Abstract
A method is for manufacturing a plurality of silicon microneedles which have a bevelled tip. The method includes providing a silicon substrate having a front face and a rear face, forming a first mask arrangement on the front face of the substrate, the first mask arrangement defining one or more gaps, and performing a SF.sub.6 based plasma etch of the front face through the gaps in the first mask arrangement to provide one or more etch features having a sloping face. The SF.sub.6 based plasma etch undercuts the first mask arrangement with an undercut that is at least 10% of the depth of a corresponding etch feature. The method further includes forming a second mask arrangement on the etch features to define locations of the microneedles, in which the second mask arrangement is located entirely on sloping faces of the etch features, and performing a DRIE (deep reactive ion etch) anisotropic plasma etch of the etched front face of the substrate to form a plurality of microneedles which have a bevelled tip, where the sloping faces of the etch features at least in part give rise to the bevelled tips of the microneedles.
Claims
1. A method of manufacturing a plurality of silicon microneedles which have a bevelled tip, the method comprising the steps of: providing a silicon substrate having a front face and a rear face; forming a first mask arrangement on the front face of the substrate, the first mask arrangement defining one or more gaps; performing a SF.sub.6 based plasma etch of the front face through the gaps in the first mask arrangement to provide one or more etch features having a sloping face, wherein the SF.sub.6 based plasma etch undercuts the first mask arrangement with an undercut that is at least 10% of the depth of a corresponding etch feature; forming a second mask arrangement on the etch features to define locations of the microneedles, in which the second mask arrangement is located entirely on sloping faces of the etch features; and performing a DRIE (deep reactive ion etch) anisotropic plasma etch of the etched front face of the substrate to form a plurality of microneedles which have a bevelled tip, wherein the sloping faces of the etch features at least in part give rise to the bevelled tips of the microneedles.
2. A method according to claim 1 in which the DRIE plasma etch of the etched front face is an anisotropic cyclical etch and deposition process.
3. A method according to claim 1 in which the first mask arrangement is an oxide mask.
4. A method according to claim 1 in which the second mask arrangement is deposited onto the etch features by PE-CVD (plasma enhanced chemical vapour deposition).
5. A method according to claim 1 in which the bevelled tips of the microneedles are formed as single bevel structures.
6. A method according to claim 1 in which the bevelled tips of the microneedles have a bevel angle of at least 60.
7. A method according to claim 1 in which: the gaps defined by the first mask arrangement each have a width; the etch features each have a base width; and the base width of each etch feature is substantially equal to the width of its corresponding gap in the first mask arrangement.
8. A method according to claim 1 in which the SF.sub.6 based plasma etch is formed in a gaseous mixture comprising SF.sub.6 and an inert diluent.
9. A method according to claim 8 in which the gaseous mixture consists essentially of SF.sub.6, O.sub.2, C.sub.4F.sub.8 and Ar.
10. A method according to claim 1 further comprising the step of performing a DRIE plasma etch of the rear face to form plurality of channels in the silicon substrate which are positioned so that, after the plurality of microneedles are formed, the channels act as bore passages extending through the microneedles.
11. A method according to claim 10 in which the step of performing a DRIE plasma etch of the rear face is performed prior to the step of performing a DRIE plasma etch of the etched front face.
12. A method according to claim 1 in which the DRIE plasma etch of the etched front face forms one or more ridge structures which are spaced apart from the microneedles.
13. A method according to claim 12 in which a plurality of interconnected ridge structures are formed to provide a plurality of microneedle surrounding fence structures each of which surround and are spaced apart from a microneedle.
14. A method according to claim 12 in which: the SF.sub.6 based plasma etch etches through a gap in the first mask arrangement to provide one or more etch features which have a pair of opposed sloping faces, and the DRIE plasma etch of the etched front face is performed so that one of the pair of opposed sloping faces at least in part gives rise to the bevelled tip of a microneedle and the other of the pair of opposed sloping faces at least in part gives rise to a ridge which is spaced apart from the microneedle.
15. A method according to claim 1 in which the bevelled tips of the microneedles are formed as double bevel structures.
16. A method according to claim 15 in which the double bevel structures are formed by controlling etch conditions during the step of performing a SF.sub.6 based plasma etch of the front face.
17. A method according to claim 15 in which the step of performing a SF.sub.6 based plasma etch of the front face produces single bevel structures, and the double bevel structures are produced during the step of performing a DRIE plasma etch of the etched front face.
