WO2011095386A2 - Procédé de fabrication pour un système de micro-aiguilles poreuses avec raccordement du côté arrière et système de micro-aiguilles poreuses correspondant - Google Patents

Procédé de fabrication pour un système de micro-aiguilles poreuses avec raccordement du côté arrière et système de micro-aiguilles poreuses correspondant Download PDF

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Publication number
WO2011095386A2
WO2011095386A2 PCT/EP2011/050549 EP2011050549W WO2011095386A2 WO 2011095386 A2 WO2011095386 A2 WO 2011095386A2 EP 2011050549 W EP2011050549 W EP 2011050549W WO 2011095386 A2 WO2011095386 A2 WO 2011095386A2
Authority
WO
WIPO (PCT)
Prior art keywords
region
porous
microneedle
layer
support
Prior art date
Application number
PCT/EP2011/050549
Other languages
German (de)
English (en)
Other versions
WO2011095386A3 (fr
Inventor
Michael Stumber
Ando Feyh
Original Assignee
Robert Bosch Gmbh
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
Application filed by Robert Bosch Gmbh filed Critical Robert Bosch Gmbh
Publication of WO2011095386A2 publication Critical patent/WO2011095386A2/fr
Publication of WO2011095386A3 publication Critical patent/WO2011095386A3/fr

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Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B81—MICROSTRUCTURAL TECHNOLOGY
    • B81C—PROCESSES OR APPARATUS SPECIALLY ADAPTED FOR THE MANUFACTURE OR TREATMENT OF MICROSTRUCTURAL DEVICES OR SYSTEMS
    • B81C1/00—Manufacture or treatment of devices or systems in or on a substrate
    • B81C1/00015—Manufacture or treatment of devices or systems in or on a substrate for manufacturing microsystems
    • B81C1/00023—Manufacture or treatment of devices or systems in or on a substrate for manufacturing microsystems without movable or flexible elements
    • B81C1/00111—Tips, pillars, i.e. raised structures
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES 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
    • A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
    • A61M37/0015—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES 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
    • A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
    • A61M37/0015—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
    • A61M2037/0023—Drug applicators using microneedles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES 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
    • A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
    • A61M37/0015—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
    • A61M2037/003—Other 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES 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
    • A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
    • A61M37/0015—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
    • A61M2037/0046—Solid microneedles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES 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
    • A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
    • A61M37/0015—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
    • A61M2037/0053—Methods for producing microneedles
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B81—MICROSTRUCTURAL TECHNOLOGY
    • B81B—MICROSTRUCTURAL DEVICES OR SYSTEMS, e.g. MICROMECHANICAL DEVICES
    • B81B2201/00—Specific applications of microelectromechanical systems
    • B81B2201/05—Microfluidics
    • B81B2201/055—Microneedles
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B81—MICROSTRUCTURAL TECHNOLOGY
    • B81C—PROCESSES OR APPARATUS SPECIALLY ADAPTED FOR THE MANUFACTURE OR TREATMENT OF MICROSTRUCTURAL DEVICES OR SYSTEMS
    • B81C2201/00—Manufacture or treatment of microstructural devices or systems
    • B81C2201/01—Manufacture or treatment of microstructural devices or systems in or on a substrate
    • B81C2201/0101—Shaping material; Structuring the bulk substrate or layers on the substrate; Film patterning
    • B81C2201/0111—Bulk micromachining
    • B81C2201/0115—Porous silicon

