WO2004035105A2 - Polymer microneedles - Google Patents

Polymer microneedles Download PDF

Info

Publication number
WO2004035105A2
WO2004035105A2 PCT/IL2003/000818 IL0300818W WO2004035105A2 WO 2004035105 A2 WO2004035105 A2 WO 2004035105A2 IL 0300818 W IL0300818 W IL 0300818W WO 2004035105 A2 WO2004035105 A2 WO 2004035105A2
Authority
WO
WIPO (PCT)
Prior art keywords
microneedle
layer
microneedles
radiation sensitive
wafer
Prior art date
Application number
PCT/IL2003/000818
Other languages
French (fr)
Other versions
WO2004035105A3 (en
Inventor
Yehoshua Yeshurun
Meir Hefetz
Erwin Berenschot
Meint De Boer
Dominique Maria Alpeter
Gerrit Boom
Original Assignee
Nano Pass Technologies Ltd.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from IL152271A external-priority patent/IL152271A/en
Application filed by Nano Pass Technologies Ltd. filed Critical Nano Pass Technologies Ltd.
Priority to JP2005501333A priority Critical patent/JP2006502831A/en
Priority to EP03753894A priority patent/EP1559130A2/en
Priority to AU2003272053A priority patent/AU2003272053A1/en
Publication of WO2004035105A2 publication Critical patent/WO2004035105A2/en
Publication of WO2004035105A3 publication Critical patent/WO2004035105A3/en

Links

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M37/00Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
    • A61M37/0015Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M37/00Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
    • A61M37/0015Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
    • A61M2037/003Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles having a lumen
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M37/00Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
    • A61M37/0015Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
    • A61M2037/0053Methods for producing microneedles
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61NELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00Electrotherapy; Circuits therefor
    • A61N1/18Applying electric currents by contact electrodes
    • A61N1/20Applying electric currents by contact electrodes continuous direct currents
    • A61N1/30Apparatus for iontophoresis, i.e. transfer of media in ionic state by an electromotoric force into the body, or cataphoresis
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B81MICROSTRUCTURAL TECHNOLOGY
    • B81BMICROSTRUCTURAL DEVICES OR SYSTEMS, e.g. MICROMECHANICAL DEVICES
    • B81B2203/00Basic microelectromechanical structures
    • B81B2203/03Static structures
    • B81B2203/0361Tips, pillars