18. A method according to claim 17 in which the second mask arrangement comprises oxide masks having a thickness in the range 3 to 5 microns.
19. A method according to claim 1 in which the SF.sub.6 based plasma etch is formed in a gaseous mixture comprising SF.sub.6 and a sidewall passivation precursor.
20. A method according to claim 19 in which the sidewall passivation precursor is at least one of C.sub.4F.sub.8 and CHF.sub.3.
21. A method according to claim 20 in which the gaseous mixture consists essentially of SF.sub.6, CHF.sub.3 and C.sub.4F.sub.8.
22. A method according to claim 19 in which the gaseous mixture further comprises O.sub.2.
23. A method according to claim 22 in which the gaseous mixture consists essentially of SF.sub.6, O.sub.2 and C.sub.4F.sub.8.
Description
BRIEF DESCRIPTION OF THE DRAWINGS
(1) Embodiments of methods in accordance with the invention will now be described with reference to the accompanying drawings, in which:
(2) FIG. 1 shows (a) a plan view of a silicon substrate with a first mask and (b) a cross sectional view of the silicon substrate at the end of a SF.sub.6 based etch;
(3) FIG. 2 shows (a) a plan and (b) a cross sectional views of the silicon substrate with a second mask arrangement on the front face;
(4) FIG. 3 shows (a) a plan and (b) a cross sectional views of the silicon substrate with a third mask on the rear face at the end of a backside etch;
(5) FIG. 4 shows (a) a plan and (b) a cross sectional views of microneedles formed at the end of a front face etch;
(6) FIG. 5 shows (a) a plan and (b) a cross sectional views of the microneedles after removal of the second mask arrangement;
(7) FIG. 6(a) shows SEM (scanning electron microscope) micrographs of a first etch feature and FIG. 6(b) shows the same of a second etch feature after a SF.sub.6 based etch;
(8) FIG. 7 shows the effect of process pressure during the SF.sub.6 based etch on bevel angle;
(9) FIG. 8(a) shows SEM micrographs of a third etch feature and FIG. 8(b) shows the same of a fourth etch feature after a SF.sub.6 based etch;
(10) FIG. 9 shows the effect of bevel angle (57 and 75) on microneedle width;
(11) FIG. 10(a) shows annotated SEM micrographs of a bore channel etched in the bulk silicon substrate and FIG. 10(b) shows the same of a microneedle formed at the end of a front face etch of the bulk silicon substrate;
(12) FIG. 11 is a SEM micrograph of a single bevelled microneedle; and
(13) FIG. 12 (a) shows a high resolution SEM micrograph of double bevelled microneedles in front of a fence, and FIG. 12(b) a lower resolution SEM micrograph of an array of double bevelled microneedles with fence structures present.
DETAILED DESCRIPTION OF EMBODIMENTS
(14) FIGS. 1 to 5 show steps in a representative but non-limiting method of the invention. FIG. 1A shows a portion of a first mask 10 which is formed on a silicon substrate 12. The first mask 10 defines a plurality of apertures 14 to reveal exposed portions of a front face of the silicon substrate 12. The first mask 10 as shown in FIG. 1A consists of a row of apertures 14. As will be explained below, this gives rise to a row of microneedles. In practice, it is common to use a more extended first mask which defines rows and columns of apertures 14. The more complicated first masks of this type give rise to an array of microneedles having both rows and columns of microneedles. The skilled reader will appreciate that the first mask can take many different forms depending on the preferred form of the microneedles desired for any particular application.
(15) The silicon substrate 12 having the first mask 10 is then subjected to a SF.sub.6 based plasma etch 15. This is shown in FIG. 1B. The plasma etch etches through the apertures 14 in the first mask 10 to produce a plurality of etch features. FIG. 1B is a cross sectional view of the silicon substrate/first mask towards the end of the SF.sub.6 based plasma etch, at which point a plurality of etch features 16 have been formed which comprise a pair of opposed sloping faces 16A, 16B. It can be seen that the SF.sub.6 based plasma etch undercuts the first mask 10. The undercut is the amount of lateral etching underneath the mask. In practice, the undercut achieved is at least 10% of the depth of a corresponding etch feature 16.
