Integrated Lithographic Molding for Microneedle-Based Devices

This paper presents a new fabrication method consisting of lithographically defining multiple layers of high aspect-ratio photoresist onto preprocessed silicon substrates and release of the polymer by the lost mold or sacrificial layer technique, coined by us as lithographic molding. The process methodology was demonstrated fabricating out-of-plane polymeric hollow microneedles. First, the fabrication of needle tips was demonstrated for polymeric microneedles with an outer diameter of 250 mum, through-hole capillaries of 75-mum diameter and a needle shaft length of 430 mum by lithographic processing of SU-8 onto simple v-grooves. Second, the technique was extended to gain more freedom in tip shape design, needle shaft length and use of filling materials. A novel combination of silicon dry and wet etching is introduced that allows highly accurate and repetitive lithographic molding of a complex shape. Both techniques consent to the lithographic integration of microfluidic back plates forming a patch-type device. These microneedle-integrated patches offer a feasible solution for medical applications that demand an easy to use point-of-care sample collector, for example, in blood diagnostics for lithium therapy. Although microchip capillary electrophoresis glass devices were addressed earlier, here, we show for the first time the complete diagnostic method based on microneedles made from SU-8

Silicon micromachined hollow microneedles for transdermal liquid transport

This paper presents a novel process for the fabrication of out-of-plane hollow microneedles in silicon. The fabrication method consists of a sequence of deep-reactive ion etching (DRIE), anisotropic wet etching and conformal thin film deposition, and allows needle shapes with different, lithography-defined tip curvature. In this study, the length of the needles varied between 150 and 350 micrometers. The widest dimension of the needle at its base was 250 /spl mu/m. Preliminary application tests of the needle arrays show that they are robust and permit skin penetration without breakage. Transdermal water loss measurements before and after microneedle skin penetration are reported. Drug delivery is increased approximately by a factor of 750 in microneedle patch applications with respect to diffusion alone. The feasibility of using the microneedle array as a blood sampler on a capillary electrophoresis chip is demonstrated

Nanolithography for oxide nanoarrays and their application in medical devices

Using lithographic patterning techniques, normally we aim for the integration of structural elements into a more complex apparatus, which can be at various length scales, for example hand-held equipment. Nanoscale fabricated pillars, holes or wires have shown unique properties already and ordering these in specific arrangements results in novel phenomena normally not present in natural occuring materials. Such materials are called nanoarrays. Engineered nanoarrays belong therefore to the class of metamaterials. One example of a metamaterial is a material with a negative refractive index created by design of artificial structure. These exciting material properties bring about also new opportunities for applications. A functional device or system demanding some level of ordering in a material also requires a carefully designed manufacturing process. Here, we will present an overview of nanolithographic techniques for oxide nanoarrays. Bio-inspired templated nanoarrays will be described in perspective to other nanolithography techniques. These nanostructures can deliver new functionality, too. Moreover, (nano)structured materials can deliver specific functionality at the interface with biological material. Developing these materials, subsequently, we can look for medical applications where the properties of oxide nanoarrays are explored. Photonic crystals, for example, can be applied in medical diagnostic devices. In this paper, therefore oxide nanoarrays are introduced and the emerging technology for modification and tuning of medical device performance utilizing oxide nanoarrays is discussed. © 2010 Copyright SPIE - The International Society for Optical Engineering

Drug delivery through microneedles

\u3cp\u3eDrug delivery through microneedles is a new form of a pharmaceutical dosage system. While single microneedles have been clinically applied already, the out-of-plane integration of a multitude of microneedles in a pharmaceutical patch is a disruptive technology. To take advantage of micro- and nanofluidics, such active patches utilize microneedle array (MNA) technology. MNAs are microsystems that adopt their technical uniqueness by the choice of a fabrication technology. MNAs can be made of solid, hollow, porous, or dissolvable materials in a cost-effective manner by the so-called MEMS technology. However, key to their success will be a proof-of-concept in the clinic, which must demonstrate that the intradermal (nano)release of drugs and vaccines serve an unmet medical need. In this chapter, we discuss recently established MNA platform technologies and by means of a case study we assess novel opportunities for MNAs in drug and vaccine delivery arising from this novel skin interface.\u3c/p\u3

Stacked hydrogels to elicit neural mechanotransduction processes in 3D

IntroductionMany different methods of patterning hydrogels are currently investigated for their advances in 3D tissue engineering [1]. Nanogrooves, demonstrating aligned neural processes to extend into 3D hydrogels in a reductionist and primary CTX brain-on-chip model, have been also reported by us [2]. Here, we aim to combine these concepts to elicit neural mechanotransduction processes in a 2-layer stack of two distinct hydrogels, of which the top hydrogel can be fined-tuned to an astrocyte feeding layer for neuronal cells in the bottom hydrogel. Experimental procedure, results and discussion Stacks were fabricated using photo-polymerizing GelMA (900496, Sigma Aldrich) and red-colored thermoset gelatin (Dr. Oetker, strawberry jelly) to demonstrate our new mechanotransduction model, Figure 1a. For proofof-principle, we performed SH-SY5Y cell line (94030304, Sigma Aldrich) cultures in a PDMS-ring confinement and added a droplet of 10µl of GelMA, which was photo-polymerized at the defined thickness of 1 mm of the ring by putting a COC (cyclic olefin copolymer) foil atop to flatten the surface. When peeling-off the COC, SH-SY5Y culture protocol was carried out according to our experience with 3D cultures of SH-SY5Y in Matrigel [2] by differentiating the cells with 10 µM retinoic acid (RA; R2625, Sigma Aldrich) to initiate neuronal differentiation at DIV 0 and adding growth medium with 50 ng/mL brain-derived neurotrophic factor (B2795, Sigma Aldrich) at DIV 3, and then with growth medium being refreshed halfway for next 48 hours. After differentiation, cells were kept in growth medium with growth medium being refreshed every other day until DIV 5, Figure 1b, c. To provide a proof-of-principle for our mechanotransduction model, next we will perform the same SH-SY5Y culture using GelMA on a nanogrooved PDMS substrate and add astrocytes in Matrigel atop. We expect that the difference in ConclusionStacks of photo-polymerized and thermoset patterned hydrogels can be consistently achieved by pipetting small droplets of the pre-cursor hydrogels into a PDMS ring confinement on glass. SH-SY5Y cells showed successful proliferation and differentiation within the interface of glass and GelMA, forming an extensive neuronal cellnetwork. Migration of cells from and to the different layers of the stack needs to be further investigated Young’s module within the distinct culture regions will influence the network formation of the neuronal cells similar to our previous results in CTX 2D cultures [3]