Definitions

  • the present invention relates to microneedles and, in particular, it concerns microneedles formed from radiation sensitive materials.
  • Microneedles have been known for many years, first being taught by U.S. Patent No. 3.964,482 to Gerstcl, filed June 1976.
  • Commercialization of microneedle technology has been difficult due to lack of an inexpensive production method as well as difficulty in finding suitable production materials which produce strong microneedles that will overcome tissue penetration problems and that will not break easily.
  • Polymer microneedle production currently employs techniques using molds to form the needle structure. These methods have inherent difficulties relating to the formation of hollow microneedles and thus are less useful for fluid transfer.
  • Prior art methods are typically expensive and the produced microneedles are relatively fragile.
  • prior art microneedles used in transdermal applications are not robust enough and therefore break upon entering the skin or the microneedles are not sharp enough and thus do not penetrate the skin effectively.
  • the present invention is a polymer microneedle construction and method of production thereof.
  • a method for producing microneedles comprising the steps of: (a) disposing a first layer of a radiation sensitive polymer on to a working surface; (b) selectively irradiating the first layer such that the first layer has at least one irradiated region and at least one non- irradiated region; and (c) developing the first layer so as to selectively remove one of the at least one irradiated region and the at least one non-irradiated region such that, at least part of at least one remaining region at least partially defines a form of at least part of a microneedle structure.
  • the at least part of the microneedle structure includes a plurality of at least partially formed microneedles.
  • each of at least two of the at least partially formed microneedles have a channel therein.
  • each of at least two of the at least partially formed microneedles have an oblique end surface.
  • At least two of the at least partially formed microneedles are different heights.
  • the at least part of the microneedle structure includes an at least partially formed microneedle having a channel therein.
  • the at least part of the microneedle structure includes an at least partially formed microneedle having an oblique end surface.
  • the base has at least one channel therein.
  • the step of irradiating the second layer is performed by selectively irradiating the second layer.
  • the step of forming at least one groove in the working surface such that the at least part of the microneedle structure is formed within the at least one groove, the at least one groove defining at least one oblique end surface of the microneedle structure.
  • the step of irradiating is performed using a light source producing visible light.
  • the step ⁇ T irradiating is performed using ultraviolet light.
  • the step of irradiating is performed using a x-ray radiation.
  • a radiation source which is used in the step of irradiating, and the working surface such that, the relative positioning of the radiation source and the working surface at least partially defining at least one oblique end surface of the microneedle structure.
  • a microneedle structure comprising a plurality of microneedles, each of the microneedles being at least partially formed from a radiation sensitive polymer.
  • a majority of each of the microneedles is formed from the radiation sensitive material.
  • a substructure configured to form a base for the microneedles, the substructure being at least partially formed from a radiation sensitive polymer.
  • the substructure has at least one channel therein.
  • each of at least two of the microneedles have a channel therein.
  • each of at least two of the microneedles have an oblique end surface.
  • At least two of the microneedles are different heights.
  • a microneedle structure comprising a microneedle, the microneedle being at least partially formed from a radiation sensitive polymer, the microneedle having a channel therein. According to a further feature of the present invention, a majority of the microneedle is formed from the radiation sensitive material.
  • a microneedle structure comprising a microneedle.
  • the microneedle being at least partially formed from a radiation sensitive polymer, the microneedle having an oblique end surface.
  • a majority of the microneedles is formed from the radiation sensitive material.
  • a method for producing microneedles comprising the steps of: (a) disposing a layer of a material on to a working surface; and (b) processing the layer so as to selectively remove one of at least one irradiated region and at least one non-irradiated region, such that, at least part of at least one remaining region at least partially defines a form of at least part of a microneedle structure, wherein the processing includes a sub-step of selectively acting upon the layer with radiation so as to effect at least one of a physical and a chemical change selectively in material of the layer.
  • Fig. 1 is a schematic isometric view of a microneedle structure that is constructed and operable in accordance with a preferred embodiment of the present invention:
  • Fig. 2 is a schematic cross-sectional view of a wafer coated with a thin layer of Silicon Nitride that is used in the construction of the microneedle structure of Fig. 1 ;
  • Fig. 3 is a schematic cross-sectional view of the wafer of Fig. 2 with a layer of photoresist coating the layer of Silicon Nitride;
  • Fig. 4 is a schematic cross-sectional view of the wafer of Fig. 3 after a series of parallel strips have been formed on the layer of photoresist;
  • Fig. 5 is a schematic cross-sectional view of the wafer of Fig. 4 after plasma etching, creating a serigs ⁇ pf parallel in the Silicon nitride layer;
  • Fig. 6 is a schematic cross-sectional view of the wafer of Fig. 5 after wet etching creating grooves therein:
  • Fi «. 7 is a schematic cross-sectional view of the wafer of Fig. 6 having a thin layer disposed Silicon Nitride thereon;
  • Fig. 8 is a schematic cross-sectional view of the wafer of Fig. 7 having a thick layer of photoresist spin coated thereon;
  • Fig. 9 is a schematic cross-sectional view of a layer of photoresist being irradiated through a mask in accordance with the prior art:
  • Fig. 10 is a schematic cross-sectional view of the wafer of Fig. 8 after selective irradiation and developing of the thick layer of photoresist, defining a form of microneedles:
  • Fig. 1 1 is a schematic cross-sectional view of a wafer having a microneedle disposed thereon, the microneedle having two oblique end surfaces that is constructed and operable in accordance with a first alternate embodiment of the present invention
  • Fig. 12 is a schematic cross-sectional view of a wafer having two microneedles disposed thereon, the microneedles being different heights that is constructed and operable in accordance with a second alternate embodiment of the present invention
  • Fig. 13 is a schematic cross-sectional view of a wafer having a thick layer of photoresist disposed thereon being selectively irradiated by a radiation source wherein the relative positioning of the radiation source and the wafer at least partially defines the oblique end surface of each microneedle that is constructed and operable in accordance with a third alternate embodiment of the present invention
  • Fig. 14 is a schematic cross-sectional view of a wafer having a thick layer of photoresist disposed thereon being selectively irradiated by a radiation source wherein the relative positioning of the radiation source and the wafer at least partially defines the oblique end surface of each microneedle that is constructed and operable in accordance with a fourth alternate embodiment of the present invention
  • Fig. 15 is a schematic cross-sectional view of possible microneedle structures that is constructed and operable in accordance with a fifth alternate embodiment of the present invention
  • Fig. 16 is a schematic cross-sectional view of the wafer of Fig. KThaving a filler layer of a polymer resist material disposed thereon surrounding the microneedles;
  • Fig. 17 is a schematic cross-sectional view of the wafer of Fig. 16 having a spin coated layer of photoresist disposed on top of the resist material and the microneedles:
  • Fig. 18 is a schematic cross-sectional view of the wafer of Fig. 17 after selectively irradiating and developing the layer of photoresist to define a base for the microneedles:
  • Fig. 19 is a schematic cross-sectional view of the microneedles and the base of Fig. 18 after being released from the wafer.
  • the present invention is a polymer microneedle construction and method of production thereof.
  • Microneedle structure 10 includes a plurality of microneedles 12 and a substructure 14 which acts as a base for microneedles 12. At least part of, and typically a majority of, each microneedle 12 and substructure 14 are formed from a radiation sensitive polymer, in that the form of microneedles 12 is typically wholly formed from a radiation sensitive material. Optionally, depending on the radiation sensitive polymer being used, microneedles 12 are coated with a material to make microneedles 12 biocompatible.
  • microneedles 12 are coated, using electrochemical techniques, with electrically conducting materials such as, titanium, gold and aluminum. These electrically conducting coated microneedles can be used for diagnosis, whereby microneedles 12 act as electrodes. Alternatively, these coated needles can be used lo enhance drug delivery by employing electrophoresis by passing an electric current between microneedles 12. Radiation sensitive materials are discussed in more detail with respect to Fig. 10. Each microneedle 12 typically has a channel therein. However, it should be noted that optionally, microneedle 12 is formed without a channel therein.
  • Substructure 14 typically has a channel therein for each channel of microneedles 12. such that therapeutic substances can be passed via the channels in substructure 14 through to the channels of microneedles 12 into the skin of the patient. Additionally, the channels can be used to remove biological fluids for sampling and/or collection from a patient. Additionally, each microneedle 12 has at least one oblique end surface giving microneedle 12 a sharp point for use in skin penetration. However, it should be noted that optionally, microneedle 12 is formed without an oblique end surface.
  • microneedles 12 of microneedle structure 10 are formed such that microneedles 12 have different heights.
  • Fig. 2 is a schematic cross-sectional view of a silicon wafer 16 coated with a thin layer of Silicon Nitride 18 that is used in the construction of microneedle structure 10 of Fig. 1.
  • wafer 16 is used as a working surface on which to form microneedle structure 10.
  • At least one groove 20 (Fig. 7) is formed in wafer 16, such that said the end portion of microneedle 12 is formed within groove 20.
  • Groove 20 defines the one or more oblique end surfaces of microneedle 12. The formation of groove 20 is described in more detail with respect to Fig. 2 to 7.
  • Initially wafer 16 is cleaned to remove all dust and contamination. The cleaning is done with alcohol based materials and drying with air.
  • Layer of Silicon Nitride 18 is disposed on wafer 16. The thickness of layer of
  • Silicon Nitride 18 is typically 300 nanometers. This coating is performed using a
  • Layer of Silicon Nitride 18 is used later as a mask for wet etching
  • FIG. 3 is a schematic cross-sectional view of wafer 16 of Fig. 2 after the following step is performed.
  • a layer of photoresist 22 is coated on lop of layer of Silicon Nitride 18. Materials suitable for layer of photoresist 22 are known to those skilled in the art.
  • Fig. 4. is a schematic cross-sectional view of wafer 16 of Fig. 3 after the following steps are performed.
  • Layer of photoresist 22 is exposed to light (photolithography process) through a KOH mask (not shown).
  • the KOH mask is configured such that when layer of photoresist 22 is developed, a series of parallel strips 24 are formed on wafer 16 in layer of photoresist 22. Radiation sources suitable for this step as well as developing techniques are known to those skilled in the art.
