The Research and Development Unit offers complete and innovative solutions in the field of parallel bioanalysis by applying spot based analytical technologies utilizing the company know-how in the fields of microarrays, assays development, pico- and nanoliter handling, surface functionalization, array imaging and data analysis.
SCIENION is committed to R&D with the aim of working with our customers to develop innovative products.
Partnerships play an important role in our activities and we value establishing and maintaining strong relationships with our contacts within the scientific, academic and business communities. We are engaged in several joint research projects at national and international levels, some of them publicly funded.
Cell Isolator – Catching Circulating Tumor Cells (CTC) in vivo
In oncology, significant progress has been made in recent decades in the early detection and treatment of cancer. Despite all these improvements, the development and growth of primary tumours can lead to a haematogenic scattering of tumour cells early in the course of the disease, which increases the risk of metastases. In addition to the general problems of selectivity and sensitivity, diagnostic methods established to date are limited by the fact that they only refer to a volume limited by the sampling technique, from which the entire organ or organism is extrapolated. A multitude of factors such as the type of sampling, the distribution of pathological cells (e.g. circulating tumor cell, CTC) in the blood or the expansion of tumor tissue in the organism influence the detection of pathological characteristics. Due to their physical and biological properties, CTCs can be isolated from the blood using various technologies and then used for further diagnostics, prognosis of the disease and therapy adaptation. According to current literature, the targeted detection limit for CTCs, for example, is approximately 9 cells per litre of human blood.
Conventional methods by taking up to 30 mL of blood are not sufficiently sensitive for this detection, only the in vivo enrichment of these cells can overcome the limitation. GILUPI GmbH is currently manufacturing the GILUPI CellCollector® with which rare cells can be enriched in vivo. This medical device essentially consists of a stainless steel wire with a diameter of 0.5 mm coated with gold and polymer. On the polymer surface (cell-repellent), specific antibodies are covalently bound (anti-epithelial cell adhesion molecule; anti-EpCAM) and make it possible to specifically bind antigen-expressing cells. After introduction into the arm vein of a patient, the rare cells are enriched on the functionalized surface. The limitation of this procedure is that due to the geometry (diameter of the vein approx. 3 mm, product diameter 0.5 mm) not all passing rare cells come into contact with the product surface. In addition, not all target cells express the antigen targeted by the covalently bound antibodies. In addition, a solution must be developed to separate the specifically bound cells from the surface of the CellCollector®. Through the consistent further development of the dispensing methods available by SCIENION AG for different types of biomolecules, it will be possible in future to print combinations of different types of capture molecules on the polymer surface of the CellCollector® and thus increase the sensitivity of the future product. In addition, SCIENION AG has the technological possibilities to separate the cells bound on the surface of the CellCollector® and thus provide a more precise diagnosis on the basis of individual cells.
Funding: BMBF Zwanzig20 – smart3 - Smart Health
Duration: 01.09.2018 till 31.08.2021
COLODOR: Integrated-optical detection of volatile organic compounds using functional polymer coatings
Quantitative analysis of volatile organic compounds (VOC) is important for a great variety of applications in consumer health and environment protection. It plays a crucial role in the food industry as frying may cause the release of toxic degradation products. For toxic VOC detection, COLODOR utilizes optical multi-parameter gas sensors. The project objective is the detection of VOCs during hot air cooking as used in modern airfryer cooking equipment. Real-time detection of VOCs will allow optimizing the cooking process to avoid toxic products and at the same time reducing the fat content of the food. Thus, the project will contribute to healthier food preparation and improved consumer well-being.
Duration: 05/2017 – 11/2019
cryoPOC: Capillary driven Platform for Multiplex Protein Analytics
BMBF KMU-innovativ Biotechnologie – Biochance
Point-of-Care (PoC) systems enable fast, easy to use and cost-efficient diagnostics on-site. These systems should be compact and preferably independent of peripheral instruments. Prominent examples include paper-based lateral flow devices (LFD), like the well-established pregnancy test. The paper is used to drive the liquid flow without pumps via capillary action. However, the transfer of other immunodiagnostic assays to LFD is still lagging behind. One major issue is the comparably high limit of detection, as compared to standard methods (like ELISA) performed in central laboratories. Main reasons for this are (among others) unspecific adsorption of analyte to the paper fibers and light scattering due to the paper’s optical properties.
