Product Sheets and Technology Offers

AquaNANO - Nanoprobes Based Fast Drinking Water Analysis

© Fraunhofer IME | Florian Schröper

Drinking water is our most important foodstuff and is therefore subject to strict and frequent controls. Nevertheless, there are always situations in which contamination with pathogens cannot be ruled out, e.g. after floods or earthquakes. In addition, bioterrorist attack scenarios cannot be ruled out, as supply facilities represent a potential target because of their nationwide infrastructure and central feed-in points. Established analyses are laboratory-based, complex and time-consuming. There is currently a lack of reliable and sensitive rapid test methods that can be used on site. The aim of the joint AquaNANO project is to develop a novel mobile analysis system that can detect impurities in drinking water in the shortest possible time.

Innovative Detection Technologies and Assay Designs

© Fraunhofer IME | Florian Schröper

Fraunhofer IME is an application-oriented research institute focusing on the development of innovative analysis platforms. In close cooperation with partners from science and industry, we develop tailor-made solutions for specific challenges. One of the research focuses of Fraunhofer IME is the development of tailor-made immunological assays and the production of specific antibodies for these purposes. In addition to adapting classical methods such as the enzyme coupled immunosorbent assay (ELISA) to specific problems, we also focus on the development of innovative rapid test platforms, e.g. using special magnetic nanoprobes.

Magn-I-tekt Magnetic Immunodetection for Mobile and Rapid IdentifIcation of Plant Pathogens

© Fraunhofer IME | Florian Schröper

Plant pathogens such as viruses and fungi have a strong global impact on crop plants and lead to considerable economic losses of up to 30 percent. The early identification and quantification of plant pathogens is of crucial importance in order to initiate appropriate measures in good time, such as the use of plant protection products, and thus prevent the spread of such diseases. Routine testing of random plant samples for the presence of certain pathogens is a suitable strategy. For this purpose, we have developed a novel rapid test method using antibody-functionalized magnetic particles. Continuous sampling in the field in combination with the mobile rapid test allows early detection of pathogenic infestations and efficient control of the amount of pesticide.

DNA-Sequencing

© Fraunhofer IME | Birgit Orthen

DNA sequencing is a very labor-intensive and time-consuming process that has become indispensable in modern biological research. It is required to characterize new genes or to verify the identity of recombinant DNA. To support our customers in their research activities, we offer a portfolio of DNA sequencing and related services:
- Plasmid DNA Preparation
- PCR Product Purification
- Preparation of sequence reactions
- Analysis of sequence reactions

Antibody Technologies

© Fraunhofer IME | Anne Peuscher

At Fraunhofer IME, murine antibodies have been produced using hybridoma technology for many years. Based on this, our expertise has expanded into other areas of antibody work. A modern cell culture laboratory with automated cell cultivation is available for the generation and selection of antibody producing cells. The purification of the produced antibodies as well as characterization and functional analysis (e.g. by gel electrophoresis, ELISA and Surface Plasmon Resonance) are routinely performed. The cloning of the genetic information of the antibodies and their further optimization as well as the conversion into other antibody formats e.g. single chain antibodies (scFv) are an integral part of our work.

Biocore Interaction Analysis

© Fraunhofer IME | Holger Spiegel

The activity of active pharmaceutical ingredients is usually based on a molecular interaction of the respective active substance with specific receptor or target molecules in the patient's body. The reliable and detailed quantitative characterization of biomolecules in terms of interaction parameters such as specificity, binding strength and stoichiometry plays a decisive role in the identification and development of new drugs and vaccines as well as in quality control in the manufacture of new drugs and vaccines.

Chronic Testing of Lothic Invertebrate Species

© Fraunhofer IME | Klaus Peter Kappest


Species Sensitivity Distributions (SSDs) are increasingly used in ecological risk assessment of chemicals. SSDs compile toxicity data for a set of species tests to estimate hazardous concentrations (HCx), which represent a specific proportion of species in a communitythat would be affected. For the risk assessment of plant protection products tests for at least eight invertebrate species of the sensitive taxonomic group are required for the SSD approach. Until now, most invertebrate SSDs for plant protection products are based on acute test data because to conduct for example chronic tests with eight different aquatic arthropoda species is difficult. The Fraunhofer IME is able to perform chronic testing of different invertebrate species which could provide toxicity data for the SSD approach.

