The term microsystems technology is often associated with computer chips, navigation systems or intelligent implants. Less present in everyday life are life sciences applications such as dosing systems used in diagnostics and research, where the use and handling of the smallest amounts of liquids is becoming more and more essential. The experts at Freiburg-based BioFluidix GmbH specialise in what is known as microfluidics. The company offers solutions for the non-contact dispensing of liquids in the range of a few nanolitres up to several microlitres. These microfluidic devices are used for lab-on-the-chip applications that integrate one or several laboratory steps on a single chip. BioFluidix GmbH, a spin-off of the University of Freiburg and member of the MicroTEC Südwest cluster, is developing the next generation of accurate dosage systems for use in research and industry.
Small droplets mean big money. Doctors and researchers alike use biological materials such as cells, enzymes and DNA, which are very expensive to produce. For example, doctors expose tissue samples taken from patients to test substances in order to identify a disease; researchers from pharmaceutical companies test hundreds of thousands of potential drugs for their biological effect. Due to the high cost of biological materials, scientists are working on the development of systems that only require minimal amounts of material. In addition to requiring small amounts of material, the test systems must be highly accurate, as well as being compatible with state-of-the-art automation techniques that enable a large number of experiments to be carried out in a very short time. “As part of our research at the University of Freiburg, we have been dealing with these kinds of issues for more than 10 years,” said Dr. Peter Koltay, assistant in the Department of Application Development led by Prof. Dr. Roland Zengerle at the Institute of Microsystems Engineering (IMTEK) at the University of Freiburg. Dr. Koltay is also the managing director of BioFluidix GmbH. “In the end, we decided to turn some of our ideas into prototypes and establish a company to further develop and market the products.”
BioFluidix GmbH was established five years ago. The company's revenues have continuously grown over the last few years. "I started as a one-man show, and BioFluidix now has ten employees," said Koltay whose company develops and markets microdosing systems: one of these systems is a complete workstation that can deposit hundreds of different liquids on a chip that is hardly bigger than a fingernail. Biologists use these microarrays to investigate the activity of genes, amongst other things. Microarrays can be used to carry out around 10,000 experiments simultaneously, something that is also of major interest for the pharmaceutical industry which also needs to test substances in a high-throughput manner. The company's technology is optimised for the highly reliable and fast printing of microarrays with spots of only a few nanometres in size. In addition, the system can be combined with established laboratory robots, which is another advantage when focusing on medium- to high-throughput applications.
The company's PipeJet nanolitre dispensers are based on the PipeJet technology, which enables the dispensing of small volumes of a broad range of liquids with dosage volumes ranging from a few nanolitres to several microlitres. The technology is characterised by non-contact dispensing, which involves a flexible tube that is pressed together by a piezoactuator to release a nanolitre-droplet. The piezoactuator exerts a force on the liquid-containing tube from where a droplet is released. The dispensed volume can be controlled by the stroke of the piezoactuator. BioFluidix non-contact pipettes and dispensers are mainly used in research, but are also suitable for medical diagnostics where care must be taken to ensure that patient samples do not come into contact with residues of other samples. "The problem of current droplet dosage systems is that it is often not possible to exchange contaminated parts cheaply," said Koltay highlighting that his company not only focuses on high-precision droplet handling but also on the inexpensive exchange of parts. All parts that contain or guide liquids are made of plastics. Therefore, they can be produced cheaply and can then be discarded after use.
The success of the BioFluidix product portfolio for use in the diagnosis of diseases or in the development of new drugs is therefore guaranteed. Nevertheless, the microsystems engineers from Freiburg are thinking even further ahead. Nowadays, microdosing is used in virtually all industries, including the field of microeletronics, where some of Koltay's clients are involved in the accurate dosage of electrical flux material or the coating of tiny components with sol-gel phases that are only a few millimetres thick. BioFluidix GmbH is a member of the BMBF-funded MicroTEC Südwest cluster, a consortium of more than 330 companies, universities, research institutions, financial service providers, etc. based in southwest Germany.
“Historically, in research and technology, innovations have generally arisen when different disciplines come into contact with each other,” said Koltay. In the MicroTEC Südwest cluster, microsystems engineers from a broad range of industry sectors and science such as the automotive, food and engine construction sectors, are working together. BioFluidix therefore not only has close connections with the IMTEK at the University of Freiburg, from where it emerged and operates, but it also has close links with industry. For example, BioFluidix and IMTEK are currently working on a project coordinated by Mannheim-based Roche Diagnostics AG, related to the development of an intelligent cartridge for the dosage of tiny amounts of liquid. This cartridge is the next generation of systems that are able to autonomously control their function, something that is believed will make in vitro diagnostics even safer. A particular challenge is to find a way to develop the parts so that they can be manufactured inexpensively.Funding received through its membership of the MicroTeC Südwest cluster helps the company to focus on the further development of an innovative pipette tip on the basis of its proprietary PipeJet technology. The goal is to manufacture pipette tips that are able to dispense even smaller droplets than its PipeJet nanolitre dispenser. BioFluidix also works with Wertheim-based BRAND GMBH+CO KG, a specialist in laboratory products such as liquid handling systems, high-quality plastics consumables and volume measurement devices made of glass and plastics. The two partners are looking for ways to produce a pipette tip using injection moulding, which would enable the tips to be produced inexpensively. Of course, like all other BioFluidix products, the new pipette tip will need to be compatible with standard laboratory devices. “Our vision for the new pipette tip is that it will also be used in other industries some time in the future,” said Koltay referring to the fact that pipetting has become something of a standard technology for many industries. “It will be interesting to see what kind of application possibilities arise from working with our partners in the MicroTEC Südwest cluster.”