(16) The first mask 10 is removed and second masks 18 are formed on one sloping face 16A of the pairs of opposing sloping faces 16A, 16B (FIGS. 2A and B). The other sloping face 16B of a pair is not protected by a mask. A third mask 20 is formed on the rear face 12A of the silicon substrate 12. The third mask 20 is formed with a plurality of apertures 20a in the mask which are aligned with the locations of the second mask 18 on the sloping faces 16A. As shown in FIGS. 3A and B, a backside plasma etch 21 of the masked rear face 12A of the silicon substrate is then performed to form a plurality of bore channels 22 which extend from the apertures 20 through the silicon substrate 12 to reach the second masks 18. The plasma etch used to form the bore channels 22 can be any convenient etch process. It is very convenient to use a DRIE etch such as a Bosch type etch. Next, a DRIE plasma etch of the front side of the silicon substrate 12 plasma etch is performed. FIGS. 4A and B show the DRIE plasma etch 24 of the front face of the silicon substrate 12. The plasma etch 24 etches the bulk silicon around the second masks 18 to leave a plurality of bevelled microneedle structures 26 upstanding from a base layer 28. It will be apparent that the plasma etch 24 can be controlled so as to control the depth of the base layer 28 and the height of the microneedle structures 26. Advantageously, the plasma etch 24 also forms a plurality of ridge structures 30 which are spaced from the microneedle structures 26. The ridge structures are associated with the etching of portions of the front face of the silicon substrate 12 which at least include the sloping faces 16B.
(17) The second masks 18 are then removed to produce the microneedle array 32 shown in FIGS. 5A and B. The microneedle array 32 comprises a plurality of bevelled microneedle structures 26. In the embodiment shown in FIGS. 5A and B, the microneedle structures 26 are hollow due to the presence of bore channels 20 extending therethrough. The embodiment shown in FIGS. 5A and B also comprises the plurality of ridge structures 30. In practice, it is usual for the microneedle array to be formed with a far greater number of microneedle structures. In the embodiment shown in FIGS. 5A and B, the third mask 20 on the rear face 12A remains in place. Optionally, the third mask 20 could be removed.
(18) Although it is desirable to provide a dry etch process which creates sloped sidewalls in a silicon substrate to a depth of several hundred microns, in practice this has been very hard to achieve. The present invention provides a SF.sub.6 based dry plasma etch which can be used to create sloped sidewalls which can be further processed to provide a plurality of bevelled microneedles. Examples of suitable SF.sub.6 based gas mixtures include: SF.sub.6/O.sub.2/C.sub.4F.sub.8; SF.sub.6/O.sub.2/C.sub.4F.sub.8/Ar; SF.sub.6/O.sub.2/A.sub.r; and SF.sub.6/CHF.sub.3/C.sub.4F.sub.8. Other SF.sub.6 based gaseous compositions might be used. These compositions may be with or without oxygen and/or with or without an inert diluent such as argon. The relative proportion of the constituents may also be varied in order to achieve desired profiles. The SF.sub.6 based plasma forms the basis of an isotropic etch. It is desirable to add a constituent such as C.sub.4F.sub.8 and/or CHF.sub.3 to achieve some sidewall passivation. The sidewall passivation restricts lateral etching and helps to maintain a profile which is free from overhang. Typically, the etch achieves a large undercut below the first mask, but the sidewalls become passivated due to ion-assisted migration or diffusion of polymeric moieties from the base of the etch feature to the sidewalls. FIGS. 6A and B show SEMs of etch features achieved using typical process conditions for the SF.sub.6/C.sub.4F.sub.8 based first plasma etch In both instances, the first mask can be clearly seen as essentially horizontal white lines towards the top of each FIGS. 6A and B. FIG. 6A shows a gap defined by the first mask. In FIG. 6A, it can be seen that the width of the opening defined by the first mask is similar to the base width of the etch feature. This is a typical but non-limiting result. In FIG. 6a, the SF.sub.6 based plasma etch has produced a substantially flat base with a pair of opposed sloping sidewalls having a 60.9 profile angle. The SF.sub.6 based plasma etch has resulted in an undercut of the first mask which is greater than 200 microns. In FIG. 6B, a sloping sidewall is produced having a profile angle of 69.1 and a depth of 188 microns.
(19) Typical process contents for the SF.sub.6 based plasma etch are: platen temperature 20 C.; pressure 60 mTorr; 4 kW source RF; 10 W platen RF; 575 sccm SF.sub.6 flow rate; 100 sccm C.sub.4F.sub.8 flow rate; 80 sccm O.sub.2 flow rate.