Eco'n'OMICS – Screening development for ecotoxicological risk prediction

© Fraunhofer IME | Sebastian Eilebrecht

Active substances of pesticides, biocides or pharmaceuticals can display adverse effects in non-target organisms. Therefore, European legislation requests manufacturers to provide data for environmental risk assessment of active substances for registration. The commonly applied OECD tests are time- and cost-consuming and come along with a substantial number of animal tests. Thus, they are conducted only in the final stage of industrial substance development, bearing the risk of a failing registration due to proven adverse environmental effects. The Eco'n'OMICs project aims at an early ecotoxicological risk prediction for active substance precursors based on substance-induced molecular changes in aquatic model organisms.

Nuclear Magnetic Resonance (NMR) Spectroscopy

© Fraunhofer IME | Studio 95

All organic compounds undergo transformation and degradation processes that generate new substances with completely different properties. Before products can be registered, it is therefore necessary to understand how they are metabolized and degraded in different environmental matrices. Regulatory approval procedures for this are challenging because highly-sensitive analytical methods are needed to detect and identify the minute quantities of transformation products generated by metabolism and environmental degradation. Nuclear magnetic resonance (NMR) spectroscopy is the most efficient analytical method for determining the structure of organic substances.The NMR suite is supported by a high-resolution OrbitrapTM Hybrid FT mass spectrometer that can determine the chemical formulae of unknown substances to complement the structural data.

Technology Offers

Combination Therapy of Type 1 Diabetes

© Fraunhofer IME | Urs Christen


The invention relates to the use of combination therapy of T1D with two drugs each specifically targeted to a different mechanism. Treatment with anti-CD3 monoclonal antibodies (MAbs) is given together with a MAb targeted to a chemokine protein that selectively directs the migration of lymphocytes to sites of inflammation or injury.

Drug Repurposing for Multiple Sclerosis

© Fraunhofer IME | Irmgard Tegeder

The invention relates to the use of a drug (TMP-001), marketed for many years for another indication, in the treatment of MS. It has been tested extensively, though without significant success, in Alzheimer’s disease patients in which safety of high doses was comparable to placebo. Surprisingly, animal studies reveal a novel spectrum of activity in models of MS. The major advantages of this asset are the extensive clinical experience with the drug, its excellent oral safety profile and novel efficacy spectrum. TMP-001 offers a relatively straightforward development pathway to a novel oral therapy for MS.

 

 

Biofeedback Controlled Analgesia

© MEV-Verlag

 

The invention comprises a new opioid infusion device that combines several advantages of TCI and PCA while avoiding certain disadvantages of the respective methods. Feedback controlled analgesia allows patients to titrate themselves with opioids until they reach adequate analgesia. The patented method allows control and maintenance of adequate and safe opioid analgesia without continuous adjustment by the patient or constant supervision by medical personnel.

 

Inhibitors for NOX-4 for the Treatment of Neuropathic Pain

© Fraunhofer IME | Achim Schmidtko

The present invention relates to the use of the enzyme Nox4 as a target for the prevention and treatment of neuropathic pain. Accordingly, the use of Nox4 inhibitors is proposed, which reduce the activity and / or expression of Nox4. Mice deficient in Nox4 demonstrate considerably reduced pain-related behavior in animal models of neuropathic pain. Moreover, demyelination of peripheral nerves that typically occurs after nerve injury (SNI) is reduced in Nox4-deficient mice.

Sphingosine-1-Phosphate Receptor Agonists for Treatment of Neuropathic Pain

© Fraunhofer IME | Klaus Scholich

 

Sphingosine-1-phosphate (S1P) is an intracellular mediator with a wide spectrum of signaling functions. In neurons, its effects depend on the neuronal sub-type. Peripherally, S1P promotes neuronal growth and excitability and S1P receptor inhibition reduces inflammatory or chemotherapeutic pain. The present invention is a screening method for activators of the S1P receptor, including FTY720, which downregulate sensitization of nociceptive neurons in the spinal cord and therefore, offer a novel approach to the relief of trauma or pain.

 

 

Lipid Receptor Agonists as Analgesics

© Fraunhofer IME | Sebastian Zinn, Michael Parnham

Many lipid mediators of inflammation act on multiple receptors to stimulate inflammatory cells. One of these mediators also acts at low affinity at receptors that are highly expressed in ganglion cells in the spinal cord. The invention relates to the finding that agonists at the low affinity lipid receptor downregulate sensitization of nociceptive neurons in the spinal cord and therefore, offer a novel approach to the relief of pain.

