van den A. Berg

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.

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.

Fabrication of micromachined pipettes in a flow channel for single molecule handling of DNA

We have developed a micromachined flow cell consisting of a flow channel integrated with micropipettes. The flow cell is used in combination with an optical trap set-up (optical tweezers) to study mechanical and structural properties of /spl lambda/-DNA molecules. The flow cell was realised using silicon micromachining including the so-called buried channel technology to fabricate the micropipettes, the wet etching of glass to create the flow channel, and the powder blasting of glass to make the fluid connections. The volume of the flow cell is 2 /spl mu/l. The pipettes have a length of 130 /spl mu/m, a width of 5-10 /spl mu/m, a round opening of 1 /spl mu/m and can be processed with different shapes. Using this flow cell we stretched single molecules (/spl lambda/-DNA) showing typical force-extension curves also found with conventional techniques. These pipettes can be also used for drug delivery, for injection of small gas bubbles into a liquid flow to monitor the streamlines, and for the mixing of two liquids to study diffusion effects. The paper describes the design, the fabrication and testing of the flow cell.

Technologies and Microstructures for (Bio)chemical Microsystems

There is a strong correlation between microreactors and microsystems for chemical and biochemical analysis. Microreactors need to be closely coupled to analysers, whereas in micro analysis systems a microreactor is often an important element. An example of a device that can be considered both as microreactor and as analyser, a catalytic gas sensor is presented. In particular the role of porous silicon material for fabrication and as support for the catalyst is shown. A modular concept for fabrication of micro analysis systems is illustrated with some components. A new capacitive pressure/flow sensor is presented with low power operation and a detection limit of 6 nl/s. Microchannels play an essential role in many micro analysis systems. Simulations made using the Flow3D programme based on the incompressible Navier-Stokes equations, give guidelines for the construction of the flow channel and positioning of sensors whereas the effects of the channel geometry on the profile of the injected plug can be predicted. Finally, a number of different techniques is presented to produce closed microchannels in silicon. Particular attention is paid to techniques that enable the fabrication of electrically insulating microchannels, which are of particular interest for capillary electrophoresis (CE) applications