The cryoPOC consortium is therefore aiming at a capillary driven platform for multiplex protein analytics, where the paper is replaced by an innovative concept including a capillary and porous polymer materials. The capillary will include a series of separate segments with different capture molecules and controls; together with a handheld device for fluorescence detection this platform will enable two-color detection and analysis of multiplex immunoassays directly at the point of need.
Duration: 07/2016 – 12/2019
Multi-analyte diagnostic methods to detect food pathogens
Food safety is dependent on timely detection of chemical, biological and/or microbial risk factors. In most cases one factor is determined in a single test (e.g. ELISA). In general, line-based lateral flow tests allow the detection of one factor as well. Both in view of the time needed to perform a test and with respect to high costs this is far from efficient. The food diagnostic sector is looking for multi-analyte diagnostic devices that can be produced at a large scale and in an economically cost-effective way.
Although some multi-analyte ELISAs are available in the human diagnostic sector, the technology would need several improvements to be applicable in the food sector. The Biomolecular Sensing & Diagnostics group at Wageningen University & Research has built up expertise in multi-analyte lateral flow and ELISA methods. Together with Scienion AG and HAN University of Applied Sciences these diagnostic methods will be further developed to commercially marketable products. Part of the project’s activities is focused on large scale production of multi-analyte diagnostic assays and it is anticipated that this can be implemented by the end of the project. The advantage of these multi-analyte diagnostic methods is that the platforms have been known for many years and, in the case of ELISA, can be fully automated on equipment that is widely available. In addition, low-cost reading equipment is available or will be further developed. Staff time to carry out such multi-analyte diagnostic methods would be the same as for a single-analyte test and, therefore, it is expected that testing can be carried out at much lower cost. This will also drive uptake of testing and encourage the exploitation of diagnostics to improve food safety. The innovation of the new diagnostic devices will also rely on the ultra-low volume dispensing of reagents in a microarray of spots that will enable the simultaneous detection of a range of risk factors in a single sample; 8 x 8 arrays per well in ELISA and 5 x 5 arrays in lateral flow tests. Machine vision technology will be applied to achieve the automated interpretation of multi-analyte diagnostic methods, objectify test outcomes and provide data management. A number of food safety-relevant multi-analyte tests will be developed by the participants and marketed world-wide by Beter Vee/ELDC . The meaning of the innovation for the sector will be the availability of highly efficient, multi-analyte diagnostic tests for the rapid (on-site) detection of food safety risk factors. Furthermore, these new and innovative multi-analyte diagnostic devices can also be adopted by the scientific community to develop multi-analyte assays in other areas. For the society it means increased safety of food products by timely and multi-analyte detection of risk factors. The innovation potential of the new multi-analyte diagnostic devices is high, especially in the human, veterinary, and food safety fields.
Duration: 06/2017 - 05/2020
• Wageningen University & Research
• SCIENION AG
• HAN University of Applied Sciences
• Beter Vee/ ELDC
Immunoplex - Label Free Screening of Autoimmune Diseases
The goal of the ImmunoPlex project is the application of the Low-Q-Whispering Gallery Modes (WGM) technology for the development of label free multiplex assays. The microscopic particle based sensors offer advantages as low price, multiplexing capabilities and robustness in the incubation step compared to established label free detection methods for the study of protein interactions as Surface Plasmon Resonance (SPR) spectroscopy. Within the project assays will be developed for the detection of autoimmune diseases using an 1-way chip measuring the immune response of immobilized capture antigens. The WGM technology allows real time measurement of the binding kinetics.
The new WGM technology for multiplexing of assays has a strong potential of application in other areas as allergy and serological testing.
Duration: 03/2018 - 04/2021
Funding is provided by the BMBF within the KMU-innovativ: Biotechnologie – BioChance Programm.