Novel Inhibitors for the Treatment of Chemotherapy-Induced Neuropathic Pain

© Fraunhofer IME | Marco Sisignano

Research findings have shown that cytotoxic drug therapy induces a specific cytochrome protein which produces large amounts of a mediator that sensitizes specific ion channels in nociceptive neu­rons. The inventive method involves the use of drugs which inhibit the function of the overexpressed protein and thus reduce the chemotherapy-induced sensitization of the neuronal ion channels. This action opens up a new approach to therapy of neuropathic pain and treatment options are limited.

Recombinant B7-H1 Fusion Protein as a Therapy Concept for Multiple Organ Failure in Sepsis

© Fraunhofer IME | Andreas von Knethen

The invention relates to a fusion protein of the extracellular part of an immunoinhibitory receptor and human immunoglobulin to be used for therapy of sepsis. The inhibitory receptor binds to a ligand on cytotoxic T (Tc) cells and the specificity of the fusion protein can be enhanced by incorporating a binding peptide selective for Tc cells. The major advantage of this fusion protein is that it replaces inhibitory B7-H1 (PD-L1) molecules on organs lost during sepsis and induces prolonged tolerance rather than just inhibition of Tc cells. The therapeutic protein thus offers more than just acute inhibition of inflammation.

Antagonist of the Nuclear Hormone Receptor PPARγ for Sepsis Therapy

© Fraunhofer IME | Thales Kronenberger, Tilo Knape

The present invention pertains to a new compound and its derivatives. The compounds are selective, competitive peroxisome proliferator-activated receptor gamma (PPARγ) antagonists indicated for the treatment of immune related diseases such as systemic inflammation, sepsis and septic shock. The advantage of PPARγ ant­agonism is the inhibition of T cell apoptosis and the prevention of “immune paralysis”. The compounds, in con­trast to available agents, are competitive inhibitors, thus facilitating control of paren­teral dosing. The new compounds permit careful timing of sepsis therapy to target hypo- rather than hyper-inflammation during sepsis.

Recombinant Human Cytokine Therapy for Chronic Inflammatory Diseases

© Fraunhofer IME | Andreas Weigert

The discovery of an N-modified interleukin (N-mod IL-X) as an endogenous antagonist of several pro-inflammatory cytokine recep­tors opens up a new approach to therapy of chronic inflammatory diseases. The invention comprises a recombinant form of N-mod IL-X which is suitable for therapeu­tic administration. Because of its antagonist action at multiple cytokine receptors, it represents a single drug candidate which targets various inflammatory processes with corresponding broad therapeutic activity.

Implant for Delayed Release of Therapeutic Biologicals

© Fraunhofer IME | Matthias Wacker

The invention relates to the use of a novel implant formulation, for subcutaneous insertion, which releases the protein drug slowly from the implant, but maintains the stability of the therapeutic protein drug. The implant formulation offers the possibility of regulating the bioavailability of biologicals, thereby reducing their toxicity and obviating the need for frequent injections.

Neutralizing Antibody for Immune Reactivation in Cancer

© Fraunhofer IME | Andreas Weigert

The discovery of an interleukin that is produced in tumors and suppresses the anti-tumor activity of a number of immune cells opens up a new approach to the therapy of cancer. The invention comprises a neutralizing antibody against this interleukin, which is suitable for therapeutic administration. Because of its activity in an experimental tumor model that is resistant to current immune checkpoint therapy (anti-PD-1), the target may be suitable for patients/entities that do not respond to immune checkpoint blockade, as well as for use in combinatorial therapy approaches.

Product Sheets

Translational Medicine – in vivo Pharmacology

© Fraunhofer IME | Natasja de Bruin

We offer a specialized spectrum of preclinical in vivo models covering the fields of neurodegenerative diseases, acute inflammation, pain (inflammatory, neuropathic, oncological and post-operative) and skin disorders. Variables determined include direct functional, imaging and behavioral analyses, as well as ex vivo immune-histological, immunological, cellular (e.g. FACS), receptor, enzyme, signaling, proteomic and genomic processes. This detailed assessment allows for distinctive phenotyping of drug effects.

Behavioral Analysis In Animal Models for the Study of Compound Effects

© Fraunhofer IME | Mike Schmidt

Animal models aim to improve the knowledge on the pathophysiological mechanisms of diseases and provide experimental tools for testing novel therapies. In these models, it is also relevant to characterize behavioral features such as motor abilities, emotional changes and cognitive performance, since often these are impaired in pain and neurodegenerative diseases. The results obtained can provide information on benefits or side effects of compounds.