  • Fig. 5 is a schematic cross-sectional view of wafer 16 of Fig. 4 after the following step is performed. Plasma etching is performed creating a series of parallel strips 26 in layer of Silicon Nitride 18.
  • Fig. 6 is a schematic cross-sectional view of wafer 16 of Fig. 5 after the following step is performed.
  • Wet etching of wafer 16 is performed creating grooves 20 at the locations of parallel strips 26 (Fig. 5) where there is no protective layer of Silicon Nitride 18.
  • the wet etching process is performed by placing wafer 16 in a chemical bath for a short time. For example, by using chemicals such as THEM A or KOH. This wet etching process etches wafer 16 in its crystallographic plans to create grooves 20 in silicon wafer.
  • groove 20 act as a working surface on which to form the tips of microneedles 12 to give the tips at least one oblique end surface.
  • Fig. 7 is a schematic cross-sectional view of wafer 16 of Fig. 6 after the following steps are performed.
  • a thin layer of Silicon Nitride 28 is now disposed thereon in order to protect wafer 16 during later stages where a KOH chemical is used.
  • a layer of polysilicon (not shown) is then deposited on top of layer of Silicon Nitride 28 using a LPCVD process. This latter layer helps release of microneedle structure 10 from wafer 16 as will be described in more detail with respect to Fig. 19
  • Fig. 8 is a schematic cross-sectional view of wafer 16 of Fig. 7 after the following step is performed.
  • a thick layer of a radiation sensitive polymer 40 (photoresist), such as SU8, is disposed, typically by spin coating, on to the working surface of wafer 16 on top of layer of Silicon Nitride 28.
  • a radiation sensitive polymer 40 photoresist
  • Other examples suitable materials for layer of radiation sensitive polymer 40 are listed below in Table 1.
  • Fig. 9. is a schematic cross-sectional view of a layer of photoresist 30 being irradiated through a mask 32 in accordance with the prior art.
  • Arrows 34 represent the radiation incident on mask 32.
  • Irradiation through mask 32 creates irradiated regions 36 in layer of photoresist 30 and non-irradiated regions 38 in layer of photoresist 30.
  • Developing of layer of photoresist 30 removes either irradiated regions 36 or non-irradiated regions 38 depending on whether layer of photoresist 30 is a positive or negative photoresist. If layer of photoresist 30 is a negative photoresist then non-irradiated regions 38 are removed on developing.
  • layer of photoresist 30 is a positive photoresist then irradiated regions 36 are removed oh developing. It will be apparent to those ordinarily skilled in the art that the radiation sensitive polymer used in the method of the present invention is either positive or negative.
  • Fig. 10 is a schematic cross-sectional view of wafer 16 of Fig. 8 after processing of layer of radiation sensitive polymer 40 (Fig. 9) defining a form of microneedles 12.
  • This processing includes selectively acting upon layer of radiation sensitive polymer 40 with radiation so as to effect a physical and/or chemical change selectively in the material of layer of radiation sensitive polymer 40.
  • This processing typically includes selective irradiation and developing of layer of radiation sensitive polymer 40.
  • layer of radiation sensitive polymer 40 is selectively irradiated, typically using a mask, such that layer of radiation sensitive polymer 40 has one or more irradiated regions (not shown) and one or more non-irradiated regions (not shown).
  • the irradiating is typically performed using a light source producing visible light, ultraviolet light or by x ⁇ -ray radiation. It will be apparent to those skilled in the art that the radiation source depends on the material used for layer of radiation sensitive polymer 40. Other radiation sources and materials are known to those skilled in the art.
  • a radiation insensitive material could be embedded with a radiation sensitive material (such as PDMS. Polydimethsiloxane and PCB) acting as a precursor to make the combined material react when exposed to a radiation source.
  • a radiation sensitive material such as PDMS. Polydimethsiloxane and PCB
  • radiation sensitive material used in the claims includes combined materials which are sensitive to a radiation source.
  • Table L below is an example of suitable radiation sources and their corresponding radiation sensitive materials.
  • PDMS, PMMA and BCB are biocompatible as well as being used in the microfabrication technology and are therefore very suited to microneedle manufacture.
  • layer of radiation sensitive polymer 40 After layer of radiation sensitive polymer 40 is exposed to the radiation, a post exposure bake is performed on layer of radiation sensitive polymer 40. Then, layer of radiation sensitive polymer 40 is developed so as to selectively remove either the irradiated regions or n'Jfrgirradiated regions of layer of radiation sensitive polymer 40, depending on the type of polymer used (positive or negative) such that,- at least part of one or more remaining regions 46 at least partially defines a form of at least part of microneedles 12. The developing process is described as defining "a form" of at least part of microneedles 12 in that further processing is typically needed to make microneedles 12 usable. Remaining regions 46 are then rinsed and dried and then generally baked.
  • the above process defines the outer surface of microneedle 12 as well as the surface of the channel within microneedle 12. It will be appreciated by those skilled in the art that .the above process may be used to create one or more microneedles with or without channels therein. It will also be appreciated by those skilled in the art that the above process may be used to create one or more microneedles with or without one or more oblique end surfaces. The steps described with respect to Figs. 8 and 10 are repeated as necessary depending on the height of microneedles required.
  • FIG. 1 1 is a schematic cross-sectional view of a wafer 48 having a microneedle 50 disposed thereon that is constructed and operable in accordance with a first alternate embodiment of the present invention.
  • Microneedle 50 has two oblique end surfaces 52. Oblique end surfaces 52 are defined by forming microneedle 50 at the middle of a groove 54 in the surface of wafer 48.
  • Fig. 12 is a schematic cross-sectional view of a wafer 56 having two microneedles 58 disposed thereon that is constructed and operable in accordance with a second alternate embodiment of the present invention.
  • Wafer 56 has a groove 60 in the surface of wafer 56.
  • Microneedles 58 are formed at differing locations on groove 60 such that microneedles 58 have different heights.
  • Microneedle arrays having microneedles of different heights are known as three- dimensional microneedle arrays.
  • Three-dimensional microneedle arrays provides a three-dimensional dispersion of injected substances for drug delivery applications as well as enhanced sampling efficacy for diagnostic applications.
  • FIG. 13 is a schematic cross-sectional view of a wafer 62 having a thick layer of photoresist 64 disposed thereon being selectively irradiated by a radiatiorj ⁇ ource (not shown) through a mask 66 that is constructed and operable in accordance with a third alternate embodiment of the present invention.
  • Wafer 62 typically has a substantially fiat surface. Incident radiation is represented by arrows 68.
  • the relative positioning of the radiation source and wafer 62 at least partially defines an oblique end surface 70 of a microneedle 72.
  • the relative positioning of the radiation source and wafer 62 is described as "at least partially defines” in that if the surface of wafer 62 is not flat then the contours of the surface of wafer 62 will also define oblique end surface 70 of microneedle 72.
  • Fig. 14 is a schematic cross-sectional view of a wafer 74 having a thick layer of photoresist 76 disposed thereon being selectively irradiated by a radiation source (not shown) that is constructed and operable in accordance with a fourth alternate embodiment of the present invention.
  • Incident radiation is represented by arrows 78.
  • the relative positioning of the radiation source and wafer 74 at least partially defines an oblique end surface 80 of each microneedle 82.
  • the examples of both Fig. 13 and Fig. 14 have been brought to show that the relative positioning of the radiation source and the wafer define the shape of the end of the microneedles.
  • the orientation of the mask defines the width of the microneedles.
  • Fig. 15 is a schematic cross-sectional view of possible microneedle structures that is constructed and operable in accordance with a fifth alternate embodiment of the present invention.
  • shape of the microneedle including the outside shape as well as the shape of the inner channel is unlimited. These shapes are only based upon the configuration of the mask, the relative positioning of the radiation source and the working surface, as well as the shape of the working surface. Typical shapes include tubes, pyramids and cones with or without channels.
  • Microneedles 90, 92, 94 have channels which are not aligned with the tip of the needle.
  • the channels can be enlarged without effecting the size of the tip or the forces needed for skin penetration. Additionally, the fact that the structure and position of the tip can be manipulated allows for developing discrete applications, such as using needles for giejcing, cutting and fixing arrays on tissue.
  • the microneedle structure can be configured to meet the requirements of various types of applications.
  • drug delivery requires sharp needles to make holes.
  • balloon mounted microneedles need cutting knife or blade-type tips.
  • vaccination applications may require enlargement of the surface area of the penetrating object necessitating making jagged edged tips and channels.
  • FIG. 16 is a schematic cross-sectional view of wafer 16 of Fig. 10 after the following step is performed.
  • a filler layer 84 of a polymer resist material is disposed at least partially, typically completely, around remaining regions 46. The term “around” includes around the outside of microneedles 12 as well as in the channel of micronecclles 12.
  • Filler layer 84 acts as a filling material on which to build substructure 14 (Fig. 1).
  • Filler layer 84 extends from- layer of Silicon Nitride 28 to just below the base of microneedles 12.
  • filler layer 84 is used to define the length of microneedles 12.
  • Fig. 17 is a schematic cross-sectional view of wafer 16 of Fig. 16 after the following step is performed.
  • a layer of radiation sensitive polymer 86 such as SU8, is disposed, typically by spin coating, on top of filler layer 84 and remaining regions 46 (microneedles 12).
  • Fig. 18 is a schematic cross-sectional view of wafer 16 of Fig. 17 after the following steps are performed.
  • Layer of radiation sensitive polymer 86 (Fig. 17) is selectively irradiated, typically using a mask (not shown). This mask is configured to define a form of channels 88 in substructure 14 which join up with the channels in microneedles 12. Then, layer of radiation sensitive polymer 86 is developed such that layer of radiation sensitive polymer 86 forms a base for microneedle structure 10. Generally, layer of radiation sensitive polymer 86 is baked after the developing step.
  • Fig. 19 is a schematic cross-sectional view of microneedle structure 10 having microneedles 12 and substructure 14 of Fig. 18 after the following step is performed.
  • Microneedle structure 10 is released from wafer 16 (Fig. 18) using a KOH- ⁇ ching material.
  • the above method has been described with reference to using a radiation sensitive polymer to form microneedles 12, typically using a process including the steps of selective irradiation, developing and baking. It will be appreciated by those skilled in the art that some of these processing steps may not be needed depending on the chosen radiation sensitive polymer.
  • microneedle 12 are formed at least partially using micro- ablation techniques. For example, but not limited to. the form of microneedles 12 being defined by selectively irradiating a material using a high power radiation source which ablates unwanted material, leaving behind the form of microneedles 12.