Nano-array lateral flow diagnostics for the rapid detection of antibiotics in food
Monitoring antibiotic residues in food is mandatory to ensure consumer protection and to comply with global regulation. The Eurostars project E*LOGIC – Nano-array lateral flow diagnostics for the rapid detection of antibiotics in food – brings together leading expertise for the development of a multiplex rapid immunodiagnostic for the simultaneous detection of 7 key antibiotic targets covering 4 family groups of significant relevance for the food industry (Nitrofurans, Tetracyclines, Nitroimidazoles and Chloramphenicol).
The objective of this project is to develop a prototype kit for multi-analyte antibiotic screening that is suitable for use in both the seafood and honey industries. E*LOGIC will provide a novel and unique rapid multiplex test which is not currently offered on the market anywhere worldwide. This user-friendly diagnostic tool will allow for results within 10 minutes and with detection limits lower than what is required to meet legislation globally.
Within the consortium, Wageningen Food & Biobased Research and SCIENION will closely collaborate to develop a miniaturized multiplex lateral flow immunoassay. An array of binding ligands will be printed on a nitrocellulose membrane by using the non-contact sciFLEXARRAYER dispenser. Carbon nanoparticles will be used as detection label. Joint efforts will also include the optimization of several test parameters such as spot volume, concentration of printed proteins, pore size of the nitrocellulose membrane, the amount of carbon nanoparticles label, etc.
Subsequent to this work package, both partners will establish a large-scale pilot batch production line to economically manufacture the multiplex diagnostics. Automation and in-line quality control will be implemented shifting low throughput R&D production into a feasible production line. Required work will also include the implementation of a vision-guided cutting system ensuring precise positioning of the sliced substrate. SCIENION will configure the sciFLEXARRAYER for processing paper-like supports such as nitrocellulose membranes (hardware and software modifications), and will finally be responsible for process integration, optimization and qualification to achieve a smooth and stable process operation.
The resulting prototype kit for the surveillance of the food supply chain will provide major advantages for end users in the seafood and honey industries as well as for government reference laboratories and service laboratories – reducing time and cost of product analysis due to its ease of use, fast sample turnaround time and multiple detection of 4 drug families simultaneously.
Duration: 06/2017 – 05/2020
OptION - Optical microring sensor for the quantitative analysis of electrolytes
In the production of the sensors for the optION project the coating and functionalization of the microring resonators (MRR) is one of the key elements which controls the sensitivity and selectivity of the electrolyte
analysis in human blood samples.
In order to enable a functionalisation of the chips a primary coating step is required. Hence, different silanization and copolymerisation protocols will be developed. In the second step, the precise deposition of
electrolyte binding molecules (ionophores) on the sensors will be carried out. It is a decisive factor to reach a high immobilization efficiency for the binding of the ionophores under preservation of their
functionalization. For the characterisation of the modified surfaces contact angle and XPS measurements will be applied. In the next step, application tests of the coated MRR chips will be conducted in collaboration with the Heinrich Hertz Institute and the Charité. The goal of this developmental project is the miniaturisation of the volumes used for the chip coating in order to allow for a cost-effective functionalization of the sensors.
Seven different work phases are planned: surface functionalisation of reference supports, chemical binding tests with a selected ionophore, characterisation of the functionalised surfaces, transfer of protocols to the MRR wafer, immobilisation of different ionophores onto the MRR wafer, application tests and analysing of quality.
The main focus of SCIENION will lie on the silanization of surfaces, the micrometer precise functionalisation of the sensors with ionophores, characterisation of surfaces and determination of the functionality, production process of the biosensors, regulatory requirements and exploitation plan and strategy.
Duration: 5/2018 - 4/2021
PoC - BoSens
Label-free POC device based on 3D photonic bottle microresonators for real-time high sensitive measurement of disease-relevant biomolecules
Lyme Borreliosis (LB) infection caused by spirochete bacteria, Borrelia burgdorferi s.l. is a growing disease in central Europe. The bacterium is transmitted by the castor bean tick (Ixodes ricinus). Current diagnostic methods are insufficient to reliably detect early-stage LB infection. Timely detection (or exclusion) of infection will lead to proper treatment in an earlier stage, which means that less patients develop additional complications. Furthermore, early exclusion of infection could drastically reduce the unnecessary use of antibiotics.