Bleomycin Mouse Model for Systemic Sclerosis

© Fraunhofer IME | Mike Schmidt, Martine Hofmann

Systemic sclerosis (SSc) or scleroderma is an inflammatory rheumatic connective tissue disease that is characterized by fibrosis of the skin and various internal organs. One of the animal models available for SSc is the murine bleomycin-induced dermal fibrosis model. The progression of the cellular infiltration and inflammatory response induced in the skin by bleomycin is monitored in vivo by luminol-based bioluminescence imaging (BLI). Also, histological analysis of the skin is performed using the Masson trichrome stain for fibrosis.

Delayed Type Hypersensitivity Mouse Model

© Fraunhofer IME | Natasja de Bruin

Allergic contact dermatitis is a T-cell-mediated hypersensitivity reaction (Delayed Type Hypersensitivity or DTH Type IV). Animal models of allergic contact dermatitis and associated responses are useful for testing new therapeutic compounds, but also provide simple means to study skin inflammation and systemic immune responses. The main in vivo outcome parameters in the DTH model are ear thickness and luminol-based bioluminescent imaging of myeloperoxidase activity.

Imiquimod Mouse Model of a Psoriasis-Like Skin Condition

© Fraunhofer IME | Mike Schmidt, Martine Hofmann

Psoriasis is an autoimmune disorder in which cells multiply too quickly and form scales on the skin’s surface. Psoriasis often occurs alongside arthritis or other joint diseases. The Imiquimod (IMQ)-induced psoriasis model develops a skin pathology which highly correlates to that of human psoriasis and is considered a potential preclinical psoriasis model. The main in vivo outcome parameters are ear/skin thickness, luminol-based bioluminescent imaging of myeloperoxidase activity and the clinical Psoriasis Area and Severity Index (PASI) score.

Cuprizone Demyelination of Murine Corpus Callosum – a Model of Multiple Sclerosis Neurodegeneration

© Fraunhofer IME | Mike Schmidt, Martine Hofmann

Cuprizone intoxication is a commonly used model to study experimental remyelination, with the corpus callosum being the most frequently investigated white matter tract. In this model, mice are fed with the copper chelator cuprizone, which leads to a primary oligodendrocyte apoptosis and secondary demyelination within weeks. After removal of the toxin, spontaneous remyelination occurs, thus making the cuprizone model appropriate for studying compounds which can prevent demyelination and/or stimulate remyelination.

Experimental Autoimmune Encephalomyelitis (EAE) Models for Multiple Sclerosis

© Fraunhofer IME | Natasja de Bruin

Experimental autoimmune encephalomyelitis (EAE) is a widely-used rodent model for multiple sclerosis (MS), but a single model can hardly capture and adequately incorporate all features of MS. A number of different EAE models are available, resulting in different disease-progression patterns and clinical features. Dependent on the antigen and rodent strain used, the animals develop different disease processes. Besides clinical scores, we offer the opportunity to include more subtle and objective behavioral measurements.

Mouse Models for Inflammatory, Non-inflammatory and Neuropathic Pain

© Fraunhofer IME | Natasja de Bruin

Several animal models are available for the study of nociception and different types of pain (inflammatory, neuropathic, oncological and post-operative). Our approach is not only to use standard readouts, but we also offer the possibility to study more subtle and objective in vivo readouts that potentially could have a higher translational value, such as measurements of balance, motor coordination, muscle strength, cognition and emotional state.

Immune Cell Function Tests

© Fraunhofer IME | Thomas Ulshöfer

A wide variety of in vitro immune cell function tests are available. Emphasis is laid on immune cell activity. Maturation, differentiation, activation, polarization and proliferation of primary human immune cells (monocytes, dendritic cells, T cells) are performed. State-of-the-art cellular, immunological, biochemical, analytical, proteomic and genomic techniques are employed.

