Freiburg, Germany
Freiburg, Germany

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Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: HEALTH-2007-2.4.1-4 | Award Amount: 4.15M | Year: 2008

Cancer accounts for nearly one-quarter of deaths in the developed world, exceeded only by heart diseases. One of the key strategies in cancer prevention is early diagnosis through cancer screening programs. Estimates of the premature deaths that could have been avoided through cancer screening vary from 3% to 35%, depending on a variety of assumptions. Beyond the potential to reduce mortality, screening may reduce cancer morbidity since treatment for earlier-stage cancers is often less aggressive than that for more advanced-stage cancers. Currently many of these screening programs, have issues with false negative results, long time delays to obtaining the results, which increase patient anxiety and delays in starting treatments. In this project we will develop a novel rapid real time PCR/probe technology, in a microarray biochip format with the corresponding automated instrumentation for use as a rapid point of care diagnostic device. Cervical cancer and its associated virus, human papilloma virus is the model system which will be used to develop this novel automated cancer screening technology. The novel real time PCR technology will permit detection of panels of multiple biomarkers in a single PCR reaction. The partners have already developed prototype technology which partly demonstrates a microarray approach to real time PCR. The project will build on this, providing the innovation needed to transform a promising technology to an integrated system suitable for practical use at point-of-care setting. The consortium includes four research institutes and two SMEs, who have extensive experience with real time PCR and microarray technologies, and are motivated to commercialise results. In addition partners 7 will act as end user, validating the system in a clinical setting.

Yusof A.,Albert Ludwigs University of Freiburg | Keegan H.,Trinity College Dublin | Keegan H.,Coombe Women and Infants University Hospital | Spillane C.D.,Trinity College Dublin | And 9 more authors.
Lab on a Chip - Miniaturisation for Chemistry and Biology | Year: 2011

Cell sorting and separation techniques are essential tools for cell biology research and for many diagnostic and therapeutic applications. For many of these applications, it is imperative that heterogeneous populations of cells are segregated according to their cell type and that individual cells can be isolated and analysed. We present a novel technique to isolate single cells encapsulated in a picolitre sized droplet that are then deposited by inkjet-like printing at defined locations for downstream genomic analysis. The single-cell-manipulator (SCM) developed for this purpose consists of a dispenser chip to print cells contained in a free flying droplet, a computer vision system to detect single-cells inside the dispenser chip prior to printing, and appropriate automation equipment to print single-cells onto defined locations on a substrate. This technique is spatially dynamic, enabling cell printing on a wide range of commonly used substrates such as microscope slides, membranes and microtiter plates. Demonstration experiments performed using the SCM resulted in a printing efficiency of 87% for polystyrene microbeads of 10 μm size. When the SCM was applied to a cervical cancer cell line (HeLa), a printing efficiency of 87% was observed and a post-SCM cell viability rate of 75% was achieved. © 2011 The Royal Society of Chemistry.

Tropmann A.,Laboratory for MEMS Applications | Tanguy L.,Laboratory for MEMS Applications | Koltay P.,Laboratory for MEMS Applications | Koltay P.,BioFluidix GmbH | And 3 more authors.
Langmuir | Year: 2012

This study presents a straightforward two-step fabrication process of durable, completely superhydrophobic microchannels in PDMS. First, a composite material of PDMS/PTFE particles is prepared and used to replicate a master microstructure. Superhydrophobic surfaces are formed by subsequent plasma treatment, in which the PDMS is isotropically etched and PTFE particles are excavated. We compare the advancing and receding contact angles of intrinsic PDMS samples and composite PTFE/PDMS samples (1 wt %, 8 wt %, and 15 wt % PTFE particle concentration) and demonstrate that both the horizontal and vertical surfaces are indeed superhydrophobic. The best superhydrophobicity is observed for samples with a PTFE particle concentration of 15 wt %, which have advancing and receding contact angles of 159° ± 4° and 158° ± 3°, respectively. © 2012 American Chemical Society.

