Bernried, Germany
Bernried, Germany

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Grant
Agency: European Commission | Branch: H2020 | Program: SME-1 | Phase: PHC-12-2014-1 | Award Amount: 71.43K | Year: 2015

Biomarkers in discovery are valuable tools to understand the pathobiology of a disease and the pharmacology of a target under investigation. In-vitro screen would be invaluable in identifying working hypothesis early in drug development process. Information provided by properly selected biomarkers can greatly influence a go/no go decision. The challenge is to identify relevant biomarkers early enough to implement them for such critical decisions. In developing in-vitro assays to identify biomarkers with potential clinical application and utility, a clear understanding and determination of what that biomarker will assess must be defined. More reliable biomarker screening protocols based on allometric scaling laws are needed to be implemented in order to gain results more respondent to human physiology. The predictive power of High Content Screening techniques can be enhanced by working with primary cells or differentiated stem cells and in 3-D culture. Nevertheless, in-vitro cell cultures are still far away from the complexity of human tissues or organs. IVTech intends to industrialize and test Multidyn, a patented advanced low-cost cell culture system made up by a 24-chambers plate complying with the multiwell standard, capable of any internal connection and flow within the cells, able to realize cheaper faster in-vitro physiologically relevant cellular systems. Multidyn will be tested for early diabetes biomarker discovery by using a developed model of liver, vascular endothelium and adipose tissues, and when equipped with the highly performing 3D scaffolds provided by the partner Scaffdex and with suitable High Content Imaging systems provided by the partner Celltool and selected scientific laboratories. IVTech Multidyn is at TRL 6. Phase 1 project will assess the activities needed to demonstrate the product in operational environment with potential end-users, establish a large scale production and test the market.


Kemper B.,University of Munster | Langehanenberg P.,University of Munster | Hoink A.,University of Munster | von Bally G.,University of Munster | And 7 more authors.
Journal of Biophotonics | Year: 2010

For a precise manipulation of particles and cells with laser light as well as for the understanding and the control of the underlying processes it is important to visualize and quantify the response of the specimens. Thus, we investigated if digital holographic microscopy (DHM) can be used in combination with microfluidics to observe optically trapped living cells in a minimally invasive fashion during laser micromanipulation. The obtained results demonstrate that DHM multi-focus phase contrast provides label-free quantitative monitoring of optical manipulation with a temporal resolution of a few milliseconds. Laser micromanipulation monitoring of optically trapped pancreas tumor cells by quantitative digital holographic phase contrast. The arrows in the false colour coded quantitative phase contrast images indicate the impact of the treatment with focussed laser light. © 2010 by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Charwat V.,University of Natural Resources and Life Sciences, Vienna | Schutze K.,CellTool GmbH | Holnthoner W.,Ludwig Boltzmann Institute for Experimental and Clinical Traumatology | Lavrentieva A.,Leibniz University of Hanover | And 5 more authors.
Journal of Biotechnology | Year: 2015

Today highly complex 3D cell culture formats that closely mimic the in vivo situation are increasingly available. Despite their wide use, the development of analytical methods and tools that can work within the depth of 3D-tissue constructs lags behind. In order to get the most information from a 3D cell sample, adequate and reliable assays are required. However, the majority of tools and methods used today have been originally designed for 2D cell cultures and translation to a 3D environment is in general not trivial. Ideally, an analytical method should be non-invasive and allow for repeated observation of living cells in order to detect dynamic changes in individual cells within the 3D cell culture. Although well-established laser confocal microscopy can be used for these purposes, this technique has serious limitations including penetration depth and availability. Focusing on two relevant analytical methods for live-cell monitoring, we discuss the current challenges of analyzing living 3D samples: microscopy, which is the most widely used technology to observe and examine cell cultures, has been successfully adapted for 3D samples by recording of so-called "z-stacks". However the required equipment is generally very expensive and therefore access is often limited. Consequently alternative and less advanced approaches are often applied that cannot capture the full structural complexity of a 3D sample. Similarly, image analysis tools for quantification of microscopic images range from highly specialized and costly to simplified and inexpensive. Depending on the actual sample composition and scientific question the best approach needs to be assessed individually. Another more recently introduced technology for non-invasive cell analysis is Raman micro-spectroscopy. It enables label-free identification of cellular metabolic changes with high sensitivity and has already been successful applied to 2D and 3D cell cultures. However, its future significance for cell analysis will strongly depend on the availability of application oriented and user-friendly systems including specific tools for easy analysis and interpretation of spectral data focusing on biological relevant information. © 2015 Elsevier B.V.


