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EP-4124355-B1 - SILICON MICRONEEDLE STRUCTURE AND PRODUCTION METHOD

EP4124355B1EP 4124355 B1EP4124355 B1EP 4124355B1EP-4124355-B1

Inventors

  • ADMATI, Gal
  • LEVIN, YOTAM
  • HAMISHA, Yoav

Dates

Publication Date
20260513
Application Date
20220702

Claims (15)

  1. A microneedle structure formed from a single crystal of silicon, the microneedle structure comprising: (a) a silicon substrate (100) having a major surface (102); (b) at least one silicon microneedle (104) integrally formed with said substrate so as to project from said major surface, said at least one microneedle comprising: (i) a penetrating tip (106) formed at an intersection between at least one upright surface (108) perpendicular to said major surface (102) of said substrate and an inclined planar surface (110) corresponding to a (1 1 1) crystallographic plane, and (ii) an expanding portion bounded by a continuation of said at least one upright surface (108) and said inclined surface (110), wherein a width (W) of said inclined surface increases monotonically from said penetrating tip (106) to an edge (114), characterized in that said edge (114) is located at a height (h 2 ) above said major surface, and in that said at least one microneedle (104) further comprises: (iii) a constant cross-section portion bounded by a continuation of said at least one upright surface (108) and a slicing plane (112) extending from said edge (114) of said inclined surface (110) towards, and perpendicular to, said major surface (102) of said substrate.
  2. The microneedle structure of claim 1, wherein a height (H) of said penetrating tip (106) from said major surface (102) of said substrate (100) is at least 750 microns, and wherein a maximum dimension of said microneedle parallel, and adjacent, to said major surface is no more than 500 microns.
  3. The microneedle structure of claim 1, wherein a height (H) of said penetrating tip (106) from said major surface (102) of said substrate (100) is at least 800 microns, and wherein a maximum dimension of said microneedle parallel, and adjacent, to said major surface is no more than 450 microns.
  4. The microneedle structure of claim 1, wherein a cross-section taken through said constant cross-section portion of said microneedle parallel to said major surface (102) of said substrate (100) has a length (L) perpendicular to said slicing plane (112) and a width (W) parallel to said slicing plane, said length being at least 50% greater than said width.
  5. The microneedle structure of claim 1, wherein said at least one upright surface (108) adjacent to said penetrating tip (106) comprises a first planar surface (108a) and a second planar surface (108b) smoothly linked by an arcuate surface (108c), said first and second planar surfaces being symmetrically deployed on opposite sides of a center plane passing through said microneedle and forming between them an angle of between 45 degrees and 75 degrees.
  6. The microneedle structure of claim 5, wherein said arcuate surface (108c) has a radius of curvature between 10 microns and 40 microns.
  7. The microneedle structure of claim 5, wherein said at least one upright surface (108) further comprises a third planar surface (108d) and a fourth planar surface (108e) arranged symmetrically on opposite sides of said center plane, said third and fourth planar surfaces forming between them an angle of between 5 degrees and 25 degrees.
  8. The microneedle structure of claim 1, further comprising a bore (116) extending from said inclined surface (110) through said expanding portion, through said constant cross-section portion and through said substrate (100) to a rear surface of said substrate.
  9. The microneedle structure of claim 1, wherein said slicing plane (112) is also an edge of said substrate (100).
  10. The microneedle structure of claim 1, wherein said at least one microneedle is implemented as a plurality of microneedles (106) integrally formed with said substrate (100), said plurality of microneedles having co-planar slicing planes (112).
  11. A method for manufacturing a microneedle structure, the method comprising the steps of: (a) providing a microneedle device precursor formed from a single crystal of silicon and comprising: (i) a substrate (100) having a major surface (102), (ii) at least one microneedle (104) integrally formed with said substrate (100) so as to project from said major surface, said at least one microneedle comprising: (A) a penetrating tip (106) formed at an intersection between at least one upright surface (108) perpendicular to said major surface of said substrate (100) and an inclined planar surface (110) corresponding to a (1 1 1) crystallographic plane, and (B) an expanding portion bounded by a continuation of said at least one upright surface (108) and said inclined surface (110), said inclined surface extending to said major surface of said substrate (100); (b) slicing said microneedle device precursor along a slicing plane (112) perpendicular to said major surface (102) of said substrate, characterized in that said slicing plane (112) passes through said inclined surface (110) of said microneedle and through at least part of said substrate (100) so as to generate a constant cross-section portion bounded by a continuation of said at least one upright surface (108) and said slicing plane (112) extending from an edge (114) of said inclined surface located at a height (h 2 ) above said major surface towards said major surface (102) of said substrate.
  12. The microneedle structure of claim 1 or the method of claim 11, wherein said slicing is performed so that said constant cross-section portion extends for at least a fifth of a height (H) of said penetrating tip (106) from said major surface (102) of said substrate (100).
  13. The microneedle structure of claim 1 or the method of claim 11, wherein said slicing is performed so that a ratio of a height (H) of said penetrating tip (106) from said major surface (102) of said substrate (100) to a maximum dimension of said microneedle adjacent to said major surface is at least 1.6, and preferably at least 1.7.
  14. The method of claim 11, wherein said slicing is performed as part of a dicing process for separating said substrate (100) into a plurality of chips each containing a microneedle structure.
  15. The method of claim 11, wherein said slicing is performed by a process or combination of processes selected from the group consisting of: mechanical cutting; laser cutting; plasma cutting; and DRIE.