Kalkandjiev K.,Albert Ludwigs University of Freiburg | Riegger L.,BioFluidix GmbH | Kosse D.,Institute For Mikro Und Informationstechnik | Welsche M.,Albert Ludwigs University of Freiburg | And 4 more authors.
Journal of Micromechanics and Microengineering | Year: 2011

We investigate TMMF photopolymer as a cost-efficient alternative to glass for the leak-tight sealing of high-density silicon microchannels. TMMF enables low temperature sealing and access to structures underneath via lamination and standard UV-lithography instead of costly glass machining and anodic bonding. TMMF is highly transparent and has a low autofluorescence for wavelengths larger than 400 nm. As the photopolymer is too thin for implementing bulky world-to-chip interfaces, we propose adhesive bonding of cyclic olefin copolymer (COC) modules. All materials were tested according ISO 10993-5 and showed no cytotoxic effects on the proliferation of L929 cells. To quantify the cost efficiency of the proposed techniques, we used an established silicon/Pyrex nanoliter dispenser as a reference and replaced structured Pyrex wafers by TMMF laminates and COC modules. Thus, consumable costs, manpower and machine time related to sealing of the microchannels and implementing the world-to-chip interface could be significantly reduced. Leak tightness was proved by applying a pressure of 0.2 MPa for 5 h without delamination or crosstalk between neighboring microchannels located only 100 μm apart. In contrast to anodic bonding, the proposed techniques are tolerant to surface inhomogeneities. They enable manufacturing of silicon/polymer microfluidics at lower costs and without compromising the performance compared to corresponding silicon/glass devices. © 2011 IOP Publishing Ltd.

Tropmann A.,Albert Ludwigs University of Freiburg | Lass N.,Albert Ludwigs University of Freiburg | Paust N.,Albert Ludwigs University of Freiburg | Metz T.,Albert Ludwigs University of Freiburg | And 5 more authors.
Microfluidics and Nanofluidics | Year: 2012

This study presents a new, simple and robust, pneumatically actuated method for the generation of liquid metal micro droplets in the nano- to picoliter range. The so-called StarJet dispenser utilizes a star-shaped nozzle geometry that stabilizes liquid plugs in its center by means of capillary forces. Single droplets of the liquid metal can be pneumatically generated by the interaction of the sheathing gas flow in the outer grooves of the nozzle and the liquid metal. For experimental validation, a print head was build consisting of silicon chips with a star-shaped nozzle geometry and a heated actuator (up to 280°C). The silicon chips are fabricated by Deep Reactive Ion Etching (DRIE). Chip designs with different star-shaped geometries were able to generate droplets with diameters in the range of the corresponding nozzle diameters. The StarJet can be operated in two modes: Either continuous droplet dispensing mode or drop on demand (DoD) mode. The continuous droplet generation mode for a nozzle with 183 μm diameter shows tear-off frequencies between 25 and 120 Hz, while droplet diameters remain constant at 210 μm for each pressure level. Metal columns were printed with a thickness of 0.5-1.0 mm and 30 mm height (aspect ratio >30), to demonstrate the directional stability of droplet ejection and its potential as a suitable tool for direct prototyping of the metal microstructures. © 2011 Springer-Verlag.

Gross A.,Albert Ludwigs University of Freiburg | Schondube J.,Albert Ludwigs University of Freiburg | Niekrawitz S.,Albert Ludwigs University of Freiburg | Streule W.,BioFluidix GmbH | And 4 more authors.
Journal of Laboratory Automation | Year: 2013

Within the past years, single-cell analysis has developed into a key topic in cell biology to study cellular functions that are not accessible by investigation of larger cell populations. Engineering approaches aiming to access single cells to extract information about their physiology, phenotype, and genotype at the single-cell level are going manifold ways, meanwhile allowing separation, sorting, culturing, and analysis of individual cells. Based on our earlier research toward inkjet-like printing of single cells, this article presents further characterization results obtained with a fully automated prototype instrument for printing of single living cells in a noncontact inkjet-like manner. The presented technology is based on a transparent microfluidic drop-on-demand dispenser chip coupled with a camera-assisted automatic detection system. Cells inside the chip are detected and classified with this detection system before they are expelled from the nozzle confined in microdroplets, thus enabling a "one cell per droplet" printing mode. To demonstrate the prototype instrument's suitability for biological and biomedical applications, basic experiments such as printing of single-bead and cell arrays as well as deposition and culture of single cells in microwell plates are presented. Printing efficiencies greater than 80% and viability rates about 90% were achieved. © 2013 Society for Laboratory Automation and Screening.

