Ansgar Waldbaur

Let there be chip—towards rapid prototyping of microfluidic devices: one-step manufacturing processes

Microfluidics is an evolving scientific field with immense commercial potential: analytical applications, such as biochemical assay development, biochemical analysis and biosensors as well as chemical synthesis applications essentially require microfluidics for sample handling, treatment or readout. A number of techniques are available to create microfluidic structures today. On industrial scale replication techniques such as injection molding are the gold standard whereas academic research mostly focuses on replication by casting of soft elastomers such as polydimethylsiloxane (PDMS). Both of these techniques require the creation of a replication master thus creating the microfluidic structure only in the second process step—they can therefore be termed two-(or multi-)step manufacturing techniques. However, very often the number of pieces to be created of one specific microfluidic design is low, sometimes even as low as one. This raises the question if two-step manufacturing is an appropriate choice, particularly if short concept-to-chip times are required. In this case one-step manufacturing techniques that allow the direct creation of microfluidic structures from digital three-dimensional models are preferable. For these processes the number of parts per design is low (sometimes as low as one), but quick adaptation is possible by simply changing digital data. Suitable techniques include, among others, maskless or mask based stereolithography, fused deposition molding and 3D printing. This work intends to discuss the potential and application examples of such processes with a detailed view on applicable materials. It will also point out the advantages and the disadvantages of the respective technique. Furthermore this paper also includes a discussion about non-conventional manufacturing equipment and community projects that can be used in the production of microfluidic devices.

Maskless Projection Lithography for the Fast and Flexible Generation of Grayscale Protein Patterns

Protein patterns of different shapes and densities are useful tools for studies of cell behavior and to create biomaterials that induce specific cellular responses. Up to now the dominant techniques for creating protein patterns are mostly based on serial writing processes or require templates such as photomasks or elastomer stamps. Only a few of these techniques permit the creation of grayscale patterns. Herein, the development of a lithography system using a digital mirror device which allows fast patterning of proteins by immobilizing fluorescently labeled molecules via photobleaching is reported. Grayscale patterns of biotin with pixel sizes in the range of 2.5 μm are generated within 10 s of exposure on an area of about 5 mm(2) . This maskless projection lithography method permits the rapid and inexpensive generation of protein patterns definable by any user-defined grayscale digital image on substrate areas in the mm(2) to cm(2) range.

Online monitoring of biofilm growth and activity using a combined multi-channel impedimetric and amperometric sensor

Biofilms are ubiquitous in water interfaces and therefore influence our daily lives in an ambivalent manner. In medicine, infections can be attributed to biofilm formation. In technical systems, biofilms are causative agents for biocorrosion, contamination, and clogging processes and are responsible for shear force modification in marine systems. To control and manipulate biofilm formation advanced technologies are needed. This paper reports on a novel real-time biofilm monitoring system using custom-made electronics. The system is able to monitor four electrochemical impedance spectroscopy (EIS) electrodes and three amperometric sensors in two microfluidic channels assessing biofilm growth and activity in parallel using Pseudomonas aeruginosa as a model system. The biofilm was characterized during its seeding and growth stages as well as during different injection intervals of a biocide (sodium azide) which allowed monitoring biofilm destabilization and deactivation effects in real time. The results obtained were confirmed by fluorescence microscopy after live/dead cell staining of the bacteria in the measured biofilm.

Microfluidics on liquid handling stations (μF-on-LHS): an industry compatible chip interface between microfluidics and automated liquid handling stations

We describe a generic microfluidic interface design that allows the connection of microfluidic chips to established industrial liquid handling stations (LHS). A molding tool has been designed that allows fabrication of low-cost disposable polydimethylsiloxane (PDMS) chips with interfaces that provide convenient and reversible connection of the microfluidic chip to industrial LHS. The concept allows complete freedom of design for the microfluidic chip itself. In this setup all peripheral fluidic components (such as valves and pumps) usually required for microfluidic experiments are provided by the LHS. Experiments (including readout) can be carried out fully automated using the hardware and software provided by LHS manufacturer. Our approach uses a chip interface that is compatible with widely used and industrially established LHS which is a significant advancement towards near-industrial experimental design in microfluidics and will greatly facilitate the acceptance and translation of microfluidics technology in industry.