Immunogenicity Test Systems

© Fraunhofer IME | Sorwe Mojtahed Poor

Introduction of biotherapeutics has been a major milestone in the treatment of different chronic diseases. Nevertheless, the immune system can recognize the administered biological as non-self and respond with generation of antidrug antibodies (ADA), including neutralizing ADA (nADA). Immunogenic responses may result in altered drug dynamics and kinetics leading to changes in safety and efficacy, therefore it is becoming increasingly important to determine immunogenicity parameters such as biological concentration, ADA and nADA levels. Since the FDA recommends to achieve a screening and a confirmatory assay, two assay systems for the determination of nADA and ADA in serum of patients treated with biologicals have been established. It is also important to exclude that co-medication and serum proteins (i.e. RF) did not interact with the assay system, therefore for the establishing of immunogenicity assays patient serum is used. The assays can be customized.

Toxicity Test Systems

© Fraunhofer IME | Marina Henke

A wide variety of toxicity test systems are available. Emphasis is laid on toxicity tests with various cell lines (colon epithelial cells, liver cells, oligodendrocytes, neuronal cells, macrophages, T-cells) and primary human immune cells (monocytes, T-cells, B-cells). To test toxicity the effect of compounds on viability, cell cycle and apoptosis will be investigated. Beside the common toxicity assays we also offer second messenger assays, since compounds that interact with the release of second messengers are very likely associated with side effects.

Assays for Compound Screening and Characterization

© Fraunhofer IME | Susanne Schiffmann

A wide variety of compound screening assays are available. Emphasis is laid on cellular signaling processes, lipid metabolism, neuronal cell responses and immune cell activity. State-of-the-art immunological, cellular, genomic, proteomic and biochemical assays as well as modern techniques for metabolome analysis are employed. Furthermore we offer a cell barrier assay to mimic the blood brain barrier or intestinal barrier.

Cell barrier assay

© Fraunhofer IME | Thomas Ulshöfer

Cell barrier assays are used to investigate the pharmacokinetic potential of drug candidates. The cell barrier assay is able to mimic the blood brain barrier or the intestinal barrier. This model allows to determine the apparent permeability coefficient (Papp) and whether compounds influence functionality of tight cell-cell junctions.

Biometric Animal Telemetry System

© Fraunhofer IME | Tilo Knape

In order to better understand pathophysiological changes in vital parameters during the course of diseases and their significance for diseases, we offer a biometric animal telemetry system for in vivo measurement of blood pressure, ECG, heart rate, temperature and physical activity. This real time understanding makes it possible to specifically develop new therapy approaches and to optimize existing therapies. Transmitters are surgically implanted into laboratory animals to acquire data changes. They detect internal animal characteristics, process the information into data, which can be externally processed.

Cecal Ligation and Puncture Model of Sepsis

© Fraunhofer IME | Tilo Knape

Systemic inflammation or sepsis is a reaction of the immune system to intensive and massive infections. To study the pathophysiology of human sepsis, we use the animal model of polymicrobial septic peritonitis: cecal ligation and puncture (CLP). Today, this test is the most widely used animal model of the systemic inflammatory response syndrome (SIRS), sepsis and septic shock because it closely mimics the progression and characteristics of human sepsis.

Flow Cytometry-Based FRET Assay for Analysis of Protein-Protein Interactions

© Fraunhofer IME | Tilo Knape

The detailed characterization of protein interactions is highly important to study the development of diseases, to identify new therapeutic targets and to detect drug-induced changes in protein interactions. We developed a flow cytometry-based FRET assay for molecular verification of protein interactions. This, for the first time, combines identification/characterization of binding intensity/affinity in a HTS system in living cells. The improved sensitivity of this assay allows its use for identification of novel therapeutic targets for treatment of human diseases and for the characterization of drug binding profile.

Sepsis Research at Fraunhofer IME

© Fraunhofer IME | Andreas von Knethen

Current approaches to treatment of sepsis focus on life support systems, drug inhibition of the hyper-inflammation of sepsis and cytotoxic mechanisms in order to suppress disease progression. However, despite recent major advances, the incidence of and mortality due to sepsis continue to increase. There is, therefore, a need for new methods for diagnosis, prevention and treatment of sepsis. Fraunhofer IME is developing novel drugs and therapy approaches to prevent T cell depletion and multiple organ failure during sepsis. Further, Fraunhofer IME studies new specific and sensitive sepsis biomarkers.

Biomedical Analysis – LC-MS/MS

© Fraunhofer IME | Nerea Ferreirós Bouzas

We use modern analytical technology (LC-MS/MS and LC-HRMS) to measure endogenous and exogenous small molecules in complex biological matrices. Our goal is to quantify compounds, such as drugs or signaling molecules, to study them in the context of pharmacokinetic studies or to discern their role in the development, progression or treatment of diseases.