Hybrid method of forming microstructure array molds, methods of making microstructure arrays, and methods of use
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) 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 a base 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:
1) Applying a layer of photoresist on the first material;
2) Applying a masking material onto the photoresist layer, wherein the masking material covers at least a portion of the photoresist layer;
3) Curing the portion of the photoresist layer not covered by the masking material;
4) Isotropic etching the substrate to create the distal tip section;
5) Etching the substrate to create the shaft portion;
6) Wet thermal oxidizing the microstructures; and
7) 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 1.
7 . The method of claim 5 , wherein the thermal oxidation process in step 1 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 SU-8.
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 3.
11 . The method of claim 5 , further comprising:
removing the masking material and any uncured photoresist material after step 3.
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 5 comprises anisotropic etching.
14 . The method of claim 5 , wherein step 5 comprises deep reactive-ion etching.
15 . The method of claim 5 , further comprising:
prior to step 1, cleaning a 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 4 and/or step 5 comprises plasma etching.
19 . The method of claim 18 , wherein the plasma etching comprises a plasma gas selected from SF6, carbon tetrachloride, oxygen, and CHF 3 .
20 . The method of claim 5 , further comprising removing any remaining photoresist from the first material after step 5.
21 . The method of claim 1 , wherein the second material is one of a polymeric material and a silicon material.
22 . The method of claim 21 , wherein the second material is selected from the group consisting of polydimethylsiloxane (PDMS), polycarbonate, polyetherimide, and polyethylene terephthalate.
23 . The method of claim 1 , wherein the electroplating metal is selected from copper, nickel, chromium, and gold.
24 . The method of claim 1 , wherein the proximal section is micromachined to have a funnel or pyramidal shape.
25 . A method of forming a casting mold comprising:
preparing a negative mold of the master mold formed in claim 1 .
26 . A method of preparing a microstructure array, comprising:
dispensing a polymer matrix solution or suspension comprising at least one therapeutic agent on a casting mold of claim 25 ;
drying the polymer matrix solution;
dispensing a polymer matrix backing solution on the casting mold;
drying the polymer matrix backing solution to form the microstructure array; and
demolding the microstructure array.