(20) A typical etch rate is in the range 10-20 microns/min, with a process time of around 20 minutes.
(21) It is possible to control the profile angle of the sloping faces by modifying the process parameters. For example, increasing the power applied to the platen can increase the profile angle. Variation of the flow of C.sub.4F.sub.8 can either increase or decrease the profile angle depending on the feature size and geometry. Additionally, the process pressure can affect the profile angle, which in turn affects the bevel angle of the eventually produced microneedles. FIG. 7 shows the variation in the bevel angle as a function of process pressure. It can be seen that lower process pressures give rise to steep bevel angles. Without wishing to be limited by any particular theory or conjecture, it is believed that increasing the process pressure and/or reducing the platen power changes the angle of distribution of the etchant species, and this directly affects the bevel angle. This, in combination with simultaneous passivation of the sidewalls, controls the overall profile. The simultaneous passivation can be of all of the sidewalls or a portion of the sidewalls. It is possible to produce microneedles having a single bevel tip or a double bevel tip by varying the process conditions of the SF.sub.6 based plasma etch in this way. Alternatively, a double bevel tip can be achieved in combination with passivation steps where the lower parts of the sidewalls and base are protected from lateral etching, whilst the upper parts of the sidewalls are etched to produce shallow profile angles.
(22) FIGS. 8A and B show SEMs of further bevel etch features achieved using a SF.sub.6/C.sub.4F.sub.8/O.sub.2 plasma etch chemistry. In FIG. 8A a strawberry etch profile is achieved, with the sloping sidewalls having a main profile angle of 59.4. The depth of the etch feature is 420 microns and an etch rate of 16.8 microns/min was achieved. In FIG. 8B, a steep profile angle of 75 is achieved and the etch depth is 331 microns. It is highly advantageous that the profile angle and hence the bevel angle can be readily controlled using the dry etch method of the invention. Additionally, it is highly advantageous that the invention can provide steep profile angles and hence steep bevel angles. FIG. 9 shows the effect of changing the bevel angle from 57 to 75 on microneedle width. It can be seen that there is a 2.5 reduction in the diameter of the microneedle if the bevel angle is increased from 57 to 75 for a fixed bevel length This is a key factor in the production of high density silicon microneedle arrays. 57 corresponds to the bevel angle produced using wet etch techniques. This bevel angle is set owing to the crystallographic nature of the wet etch. Consequently, the prior art wet etch technique places a fundamental constraint on the design of the microneedle array. The present invention overcomes this limitation in the prior art. A further advantage of the dry etch method provided by the invention is that there is a substantial reduction in process time compared to a standard KOH wet etch. Typical process times for a dry etch of the invention are around 20 minutes to produce microneedles of 400 micron length. In contrast, a KOH wet etch would take about 22 hours microneedles of the same length. Additionally, the dry etch method of the invention avoids problems associated with roughness that are caused by a wet etch technique. The present invention can produce profile angles of 50-80 and etch feature depths of 150-400 microns. However, the invention is not limited to these angles and depths.
(23) After the first etch is completed, the first mask is removed using known means. FIGS. 10A and B are annotated SEMs depicting further stages in the production of the microneedles. FIG. 10A shows the silicon substrate 106 after exposure to the backside plasma etch 100. A second mask 104 is positioned on a sloping sidewall partially to act as an etch stop for the backside plasma etch. The third mask 104 is positioned on the rear face of the silicon substrate 104 and is patterned to expose portions of the silicon to the backside plasma etch in order to form bore channels 108. The masks 102, 104 are aligned to ensure that the etching of the bore channel 108 stops at the second mask 104. The silicon substrate 106 is placed with the third mask 102 facing the plasma 100, and the bore channel etch is completed once all of the silicon above the aperture in the third mask has been removed, resulting in a bore channel 108. FIG. 10B shows the subsequent plasma etch of the front face of the silicon substrate using a DRIE plasma etch 110. The second mask 104 protects the silicon underneath it from the plasma 110 whilst bulk silicon is removed by the plasma 110 in unmasked areas. The plasma 110 is substantially anisotropic in nature, resulting in the formation of a hollow, bevelled microneedle 112. The plasma 110 also produces a ridge 114. The ridge 114 is associated with the sloping face of the etch feature which is opposite to the sloping face which produces the microneedle 112. After the processing of the plasma 110 is completed, the second and, optionally, the third masks can be removed using known means. Typically, a PE-CVD oxide is used to form a hard second mask 104. However, alternative materials such as a photo resist or a metal mask could be used instead. The third mask 102 may also be formed from a hard mask, photo resist or metal mask. Conveniently, the second and third masks are formed form the same material. The front side plasma etch which forms the microneedles is a DRIE plasma etch. Conveniently, a typical cyclical etch and deposition process can be used with ICP HF source powers 3-6 kW, bias power 0.12-1.5 kW, process pressures 40-50 mT, cycle time 1-5 seconds and principally SF.sub.6 during the etch cycle and C.sub.4F.sub.8 during the deposition cycle.
