Holger Becker

Polymer microfabrication methods for microfluidic analytical applications

A growing number of microsystem technology (MST) applications, particularly in the field of microfluidics with its applications in the life sciences, have a need for novel fabrication methods which account for substrates other than silicon or glass. We present in this paper an overview of existing polymer microfabrication technologies for microfluidic applications, namely replication methods such as hot embossing, injection molding and casting, and the technologies necessary to fabricate the molding masters. In addition, techniques such as laser ablation and layering techniques are examined. Methods for bonding and dicing of polymer materials, which are necessary for complete systems, are evaluated.

Fabrication of plastic microchips by hot embossing

Plastic microchips with microchannels (100 microm wide, 40 microm deep) of varying designs have been fabricated in polymethylmethacrylate by a hot embossing process using an electroform tool produced starting with silicon chip masters. Hot-embossed chips were capped with a polymethylmethacrylate top using a proprietary solvent bonding process. Holes were drilled through the top of the chip to allow access to the channels. The chips were tested with fluid and shown to fill easily. The seal between the top of the chip and the hot embossed base was effective, and there was no leakage from the channels when fluid was pumped through the microchannels. The chips were also tested with a semen sample and the plastic chip performed identically to the previous silicon-glass and glass versions of the chip. This microfabrication technique offers a viable and potentially high-volume low cost production method for fabricating transparent microchips for analytical applications.

Polymer based micro-reactors.

In this paper, we describe the fabrication technologies necessary for the production of polymer-based micro-fluidic devices. These technologies include hot embossing as a micro-structuring method as well as so-called back-end processes to complete the micro-devices. Applications such as capillary electrophoresis, micro-mixers and nanowell plates are presented.

Microfluidic devices for μ -TAS applications fabricated by polymer hot embossing

Polymer microfabrication methods are becoming increasingly important as low-cost alternatives to the silicon or glass- based MEMS technologies. We present in this paper hot embossing as a replication method for planar microstructures based on polymer substrates. Several chips containing microchannels for capillary electrophoresis applications with a range of channel widths between 0.8 micrometers and 100 micrometers have been produced by this method, yielding a very good structural replication and short production times.

Microfluidically supported biochip design for culture of endothelial cell layers with improved perfusion conditions

Hemodynamic forces generated by the blood flow are of central importance for the function of endothelial cells (ECs), which form a biologically active cellular monolayer in blood vessels and serve as a selective barrier for macromolecular permeability. Mechanical stimulation of the endothelial monolayer induces morphological remodeling in its cytoskeleton. For in vitro studies on EC biology culture devices are desirable that simulate conditions of flow in blood vessels and allow flow-based adhesion/permeability assays under optimal perfusion conditions. With this aim we designed a biochip comprising a perfusable membrane that serves as cell culture platform multi-organ-tissue-flow (MOTiF biochip). This biochip allows an effective supply with nutrition medium, discharge of catabolic cell metabolites and defined application of shear stress to ECs under laminar flow conditions. To characterize EC layers cultured in the MOTiF biochip we investigated cell viability, expression of EC marker proteins and cell adhesion molecules of ECs dynamically cultured under low and high shear stress, and compared them with an endothelial culture in established two-dimensionally perfused flow chambers and under static conditions. We show that ECs cultured in the MOTiF biochip form a tight EC monolayer with increased cellular density, enhanced cell layer thickness, presumably as the result of a rapid and effective adaption to shear stress by remodeling of the cytoskeleton. Moreover, endothelial layers in the MOTiF biochip express higher amounts of EC marker proteins von-Willebrand-factor and PECAM-1. EC layers were highly responsive to stimulation with TNFα as detected at the level of ICAM-1, VCAM-1 and E-selectin expression and modulation of endothelial permeability in response to TNFα/IFNγ treatment under flow conditions. Compared to static and two-dimensionally perfused cell culture condition we consider MOTiF biochips as a valuable tool for studying EC biology in vitro under advanced culture conditions more closely resembling the in vivo situation.

Micro free-flow electrophoresis with injection molded chips

In this work we present an approach towards economic free-flow electrophoresis chips fabricated by injection molding as mass replication process. This is achieved by the development of a free-flow electrophoresis chip design suitable for one step molding fabrication. Integrated partitioning bars are incorporated as key elements for bubble segregation. A defined open gap of 20 μm in height and 500 μm in width was integrated between the separation chamber and the electrode channels, acting as a barrier for gas bubbles while maintaining electrical contact by the fluidic junction. Additionally, we present an approach to avoid internal electrodes in FFE microchips for a facile mass production process. The injection molded thermoplastic μFFE chips are ready to use without subsequent labor-intensive implementation of membranes or comparable structures serving as salt bridges.

Microfluidic Manifolds by Polymer Hot Embossing for μ-Tas Applications

In this paper we present a low-cost replication method for planar microstructures based on polymer substrates. Several microfluidic chips for capillary electrophoresis (CE) applications with a range of channel widths between 0.8 μm and 100 μm have been produced by this method, yielding a very good structural replication and short production times.

Microfluidic toolbox: tools and standardization solutions for microfluidic devices for life sciences applications

After more than a decade of activities in the field of microfluidics, an increasing need for standardized modules and off-the-shelf components can be observed. In particular the compatibility with existing laboratory equipment o procedures greatly helps the acceptance of miniaturized systems, as in practice, miniaturized systems are very likely to be used in parallel with existing equipment and are not totally replacing this. In this paper we present the basic concept of a microfluidic toolbox with interchangeable components where the external dimensions are adopted from existing standards. Furthermore the fluidic interfaces were selected for compatibility to established systems.

Methods and instruments for continuous-flow PCR on a chip

PCR is the most commonly used method to identify DNA segments. Several methods have been used to miniaturize PCR and perform it in a microfluidic chip. A unique approach is the continuous-flow PCR, where the conventional thermocycling is replaced by pumping the sample through a channel which meanders over stationary temperature zones, allowing fast temperature changes in the sample due to the low thermal mass as well as a continuous production of PCR products. In this paper we present a system comprising a polymer microfluidic chip, a thermocycler unit and the protocols necessary to perform fast continuous-flow PCR including experimental results in comparison with a conventional PCR system.

Microfluidics and the Life Sciences

The field of microfluidics, often also referred to as “Lab-on-a-Chip” has made significant progress in the last 15 years and is an essential tool in the development of new products and protocols in the life sciences. This article provides a broad overview on the developments on the academic as well as the commercial side. Fabrication technologies for polymer-based devices are presented and a strategy for the development of complex integrated devices is discussed, together with an example on the use of these devices in pathogen detection.