Definitions

  • the present invention relates to a manufacturing method for a porous micro-needle assembly with backside connector and a corresponding porous microneedle assembly.
  • Porous microneedle arrays which consist for example of porous silicon, are used in the field of "transdermal drug delivery” as an extension of medicament patches, as a carrier of a vaccine or for the recovery of body fluid (so-called “Transdermal fluid”) for the diagnosis and Analysis of body parameters (eg glucose, lactate, ..) used.
  • Transdermal patches for small molecules are widely known.
  • chemical enhancers or various physical methods are used, which help to overcome the protective coat of the skin.
  • Another method for this purpose is the mechanical penetration of the outer layers of the skin (stratum corneum) by means of fine porous microneedles combined with the administration of an active substance, preferably via an active substance plaster into which the microneedles can already be integrated, or via a metering device which has a targeted Delivery (bolus, pause, increase, ..) of active ingredients allows.
  • DE 10 2006 028 781 A1 discloses a method for the production of porous micro-needles arranged on a silicon substrate in an array for the transdermal administration of medicaments.
  • the method includes forming a microneedle array having a plurality of microneedles on the front side of a semiconductor substrate rising from a support region of the semiconductor substrate, and partially porosifying the semiconductor substrate to form porous microneedles, the porosification starting from the front side of the semiconductor substrate and a porous one Reservoir is formed.
  • Fig. 2 is a schematic cross-sectional view for explaining a known from DE 10 2006 028 781 A1 manufacturing method for a porous micro-needle assembly with backside connection.
  • reference numeral 100 denotes a partially porosified silicon substrate having an upper porosified region 100a and a lower non-porosified region 100b.
  • An array of porous microneedles 40 rises from the porosified region 100a.
  • an additional etch process provides a feedthrough 150 in the microneedles 40 which allows drug delivery from the back side of the silicon substrate 100.
  • the production process according to the invention for a porous microneedle arrangement with backside connection and the corresponding porous microneedle arrangement defined in claim 1 have the advantage that both a porosification is achieved in a single anodic etching process and a backside connection to the through openings of the masking layer is obtained ,
  • the idea underlying the present invention consists in focusing the electric current density in the anodic etching process by the back masking.
  • the anodic etching process is carried out in such a way that, after porosification, a non-porous residual region of the support layer remains on the masking layer laterally of the passage opening.
  • the anodic etching process is carried out in such a way that, after porosification, a flank region of the non-porous residual region of the support layer is formed, which drops off towards the passage opening.
  • FIG. 2 shows schematic cross-sectional representations for explaining an embodiment of the production method according to the invention for a porous micro-needle arrangement with rear-side connection
  • Fig. 2 is a schematic cross-sectional view for explaining a DE
  • FIG. 1 ac show schematic cross-sectional views for explaining an embodiment of the manufacturing method according to the invention for a porous micro-needle assembly with backside connection.
  • reference numeral 1 denotes a silicon semiconductor substrate having a front side VS and a back side RS.
  • a microneedle arrangement 4 is formed by an etching process known for example from EP 0 625 285 B1, which has a plurality of microneedles 4a, 4b which rise from a support region 1b of the semiconductor substrate 1. At the edge of the substrate, an edge region 1 a rises from the support area 1 b. The edge region 1 a forms a lateral support structure for subsequent separation of the microneedle assembly.
  • a masking layer 2 is formed with through-holes 3a, 3b, which are located in a respective backside region RS 'or RS "of the microneedles 4a and 4b.
  • the masking layer 2 is formed before the formation of the microneedles 4a, 4b is applied to the backside RS of the semiconductor substrate 1 and the through-holes 3a, 3b are formed therein.
  • the masking layer 2 should be resistant to the anodic etching process when porosifying the microneedle array 4, ie have a sufficiently high selectivity with respect to the microneedle array 4. In other words, the masking layer should be electrically insulating and have good HF (hydrofluoric acid) resistance.
  • the masking layer 2 for example, an SiC layer, an SiN layer or a polymer layer (eg, SU8) may be used.
  • the height H of the microneedles 4a, 4b is typically in the range 100-400 ⁇ m, the height h of the underlying support region 1b of the substrate 1 is preferably a few 10-100 ⁇ m.
  • the passage openings 3a, 3b of the masking layer 2 typically move in the range of a few to a few 10 ⁇ m diameter or edge length.
  • a porosification of the microneedle assembly 4 and a part of the edge region 1 a and of the support region 1 a is carried out in an anodic etching process which selectively places the microneedle assembly 4, the edge region 1 a and the support region 1 b opposite the masking layer 2 etches.
  • silicon of the semiconductor Substrate 1 electrochemically etched in HF (hydrofluoric acid) -containing electrolyte under the action of an electric current flow I, whereby pores are formed in the silicon.
  • the concentration of hydrofluoric acid is typically between 20% and 50%, advantageously between 22% and 28%.
  • the current density is between 5 mA / cm 2 and 300 mA / cm 2 , advantageously between 80 and 300 mA / cm 2 , most preferably between 120 and 200 mA cm 2 .
  • the current density can also be varied advantageously over the etching depth.
  • the support structure must ensure a certain stability, which is why it should advantageously not fall below 50 ⁇ , resulting in etch times of typically 10 to 15 minutes.
  • the electric field lines reach the needle assembly 4 or the porous microneedle assembly 4 'very homogeneously. Due to the back masking layer 2, the field lines are increasingly focused with increasing etch depth, as illustrated in areas A and C by arrows becoming increasingly narrower. This focusing drastically increases the electrical current density. In this way, even the critical current density can be exceeded in region C, above which the porosification passes into an electropolishing process.
  • the state shown in Fig. 1 b corresponds to the state at the end of the anodic etching process, which is illustrated in Fig. 1 c without the current density arrows.
  • microneedles 4a, 4b are transferred into porosified microneedles 4a ', 4b' of the porous microneedle assembly 4 '.
  • a region of the support layer 1b lying in the rear side region RS 'or RS "above the passage opening 3a or 3b is porosified in such a way that the respective porous microneedle 4a' or 4b 'is connected to the corresponding through opening 3a or 3b as the rear side connection.
  • a flank region 9 of this non-porous remaining region 8 of the support layer 1b falls in a funnel shape in accordance with the course of the field lines towards the through-opening 3a, 3b. This also supports the introduction of the active substance into the porous microneedle assembly 4 'or the adhesion of the porous microneedle assembly 4' to the remaining support layer 1b.
  • part of the edge region 1 a of the semiconductor substrate is also porosified, but the remaining region is sufficient to effectively support the singulation.