(24) The front side plasma etch is desirably substantially anisotropic, and in fact it is possible to produce microneedles with completely vertical upstanding walls. However, it is generally preferred to provide microneedles having a re-entrant shape (wider top, narrower base) because the plasma etch processes which create re-entrant angles are typically less polymeric in nature, and hence more repeatable and robust. The backside plasma etch may be of the same type as the front face plasma etch which is used to produce the microneedles. In some embodiments, the same etch process is used for both the backside and front face etches.
(25) The front face plasma etch can be used to obtain single or double bevelled microneedle tips. It has been found that if a relatively thick oxide second mask having a thickness of greater than 5 microns is used, then a single bevel structure can be obtained as can be seen in FIG. 11 As noted previously, a double bevelled microneedle tip can be obtained through appropriate control of the SF.sub.6 based first etch. It has been found that double bevel tips can also be obtained through control of the front face etch of the silicon substrate which produces the microneedles. Due the higher incidents of energetic ions, the etch rate of the second mask at the bottom of the bevelled structure is much higher than at the top. As a result, the portions of the second mask at the bottom of the bevelled structure experience a much higher etch rate than the portions of the mask at the top. Therefore, the portions of the second mask at the bottom of the bevel structure are consumed more quickly, leading to etching of the underlying silicon. This leads to the formation of a double bevelled structure. It has been found that the use of an oxide second mask having a thickness in the range 3-5 microns results in double bevelled structures. Second masks formed from different materials may require a different range of thicknesses used in order to produce double bevelled structures. Both single and double bevelled structures are of practical utility, and it is advantageous that the present invention can provide microneedles having either structure. Double bevelled structures have improved skin penetration yields. FIGS. 12A and B show SEM images of double bevelled microneedles in which the top bevel angle is about 60 and the bottom bevel angle is steeper at about 80. Microneedles having bevelled tips of a diamond shape result in the most effective skin puncture. The microneedles shown in FIGS. 12A and B have the desired diamond shaped tips, and in fact microneedles with diamond shaped tips can be readily produced using the present invention.
(26) As explained above, it is possible to form a ridge which is spaced apart from an adjacent microneedle. When an array of microneedles is produced using a first mask that comprises rows and columns of apertures, the ridges can form a plurality of fence structures which surround the microneedles. This can be seen particularly clearly in FIG. 12B. The perimeter of the silicon substrate which was masked by the first mask forms a frame structure which surrounds the array of microneedles. The ridges are typically formed at a distance of 100-200 microns from the base of the adjacent microneedles. However, smaller or greater distances can be utilised, primarily through appropriate design of the first mask but also through control of the etch processes. The presence of the ridges/frame structures is advantageous for a number of reasons. The likelihood of breakage of the microneedles (which is primarily caused by shear forces during injection of the microneedles into the skin) is reduced. The ridge/fence structures also allow stretching and bunching of the skin area local to the microneedles to give better skin penetration. Another advantage is that the ridge/fence structures can be used to define the microneedle penetration depth. The positioning of the microneedle shaft alongside the ridge/fence structures defines a needle penetration depth which is related to the difference between the microneedle height and the ridge height. This enables target drug delivery depth to be achieved.
(27) Many variations to the method as described above would readily suggest themselves to the skilled reader. For example, it is not essential that hollow microneedles are produced. Instead, solid microneedles might be manufactured by omitting the backside etch step. Alternatively, pocketed microneedles might be produced having pockets or cavities formed either in the tip or in the microneedle body. Although the microneedles exemplified above have a cylindrical body shape, it is possible to instead produce microneedles having non-cylindrical body shapes of various forms.