Abstract

The method including disposing a first layer of a radiation sensitive polymer on to a working surface and selectively irradiating the first layer such that the first layer has at least one irradiated region and at least one non-irradiated region. The method also including developing the first layer so as to selectively remove one of the at least one irradiated region and the at least one non-irradiated region such that, at least part of at least one remaining region at least partially defines a form of at least part of a microneedle structure. A microneedle structure including a plurality of microneedles at least partially formed from a radiation sensitive polymer.

Description

POLYMER MJCRONEEDLES
FIELD AND BACKGROUND OF THE INVENTION
The present invention relates to microneedles and, in particular, it concerns microneedles formed from radiation sensitive materials.
Microneedles have been known for many years, first being taught by U.S. Patent No. 3.964,482 to Gerstcl, filed June 1976. However commercialization of microneedle technology has been difficult due to lack of an inexpensive production method as well as difficulty in finding suitable production materials which produce strong microneedles that will overcome tissue penetration problems and that will not break easily. Polymer microneedle production currently employs techniques using molds to form the needle structure. These methods have inherent difficulties relating to the formation of hollow microneedles and thus are less useful for fluid transfer. Prior art methods are typically expensive and the produced microneedles are relatively fragile. Generally, prior art microneedles used in transdermal applications are not robust enough and therefore break upon entering the skin or the microneedles are not sharp enough and thus do not penetrate the skin effectively.
Therefore there is a need for a method to produce an inexpensive, robust, sharp, hollow as well as non-hollow array of microneedles, typically for drug delivery and diagnostics. SUMMARY OF THE INVENTION
The present invention is a polymer microneedle construction and method of production thereof.
According to the teachings of the present invention there is provided, a method for producing microneedles, comprising the steps of: (a) disposing a first layer of a radiation sensitive polymer on to a working surface; (b) selectively irradiating the first layer such that the first layer has at least one irradiated region and at least one non- irradiated region; and (c) developing the first layer so as to selectively remove one of the at least one irradiated region and the at least one non-irradiated region such that, at least part of at least one remaining region at least partially defines a form of at least part of a microneedle structure. According to a further feature of the present invention, the at least part of the microneedle structure includes a plurality of at least partially formed microneedles.
According to a further feature of the present invention, each of at least two of the at least partially formed microneedles have a channel therein.
According to a further feature of the present invention, each of at least two of the at least partially formed microneedles have an oblique end surface.
According to a further feature of the present invention, at least two of the at least partially formed microneedles are different heights.
According to a further feature of the present invention, the at least part of the microneedle structure includes an at least partially formed microneedle having a channel therein.
According to a further feature of the present invention, the at least part of the microneedle structure includes an at least partially formed microneedle having an oblique end surface.
According to a further feature of the present invention, there is also provided, after the step of developing, the steps of: (a) disposing a filler at least partially around the at least one remaining region; (b) disposing a second layer of a radiation sensitive polymer on to: (i) at least part of the at least one remaining region; and (ii) at least part of the filler; (c) irradiating the second layer; and (d) developing the second layer such that, the second layer forms a base for at least part of the microneedle structure.
According to a further feature of the present invention, the base has at least one channel therein.
According to a further feature of the present invention, the step of irradiating the second layer is performed by selectively irradiating the second layer.
According to a further feature of the present invention, there is also provided the step of forming at least one groove in the working surface, such that the at least part of the microneedle structure is formed within the at least one groove, the at least one groove defining at least one oblique end surface of the microneedle structure.
According to a further feature of the present invention, the step of irradiating is performed using a light source producing visible light. According to a further feature of the present invention, the step όT irradiating is performed using ultraviolet light.
According to a further feature of the present invention, the step of irradiating is performed using a x-ray radiation.
According to a further feature of the present invention, there is also provided disposing a radiation source, which is used in the step of irradiating, and the working surface such that, the relative positioning of the radiation source and the working surface at least partially defining at least one oblique end surface of the microneedle structure.
According to the teachings of the present invention there is also provided, a microneedle structure, comprising a plurality of microneedles, each of the microneedles being at least partially formed from a radiation sensitive polymer.
According to a further feature of the present invention, a majority of each of the microneedles is formed from the radiation sensitive material.
According to a further feature of the present invention, there is also provided a substructure configured to form a base for the microneedles, the substructure being at least partially formed from a radiation sensitive polymer.
According to a further feature of the present invention, the substructure has at least one channel therein.
According to a further feature of the present invention, each of at least two of the microneedles have a channel therein.
According to a further feature of the present invention, each of at least two of the microneedles have an oblique end surface.
According to a further feature of the present invention, at least two of the microneedles are different heights.
According to the teachings of the present invention there is also provided, a microneedle structure, comprising a microneedle, the microneedle being at least partially formed from a radiation sensitive polymer, the microneedle having a channel therein. According to a further feature of the present invention, a majority of the microneedle is formed from the radiation sensitive material.
According to the teachings of the present invention there is also provided, a microneedle structure, comprising a microneedle. the microneedle being at least partially formed from a radiation sensitive polymer, the microneedle having an oblique end surface.
According to a further feature of the present invention, a majority of the microneedles is formed from the radiation sensitive material.
According to the teachings of the present invention there is also provided, a method for producing microneedles, comprising the steps of: (a) disposing a layer of a material on to a working surface; and (b) processing the layer so as to selectively remove one of at least one irradiated region and at least one non-irradiated region, such that, at least part of at least one remaining region at least partially defines a form of at least part of a microneedle structure, wherein the processing includes a sub-step of selectively acting upon the layer with radiation so as to effect at least one of a physical and a chemical change selectively in material of the layer. BRIEF DESCRIPTION OF THE DRAWINGS
The invention is herein described, by way of example only, with reference to the accompanying drawings, wherein:
Fig. 1 is a schematic isometric view of a microneedle structure that is constructed and operable in accordance with a preferred embodiment of the present invention:
Fig. 2 is a schematic cross-sectional view of a wafer coated with a thin layer of Silicon Nitride that is used in the construction of the microneedle structure of Fig. 1 ;
Fig. 3 is a schematic cross-sectional view of the wafer of Fig. 2 with a layer of photoresist coating the layer of Silicon Nitride;
Fig. 4 is a schematic cross-sectional view of the wafer of Fig. 3 after a series of parallel strips have been formed on the layer of photoresist;
Fig. 5 is a schematic cross-sectional view of the wafer of Fig. 4 after plasma etching, creating a serigs^pf parallel in the Silicon nitride layer; Fig. 6 is a schematic cross-sectional view of the wafer of Fig. 5 after wet etching creating grooves therein:
Fi«. 7 is a schematic cross-sectional view of the wafer of Fig. 6 having a thin layer disposed Silicon Nitride thereon;
Fig. 8 is a schematic cross-sectional view of the wafer of Fig. 7 having a thick layer of photoresist spin coated thereon;
Fig. 9 is a schematic cross-sectional view of a layer of photoresist being irradiated through a mask in accordance with the prior art:
Fig. 10 is a schematic cross-sectional view of the wafer of Fig. 8 after selective irradiation and developing of the thick layer of photoresist, defining a form of microneedles:
Fig. 1 1 is a schematic cross-sectional view of a wafer having a microneedle disposed thereon, the microneedle having two oblique end surfaces that is constructed and operable in accordance with a first alternate embodiment of the present invention;
