**9. Fabricating devices for drug delivery applications**

Over the past decades, there has been no shortage of interest in nano- or micro-fabrication in the field of drug delivery. Among all drug delivery devices, micro-needles appear to be the most popular apparatus in terms of the number of papers that have been published over the past three decades. With the above fabrication technique, fabricating a micro-needle or similar devices would be as easy as brewing coffee. Formation of hollow objects at micro-scale is undoubtedly one of known challenges in the field of micro-fabrication, especially polymer micro-fabrication. The following sections demonstrate how the previously developed techni‐ ques [14–19] can be employed for realization of conical micro-funnels for drug delivery applications. As explained in the previous sections, our fabrication methodology is based purely on photo-lithography.

In step 1, as shown in **Figure 3a**, we need to prepare a pre-cured SU-8 which is UV opaque. A standard SU-8 monomer resin is first mixed with a UV-opaque impurity at an elevated temperature until the final mixture becomes almost opaque in the UV spectrum. This UVopaque impurity can be an appropriate plasticine that is opaque to UV lights and does not form any complex in SU-8. In addition, this UV-opaque SU-8 resin will have to undergo a prolonged dehydration bake to increase its viscosity and to decrease its surface adhesion. The wafer of this pre-cured SU-8 will be maintained at an elevated temperature (preferably slightly above the glass transition temperature) so that this UV-opaque SU-8 resin becomes partially molten and its upper surface becomes non-adhesive. In so doing, this UV-opaque SU-8 resin should be able to be reshaped upon heating without excessive change in its physical and chemical properties.

In step 2, as shown in **Figure 3b**, we need to fabricate an embossing stamp which is basically a master mold having an array of cylindrical rods. This embossing stamp will be used as a patterned template for casting of the inverted conical patterns on the surface of the UV-opaque SU-8 from step 1. A variety of methods can be employed to fabricate this embossing stamp. In the present study, an embossing stamp with high aspect ratio micro-rods was fabricated using a high-quality standard UV-lithographic process but high aspect ratio is not really a prerequisite in the present application.

In step 3, as shown in **Figure 3c**, the upper surface of the UV-opaque SU-8 resin from step 1 is physically deformed by a mechanical impact produced by the embossing stamp moving downwards at high speed. At the same time, the wafer temperature is tuned down. As a result of this impact, an array of micro-conical wells will be 3D cast on the upper surface of the UVopaque SU-8. It is important to understand that the stroke speed of stamping will determine the sharpness of the tip of each conical well and the surface profile of the inner wall. In general, if the stroke speed is higher, the sharp tip of each conical well will accordingly become sharper.

In step 5, as shown in **Figure 3d**, the embossing stamp is removed from the wafer while the wafer is being cooled down. Following this cooling step, the conical micro-wells will become highly solidified.

Fabrication of Three-Dimensional Concave or Convex Shell Structures with Shell Elements at Micrometer Resolution in SU-8 http://dx.doi.org/10.5772/62405 11

**9. Fabricating devices for drug delivery applications**

purely on photo-lithography.

10 Lab-on-a-Chip Fabrication and Application

chemical properties.

highly solidified.

requisite in the present application.

Over the past decades, there has been no shortage of interest in nano- or micro-fabrication in the field of drug delivery. Among all drug delivery devices, micro-needles appear to be the most popular apparatus in terms of the number of papers that have been published over the past three decades. With the above fabrication technique, fabricating a micro-needle or similar devices would be as easy as brewing coffee. Formation of hollow objects at micro-scale is undoubtedly one of known challenges in the field of micro-fabrication, especially polymer micro-fabrication. The following sections demonstrate how the previously developed techni‐ ques [14–19] can be employed for realization of conical micro-funnels for drug delivery applications. As explained in the previous sections, our fabrication methodology is based

