introducing step are thus either the pristine surface properties that were originally prevalent for the substrate or an appropriately altered surface modifying material. Consequently, the surface at the structured/micromachined site usually exposing native substrate material is surrounded by a substrate surface defined by the surface modification step.

hi cases where energies released during the micromachining step (first introducing step) are of such a magnitude as to create too much of a change of the surface modification (e.g. area too large), the surface modification step can follow the micromachining step. However, the micromachining step is repeated after this modification with an energy appropriate for the intended remodification of modified surface (second introducing step). Since no structuring will take place in this second micromachining step, energies required relate solely to surface modification or removal of modified surfaces. An example is the removal of silanes or Teflon surrounding a hole on a silanized/teflonized surface by electric discharge as described further above. In some situations it was useful to (1) produce a hole in a (glass) substrate (2) silanize the surface and (3) use the same or a similar hole producing device and method with a lower energy, e.g. achieved by current limitation with a high resistance (e.g. 10 GOhm) in series with the electrodes. During the remodifying step, time, voltage and current were controlled to define the correct energy density and duration which defined in turn the extension of the area where silane was removed.

Figures:

Figure 1 illustrates schematically a substrate (1) having a modified surface with a modifying material (2), that, after undergoing the presented micromachining method, exhibits a structure

(3) and a region (4) surrounding this structure being freed of the surface modifying substances/compounds.

Figure 2 illustrates a typical embodiment for creating both a substrate structure and localized substrate surface remodification using electrical discharge. Using one method, the surface modified substrate (1) is placed between the electrodes (5) and a controlled electric discharge (using a controlled high voltage supply (6), preferably computer controlled) removes substrate material as well as surface material surrounding this structure, performing effectively the micromachining step indicated in Figure 1. The method may be performed in a defined gaseous atmosphere (7). Instead of using electric discharge, other shot methods such as laser ablation or FIB can equally well be used. Alternatively, a structure is created inside an unmodified substrate, which thereafter is surface modified and placed back between the electrodes (or any other shot device) to solely remove surface material. Adjusting the energy (e.g. voltage, maximum current and duration of the power application in case of electric discharge structuring), this second method allows to control precisely the amount of surface material removed. Both, the size of the affected region and the rate and duration (leading to a controlled density of the surface modifying material on the substrate surface) with which material is removed can be precisely controlled.

Figures 3, 4 and 5 provide exemplary images illustrating the alignment between structure and remodified surface.

Figure 3 shows a hole structure surrounded by remodified glass surface surrounded by a modified glass surface. A glass slide (Menzel Sl) was cleaned and one layer of red paint (Staedtler LUMOCOLOR M 317) was added to the upper surface. Subsequently a d = 1.5 μm hole was introduced according to PCT/EP2005/003319. The high temperature of the electric arc as well as the activated atmospheric gas molecules (i.e. plasma) lead to a removal of paint at and near the created hole structure. The continuous fading of red colour shown in the figure by a fading of the greyness towards the hole indicates a gradient of the density of colour molecules caused by the introducing step. Scale bar 200 μm.

Figure 4 shows a hole structure made in an unmodified glass slide; after this (first) structure introducing step the entire surface was covered by one layer of red paint (Staedtler LUMOCOLOR M 317) (surface modifying step) Scale bar 50 μm. One can see that the color is evenly distributed over the entire surface including the region where the hole structure has been introduced.

Figure 5 shows the glass slide of Figure 4 after performing a second introducing step (2ⁿ introducing step according to PCT/EP2005/003319); reduction of the energy content of the 2^nd introducing step when compared to the first results in a smaller region around the structure where paint is removed.

The features of the present invention disclosed in the specification, the claims and/or in the accompanying drawings, may, both separately, and in any combination thereof, be material for realizing the invention in various forms thereof.

Claims

1. A method of manufacturing a substrate having a structure, preferably a hole or cavity or channel, in said substrate, said substrate having a surface, said method comprising the steps:

- modifying said surface of said substrate so as to alter the surface properties of said substrate,

- introducing a structure, preferably a hole or cavity or channel, in a region in said substrate by a method which alters the surface properties of said substrate within said region but not outside of said region.

2. The method according to claim 1, characterized in that said modifying said surface of said substrate occurs by application of a layer of a compound or of a composition of compounds to said surface, or by abrasion of said surface.

3. The method according to claim 2, characterized in that application of layer of a compound or of a composition of compounds to said surface occurs by sorption or covalent binding, including processes such immersion of said substrate in a solution or atmosphere of said compound or said composition of compounds, drop casting, spin coating, doctor blading, Langmuir Blodgett techniques, and vapor deposition of said compound or composition of compounds on said substrate.

4. The method according to any of the foregoing claims, characterized in that said modifying said surface of said substrate is done on said surface in a defined area, preferably on said surface of said substrate in its entirety.