Fig. 12 is a schematic cross-sectional view of a wafer having two microneedles disposed thereon, the microneedles being different heights that is constructed and operable in accordance with a second alternate embodiment of the present invention;
Fig. 13 is a schematic cross-sectional view of a wafer having a thick layer of photoresist disposed thereon being selectively irradiated by a radiation source wherein the relative positioning of the radiation source and the wafer at least partially defines the oblique end surface of each microneedle that is constructed and operable in accordance with a third alternate embodiment of the present invention;
Fig. 14 is a schematic cross-sectional view of a wafer having a thick layer of photoresist disposed thereon being selectively irradiated by a radiation source wherein the relative positioning of the radiation source and the wafer at least partially defines the oblique end surface of each microneedle that is constructed and operable in accordance with a fourth alternate embodiment of the present invention;
Fig. 15 is a schematic cross-sectional view of possible microneedle structures that is constructed and operable in accordance with a fifth alternate embodiment of the present invention; Fig. 16 is a schematic cross-sectional view of the wafer of Fig. KThaving a filler layer of a polymer resist material disposed thereon surrounding the microneedles;
Fig. 17 is a schematic cross-sectional view of the wafer of Fig. 16 having a spin coated layer of photoresist disposed on top of the resist material and the microneedles:
Fig. 18 is a schematic cross-sectional view of the wafer of Fig. 17 after selectively irradiating and developing the layer of photoresist to define a base for the microneedles: and
Fig. 19 is a schematic cross-sectional view of the microneedles and the base of Fig. 18 after being released from the wafer.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
The present invention is a polymer microneedle construction and method of production thereof.
The principles and method of production of the polymer microneedle construction according to the present invention may be better understood with reference to the drawings and the accompanying description.
A publication entitled "Process development for polymer needles by using SU-8 technology and silicon molding techniques'" by Dominique Maria Altpeter of Mesa-t- Institute, University of Twente, Enschede, Netherlands is incorporated by reference for all purposes as if fully set forth herein.
Reference is now made to Fig. 1 , which is a schematic isometric view of a microneedle structure 10 that is constructed and operable in accordance with a preferred embodiment of the present invention. Microneedle structure 10 includes a plurality of microneedles 12 and a substructure 14 which acts as a base for microneedles 12. At least part of, and typically a majority of, each microneedle 12 and substructure 14 are formed from a radiation sensitive polymer, in that the form of microneedles 12 is typically wholly formed from a radiation sensitive material. Optionally, depending on the radiation sensitive polymer being used, microneedles 12 are coated with a material to make microneedles 12 biocompatible. Optionally, microneedles 12 are coated, using electrochemical techniques, with electrically conducting materials such as, titanium, gold and aluminum. These electrically conducting coated microneedles can be used for diagnosis, whereby microneedles 12 act as electrodes. Alternatively, these coated needles can be used lo enhance drug delivery by employing electrophoresis by passing an electric current between microneedles 12. Radiation sensitive materials are discussed in more detail with respect to Fig. 10. Each microneedle 12 typically has a channel therein. However, it should be noted that optionally, microneedle 12 is formed without a channel therein.
Substructure 14 typically has a channel therein for each channel of microneedles 12. such that therapeutic substances can be passed via the channels in substructure 14 through to the channels of microneedles 12 into the skin of the patient. Additionally, the channels can be used to remove biological fluids for sampling and/or collection from a patient. Additionally, each microneedle 12 has at least one oblique end surface giving microneedle 12 a sharp point for use in skin penetration. However, it should be noted that optionally, microneedle 12 is formed without an oblique end surface.
Optionally, microneedles 12 of microneedle structure 10 are formed such that microneedles 12 have different heights. These and other features and their method of manufacture are described in more detail with respect to Figs. 2 to 19.
Reference is now made to Fig. 2, which is a schematic cross-sectional view of a silicon wafer 16 coated with a thin layer of Silicon Nitride 18 that is used in the construction of microneedle structure 10 of Fig. 1. By way of introduction, wafer 16 is used as a working surface on which to form microneedle structure 10. At least one groove 20 (Fig. 7) is formed in wafer 16, such that said the end portion of microneedle 12 is formed within groove 20. Groove 20 defines the one or more oblique end surfaces of microneedle 12. The formation of groove 20 is described in more detail with respect to Fig. 2 to 7. Initially wafer 16 is cleaned to remove all dust and contamination. The cleaning is done with alcohol based materials and drying with air. Layer of Silicon Nitride 18 is disposed on wafer 16. The thickness of layer of
Silicon Nitride 18 is typically 300 nanometers. This coating is performed using a
LPCVD process. Layer of Silicon Nitride 18 is used later as a mask for wet etching
(Fig. 6). Reference is now made to Fig. 3. which is a schematic cross-sectional view of wafer 16 of Fig. 2 after the following step is performed. A layer of photoresist 22 is coated on lop of layer of Silicon Nitride 18. Materials suitable for layer of photoresist 22 are known to those skilled in the art.
Reference is now made to Fig. 4. which is a schematic cross-sectional view of wafer 16 of Fig. 3 after the following steps are performed. Layer of photoresist 22 is exposed to light (photolithography process) through a KOH mask (not shown). The KOH mask is configured such that when layer of photoresist 22 is developed, a series of parallel strips 24 are formed on wafer 16 in layer of photoresist 22. Radiation sources suitable for this step as well as developing techniques are known to those skilled in the art.
Reference is- now made to Fig. 5, which is a schematic cross-sectional view of wafer 16 of Fig. 4 after the following step is performed. Plasma etching is performed creating a series of parallel strips 26 in layer of Silicon Nitride 18.
Reference is now made to Fig. 6, which is a schematic cross-sectional view of wafer 16 of Fig. 5 after the following step is performed. Wet etching of wafer 16 is performed creating grooves 20 at the locations of parallel strips 26 (Fig. 5) where there is no protective layer of Silicon Nitride 18. The wet etching process is performed by placing wafer 16 in a chemical bath for a short time. For example, by using chemicals such as THEM A or KOH. This wet etching process etches wafer 16 in its crystallographic plans to create grooves 20 in silicon wafer. As described above with respect to Fig. 2, groove 20 act as a working surface on which to form the tips of microneedles 12 to give the tips at least one oblique end surface.
Reference is now made to Fig. 7, which is a schematic cross-sectional view of wafer 16 of Fig. 6 after the following steps are performed. A thin layer of Silicon Nitride 28 is now disposed thereon in order to protect wafer 16 during later stages where a KOH chemical is used. A layer of polysilicon (not shown) is then deposited on top of layer of Silicon Nitride 28 using a LPCVD process. This latter layer helps release of microneedle structure 10 from wafer 16 as will be described in more detail with respect to Fig. 19 Reference is now made to Fig. 8, which is a schematic cross-sectional view of wafer 16 of Fig. 7 after the following step is performed. A thick layer of a radiation sensitive polymer 40 (photoresist), such as SU8, is disposed, typically by spin coating, on to the working surface of wafer 16 on top of layer of Silicon Nitride 28. Other examples suitable materials for layer of radiation sensitive polymer 40 are listed below in Table 1.
Reference is now made to Fig. 9. which is a schematic cross-sectional view of a layer of photoresist 30 being irradiated through a mask 32 in accordance with the prior art. Arrows 34 represent the radiation incident on mask 32. Irradiation through mask 32 creates irradiated regions 36 in layer of photoresist 30 and non-irradiated regions 38 in layer of photoresist 30. Developing of layer of photoresist 30 removes either irradiated regions 36 or non-irradiated regions 38 depending on whether layer of photoresist 30 is a positive or negative photoresist. If layer of photoresist 30 is a negative photoresist then non-irradiated regions 38 are removed on developing. If layer of photoresist 30 is a positive photoresist then irradiated regions 36 are removed oh developing. It will be apparent to those ordinarily skilled in the art that the radiation sensitive polymer used in the method of the present invention is either positive or negative.
