Hybrid method of forming microstructure array molds, methods of making microstructure arrays, and methods of use

Abstract

A method of forming a master mold (52), comprising: a) forming a plurality of microstructure portions (42) in a substrate formed of a first material by a first micromachining process, each microstructure portion comprising a shaft (40) and a distal tip (38); b) in preparing a negative mold (46) of the plurality of microstructure portions, wherein the mold is formed of a second material and comprises a plurality of cavities (48) corresponding to each microstructure portion in the plurality of microstructure portions (42); c) electroplating a metal (50) onto the negative mold to fill each cavity in the plurality of cavities and to form abase layer (54) extending from the negative mold; d) forming a proximal section (56) for each of the microstructures in the base layer using a second micromachining process (e.g. mechanical micromachining); and e) before or after said step d), removing the negative mold from the metal to form a master mold.

1 . A method of forming a master mold, comprising:
 a) forming a plurality of microstructure portions in a substrate formed of a first material by a first micromachining process, each microstructure portion comprising a shaft and a distal tip;   b) preparing a negative mold of the plurality of microstructure portions, wherein the mold is formed of a second material and comprises a plurality of cavities corresponding to each microstructure portion in the plurality of microstructure portions;   c) electroplating a metal onto the negative mold to fill each cavity in the plurality of cavities and to form a base layer extending from the negative mold;   d) forming a proximal section for each of the microstructures in the base layer using a second micromachining process; and   e) before or after said step d), removing the negative mold from the metal to form a master mold.   
     
     
         2 . The method of  claim 1 , wherein the second micromachining process is a mechanical micromachining process. 
     
     
         3 . The method of  claim 1 , wherein the first material is selected from silicon and a positive photoresist material. 
     
     
         4 . The method of  claim 1 , wherein said first micromachining process comprises a photolithography process. 
     
     
         5 . The method of  claim 4 , wherein said photolithography comprises:
 (i) applying a layer of photoresist on the first material;   (ii) applying a masking material onto the photoresist layer, wherein the masking material covers at least a portion or the photoresist layer;   (iii) curing the portion of the photoresist layer not covered by the masking material;   (iv) isotropic etching the substrate to create the distal tip section;   (v) etching the substrate to create the shaft portion;   (vi) wet thermal oxidizing the microstructures; and   (vii) isotropic wet etching the microstructures.   
     
     
         6 . The method of  claim 5 , wherein the first material is silicon, and the method further comprises forming a layer of silicon dioxide on the silicon substrate using a thermal oxidation process prior to step DI. 
     
     
         7 . The method of  claim 5 , wherein the thermal oxidation process in step DI is a wet thermal oxidation process. 
     
     
         8 . The method of  claim 5 , wherein the photoresist material is an epoxy-based negative photoresist. 
     
     
         9 . The method of  claim 8 , wherein the photoresist material is SUB. 
     
     
         10 . The method of  claim 5 , wherein the masking material comprises a plurality of apertures, wherein the photoresist layer exposed by the apertures is cured in step (iii). 
     
     
         11 . The method of  claim 5 , further comprising:
 removing the masking material and any uncured photoresist material after step (iii).   
     
     
         12 . The method of  claim 11 , wherein the masking material and uncured photoresist are removed using a solvent. 
     
     
         13 . The method of  claim 5 , wherein the etching of step (v) comprises anisotropic etching. 
     
     
         14 . The method of  claim 5 , wherein step (v) comprises deep reactive-ion etching. 
     
     
         15 . The method of  claim 5 , further comprising prior to step DI, cleaning the polymeric material. 
     
     
         16 . The method of  claim 15 , wherein said cleaning comprises chemical cleaning. 
     
     
         17 . The method of  claim 16 , wherein the chemical cleaning comprises an RCA cleaning process. 
     
     
         18 . The method of  claim 5 , wherein step (iv) and/or step (v) comprises plasma etching. 
     
     
         19 . The method of  claim 18 , wherein the plasma etching comprises a plasma gas selected from SF 6 , carbon tetrachloride, oxygen, and CHF 3 . 
     
     
         20 . The method of  claim 5 , further comprising removing any remaining photoresist from the first material after step (v). 
     
     
         21 . The method of  claim 1 , wherein the second material is a polymeric material. 
     
     
         22 . The method of  claim 1 , wherein the second material is a silicone material. 
     
     
         23 . The method of  claim 21 , wherein the second polymeric material is selected from the group consisting of polydimethylsiloxane (PDMS), polycarbonate, polyetherimide, and polyethylene terephthalate. 
     
     
         24 . The method of  claim 1 , wherein the electroplating metal is selected from copper, nickel, chromium, and gold. 
     
     
         25 . The method of  claim 1 , wherein the proximal section is micromachined to have a funnel or pyramidal shape. 
     
     
         26 . A method of forming a casting mold comprising:
 preparing a negative mold of the master mold formed in  claim 1 .   
     
     
         27 . A method of preparing a microstructure array, comprising:
 (i′) dispensing a polymer matrix solution or suspension comprising at least one therapeutic agent on a casting mold of  claim 26 ;   (ii′) drying the polymer matrix solution;   (iii′) dispensing a polymer matrix backing solution on the casting mold;   (iv′) drying the polymer matrix backing solution to form the microstructure array; and   (v′) demolding the microstructure array.