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  • Engineering & Computer Science (AREA)
  • Health & Medical Sciences (AREA)
  • Manufacturing & Machinery (AREA)
  • Anesthesiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Analytical Chemistry (AREA)
  • Dermatology (AREA)
  • Medical Informatics (AREA)
  • Chemical & Material Sciences (AREA)
  • Biomedical Technology (AREA)
  • Microelectronics & Electronic Packaging (AREA)
  • Hematology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Micromachines (AREA)
  • Media Introduction/Drainage Providing Device (AREA)

Abstract

La présente invention fournit un procédé de fabrication pour un système de micro-aiguilles poreuses avec raccordement du côté arrière et un système de micro-aiguilles poreuses correspondant. Le procédé comprend les étapes suivantes: formation d'un système de micro-aiguilles (4) comprenant au moins une micro-aiguille (4a; 4b) sur le côté avant (VS) d'un substrat semi-conducteur (1), lequel système peut se soulever d'une zone d'appui (1b) du substrat semi-conducteur (1); formation d'une couche de masquage (2) sur le côté arrière du substrat semi-conducteur (1), la couche de masquage (2) présentant une ouverture de passage (3a; 3b) dans la zone du côté arrière (RS'; RS") de cette micro-aiguille (4a; 4b); et porosification du système de micro-aiguilles (4) et d'au moins une partie de la zone d'appui (1b) dans un processus de gravure anodique qui grave le système de micro-aiguilles (4) et la couche d'appui (4) sélectivement par rapport à la couche de masquage (2), un flux de courant (I) passant l'ouverture de passage (3a; 3b) en partant du système de micro-aiguilles (4); cette micro-aiguille (4a; 4b) et une zone de la couche d'appui (1b) se trouvant dans la zone de son côté arrière (RS'; RS") au-dessus de l'ouverture de passage (3a; 3b) étant porosifiées de telle manière qu'une micro-aiguille poreuse (4a1; 4b') se forme avec l'ouverture de passage (3a; 3b) comme raccordement du côté arrière.
PCT/EP2011/050549 2010-02-08 2011-01-17 Procédé de fabrication pour un système de micro-aiguilles poreuses avec raccordement du côté arrière et système de micro-aiguilles poreuses correspondant WO2011095386A2 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE102010001667.5 2010-02-08
DE201010001667 DE102010001667A1 (de) 2010-02-08 2010-02-08 Herstellungsverfahren für eine poröse Mikronadelanordnung mit Rückseitenanschluss und entsprechende poröse Mikronadelanordnung

Publications (2)

Publication Number Publication Date
WO2011095386A2 true WO2011095386A2 (fr) 2011-08-11
WO2011095386A3 WO2011095386A3 (fr) 2012-03-01

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DE (1) DE102010001667A1 (fr)
WO (1) WO2011095386A2 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104707240A (zh) * 2015-03-06 2015-06-17 中山大学 磁引导纳米连通多孔微针阵列的制作方法
CN107405478A (zh) * 2015-03-10 2017-11-28 富士胶片株式会社 经皮吸收片的制造方法

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP6317690B2 (ja) 2015-03-03 2018-04-25 富士フイルム株式会社 経皮吸収シート、及びその製造方法
JP6482323B2 (ja) * 2015-03-03 2019-03-13 富士フイルム株式会社 経皮吸収シート
US20190001108A1 (en) * 2015-12-18 2019-01-03 Labo Juversa Co., Ltd. Microneedle and microneedle patch

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0625285B1 (fr) 1992-12-05 2000-03-22 Robert Bosch Gmbh Procede d'attaque anisotrope du silicium
DE102006028781A1 (de) 2006-06-23 2007-12-27 Robert Bosch Gmbh Verfahren zur Herstellung von porösen Mikronadeln und ihre Verwendung

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1187653B1 (fr) * 1999-06-04 2010-03-31 Georgia Tech Research Corporation Dispositifs permettant d'ameliorer la penetration d'une microaiguille a travers des barrieres tissulaires

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0625285B1 (fr) 1992-12-05 2000-03-22 Robert Bosch Gmbh Procede d'attaque anisotrope du silicium
DE102006028781A1 (de) 2006-06-23 2007-12-27 Robert Bosch Gmbh Verfahren zur Herstellung von porösen Mikronadeln und ihre Verwendung

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104707240A (zh) * 2015-03-06 2015-06-17 中山大学 磁引导纳米连通多孔微针阵列的制作方法
CN107405478A (zh) * 2015-03-10 2017-11-28 富士胶片株式会社 经皮吸收片的制造方法
CN107405478B (zh) * 2015-03-10 2020-12-08 富士胶片株式会社 经皮吸收片的制造方法
US11135413B2 (en) 2015-03-10 2021-10-05 Fujifilm Corporation Method of producing transdermal absorption sheet

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Publication number Publication date
WO2011095386A3 (fr) 2012-03-01
DE102010001667A1 (de) 2011-08-11

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