Reference is now made to Fig. 10, which is a schematic cross-sectional view of wafer 16 of Fig. 8 after processing of layer of radiation sensitive polymer 40 (Fig. 9) defining a form of microneedles 12. This processing includes selectively acting upon layer of radiation sensitive polymer 40 with radiation so as to effect a physical and/or chemical change selectively in the material of layer of radiation sensitive polymer 40. This processing typically includes selective irradiation and developing of layer of radiation sensitive polymer 40. These steps are described in more detail below. First, layer of a radiation sensitive polymer 40 (Fig. 9) is selectively irradiated, typically using a mask, such that layer of radiation sensitive polymer 40 has one or more irradiated regions (not shown) and one or more non-irradiated regions (not shown). The irradiating is typically performed using a light source producing visible light, ultraviolet light or by x^-ray radiation. It will be apparent to those skilled in the art that the radiation source depends on the material used for layer of radiation sensitive polymer 40. Other radiation sources and materials are known to those skilled in the art.
It should be noted that a radiation insensitive material could be embedded with a radiation sensitive material (such as PDMS. Polydimethsiloxane and PCB) acting as a precursor to make the combined material react when exposed to a radiation source.
The term "radiation sensitive material" used in the claims includes combined materials which are sensitive to a radiation source.
Table L below, is an example of suitable radiation sources and their corresponding radiation sensitive materials.
Figure imgf000012_0001
It should be noted that PDMS, PMMA and BCB are biocompatible as well as being used in the microfabrication technology and are therefore very suited to microneedle manufacture.
After layer of radiation sensitive polymer 40 is exposed to the radiation, a post exposure bake is performed on layer of radiation sensitive polymer 40. Then, layer of radiation sensitive polymer 40 is developed so as to selectively remove either the irradiated regions or n'Jfrgirradiated regions of layer of radiation sensitive polymer 40, depending on the type of polymer used (positive or negative) such that,- at least part of one or more remaining regions 46 at least partially defines a form of at least part of microneedles 12. The developing process is described as defining "a form" of at least part of microneedles 12 in that further processing is typically needed to make microneedles 12 usable. Remaining regions 46 are then rinsed and dried and then generally baked. The above process defines the outer surface of microneedle 12 as well as the surface of the channel within microneedle 12. It will be appreciated by those skilled in the art that .the above process may be used to create one or more microneedles with or without channels therein. It will also be appreciated by those skilled in the art that the above process may be used to create one or more microneedles with or without one or more oblique end surfaces. The steps described with respect to Figs. 8 and 10 are repeated as necessary depending on the height of microneedles required.
Reference is now made to Fig. 1 1 , which is a schematic cross-sectional view of a wafer 48 having a microneedle 50 disposed thereon that is constructed and operable in accordance with a first alternate embodiment of the present invention. Microneedle 50 has two oblique end surfaces 52. Oblique end surfaces 52 are defined by forming microneedle 50 at the middle of a groove 54 in the surface of wafer 48.
Reference is now made to Fig. 12, which is a schematic cross-sectional view of a wafer 56 having two microneedles 58 disposed thereon that is constructed and operable in accordance with a second alternate embodiment of the present invention. Wafer 56 has a groove 60 in the surface of wafer 56. Microneedles 58 are formed at differing locations on groove 60 such that microneedles 58 have different heights. Microneedle arrays having microneedles of different heights are known as three- dimensional microneedle arrays. Three-dimensional microneedle arrays provides a three-dimensional dispersion of injected substances for drug delivery applications as well as enhanced sampling efficacy for diagnostic applications.
Reference is now made to Fig. 13, which is a schematic cross-sectional view of a wafer 62 having a thick layer of photoresist 64 disposed thereon being selectively irradiated by a radiatiorj^ource (not shown) through a mask 66 that is constructed and operable in accordance with a third alternate embodiment of the present invention.
Wafer 62 typically has a substantially fiat surface. Incident radiation is represented by arrows 68. The relative positioning of the radiation source and wafer 62 at least partially defines an oblique end surface 70 of a microneedle 72. The relative positioning of the radiation source and wafer 62 is described as "at least partially defines" in that if the surface of wafer 62 is not flat then the contours of the surface of wafer 62 will also define oblique end surface 70 of microneedle 72.
Reference is now made to Fig. 14, which is a schematic cross-sectional view of a wafer 74 having a thick layer of photoresist 76 disposed thereon being selectively irradiated by a radiation source (not shown) that is constructed and operable in accordance with a fourth alternate embodiment of the present invention. Incident radiation is represented by arrows 78. The relative positioning of the radiation source and wafer 74 at least partially defines an oblique end surface 80 of each microneedle 82. The examples of both Fig. 13 and Fig. 14 have been brought to show that the relative positioning of the radiation source and the wafer define the shape of the end of the microneedles. The orientation of the mask defines the width of the microneedles.
Reference is now made to Fig. 15, which is a schematic cross-sectional view of possible microneedle structures that is constructed and operable in accordance with a fifth alternate embodiment of the present invention. It will be appreciated by those skilled in the art that the shape of the microneedle including the outside shape as well as the shape of the inner channel is unlimited. These shapes are only based upon the configuration of the mask, the relative positioning of the radiation source and the working surface, as well as the shape of the working surface. Typical shapes include tubes, pyramids and cones with or without channels. Microneedles 90, 92, 94 have channels which are not aligned with the tip of the needle. Therefore, if a greater flow of fluids is needed, the channels can be enlarged without effecting the size of the tip or the forces needed for skin penetration. Additionally, the fact that the structure and position of the tip can be manipulated allows for developing discrete applications, such as using needles for giejcing, cutting and fixing arrays on tissue. The microneedle structure can be configured to meet the requirements of various types of applications.
By way of a first example, drug delivery requires sharp needles to make holes. By way of a second example, balloon mounted microneedles need cutting knife or blade-type tips. By way of a third example, vaccination applications may require enlargement of the surface area of the penetrating object necessitating making jagged edged tips and channels.
Reference is now made to Fig. 16. which is a schematic cross-sectional view of wafer 16 of Fig. 10 after the following step is performed. A filler layer 84 of a polymer resist material is disposed at least partially, typically completely, around remaining regions 46. The term "around" includes around the outside of microneedles 12 as well as in the channel of micronecclles 12. Filler layer 84 acts as a filling material on which to build substructure 14 (Fig. 1). Filler layer 84 extends from- layer of Silicon Nitride 28 to just below the base of microneedles 12. Optionally filler layer 84 is used to define the length of microneedles 12.
Reference is now made to Fig. 17, which is a schematic cross-sectional view of wafer 16 of Fig. 16 after the following step is performed. A layer of radiation sensitive polymer 86, such as SU8, is disposed, typically by spin coating, on top of filler layer 84 and remaining regions 46 (microneedles 12).
Reference is now made to Fig. 18, which is a schematic cross-sectional view of wafer 16 of Fig. 17 after the following steps are performed. Layer of radiation sensitive polymer 86 (Fig. 17) is selectively irradiated, typically using a mask (not shown). This mask is configured to define a form of channels 88 in substructure 14 which join up with the channels in microneedles 12. Then, layer of radiation sensitive polymer 86 is developed such that layer of radiation sensitive polymer 86 forms a base for microneedle structure 10. Generally, layer of radiation sensitive polymer 86 is baked after the developing step.
Reference is now made to Fig. 19, which is a schematic cross-sectional view of microneedle structure 10 having microneedles 12 and substructure 14 of Fig. 18 after the following step is performed. Microneedle structure 10 is released from wafer 16 (Fig. 18) using a KOH-^ching material. The above method has been described with reference to using a radiation sensitive polymer to form microneedles 12, typically using a process including the steps of selective irradiation, developing and baking. It will be appreciated by those skilled in the art that some of these processing steps may not be needed depending on the chosen radiation sensitive polymer. It will also be appreciated by those skilled in the art that, optionally, microneedle 12 are formed at least partially using micro- ablation techniques. For example, but not limited to. the form of microneedles 12 being defined by selectively irradiating a material using a high power radiation source which ablates unwanted material, leaving behind the form of microneedles 12.
It will be appreciated by persons skilled in the art that the present invention is not limited to what has been particularly shown and described hereinabove. Rather, the scope of the present invention includes both combinations and sub-combinations of the various features described hereinabove, as well as variations and modifications thereof that are not in the prior art which would occur to persons skilled in the art -upon reading the foregoing description.

