WO2009152562A1

WO2009152562A1 - A method of fabricating a micro-cavity in a solid

Info

Publication number: WO2009152562A1
Application number: PCT/AU2009/000764
Authority: WO
Inventors: Jennifer Forrester; Heather Goodshaw; Erich Kisi; Gregg Suaning
Original assignee: Newcastle Innovation Limited
Priority date: 2008-06-16
Filing date: 2009-06-16
Publication date: 2009-12-23

Abstract

The present invention provides a method (1) of fabricating a shaped micro-cavity in a solid, the method comprising the steps of milling a base material to be formed into the solid (2), locating a template at least partially within the milled material (3), and sintering the template and milled material to form the solid (4), such that the template diffuses into the milled material to form the micro-cavity having a shape substantially corresponding to the shape of the template. The invention also provides a device, a biocompatible medical device and a micromachine having a micro-cavity produced according to the method.

Description

"A METHOD OF FABRICATING A MICRO-CAVITY IN A SOLID"

FIELD OF THE INVENTION

The present invention relates to a method of fabricating a micro-cavity in a solid body and devices containing one or more of such micro-cavities. It has been developed primarily for producing micro-cavities in biocompatible ceramics suitable to manufacture medical devices, and will be described hereinafter with reference to this application. However, it will be appreciated that the invention is not limited to this particular field of use, and may extend to the production of other devices containing micro-cavities for other applications, such as filtration membranes and catalytic devices.

BACKGROUND TO THE INVENTION

There is widespread interest in a variety of micro-devices for applications in medicine, biology, chemistry, physics and engineering. Potential applications include implantable micro-fluidic systems (e.g. drug delivery devices, micro-biological sensors, artificial vestibular systems, etc.), instrumentation (e.g. flow measurement and pressure transducers) and micro-machines (e.g. micro -internal combustion engines, Micro Electro-Mechanical Systems or MEMS, etc).

These devices often involve internal cavities (channels, tubes, chambers, nozzles) for the storage, transport and manipulation of fluids. As devices with greater and greater intricacy have been designed, the fabrication of the associated complex internal cavities has become problematic.

Current methods for producing micro-devices with internal cavities rely upon thin film methods whereby layers of material are added to a suitable substrate. Methods for depositing thin films include the various forms of physical vapour deposition (PVD) and chemical vapour deposition (CVD). With the addition of masks, selective chemical etching or laser ablation, channels and open cavities are formed. Successive layers then cap the internal structure of the device to enclose the cavity and complete the fabrication. Substrates are typically single crystal silicon or sapphire wafers and therefore thin film deposition must be conducted under ultra-clean conditions.

Although successful at producing many types of device, these methods have a number of inadequacies. These include but are not restricted to: i) the costs associated with thin film methods are very high; ii) the internal cavities are limited to prismatic shapes, for e.g. flow channels are of square or rectangular cross-section, or internal chambers are rectangular prisms, etc.; iii) channels joining different parts of the device must generally travel either parallel or perpendicular to the plane of film deposition; iv) the surface structure of the internal channels or cavities cannot be controlled; and vii) the range of materials that may be successfully deposited is limited and many are not biocompatible.

It has been particularly difficult to apply these current methods to ceramics, such as alumina (Al₂O₃). Ceramics have been broadly applied in industry for their useful properties. In particular, alumina is widely used because it is electrically insulating and chemically inert, and has good high temperature properties, such as creep resistance. It is also one of the hardest materials and is generally believed to be superior to other biocompatible materials for bone-contacting implants, because of the greater in vivo affinity of bone to alumina. A method for creating complex micro -cavities in ceramic and related materials is of great interest in a wide range of applications.

In particular, in the biomedical field there is considerable interest in the development of composite devices having micro-cavities using both biocompatible metallic and ceramic components, such as titanium and alumina. One area of interest is to provide devices sufficiently strong and durable to be implanted in the human body for long periods of time without replacement or repair, while at the same time biocompatible with the recipient of the device. Such devices have been generally produced by using graded glass seals or brazing or diffusion-bonding components made from the individual materials. A problem with this approach has been that the metallic and ceramic components are typically produced separately and then subsequently assembled. This increases to the cost of producing such composite devices. It is an object of the present invention to overcome or ameliorate at least one of the disadvantages of the prior art, or to provide a useful alternative.

SUMMARY OF THE INVENTION

According to a first aspect of the invention, there is provided a method of fabricating a micro-cavity in a solid, the method comprising the steps of: milling a base material to be formed into the solid; locating a template at least partially within the milled material; and sintering the template and milled material to form the solid, such that the template diffuses into the milled material to form the micro-cavity having a shape substantially corresponding to the shape of the template.

Unless the context clearly requires otherwise, throughout the description and the claims, the words "comprise", "comprising", and the like are to be construed in an inclusive sense as opposed to an exclusive or exhaustive sense; that is to say, in the sense of "including, but not limited to".

Preferably, the solid is selected from the group consisting essentially of a ceramic, a metal, an alloy or an intermetallic compound. Throughout the description and claims, the word "ceramic" is taken to mean any inorganic material that is a chemical compound of one or more metallic elements with one or more non-metallic elements that is resistant to chemical attack and can survive high temperatures.