In step 1, as shown in **Figure 3a**, we need to prepare a pre-cured SU-8 which is UV opaque. A standard SU-8 monomer resin is first mixed with a UV-opaque impurity at an elevated temperature until the final mixture becomes almost opaque in the UV spectrum. This UVopaque impurity can be an appropriate plasticine that is opaque to UV lights and does not form any complex in SU-8. In addition, this UV-opaque SU-8 resin will have to undergo a prolonged dehydration bake to increase its viscosity and to decrease its surface adhesion. The wafer of this pre-cured SU-8 will be maintained at an elevated temperature (preferably slightly above the glass transition temperature) so that this UV-opaque SU-8 resin becomes partially molten and its upper surface becomes non-adhesive. In so doing, this UV-opaque SU-8 resin should be able to be reshaped upon heating without excessive change in its physical and

In step 2, as shown in **Figure 3b**, we need to fabricate an embossing stamp which is basically a master mold having an array of cylindrical rods. This embossing stamp will be used as a patterned template for casting of the inverted conical patterns on the surface of the UV-opaque SU-8 from step 1. A variety of methods can be employed to fabricate this embossing stamp. In the present study, an embossing stamp with high aspect ratio micro-rods was fabricated using a high-quality standard UV-lithographic process but high aspect ratio is not really a pre-

In step 3, as shown in **Figure 3c**, the upper surface of the UV-opaque SU-8 resin from step 1 is physically deformed by a mechanical impact produced by the embossing stamp moving downwards at high speed. At the same time, the wafer temperature is tuned down. As a result of this impact, an array of micro-conical wells will be 3D cast on the upper surface of the UVopaque SU-8. It is important to understand that the stroke speed of stamping will determine the sharpness of the tip of each conical well and the surface profile of the inner wall. In general, if the stroke speed is higher, the sharp tip of each conical well will accordingly become sharper.

In step 5, as shown in **Figure 3d**, the embossing stamp is removed from the wafer while the wafer is being cooled down. Following this cooling step, the conical micro-wells will become

**Figure 3.** Cross-sectional illustration of the procedure for fabrication of a micro-funnel. (a) A wafer containing a bath of UV-opaque highly dehydrated SU-8 resin. (b) Cross-sectional view that illustrates the embossing stamp with microrods. The diameter of each micro-rod is 40 μm. The length of each micro-rod is 200 μm. (c) Casting of micro-wells by surface deformation using the embossing stamp. (d) Removal of the embossing stamp from the wafer. (e) UV expo‐ sure. (f) Removal of uncured SU-8 resin by melting at an elevated temperature.

In step 4, as shown in **Figure 3e**, the shell of each micro-funnel is formed and thickened by increasing the dosage of UV exposure. The micro-well patterns on the wafer can be photolithographically defined, patterned, and exposed to a UV light using a photomask. Since the SU-8 resin in the wafer contains a UV-opaque impurity, the micro-wells become partially transparent at ultraviolet spectrum. In the presence of the UV-opaque impurity, the interior surface of each micro-well is the only region fully exposed to the UV lights. The SU-8 resin attached to the opposite side of the UV-exposed surface will be partially cured. As a result, the interior surface of each micro-well will be polymerized into a hard and thick layer. The thickness of this polymeric layer can be easily increased by increasing the duration of the UV exposure. In general, this polymeric layer can be as thin as a membrane or as thick as the application demands, depending on the duration of UV exposure.

In step 5, the uncured UV-opaque SU-8 resin attached to each of the micro-well is removed from the micro-well by melting at an elevated temperature. The SU-8 resin attached to the opposite side of the UV-exposed surface will remain uncured and melted into a liquid when the wafer is subjected to a strong heat. As a result of this heat, the UV-exposed surface will be significantly hardened. Traces of the uncured photosensitive resin which remain attached to the micro-well array can be stripped off by developing in 1-methoxy-2-propanol acetate.

In step 6, a hole is formed on the tip of each conical micro-well by dry etching. This step is intended to turn each conical micro-well into a micro-funnel. A hole can be formed on the tip of each conical micro-well by dry-etching the wafer in oxygen plasma for 100 seconds using a Trion RIE/PECVD tool. The oxygen plasma also sharpens the tip of each micro funnel during the dry etching process. In the present study, the process parameters were 90% O2, 10% CF4, an RF power of 100 w, and a chamber pressure of 1.6 Torr.