Ramm Sander P.,University of Regensburg | Hau P.,University of Regensburg | Koch S.,CellTool GmbH | Schutze K.,CellTool GmbH | And 3 more authors.
Trends in Biotechnology | Year: 2013

Stem cells offer great potential for regenerative medicine because they regenerate damaged tissue by cell replacement and/or by stimulating endogenous repair mechanisms. Although stem cells are defined by their functional properties, such as the potential to proliferate, to self-renew, and to differentiate into specific cell types, their identification based on the expression of specific markers remains vague. Here, profiles of stem cell metabolism might highlight stem cell function more than the expression of single genes/markers. Thus, systematic approaches including spectroscopy might yield insight into stem cell function, identity, and stemness. We review the findings gained by means of metabolic and spectroscopic profiling methodologies, for example, nuclear magnetic resonance spectroscopy (NMRS), mass spectrometry (MS), and Raman spectroscopy (RS), with a focus on neural stem cells and neurogenesis. © 2013 Elsevier Ltd.


Patent
CellTool GmbH | Date: 2011-06-09

In order to quantitatively characterize biological objects, for example individual cells, a stimulus is applied to a biological object in a contactless fashion. A measurement and a further measurement are performed on the biological object in order to ascertain a response of the biological object to the stimulus, wherein the measurement and the further measurement comprise detecting Raman scattering on and/or in the biological object and/or capturing data using digital holographic microinterferometry (DHMI). The biological object is characterized according to a result of the measurement and is sorted if needed. The stimulus can be applied by means of a laser beam that creates optical tweezers or an optical trap, by means of ultrasonic waves or an electric or magnetic radio frequency field.


Grant
Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2011.1.4-2 | Award Amount: 7.65M | Year: 2012

Regenerative medicine focuses on repairing or replacing tissue or organ function lost due to damage or congenital defects using appropriate cells for therapy that have healing capacities like stem cells or progenitor cells. Although regenerative medicine has the potential for more effective therapeutic interventions major improvement in three areas are still needed for a wider establishment of such new concepts in clinical practise: identification of the appropriate cells with healing capacity for the use in therapy, homing of these cells to the damaged tissue, and monitoring of the therapeutic intervention and effect. Thus, a multidisciplinary consortium has set up IDEA, a 60 month collaborative project to develop and establish: Photonic methods that allow a contact and marker-free identification and selection of cells with healing capacity for vascular, musculoskeletal and neuronal tissue defects; Magnetic cell select devices that capture and transport cells with healing potential through the circulatory system to damaged tissue and organs improving homing; Tracer and imaging technologies to monitor the therapeutic effects of interventional regenerative medicine by showing anatomic structure AND demonstrating cellular function using magnetic resonance imaging (MRI) and a new imaging technology known as magnetic particle imaging (MPI). The IDEA project is intended to provide collaboration between scientists and clinicians from Karolinska Institute (Stockholm, Sweden), Kings College (London, UK), Paracelsus Medical University (Salzburg, Austria) and Julius-Maximilians-University (Wrzburg, Germany) together with experts from SMEs specialized in photonic technologies for tissue engineering, medical device manufacturing with extensive experience in regulatory approval, the design, synthesis and up-scaling of nanoparticles for molecular imaging, and regulatory affairs. This multidisciplinary consortium will address scale-up, regulatory work and exploratory clinical investigations using the developed tools, technologies and devices in the time frame of the project.


A method and device for manipulating a biological object (36) are provided. The biological object (36) is positioned at a distance from a reflecting surface (39). A beam (33) of electromagnetic radiation is directed towards the reflecting surface (39) such that the beam (33) impinges on a first face of the biological object (36) and that at least a portion of the beam (33) is reflected by the reflecting surface (39) into a reflected beam (35) which directly impinges on a second face of the biological object (36). The beam (33) directed towards the reflecting surface (39) is adjusted to effect a deformation or rotation of the biological object (36).