Preferably, the template defines a conduit within the solid for conveying a fluid. More preferably, the template defines a plurality of conduits within the solid for conveying a fluid.

Alternatively, the template defines a path for growing an organic material within the micro-cavity. In one preferred form, the organic material comprises tissue or bone.

In a further alternative, the template defines a path for electrical conduction.

Preferably, the template defines a reservoir for containing or holding fluid. Preferably, the micro-cavity is enclosed within the solid. Alternatively, the micro- cavity is partially enclosed within the solid. In one preferred form, the micro-cavity extends through the solid to an outer surface to define an opening in the solid. In another preferred form, the micro-cavity extends through the solid to define a passage or conduit. More preferably, the micro-cavity defines two openings of the passage or conduit.

Preferably, the template diffuses into the milled material so as to form a boundary layer surrounding the micro-cavity and having an inner surface. Preferably, the inner surface is chemically active. In one preferred form, the inner surface is a catalytic surface for reacting with fluid conveyed within the micro-cavity. In this particular preferred form, the ceramic is formed for use in a catalytic device.

Preferably, the template is a metallic template. Preferably, the composition of the metallic template is selected from the group consisting essentially of zirconium, titanium, iron and nickel. In a particularly preferred form, the metallic template is composed of titanium. The template may adopt any number of shapes, including complex shapes. For example, the template preferably has a shape selected from the group consisting essentially of geometrical shapes, polygons, lattice-type structures and network-type structures.

In one preferred form, the template is a metallic wire. Preferably, the wire has a diameter of approximately between 10 μm and 500 μm. In one preferred form, the wire has a diameter of at least 125 μm. In another preferred form, the wire has a diameter of at least 500 μm. The choice of diameter is determined by the desired diameter of the end cavity, the material comprising the template, and the time and temperature of sintering. In other words, the diameter of the wire is selected according to the desired diameter of the micro-cavity, the material comprising the template, the time of sintering, the temperature of sintering or any combination thereof.

Preferably, the micro-cavity has dimensions that are proportionate to the dimensions of the template. In one preferred form, the micro-cavity has dimensions that are proportionately less than the dimensions of the template. In another preferred form, the micro-cavity has dimensions that are proportionately greater than the dimensions of the template. In a further preferred form, the micro-cavity has dimensions substantially the same as the dimensions of the template.

Preferably, the milling step comprises mechanically milling the base material.

Preferably, the milling step comprises milling the base material into a powder having a crystallite size of approximately 5 to 100 nm, preferably 10 to 60 nm, more preferably 12 to

40 nm, even more preferably 12 to 20 nm. Preferably, the milling step comprises milling the base material approximately between 1 and 64 hours, preferably approximately between 2 and 64 hours, more preferably approximately between 4 and 32 hours, even more preferably approximately between 4 and 24 hours and yet more preferably approximately between 4 and 16 hours. Preferably, the milling step comprises milling the base material with a milling medium to base material ratio of approximately between 3:1 and 30:1, preferably approximately between 10:1 and 25:1 and more preferably 20:1.

Preferably, the milling step comprises milling the base material with a non-ferrous milling medium. Alternatively, the base material is milled with a ferrous milling medium. Preferably, the milling medium is hardened steel. In this case, the method further comprises the step of cleaning the milled material to remove iron contaminants. Preferably, the cleaning step comprises using an acid to leach out the iron contaminants. More preferably, the acid is an inorganic acid. In one preferred form, the inorganic acid is selected from the group consisting essentially of hydrochloric acid, sulphuric acid and nitric acid. Alternatively, the acid is an organic acid. In one preferred form, the organic acid comprises acetic acid.

Preferably, the milling medium has the substantially same composition as the base material. Alternatively, the milling medium has negligible solubility in the base material. Preferably, the milling medium is selected from the group consisting essentially of hardened steel, alumina (Al₂O₃), zirconium dioxide (ZrO₂) and bonded tungsten carbide (WC). Where the base material is alumina, it is preferred that the milling medium is alumina (Al₂O₃), zirconium dioxide (ZrO₂) or steel.

Preferably, the method further comprises the step of compressing the milled material and the template before or during the sintering step. Preferably, the compressing step comprises mechanically compressing the milled material and the template. In one preferred form, the compressing step comprises hot-pressing or hot-iso statically pressing.

Preferably, the method further comprises the step of moulding the milled material to form a shape for the solid. Preferably, the moulding step comprises placing the milled material in a mould. Preferably, the moulding step is performed before or simultaneously with the compressing step.

Alternatively, the moulding step is performed before or simultaneously with the locating step. Where the moulding step is performed simultaneously with the locating step, moulding is performed using slip casting or gel casting.

Preferably, the locating step comprises embedding the template into the milled material. Preferably, the locating step comprises locating the template between two layers of the milled material. Preferably, the locating step comprises laying a first layer of the milled material, placing the template on the first layer and laying a second layer of the milled material onto the first layer and the template. Preferably, the layers are compressed before the sintering step.