Claims

WHAT IS CLAIMED IS:
1. A method for producing microneedles, comprising the steps of:
(a) disposing a first layer of a radiation sensitive polymer on to a working surface:
(b) selectively irradiating said first layer such that said first layer has at least one irradiated region and at least one non-irradiated region; and
(c) developing said first layer so as to selectively remove one of said at least one irradiated region and said at least one non-irradiated region such that, at least part of at least one remaining region at least partially defines a form of at least part of a microneedle structure.
2. The method of claim 1 , wherein said at least part of said microneedle structure includes a plurality of at least partially formed microneedles.
3. The method of claim 2, wherein each of at least two of said at least partially formed microneedles have a channel therein.
4. The method of claim 2, wherein each of at least two of said at least partially formed microneedles have an oblique end surface.
5. The method of claim 2, wherein at least two of said at least partially formed microneedles are different heights.
6. The method of claim 1 , wherein said at least part of said microneedle structure includes an at least partially formed microneedle having a channel therein.
7. The method of claim 1. wherein said at least part of said microneedle structure includes an at least partially formed microneedle having an oblique end surface.
8. The method of claim 1. further comprising, after said step of developing, the steps of:
(a) disposing a filler at least partially around said at least one remaining region:
(b) disposing a second layer of a radiation sensitive polymer on to: (i) at least part of said at least one remaining region: and (ii) at least part of said filler;
(c) irradiating said second layer; and
(d) developing said second layer such that, said second layer forms a base for at least part of said microneedle structure.
9. The method of claim 8, wherein said base has at least one channel therein.
10. The method of claim 8, wherein said step of irradiating said second layer is performed by selectively irradiating said second layer.
1 1. The method of claim 1 , further comprising the step of forming at least one groove in said working surface, such that said at least part of said microneedle structure is formed within said at least one groove, said at least one groove defining at least one oblique end surface of aid microneedle structure.
12. The method of claim 1 , wherein said step of irradiating is performed using a light source producing visible light.
13. The method of claim 1 , wherein said step of irradiating is performed using ultraviolet light.
14. The method of claim 1 , wherein said step of irradiating is performed using a x-ray radiation.
15. The method of claim 1. further comprising disposing a radiation source, which is used in said step of irradiating, and said working surface such that, the relative positioning of said radiation source and said working surface at least partially defining at least one oblique end surface of said microneedle structure.
16. A microneedle structure, comprising a plurality of "microneedles. each of said microneedles being at least partially formed from a radiation sensitive polymer.
17. The structure of claim 16, wherein a majority of each of said microneedles is formed from said radiation sensitive material.
18. The structure of claim 16, further comprising a substructure configured to form a base for said microneedles, said substructure being at least partially formed from a radiation sensitive polymer.
19. The structure of claim 18, wherein said substructure has at least one channel therein.
20. The structure of claim 16, wherein each of at least two of said microneedles have a channel therein.
21. The structure of claim 16, wherein each of at least two of said microneedles have an oblique end surface.
22. The structure of claim 16, wherein at least two of said microneedles are different heights.
23. A microneedle structure, comprising a microneedle, said microneedle being at least partially formed from a radiation sensitive polymer, said microneedle having a channel therein.
24. The microneedle structure of claim 23, wherein a majority of said microneedle is formed from said radiation sensitive material.
25. A microneedle structure, comprising a microneedle, said microneedle being at least partially formed from a radiation sensitive polymer, said microneedle having an oblique end surface.
26. The microneedle structure of claim 25, wherein a majority of said microneedles is formed from said radiation sensitive material.
27. A method for producing microneedles, comprising the steps of:
(a) disposing a layer of a material on to a working surface; and
(b) processing said layer so as to selectively remove one of at least one irradiated region and at least one non-irradiated region, such that, at least part of at least one remaining region at least partially defines a form of at least part of a microneedle structure, wherein said processing includes a sub-step of selectively acting upon said layer with radiation so as to effect at least one of a physical and a chemical change selectively in material of said layer.
PCT/IL2003/000818 2002-10-13 2003-10-09 Polymer microneedles WO2004035105A2 (en)