Description

TECHNICAL FIELD The present invention relates to microneedles and, in particular, it concerns a silicon microneedle structure and corresponding production methods. BACKGROUND Much interest has been shown in microneedles for a wide range of applications. As a replacement for hollow metal needles, hollow microneedles have potential to offer a wide range of advantages, including one or more of: painless or reduced-pain penetration, enhanced safety, reliable intradermal drug delivery, better control over delivery depth, lack of bending and blunting, and reduced needle visibility for patients with a fear of needles. Silicon has been proposed as a material for microneedles due to its biocompatibility and the availability of well-developed, scalable manufacturing techniques similar to those used in MEMS. However, many proposed silicon microneedle designs have failed to achieve commercial success due to difficulties implementing a microneedle which is sufficiently sharp to penetrate the skin while at the same time being sufficiently robust to minimize risk of breakage during insertion. A particularly effective hollow silicon microneedle structure has been developed by NanoPass Technologies Ltd. (Israel) and is commercially available under the tradename MICRONJET®. The microneedles are formed with upright walls perpendicular to an underlying substrate surface, and an oblique surface corresponding to a (1 1 1) crystallographic plane intersecting those walls so as to extend from a sharp penetrating tip to the substrate surface. This structure defines a generally triangular microneedle shape as viewed from the side, which provides a highly advantageous combination of a sharp penetrating tip and a robust needle body which is highly resistant to breaking. An example of such a needle is shown in the SEM image reproduced here as FIG. 5. A US2006015061A1 discloses a microneedle array device and its fabrication method. The microneedle array device comprises a supporting pad and plural of microneedles. Each microneedle has a top portion with a via thereon, thereby the microfluid may flow in or out. The intersection between the top portion and the inner tube of a microneedle forms a convex needle structure, and is almost perpendicular to the upper surface. For each microneedle, a hollow closed tube is formed between the top portion and the supporting pad. The fabrication method uses the substrates with high transmittance and plural of convex area thereon as the upper and lower caps, and applies a photolithography process to fabricate a microneedle array mold. It then sputters or electroplates metal material on the mold. The microneedle array is formed after having taken off the mold. A CN108328567A discloses a method for obtaining a high-density curved surface or a beveled microneedle array. According to the method, the beveled or curved surface microneedle array is generated by changing the shapes and sizes of masks to generate needle-shaped quartz bosses with different heights. The shapes of the masks in the method can be circles or triangles, and different calculation modesare provided for different mask shapes and different mask sizes. A CN213048990U discloses a microneedle for intradermal injection or diagnosis, which is configured to include: a protrusion arranged above a substrate, and a shape of the protrusion is composed of a plurality of vertical side surfaces. It is configured to be approximately symmetrical to a vertical symmetry plane, and to intersect along a vertical front edge, and to intersect through an inclined surface intersecting the side surface, the microneedle also includes a vertical hole, arranged at a central position between the two side surfaces, substantially close to the front edge. A US2015306363A1 discloses articles having a polymeric substrate with a plurality of solid and/or hollow microneedles extending therefrom. Each solid microneedle is formed by a molding process and the microneedle has body with first and second cavities extending therein. The hollow microneedles are formed by removing a portion of the polymeric material disposed between the first cavity and the second cavity. A method for determining the location of a microneedle in an article comprising solid microneedles is also provided. The method comprises directing electromagnetic radiation toward an article comprising a plurality of microneedles and imaging the article. SUMMARY OF THE INVENTION The present invention is a silicon microneedle structure and corresponding production methods according to the appended claims. According to the teachings of an embodiment of the present invention there is provided, a microneedle structure formed from a single crystal of silicon, the microneedle structure comprising: (a) a silicon substrate having a major surface; (b) at least one silicon microneedle integrally formed with the substrate so as to project from the major surface, the at least one microneedle comprising: (i) a penetrating tip