Preferably, the sintering step comprises sintering the milled material and the template until a predetermined temperature is reached. Where the base material is alumina and the template is composed of titanium, the predetermined temperature is approximately between 1100 and 1500⁰C, preferably approximately between 1130 and 1350°C. More preferably, the sintering step further comprises continuing sintering at 1350°C for between 0 minutes and 24 hours. Even more preferably, the sintering step comprises sintering for 30 minutes, preferably 1 hour, more preferably 2 hours, even more preferably 4 hours and yet more preferably 8 hours.

Preferably, the base material is selected from the group consisting essentially of alumina, titanium dioxide (TiO₂), zirconium dioxide (ZrO₂) and other suitable ceramics. In a particularly preferred form, the base material is alumina.

According to a second aspect, there is provided a device having a micro-cavity produced according to the method of the first aspect. Preferably, the device is adapted for use as a medical device. Alternatively, the device is a catalytic device. Alternatively, the device is a filter.

According to a third aspect, there is provided a biocompatible medical device having a micro-cavity produced according to the method of the first aspect.

According to a fourth aspect, there is provided a micromachine having a micro-cavity produced according to the method of the first aspect.

By milling the base material prior to sintering, it has been unexpectedly and surprisingly discovered that when a template is located within the pre-milled base material and is sintered to form the solid, the template substantially diffuses into the surrounding milled material, leaving a regularly shaped micro-cavity of substantially the same dimensions as the template in the solid. It is believed that this cavity formation is due to a type of Kirkendall effect, where due to the prevailing diffusion conditions, the Kirkendall porosity is concentrated in the centre of the template rather than at the boundary between the template and the base material, as would occur with an unmilled base material. It is also believed that milling the base material changes its physical and chemical properties by creating a nano-crystalline size and high defect concentration that unexpectedly and surprisingly control the micro-cavity formation effect.

BRIEF DESCRIPTION OF THE DRAWINGS

Preferred embodiments of the invention will now be described, by way of example only, with reference to the accompanying drawings in which:

Figure 1 is a schematic diagram illustrating the method according to the invention;

Figure 2 is a schematic diagram illustrating the method according to one embodiment of the invention;

Figure 3 is an exploded schematic diagram of the ceramic in the mould in accordance with the method of Figure 2; Figure 4 shows backscattered electron (BSE) micrographs of cross-sections through sintered compacts comparing control samples (Figures 4a and 4b) with an example made in accordance with the method of Figures 2 and 3 (Figure 4c);

Figure 5 shows energy dispersive (fluorescent X-ray) spectra (EDS) for the diffusion zone of Figure 4c.

Figure 6 shows BSE micrographs of cross-sections through sintered compacts for two examples (Figures 6a and 6b) made in accordance with the method of Figures 2 and 3;

Figure 7 shows a BSE micrograph of a cross-section through a sintered compact for an example made in accordance with the method of Figures 2 and 3;

Figure 8 is a schematic diagram illustrating the method according to another embodiment of the invention;

Figures 9 to 14 show BSE micrographs of cross-sections through sintered pellets of examples made in accordance with the method of Figure 8;

Figure 15 show (a) a secondary-electron micrograph and (b) a BSE micrograph of the end of a sintered pellet of an example made in accordance with the method of Figure 8;

Figure 16 show (a) a secondary-electron micrograph and (b) a BSE micrograph of a section of the sintered pellet of Figure 15, cut longitudinally with respect to the micro-cavity;

Figure 17 show a BSE micrograph of a cross-section through a sintered pellet of an example made in accordance with the method of Figure 8;

Figure 18 is a schematic diagram illustrating a drug delivery device fabricated according to an embodiment of the invention; and

Figures 19a to 19i show some possible configurations for the templates used in the method of the invention. PREFERRED EMBODIMENTS OF THE INVENTION

A preferred application of the invention is in the field of biocompatible medical devices suitable for implantation or insertion into the human body. As titanium and alumina are suitable biocompatible materials, and have similar coefficients of thermal expansion, co- firing these materials can lead to suitably dense ceramic composite products. Although the embodiments of the invention described below have focussed on the co-firing of titanium and alumina, it will be appreciated by one skilled in the art that the invention is readily applicable to other solid materials, solid/solid combinations or metal/ceramic combinations, such as nickel and zirconium dioxide.

Referring to Figure 1, a method 1 of fabricating a micro-cavity in a ceramic comprises the steps of milling a base material to be formed into the ceramic (step 2), locating a template at least partially within the milled material (step 3), and sintering the milled material and template to form the ceramic (step 4), such that the metal template diffuses into the milled material to form the micro -cavity having a shape substantially corresponding to the shape o f the template .

The method of the invention has found particular application to the sintering of a metallic template within a ceramic to produce a composite product having a micro-cavity substantially the same dimensions as the template. As discussed above, it is believed that sintering of the metal template and the milled material results in the metal template substantially diffusing into the milled material via the Kirkendall effect, leaving a cavity behind in the formed ceramic substantially corresponding to the shape of the metal template. The Kirkendall porosity effect describes the diffusion of different chemical species at different rates when heated. In the invention, it is believed that the cavity formation is a type of Kirkendall porosity which results when co-diffusing species travel in opposite directions at quite different rates. Vacancies left behind by the faster diffusing species coalesce into pores and in the invention into larger cavities.