Priority Applications (3)

Application Number Priority Date Filing Date Title
JP2005501333A JP2006502831A (en) 2002-10-13 2003-10-09 Resin microneedle
EP03753894A EP1559130A2 (en) 2002-10-13 2003-10-09 Polymer microneedles
AU2003272053A AU2003272053A1 (en) 2002-10-13 2003-10-09 Polymer microneedles

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
IL152271A IL152271A (en) 2002-10-13 2002-10-13 Microneedles structures and production methods
IL152271 2002-10-13
US10/397,359 2003-03-27
US10/397,359 US6924087B2 (en) 2002-10-13 2003-03-27 Polymer microneedles

Publications (2)

Publication Number Publication Date
WO2004035105A2 true WO2004035105A2 (en) 2004-04-29
WO2004035105A3 WO2004035105A3 (en) 2004-09-30

Family

ID=32109297

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IL2003/000818 WO2004035105A2 (en) 2002-10-13 2003-10-09 Polymer microneedles

Country Status (4)

Country Link
EP (1) EP1559130A2 (en)
JP (1) JP2006502831A (en)
AU (1) AU2003272053A1 (en)
WO (1) WO2004035105A2 (en)

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006018642A1 (en) * 2004-08-16 2006-02-23 Functional Microstructures Limited Method of producing a microneedle or microimplant
WO2006075716A1 (en) * 2005-01-14 2006-07-20 Fujikura Ltd. Drug delivery instrument and method of producing the same
US9394547B2 (en) 2012-01-03 2016-07-19 City University Of Hong Kong Method and apparatus for delivery of molecules to cells
US9526884B2 (en) 2012-11-16 2016-12-27 City University Of Hong Kong Mechanically robust fast-dissolving microneedles for transdermal drug and vaccine delivery
CN111643804A (en) * 2015-03-18 2020-09-11 凸版印刷株式会社 Medicament administration device
US11717660B2 (en) 2021-07-29 2023-08-08 Nanopass Technologies Ltd. Silicon microneedle structure and production method

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP5028872B2 (en) * 2006-03-02 2012-09-19 凸版印刷株式会社 Manufacturing method of needle-shaped body

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6093520A (en) * 1994-09-09 2000-07-25 Board Of Supervisors Of Louisiana State University And Agricultural And Mechanical College High aspect ratio microstructures and methods for manufacturing microstructures
US20020155737A1 (en) * 2000-08-21 2002-10-24 The Cleveland Clinic Foundation Microneedle array module and method of fabricating the same

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6093520A (en) * 1994-09-09 2000-07-25 Board Of Supervisors Of Louisiana State University And Agricultural And Mechanical College High aspect ratio microstructures and methods for manufacturing microstructures
US20020155737A1 (en) * 2000-08-21 2002-10-24 The Cleveland Clinic Foundation Microneedle array module and method of fabricating the same

Cited By (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006018642A1 (en) * 2004-08-16 2006-02-23 Functional Microstructures Limited Method of producing a microneedle or microimplant
EP2272430A1 (en) * 2004-08-16 2011-01-12 Functional Microstructures Limited Method of producing a microneedle or microimplant
EP2289646A1 (en) * 2004-08-16 2011-03-02 Functional Microstructures Limited Microneedle or microimplant and method for making same
US8192787B2 (en) 2004-08-16 2012-06-05 Innoture Limited Method of producing a microneedle or microimplant
WO2006075716A1 (en) * 2005-01-14 2006-07-20 Fujikura Ltd. Drug delivery instrument and method of producing the same
JP5053645B2 (en) * 2005-01-14 2012-10-17 久光製薬株式会社 Medicinal product carrying device and method for producing the same
US9394547B2 (en) 2012-01-03 2016-07-19 City University Of Hong Kong Method and apparatus for delivery of molecules to cells
US9526884B2 (en) 2012-11-16 2016-12-27 City University Of Hong Kong Mechanically robust fast-dissolving microneedles for transdermal drug and vaccine delivery
CN111643804A (en) * 2015-03-18 2020-09-11 凸版印刷株式会社 Medicament administration device
US11717660B2 (en) 2021-07-29 2023-08-08 Nanopass Technologies Ltd. Silicon microneedle structure and production method

Also Published As

Publication number Publication date
JP2006502831A (en) 2006-01-26
WO2004035105A3 (en) 2004-09-30
AU2003272053A1 (en) 2004-05-04
EP1559130A2 (en) 2005-08-03
AU2003272053A8 (en) 2004-05-04

Similar Documents

Publication Publication Date Title
US6924087B2 (en) Polymer microneedles
US8250729B2 (en) 3D fabrication of needle tip geometry and knife blade
JP4778669B2 (en) Method for manufacturing microneedles structures using soft lithography and photolithography
CA2376286C (en) Intracutaneous edged microneedle structure
US6451240B1 (en) Method of manufacturing an intracutaneous microneedle array
EP1183065B1 (en) Intracutaneous microneedle array apparatus
KR100563330B1 (en) Method for manufacturing of polymer micro needle array with liga process
US6899838B2 (en) Method of forming a mold and molding a micro-device
CN107073210B (en) Microfluidic device and fabrication
JP2004529726A (en) Minimal surgical instruments
KR100679714B1 (en) Microspikes structured of three dimensions and method of manufacturing the same
EP1559130A2 (en) Polymer microneedles
CN101862503B (en) Method for preparing off-plane hollow microneedle array for use in transdermal medicament administration
JP7256821B2 (en) Electrofunctional polymer microneedle array
Park et al. High-aspect-ratio tapered structures using an integrated lens technique
WO2019243915A1 (en) Hollow microneedle for transdermal delivery of active molecules and/or for the sampling of biological fluids and manufacturing method of such hollow microneedle
JP3784014B2 (en) Puncture needle
Zhang Fabrication of Hollow Silicon Microneedle Arrays for Transdermal Biological Fluid Extraction

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A2

Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BY BZ CA CH CN CO CR CU CZ DE DK DM DZ EC EE EG ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NI NO NZ OM PG PH PL PT RO RU SC SD SE SG SK SL SY TJ TM TN TR TT TZ UA UG US UZ VC VN YU ZA ZM ZW

AL Designated countries for regional patents

Kind code of ref document: A2

Designated state(s): GH GM KE LS MW MZ SD SL SZ TZ UG ZM ZW AM AZ BY KG KZ MD RU TJ TM AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IT LU MC NL PT RO SE SI SK TR BF BJ CF CG CI CM GA GN GQ GW ML MR NE SN TD TG

121 Ep: the epo has been informed by wipo that ep was designated in this application
WWE Wipo information: entry into national phase

Ref document number: 2005501333

Country of ref document: JP

WWE Wipo information: entry into national phase

Ref document number: 2003753894

Country of ref document: EP

WWP Wipo information: published in national office

Ref document number: 2003753894

Country of ref document: EP