PubMed | CellTool GmbH and University of Würzburg
Type: Journal Article | Journal: Biomaterials | Year: 2014

To investigate interrelations of human obligate airway pathogens, such as Bordetella pertussis, and their hosts test systems with high invitro/invivo correlation are of urgent need. Using a tissue engineering approach, we generated a 3D test system of the airway mucosa with human tracheobronchial epithelial cells (hTEC) and fibroblasts seeded on a clinically implemented biological scaffold. To investigate if hTEC display tumour-specific characteristics we analysed Raman spectra of hTEC and the adenocarcinoma cell line Calu-3. To establish optimal conditions for infection studies, we treated human native airway mucosa segments with B.pertussis. Samples were processed for morphologic analysis. Whereas our test system consisting of differentiated epithelial cells and migrating fibroblasts shows high invitro/invivo correlation, hTEC seeded on the scaffold as monocultures did not resemble the invivo situation. Differences in Raman spectra of hTEC and Calu-3 were identified in distinct wave number ranges between 720 and 1662cm(-1) indicating that hTEC do not display tumour-specific characteristics. Infection of native tissue with B.pertussis led to cytoplasmic vacuoles, damaged mitochondria and destroyed epithelial cells. Our test system is suitable for infection studies with human obligate airway pathogens by mimicking the physiological microenvironment of the human airway mucosa.


Steinke M.,Fraunhofer Project Group Regenerative Technologies in Oncology | Steinke M.,University of Würzburg | Gross R.,University of Würzburg | Walles H.,Fraunhofer Project Group Regenerative Technologies in Oncology | And 4 more authors.
Biomaterials | Year: 2014

To investigate interrelations of human obligate airway pathogens, such as Bordetella pertussis, and their hosts test systems with high invitro/invivo correlation are of urgent need. Using a tissue engineering approach, we generated a 3D test system of the airway mucosa with human tracheobronchial epithelial cells (hTEC) and fibroblasts seeded on a clinically implemented biological scaffold. To investigate if hTEC display tumour-specific characteristics we analysed Raman spectra of hTEC and the adenocarcinoma cell line Calu-3. To establish optimal conditions for infection studies, we treated human native airway mucosa segments with B.pertussis. Samples were processed for morphologic analysis. Whereas our test system consisting of differentiated epithelial cells and migrating fibroblasts shows high invitro/invivo correlation, hTEC seeded on the scaffold as monocultures did not resemble the invivo situation. Differences in Raman spectra of hTEC and Calu-3 were identified in distinct wave number ranges between 720 and 1662cm-1 indicating that hTEC do not display tumour-specific characteristics. Infection of native tissue with B.pertussis led to cytoplasmic vacuoles, damaged mitochondria and destroyed epithelial cells. Our test system is suitable for infection studies with human obligate airway pathogens by mimicking the physiological microenvironment of the human airway mucosa. © 2014 Elsevier Ltd.


PubMed | Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, CellTool GmbH, University of Natural Resources and Life Sciences, Vienna, Leibniz University of Hanover and Cellendes GmbH
Type: | Journal: Journal of biotechnology | Year: 2015

Today highly complex 3D cell culture formats that closely mimic the in vivo situation are increasingly available. Despite their wide use, the development of analytical methods and tools that can work within the depth of 3D-tissue constructs lags behind. In order to get the most information from a 3D cell sample, adequate and reliable assays are required. However, the majority of tools and methods used today have been originally designed for 2D cell cultures and translation to a 3D environment is in general not trivial. Ideally, an analytical method should be non-invasive and allow for repeated observation of living cells in order to detect dynamic changes in individual cells within the 3D cell culture. Although well-established laser confocal microscopy can be used for these purposes, this technique has serious limitations including penetration depth and availability. Focusing on two relevant analytical methods for live-cell monitoring, we discuss the current challenges of analyzing living 3D samples: microscopy, which is the most widely used technology to observe and examine cell cultures, has been successfully adapted for 3D samples by recording of so-called z-stacks. However the required equipment is generally very expensive and therefore access is often limited. Consequently alternative and less advanced approaches are often applied that cannot capture the full structural complexity of a 3D sample. Similarly, image analysis tools for quantification of microscopic images range from highly specialized and costly to simplified and inexpensive. Depending on the actual sample composition and scientific question the best approach needs to be assessed individually. Another more recently introduced technology for non-invasive cell analysis is Raman micro-spectroscopy. It enables label-free identification of cellular metabolic changes with high sensitivity and has already been successful applied to 2D and 3D cell cultures. However, its future significance for cell analysis will strongly depend on the availability of application oriented and user-friendly systems including specific tools for easy analysis and interpretation of spectral data focusing on biological relevant information.

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