Figures 2 and 3 illustrate an application of the method of Figure 1 in one preferred embodiment, where corresponding features have been given the same reference numerals. In this particular application, the method is applied to form a substantially cylindrical tubular passage in an alumina ceramic using a titanium wire as a template for the passage. The method is first performed by mechanically milling the alumina material at step 2 with a milling medium for 16 hours to produce a fine alumina powder having a crystallite size in the range 5-100 nm. At step 5, a first layer 6 of the milled alumina powder is laid in a bottom half 7 of a mould 8. At step 9, a 10 mm long titanium wire 10 having a diameter of 125 μm is laid on the first alumina layer 6. At step 11, a second layer of the milled alumina powder 12 is laid on top of the first layer 6 and the wire 10. A top half 13 of the mould 8 is then placed on top of the layers. At step 14, the composite layers are then compressed in the mould 8 at approximately 30 MPa for one minute. At step 4, the layers 6 and 12 and the titanium wire 10 are sintered in air at 1350°C for 4 hours to form the ceramic. After sintering, it was surprisingly and unexpectedly discovered that the titanium wire 10 had diffused completely within the milled alumina material, comprising the first layer 6 and the second layer 12, so as to leave a cavity behind in the formed ceramic substantially corresponding to the shape of the titanium wire 10, thus producing a tubular passage within the ceramic.

This method of Figures 2 and 3 was repeated using three wires 10 arranged parallel between the first layer 6 and the second layer 12 with the same results. Examples of ceramics made with regularly shaped micro -cavities in accordance with the method of Figures 2 and 3 are described below.

In the examples, a base powder was mechanically milled for 16 hours in a SPEX8000 high energy mixer-mill with a milling ball to powder ratio of 20:1. Three titanium wires 10 mm long and 125 μm in diameter were completely encased within powder compacts formed with the milled powder using a steel die as the mould. Each of the first and second layers was evenly spread in the die and hand pressed. The layers were then compressed uniaxially at 30 MPa for approximately 1 min. The formed compacts were placed in alumina crucibles with lids and sintered in air at 1350°C for 4 hours.

Examples 1 to 3 used alumina powder (corundum structure, 99.9% purity (ie. < 0.1% by weight of impurities), Aldrich Pty Ltd) with different milling media. Example 1 was milled with hardened steel balls, Example 2 was milled with alumina balls and Example 3 was milled with zirconium dioxide milling balls. Example 4 replaced the alumina powder with zirconium dioxide (99.9%), which was milled for the same time with zirconium dioxide milling balls. For comparison purposes, two control compacts were produced, one being an unmilled alumina powder from Aldrich Pty Ltd and the other being a slipcast alumina powder from Sumitomo Japan (AKP-50, 99.99%, particle size 500nm). A summary of the powders used and their preparation in these examples is given in Table 1.

Table 1

As shown in Table 1 above, the AKP-50 slip cast compacts was pre-treated differently and thus was slowly sintered at a higher temperature of 1450°C for 2 hours.

The sintered compacts were then sectioned perpendicular to the wires and polished, generally to approximately 6 μm, for scanning electron microscope (SEM) analysis. All samples for SEM were carbon coated prior to examination. For quantitative backscattered electron (BSE) analyses, the compacts were embedded in epoxy resin and polished to a 1 μm finish using diamond paste. BSE images were obtained using a Philips XL30 scanning electron microscope, operated at 15 kV. Energy Dispersive fluorescent x-ray Spectra (EDS) were recorded using an Oxford ISIS Si/(Li) energy dispersive spectroscopy detector. A comparison between Ti wires sintered in alumina of different origins demonstrates that the diffusion of the titanium wire into the surrounding ceramic material and subsequent formation of micro-cavities was effective where the alumina had been pre-milled. Figure 4 shows BSE micrographs of cross-sections through sintered compacts, with Figure 4a being a BSE micrograph of Control 1 (unmilled alumina), Figure 4b being a BSE micrograph of

Control 2 (AKP-50 alumina slip) and Figure 4c being a BSE micrograph of Example 1

(milled alumina powder). It can be seen from these figures that while there has been some diffusion of the titanium wire 10 into the surrounding ceramic 16 to form a diffusion zone

17, a shaped micro-cavity 18 is formed only where the alumina powder has been milled prior to sintering.

In the case of Control 1, there is abundant cracking and porosity in the alumina matrix 16 due to the sintering temperature being insufficient to form a dense ceramic from unmilled and undoped alumina powder. In addition, the titanium wire 10 appears to be still present in the alumina, as best shown in Figure 4a. It is believed that the voids are formed both internally in the titanium wire in the form of extended radial pores and externally to the wire at the titanium-alumina interface. The formation of an annular cavity 19 between the titanium and the alumina effectively prevents any further diffusive transfer of titanium into the surrounding alumina.

In relation to Control 2, the alumina in the sintered AKP-50 compact is much denser and relatively defect free compared to the unmilled alumina in Figure 4a and the titanium wire appears more intact, as best shown in Figure 4b. However, an annular cavity 19 has formed around the titanium wire 10 and hampered further diffusion.

In stark contrast to Control 1 and Control 2, in Example 1 the titanium wire 10 has almost completely diffused into the surrounding alumina 16 leaving behind the cylindrical cavity 18, which was completely enclosed within the sintered alumina compact before sectioning.