Agency: European Commission | Branch: FP7 | Program: BSG-SME | Phase: SME-2013-1 | Award Amount: 1.40M | Year: 2013

This project is focused on development of technologies for separation and manipulation of single biological cells for life science research and medical applications. The research plan is built upon the results of the FP7 project PASCA (GA 257073, started 01.09.2010). The single cell manipulation technology (SCM technology) developed there is based on inkjet-like printing of single biological cells confined in free flying micro droplets. It constitutes a universal platform for single cell analysis that has been proven to have high potential for many life science applications. The objective of this project is to support the participating SMEs and companies to take up the SCM technology, to realize their own applications and to develop them into innovative products for the medical, biomedical and pharmaceutical markets. Central element of the research is the SCM prototype instrument as presented in numerous publications (see The actual project will provide validation and extension of the use of this prototype instrument and deal with necessary improvements and modifications of pre-production prototypes towards the specific needs and applications of the SME partners. In particular also topics affecting commercial exploitation like e.g. application development, design for manufacturability, reliability issues, cost and throughput optimization, extension of technical specifications, and preparation of CE IVD labeling will be investigated. Applications targeted by the individual SMEs are considering fast pathogen detection for clinical use by combining the SCM technology with MALDI TOF mass spectroscopy of single bacteria, instruments for single cell cancer and stem cell research, methods for monoclonal cell line development and in-vitro medical diagnostic applications. The anticipated innovations stemming from this research will be exploited by the involved SMEs individually as well as jointly through several innovative products targeted for different markets and applications.

Agency: European Commission | Branch: FP7 | Program: CP | Phase: ICT-2009.3.9 | Award Amount: 3.94M | Year: 2010

Analysis of biological cells down to single cell resolution is a prospective technique in nearly all fields of life science research. In particular manipulation and analysis of single cells can open up a new dimension in cell biology, tissue engineering, drug development and diagnostics. The advancement of single cell technology as a whole requires tools and instrumentation to sort, transport and manipulate single living cells. Micro system technology with its sophistications can provide in this context capabilities far beyond todays methods.\n\nTherefore, this project aims to develop a single cell manipulator (SCM) micro instrument for inkjet like printing of single living cells confined in micro droplets of only 50m size. Such a device can serve as a universal tool for manipulating cells in a non-invasive flexible manner. Within the project the SCM device will be applied to cell biological applications in cancer research and drug development to demonstrate and validate the performance of the device, as well as to establish a flexible platform for advanced single cell-manipulation and analysis (PASCA).\n\nIn order to achieve these objectives crosscutting technological challenges have to be faced which can be overcome by integrating and interfacing multiple core technologies, only. Cutting edge bio-sensing technology like impedance spectroscopy and state of the art micro dispensing methods will be applied and combined with latest cell biological methods to establish the SCM instrument as multifunctional microsystem for cell manipulation. Through the highly innovative integrated approach and the validation within the PASCA platform the SCM instrument has excellent exploitation perspectives in multiple application sectors.\n\nAlso the project structure as a whole supports the objectives of the work program:By intensively involving SMEs to feed the innovation cycle and by bringing the user into research cycles through the open access partner structure.

Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: NMP.2013.1.4-1 | Award Amount: 4.22M | Year: 2014

Accurate design and modeling of nano-enabled systems requires a multi-scale simulation approach that can link phenomena on the nano-, micro-, meso-, and macroscales. Numerous simulation methods and tools are available for describing a material accurately and efficiently on each of the scales separately. In addition, several approaches for linking and coupling various hierarchal scales are also available. However, an integrated multi-scale simulation framework that allows a seamless and efficient coupling of various scales and methods is still lacking. The main goal of the present consortium is to develop an integrated multi-scale modeling environment for nano-materials and system design. The tools will be formed mainly by augmenting existing open-source and commercial simulation tools and supplementing them with sophisticated interface libraries that allow flow of information from one component to the other and from one scale to another. The simulation environment will also act as a platform for harmonizing and accelerating the development of new simulation modules by providing interface libraries to powerful pre- and postprocessing tools and to computational modules, which can be integrated and readily reused in new applications. The efficiency of the new developed simulation environment specifically for shortening the development process and time to discover novel nano-enabled products will be demonstrated through a proof-of-concept design of novel simulation tools for micro- and nanofluidic devices.

BioFluidix GmbH | Date: 2015-03-26

A pressure sensor for measuring a fluid pressure of a fluid within a measurement chamber has the measurement chamber having a mechanical deformable wall, a shape of the measurement chamber varying depending on a pressure within the measurement chamber. The pressure sensor further has a measurement electrode, wherein the measurement chamber is arranged relative to the measurement electrode to be arranged within a region of an electrical field originating from the measurement electrode upon application of a potential to the measurement electrode, wherein an influence of a variation of the shape of the measurement chamber on the electrical field can be detected.

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