5. The method according to claim 4, characterized in that said defined area at least partially surrounds said region where said structure is introduced, or characterized in that said defined area is adjacent to said region where said structure is introduced.

6. The method according to any of the foregoing claims, characterized in that said region in which said structure is introduced has an area in the range of from 0.005 μm² to 10 mm , preferably 0.01 μm² to 1 mm², more preferably 0.1 μm² to 0.1 mm², and even more preferably 0.3 μm² to 0.02 mm².

7. The method according to any of the foregoing claims, characterized in that said modifying occurs before introducing said structure.

8. The method according to claim 7 characterized in that said introducing said structure removes any altered surface properties resulting out of said modifying said surface, in said region where said structure is introduced, thereby effectively restoring surface properties that were present prior to the modifying step, or, in addition thereto, also removing any contaminants from said region, such as dust particles etc., in those circumstances where such contaminants were present prior to the modifying step.

9. The method according to any of claims 1-6, characterized in that said modifying occurs after introducing said structure (first introducing step), and thereafter a second introducing step is performed in said region, at an energy chosen such that no new structure is created but that said surface properties altered by said modifying step in said region are remodified, e.g. removed in said region where said structure has been introduced, and/or in said structure itself.

10. The method according to claim 9, characterized in that said second introducing step is performed in said region at an energy lower than was used for the first introducing step.

11. The method according to any of claims 9-10, characterized in that by said second introducing step surface properties are restored in said region that were present prior to the modifying step.

12. The method according to any of claims 9-11, characterized in that said second introducing step occurs by a method, such as controlled dielectric breakdown (controlled high voltage discharge), which by itself centers remodification (i.e. energy dissipation) in and/or around said structure and which remodifies the surface in and/or around said structure.

13. The method according to any of claims 9-12, characterized in that the power, power dissipation and/or power duration used for the first and/or second introducing step is chosen such as to define the spatial extension of said region where altered surface properties are to be removed, and/or is chosen such as to define a surface density of said compound or composi- tion of compounds applied by said modifying step and remaining after said introducing step(s) in said region.

14. The method according to any of claims 9-13, characterized in that the power, power dissipation and/or power duration is chosen such as to produce within said region a density gradient of said compound or composition of compounds applied by said modifying step.

15. The method according to claim 14, characterized in that said density gradient shows the lowest density in and/or nearest to said structure and a density increasing with distance from said structure, preferably up to a density achieved by the modifying step, more preferably in a radial fashion around said structure.

16. The method according to any of claims 3-6, 9-15 characterized in that said modifying step occurs at the same time as said first introducing step and/or, if present, at the same time as said second introducing step, preferably by performing said introducing step(s) in a gaseous atmosphere of said compound or composition of compounds or their precursors.

17. The method according to any of the foregoing claims, characterized in that said introducing step(s) is (are) selected from the group of shot based methods, such as local laser ablation methods or electric discharge methods or dielectric breakdown methods.

18. The method according to any of the foregoing claims, characterized in that said structure has dimensions, preferably a diameter or length of the smallest spatial extension, in case of a more rectangular structure, in the range of from 0.01 μm to 500 μm, preferably in the range of from 0.01 μm to 50 μm, more preferably 0.1 μm to 10 μm and even more preferably 0.3 μm to 5 μm.

19. A device for performing the method according to any of claims 1-18, comprising:

- means for modifying a surface of a substrate so as to alter the surface properties of said substrate,

20. The device according to claim 19, wherein said means for modifying a surface of a substrate are means to deposit a compound or composition of compounds on said substrate.

21. The device according to any of claims 19-20, characterized in that said means for introducing a structure are means to generate a controlled dielectric breakdown (controlled electric discharge), preferably comprising electrodes placed on opposite sides of said substrate, or said means for introducing a structure are a laser.

22. The device according to any of claims 19-21, further comprising means for re- modifying a surface of said structure and/or for re-modifying a surface of said region.

23. The device according to claim 22, characterized in that said means for re-modifying are the same as said means for introducing a structure, which after introducing a structure in a first step are adjusted, preferably by a computer, so as to not introduce a new structure but so as to only re-modify said surface in said structure and/or in said region.

24. The device according to any of claims 22-23, characterized in that said means for re- modifying are means that center remodification by inherent physical properties on said surface of said structure and/or of said region, even when said substrate is slightly misaligned in said device.

25. The device according to claim 24, characterized in that said means for re-modifying are means to generate controlled electric discharge(s), preferably comprising electrodes placed on opposite sides of said substrate.

26. A substrate, having a structure, preferably a hole or cavity or channel, in a region of said substrate, produced by the method according to any of claims 1-18 and/or by the device according to any of claims 19-25, characterized in that said region of said substrate has surface properties which are different to surface properties of said substrate outside of said region, and wherein, preferably, the extension, preferably the radial extension of said region may be below 1 micrometer and/or the region may possess a radially oriented density gradient of substrate surface modifying material having the lowest density adjacent to the structure.