In addition, the diffusion zone 17 is composed of an inner ring 20 and an outer ring 21, as best shown in Figure 4c. Typical EDS spectra from the two rings 20 and 21 are shown in Figure 5, where it can be seen that the inner ring only shows titanium (Figure 5a), suggesting that the only remnant of the wire 10 is found in this inner ring 20. Unlike the compacts prepared using unmilled alumina (Control 1 and Control 2), the diffusion zone 17 appears to be a compound. The EDS spectrum for the outer ring 21 of the diffusion zone 17 appears to have a ratio of aluminium to titanium of approximately 2:1, as best shown in Figure 5b. Eight areas within the outer ring 21 were analysed using quantitative EDS, and the results of these analyses are shown in Table 2 on the basis that the compound is an oxide.

Table 2: Quantitative EDS analysis of the diffusion zone 16 in Fig. 4(c)

Referring to Figure 6, where corresponding features have been given the same reference numerals, BSE micrographs for cross-sections through sintered compacts of Examples 2 and 3 are shown. In relation to Example 2, the alumina milling media proved brittle such that milling was limited to 4 hours. Nevertheless, a cavity 18 has formed, as best shown in Figure 6a.

In respect of Figure 6b, Example 3 (alumina milled with zirconium dioxide), the cylindrical cavity 18 has clearly formed and most of the features of the diffusion zone 17 from Figure 4c are observable. Therefore, it is believed that the formation of the cylindrical micro-cavity is due to the physical changes induced by milling of the alumina, especially high energy milling. In Example 3, the diffusion zone 17 is more complex than the diffusion zone in Figure 4c, which is believed to be caused by the different milling intensity with zirconium dioxide balls compared with steel balls and/or the lack of iron contamination. It is therefore believed that a relatively small adjustment to the sintering time or temperature is only necessary to permit the titanium to completely diffuse to form a more complete micro- cavity in alumina milled in zirconium dioxide media. For example, longer sintering times of up to 24 hours at similar temperatures to 1350°C have demonstrated improved diffusion of titanium in alumina milled in zirconium dioxide media.

Referring to Figure 7, where corresponding features have been given the same reference numerals, a BSE micrograph for a cross-section through the sintered compacts of Example 4 (zirconium dioxide milled with zirconium dioxide balls) is shown. While this figure shows that the titanium wire 10 did not diffuse completely into the zirconia matrix 22 to form a cylindrical cavity, a sponge-like micro -structure had developed with fine ligands 23 connecting the wire remnants to the surrounding zirconia powder 22. It is believed that the micro-cavity effect would also occur in zirconium dioxide in accordance with the method if the sintering temperature and time were suitably adjusted as a solid connection between the core and the zirconia matrix or base has been maintained. It is contemplated that such sintering temperatures are in the range of 1200° to 1700°C. Referring to Figure 8, another embodiment of the invention is illustrated, where corresponding features have been given the same reference numerals. In this embodiment, the method of Figures 2 and 3 was varied to incorporate the use of an iron based milling medium in the form of hardened steel balls. The method involves, at step 2, initially mechanically milling alumina powder with the steel balls for 16 hours in a high energy mixer-mill with a milling ball to powder ratio of 20:1 to a crystallite size approximately 10- 20 run. At step 23, the milled alumina powder was then "cleaned" by treating it in a hot hydrochloric acid (HCl) solution to dissolve as much iron contaminants as possible that may have entered the milled alumina powder from the steel milling balls. At step 6, a first layer of the cleaned, milled alumina powder 9 is laid in the pellet press. At step 9, a 10 mm long titanium wire 10 having a diameter of 125 μm is laid on the first layer 6. At step 11, a second layer 12 is laid on top of the first layer 6 and the wire 10. In steps 6 and 11, the first layer 6 and second layer 12 of the milled alumina powder were spread evenly and hand pressed in the pellet press. At step 14, the composite layers were then uniaxially compressed at 30 MPa for approximately 1 minute with the pellet press to produce a pellet. The pellet was then placed in an alumina crucible with a lid and sintered in air at a rate of 5°C/min until the temperate of 1350°C was reached, at which time either sintering was immediately stopped (by removing the pellet) or sintering was permitted to continue at 1350°C for a predetermined period of time. After sintering, the pellet was allowed to cool in air.

This method of Figure 8 was repeated using three wires 10 arranged parallel between the first layer 6 and the second layer 12 with the same results. Examples of ceramic pellets were made in accordance with the method of Figure 8, with sintering at 1350°C for 0 minutes, 15 minutes, 30 minutes, 1 hour, 2 hours, 4 hours and 24 hours, after which time sintering was stopped.

After sintering was completed, the pellets were air quenched so that no further diffusion or phase transitions could easily occur. The sintered pellets were then sectioned perpendicularly using a diamond saw. SEM samples were prepared by polishing and carbon coating the sample surfaces for examination by a Philips XL30 SEM operated at 15 kV. In addition, EDS were recorded using an Oxford ISIS Si/Li energy dispersive spectroscopy detector.