Long-Term Stability of Polymer-Coated Surface Transverse Wave Sensors for the Detection of Organic Solvent Vapors

Arrays with polymer-coated acoustic sensors, such as surface acoustic wave (SAW) and surface transverse wave (STW) sensors, have successfully been applied for a variety of gas sensing applications. However, the stability of the sensors’ polymer coatings over a longer period of use has hardly been investigated. We used an array of eight STW resonator sensors coated with different polymers. This sensor array was used at semi-annual intervals for a three-year period to detect organic solvent vapors of three different chemical classes: a halogenated hydrocarbon (chloroform), an aliphatic hydrocarbon (octane), and an aromatic hydrocarbon (xylene). The sensor signals were evaluated with regard to absolute signal shifts and normalized signal shifts leading to signal patterns characteristic of the respective solvent vapors. No significant time-related changes of sensor signals or signal patterns were observed, i.e., the polymer coatings kept their performance during the course of the study. Therefore, the polymer-coated STW sensors proved to be robust devices which can be used for detecting organic solvent vapors both qualitatively and quantitatively for several years.

Rapid prototyping of glass microfluidic chips

In academia the rapid and flexible creation of microfluidic chips is of great importance for microfluidic research. Besides polymers glass is a very important material especially when high chemical and temperature resistance are required. However, glass structuring is a very hazardous process which is not accessible to most members of the microfluidic community. We therefore sought a new method for the rapid and simple creation of transparent microfluidic glass chips by structuring and sintering amorphous silica suspensions. The whole process from a digital mask layout to a microstructured glass sheet can be done within two days. In this paper we show the applicability of this process to fabricate capillary driven microfluidic systems.

Microfluidics on liquid handling stations (μF-on-LHS): a new industry-compatible microfluidic platform

Since the early days microfluidics as a scientific discipline has been an interdisciplinary research field with a wide scope of potential applications. Besides tailored assays for point-of-care (PoC) diagnostics, microfluidics has been an important tool for large-scale screening of reagents and building blocks in organic chemistry, pharmaceutics and medical engineering. Furthermore, numerous potential marketable products have been described over the years. However, especially in industrial applications, microfluidics is often considered only an alternative technology for fluid handling, a field which is industrially mostly dominated by large-scale numerically controlled fluid and liquid handling stations. Numerous noteworthy products have dominated this field in the last decade and have been inhibited the widespread application of microfluidics technology. However, automated liquid handling stations and microfluidics do not have to be considered as mutually exclusive approached. We have recently introduced a hybrid fluidic platform combining an industrially established liquid handling station and a generic microfluidic interfacing module that allows probing a microfluidic system (such as an essay or a synthesis array) using the instrumentation provided by the liquid handling station. We term this technology “Microfluidic on Liquid Handling Stations (μF-on-LHS)” – a classical “best of both worlds”- approach that allows combining the highly evolved, automated and industry-proven LHS systems with any type of microfluidic assay. In this paper we show, to the best of our knowledge, the first droplet microfluidics application on an industrial LHS using the μF-on-LHS concept.

Rapid biochemical functionalization of technical surfaces by means of a photobleaching-based maskless projection lithography process

MEMS/MOEMS based systems are increasingly applied in the biological and biomedical context, e.g. in form of biosensors or substrates for monitoring biological responses such as cell migration. For such applications, technical surfaces have to be provided with suitable biochemical functionalization. Typical functionalization procedures include wet-chemical techniques based on self-assembled monolayers of thiols on gold or silanes on glass. These processes create binary patterns and are often of limited use if spatially constrained non-binary patterns like surface bound biochemical gradients have to be provided. In order to create gradients or patterns, methods such as direct spotting or dip pen nanolithography can be used. Here, gradients can be emulated by varying the spot density or the concentration of the solutions employed. However, these methods are serial in nature and are thus of limited use if large surface areas have to be patterned. We present a technique to generate gradients of biochemical function by a photobleaching-based process allowing fast large-scale patterning. The process is based on photobleaching resulting in light-induced coupling of a fluorescently tagged biomolecule to a technical surface by concerted bleaching of the fluorophore. We custom designed a maskless projection lithography system based on a digital mirror device that allows the rapid creation of 8-bit grayscale protein patterns on any technical surface from digital data (e.g. bitmap files). We demonstrate how this process can be used to obtain patterns of several cm2 lateral size at micrometer resolution within minutes.