Figures 9 to 14 show BSE micrographs of cross-sections through sintered pellets of each example, where corresponding features have been given the same reference numerals. It was found in the samples of each example that a cylindrical micro-cavity 18 substantially corresponding to the shape of the titanium wire 10 had formed once the sintering temperature reached 1350°C. In respect of the sample removed at 0 minutes, the micro- cavity has substantially formed, as best shown in Figure 9a, with the diffusion zone 17 comprising a series of annular rings or layers, indicating the level of diffusion of the titanium into the alumina 16, as illustrated in more detail in Figure 9b. These rings have been labelled (1) to (5) from the innermost ring to the outermost ring. EDS spectra for rings 3 and 5 are shown adjacent Figure 9b.

In the sample removed from the furnace after 15 minutes, a micro-cavity 18 is formed, as best shown in Figure 10a. The primary difference between the samples of Figures 9 and

10 is the number of rings in the diffusion zone 17 have reduced from five to four in the sample of Figure 10, as best shown in Figure 10b, indicating that continued sintering at

1350°C leads to increased diffusion of the titanium into the milled alumina 16. In the sample removed from the furnace after 30 minutes, a micro-cavity 18 is formed, as best shown in the BSE micrographs and associated EDS spectra in Figures 11a and l ib.

Figures 12, 13 and 14 respectively show BSE micrographs of cross-sections through sintered pellets for the samples taken at 1 hour, 2 hours and 4 hours according to the method of Figure 8. In these samples, the micro-cavity 18 has become larger and the diffusion zone 17 surrounding the micro-cavity 18 becomes more uniform as the sintering time increases. In addition, the grain sizes of the rings in the diffusion zone 17 become larger as the sintering time increases.

It was also confirmed upon examination that in the sintered pellet samples the micro - cavity formation was relatively uniform across the length of the titanium wire 10. A sample sintered for 2 hours was sectioned along its length and secondary electron and BSE micrographs were taken of the end and section through the sample, as shown in Figures 15 and 16. The secondary electron micrographs of the end (Figure 15a) and the section (Figure 16a) show that the micro-cavity 18 substantially corresponds to the original location of the diffused titanium wire 10. Similarly, the BSE micrographs of the end (Figure 15b) and the section (Figure 16b) show that the titanium wire 10 has diffused topochemically in a regular pattern so that the micro-cavity 18 substantially corresponds to the original location of the diffused titanium wire. Thus, the titanium has coated or combined with the surface of the micro-cavity 18 at a relatively even thickness.

In the sample sintered for 24 hours, the micro-cavity 18 has been distinctly formed with a uniform diffusion zone 17 defining a boundary ring surrounding the micro-cavity and forming a border with the remaining alumina 16, as best shown in the BSE micrographs of cross-sections through the sintered pellet of Figure 17.

While preferred embodiments have been described in relation to performing the method with a titanium wire and milled alumina, it will be appreciated that the invention can be extended to similar materials, such as nickel and zirconium dioxide. Furthermore, it will be appreciated that the device can be moulded by any suitable processing methods. For example, where the solid is a ceramic, standard ceramic processing methods other than the moulding, slip casting and gel casting methods described above. Another advantage of the invention is that milling the ceramic material reduces the sintering temperatures for the ceramic, thus enabling the method to be applied across a broader range of sintering temperatures, depending on the composition of the template and the base ceramic material. Thus, the inventors have established that effective sintering temperatures range between 1100 and 1500⁰C, preferably between 1130 and 1350°C for alumina.

It is contemplated that one particular application of the invention is the production of ceramic devices in the biomedical field. One such application is the production of implantable drug delivery devices that can store and administer small, highly localised doses of medication to patients.

One such device is illustrated in Figure 18. The drug delivery device 30 has a discharge conduit 31 for delivering a drug contained in a reservoir 32. A conduit 33 is fluidly connected to a platinum diaphragm 34 that seals one end of the reservoir 32. The tubular conduit 33 transmits pressure pulses delivered from the body either through muscle activity or normal blood pressure pulses from the heart to actuate the platinum diaphragm 34, causing a dose of the drug contained within the reservoir 32 to be discharged into the body via the discharge conduit 31. It is contemplated that using appropriately shaped titanium templates for discharge conduit 31, reservoir 32 and the conduit 33, the device 30 can be manufactured in accordance with the method as described in the above embodiments of the invention. Since platinum is an inert material, it can be used to partition the micro- cavities that define the reservoir 32 and the conduit 33.

Other biomedical applications include the production of biological sensors, or a combination of a biological sensor and drug delivery device, which would be advantageous in blood-sugar measurement and insulin delivery for the treatment of diabetes.

In other embodiments, templates of more complex shapes may be used instead of a single wire. For example, similar wires can be connected together, or a single template used to define a network-like structure or a lattice-type structure so as to define a series of conduits for conveying fluid within a ceramic device. It is also contemplated that templates of polygonal shapes can be used where it is desired to shape a particular surface, such as a reservoir or a relatively larger area than a single passage. Examples of some possible shapes for the template are shown in Figure 19. Figure 19a illustrates the single wire 10. Figure 19b illustrates an open hoop-like structure 40 that could be made by suitably bending the wire 10. Figure 19c illustrates a cone-like structure 41. Figure 19d illustrates a circular shape 42 that is formed by a single wire 10, although it may be formed as an integrated piece. Figure 19e illustrates a triangular shape 43 formed with three wires 10. Figure 19f illustrates rectangle or square 44 formed with four wires 10. Figure 19g illustrates a complex network 45 having a mesh- like structure 40. Figure 19h illustrates a three- dimensional lattice-type structure 46. Figure 19i illustrates a three-dimensional hemispherical structure 47 that could be used to define a larger cavity. While shapes illustrated in Figures 19e to 19h are made of separate components, it will be appreciated that these shapes can be formed out of an integrally formed template. It will also be appreciated that other shapes may be formed and that the illustrated shapes do not limit the configurations of the template for use in the method of the invention.

In addition, it may be possible to use inert materials to partition or interact with the micro-cavities, such as platinum.

While the invention has been primarily described in respect of forming a ceramic, especially a titanium-alumina ceramic for biomedical use, it is also contemplated that the invention can be applied to other solid materials and other technical fields to produce internal micro -cavities that are partially or fully enclosed. For example, the method may be used to produce flow measurement instrumentation using an oxide matrix with completely enclosed internal micro-cavities, micro -machines (for example, small-scale internal combustion engines) and catalytic devices. In the case of a catalytic device, the template diffuses into the milled material so as to form a boundary layer surrounding the micro-cavity and having an inner surface that is chemically active so that the inner surface reacts with fluid conveyed within the micro-cavity.

It will be appreciated by one skilled in the art that the above described embodiments and examples show that shaped internal micro-cavities can be formed within a solid, especially a ceramic, by mechanically milling the base material and co-firing a template with the milled material. Therefore, the invention enables the production of devices without requiring separate assembly of individual components. This is of particular advantage in the production of ceramic devices in the biomedical field, as the ability to fabricate shaped micro-cavities avoids the inconvenience and costs in separate production of titanium and alumina components that are subsequently assembled for use. In addition, the invention permits the manufacture of biocompatible titanium-alumina devices suitable for implantation and placement within the human body. In all these respects, the invention represents a practical and commercially significant improvement over the prior art.

Although the invention has been described with reference to specific examples, it will be appreciated by those skilled in the art that the invention may be embodied in many other forms.

Claims

THE CLAIMS DEFINING THE INVENTION ARE AS FOLLOWS:-

1. A method of fabricating a shaped micro-cavity in a solid, the method comprising the steps of: milling a base material to be formed into the solid; locating a template at least partially within the milled material; and sintering the template and milled material to form the solid, such that the template diffuses into the milled material to form the micro-cavity having a shape substantially corresponding to the shape of the template.

2. The method of claim 1, wherein the solid is selected from the group consisting essentially of a ceramic, a metal, an alloy or an intermetallic compound.

3. The method of claim 1 or claim 2, wherein the template defines one or more conduits within the solid for conveying a fluid.

4. The method of claim 1 or claim 2, the template defines a path for growing an organic material within the micro-cavity.

5. The method of claim 4, wherein the organic material comprises tissue or bone.

6. The method of claim 1 or claim 2, wherein the template defines a path for electrical conduction.

7. The method of any one of the preceding claims, wherein the template defines a reservoir for containing or holding fluid.

8. The method of any one of the preceding claims, wherein the micro-cavity is enclosed within the solid.

9. The method of any one of claims 1 to 8, wherein the micro-cavity is partially enclosed within the solid.

10. The method of claim 9, wherein the micro-cavity extends through the solid to an outer surface to define an opening in the solid.

11. The method of claim 9 or 10, wherein the micro-cavity extends through the solid to define a passage or conduit.

12. The method of claim 11, wherein the micro-cavity defines two openings of the passage or conduit.

13. The method of any one of the preceding claims, wherein the template diffuses into the milled material so as to form a boundary layer surrounding the micro-cavity and having an inner surface.

14. The method of claim 13, wherein the inner surface is chemically active.

15. The method of claim 14, wherein the inner surface is a catalytic surface for reacting with fluid conveyed within the micro -cavity.

16. The method of claim 15, wherein the solid is a ceramic and is formed for use in a catalytic device.

17. The method of any one of the preceding claims, wherein the template is a metallic template.

18. The method of claim 17, wherein the composition of the metallic template is selected from the group consisting essentially of zirconium, titanium, iron and nickel. .

19. The method of claim 18, wherein the metallic template is composed of titanium.

20. The method of any one of the preceding claims, wherein template has a shape selected from the group consisting essentially of geometrical shapes, polygons, lattice- type structures and network-type structures.

21. The method of any one of the preceding claims, wherein the template is a metallic wire.

22. The method of claim 21, wherein the wire has a diameter of approximately between 10 μm and 500 μm, preferably a diameter of at least 125 μm and more preferably a diameter of at least 500 μm.

23. The method of claim 21 or 22, wherein the diameter of the wire is selected according to the desired diameter of the micro-cavity, the material comprising the template, the time of sintering, the temperature of sintering or any combination thereof.

24. The method of any one of claims 1 to 23, wherein the micro-cavity has dimensions that are proportionate to the dimensions of the template.

25. The method of claim 24, wherein the micro-cavity has dimensions that are proportionately less than the dimensions of the template.

26. The method of claim 24, wherein the micro-cavity has dimensions that are proportionately greater than the dimensions of the template.

27. The method of claim 24, wherein the micro-cavity has dimensions substantially the same as the dimensions of the template.

28. The method of any one of the preceding claims, wherein the milling step comprises mechanically milling the base material.

29. The method of any one of the preceding claims, wherein the milling step comprises milling the base material into a powder having a crystallite size of approximately 5 to 100 nm, preferably 10 to 60 nm, more preferably 12 to 40 run, even more preferably 12 to 20 nm.

30. The method of any one of the preceding claims, wherein the milling step comprises milling the base material approximately between 1 and 64 hours, preferably approximately between 2 and 64 hours, more preferably approximately between 4 and 32 hours, even more preferably approximately between 4 and 24 hours and yet more preferably approximately between 4 and 16 hours.

31. The method of any one of the preceding claims, wherein the milling step comprises milling the base material with a milling medium to base material ratio of approximately between 3:1 and 30:1, preferably approximately between 10:1 and 25:1 and more preferably 20:1.

32. The method of any one of the preceding claims, wherein the milling step comprises milling the base material with a non-ferrous milling medium.

33. The method of any one of claims 1 to 31, wherein the base material is milled with a ferrous milling medium.

34. The method of claim 33, wherein the ferrous milling medium is the milling medium is hardened steel.

35. The method of claim 33 or 34, further comprising the step of cleaning the milled material to remove iron contaminants.

36. The method of claim 35, wherein the cleaning step comprises using an acid to leach out the iron contaminants.

37. The method of claim 36, wherein the acid is an inorganic acid.

38. The method of claim 37, wherein the inorganic acid is selected from the group consisting essentially of hydrochloric acid, sulphuric acid and nitric acid.

39. The method of claim 36, wherein the acid is an organic acid.

40. The method of claim 39, wherein the organic acid comprises acetic acid.

41. The method of any one of the preceding claims, wherein the milling medium has the substantially same composition as the base material.

42. The method of any one of the preceding claims, wherein the milling medium has negligible solubility in the base material.

43. The method of any one of the preceding claims, wherein the milling medium is selected from the group consisting essentially of hardened steel, alumina (Al₂O₃), zirconium dioxide (ZrO₂) and bonded tungsten carbide (WC).

44. The method of any one of claims 1 to 40, wherein the base material is alumina and the milling medium is selected from the group consisting essentially of alumina

(Al₂O₃), zirconium dioxide (ZrO₂) and steel.

45. The method of any one of the preceding claims, further comprising the step of compressing the milled material and the template before or during the sintering step.

46. The method of claim 45, wherein the compressing step comprises mechanically compressing the milled material and the template.

47. The method of claim 45 or 46, wherein the compressing step comprises hot- pressing or hot-isostatically pressing.

48. The method of any one of claims 45 to 47, further comprising the step of moulding the milled material to form a shape for the solid, wherein the moulding step is performed before or simultaneously with the compressing step.

49. The method of any one of claims 1 to 47, further comprising the step of moulding the milled material to form a shape for the solid.

50. The method of claim 49, wherein the moulding step comprises placing the milled material in a mould.

51. The method of claim 49 or 50, wherein the moulding step is performed before or simultaneously with the locating step.

52. The method of claim 51, wherein the moulding step is performed simultaneously with the locating step and the moulding step is performed using slip casting or gel casting.

53. The method of any one of the preceding claims, wherein the locating step comprises embedding the template into the milled material.

54. The method of any one of the preceding claims, wherein the locating step comprises locating the template between two layers of the milled material.

55. The method of claim 54, wherein the locating step comprises laying a first layer of the milled material, placing the template on the first layer and laying a second layer of the milled material onto the first layer and the template.

56. The method of claim 54 or 55, wherein the layers are compressed before the sintering step.

57. The method of any one of the preceding claims, wherein the sintering step comprises sintering the milled material and the template until a predetermined temperature is reached.

58. The method of claim 57, wherein the base material is alumina, the template is composed of titanium and the predetermined temperature is approximately between 1100 and 1500°C, preferably approximately between 1130 and 1350°C.

59. The method of claim 57 or 58, wherein the sintering step further comprises continuing sintering at 135O⁰C for between 0 minutes and 24 hours.

60. The method of claim 59, wherein the sintering step comprises sintering for 30 minutes, preferably 1 hour, more preferably 2 hours, even more preferably 4 hours and yet more preferably 8 hours.

61. The method of any one of the preceding claims, wherein the base material is selected from the group consisting essentially of alumina, titanium dioxide (TiO₂), zirconium dioxide (ZrO₂) and other suitable ceramics.

62. The method of claim 62, wherein the base material is alumina.

63. A device having a micro-cavity produced according to the method of any one of the preceding claims.

64. The device of claim 63, wherein the device is adapted for use as a medical device.

65. The device of claim 62, wherein the device is a catalytic device.

66. The device of claim 62, wherein the device is a filter.

67. A biocompatible medical device having a micro-cavity produced according to the method of any one of claims 1 to 62.

68. A micro machine having a micro-cavity produced according to the method of any one of claims 1 to 62.

69. The method, device, biocompatible medical device or micromachine of any one of the preceding claims, wherein the solid is a ceramic.