Then PoC-BoSens’ goal consists of the development of a portable diagnostic system for early detection of LB infected patients based on a cellular stimulation assay. The second step of the assay, the quantitative determination of released cytokine biomarkers in a fast (~15 minutes), reliable and high-sensitive system, is the focus of this project.
The technology behind the sensing platform will be defined by the combination of an array of photonic transducing elements based on integrated bottle microresonators and a microfluidic system for transportation of the test sample. The main challenge here is the successful package and readout of optical resonators without altering their sensing properties. PoC-BoSens will overcome this challenge by exploring photonic integrated circuit platform technologies, assembly, biorecognition and electronic miniaturization strategies, which will be developed by a high-qualified multidisciplinary consortium. This new technology can also be the basis for many other diagnostic applications.
SCIENION is the main responsible for the development of biofuncionalization protocols in order to activate the biocompatibility and biorecognition of the sensor surface.
Duration: 04/2018 - 03/2021
Roll-to-Roll Biofluidics - Large scale micro-and nanofabrication technologies for bioanalytical devices based on R2R imprinting
Roll-to-roll (R2R) technologies are mature core processes in manufacturing lines for graphical printing industry. In several other areas (e.g. electronics or optics) R2R techniques are emerging, being expected to notably lower the unit prices of flexible devices. In particular, recently developed roller-based nanoimprinting methods enable unrivalled throughput and productivity for precise fabrication of micro- and nanoscale patterns. Areas that will benefit strongly from adopting such R2R nanoimprinting technologies are microfluidics and lab-on-chip products for diagnostics, drug discovery and food control. Such devices require combined printing of micro- and nanostructures and large quantities at low unit costs. The project R2R Biofluidics aims on the development of a complete process chain for first-time realization of production lines for two selected bioanalytical lab-on-chip devices based on high throughput R2R nanoimprinting in combination with complementary printing and manufacturing technologies. Two types of demonstrators will be fabricated targeting application areas, which would clearly benefit from technology advancement in high volume manufacturing, show large potential for commercial exploitation and adopt current standard formats (microtiter plate and microscope slides). Demonstrator 1 will represent an in-vitro diagnostic chip suitable for point-of-care applications, showing improved sensitivity thanks to imprinted nanoscale optical structures and microfluidic channels. R2R fabrication will further greatly reduce production costs and increase manufacturing capacity with respect to currently used products. Demonstrator 2 will provide a device for improved neuron based high-throughput screening assays in drug development. It will consist of nano– to microstructured, interconnected channels in combination with dedicated biofunctionalized surfaces for alignment and controlled growth of neurons.
The eleven R2R Biofluidics project partners jointly develop a completely new process chain for large scale production of selected lab-on-a-chip devices suitable for point-of-care applications, e.g. for detecting antibiotic-resistant pathogens. The novel chips designed for chemiluminescence detection provide improved sensitivity thanks to imprinted nanoscale optical structures and microfluidic channels. A second subproject aims at developing cell chips containing imprinted cavities and micro- to nanoscale channels for controlled neuron culturing to be applied in high-throughput drug screening. SCIENION’s responsibilities in both subprojects include the surface functionalization of the flexible materials and deposition of biomaterials. For this purpose, SCIENION developed a customized sciFLEXARRAYER which was included in the R2R pilot line for high throughput production of biosensor and cell culture chips.
In September 2018, R2R Biofluidics received the Austrian Fast Forward Award 2018 for the pioneering work to develop novel diagnostics for rapid and reliable pathogen detection. This innovation prize of the Austrian region Styria was awarded to JOANNEUM RESEARCH, coordinator of the R2R Biofluidics project.
Duration: 02/2015 - 07/2019
Program Type: Horizon 2020 - The EU Framework Programme for Research and Innovation (grant number 646260)
Safe Transplant Analytics
Development of a universal immunological detection system based on filter membranes
Worldwide, up to 100,000 organ transplants are performed annually. The patient’s compatibility with the donor organ is a key factor for successful transplantations. The Human leukocyte antigens (HLA) system plays a major role in this context. HLAs are characteristic for an individual and represent the major cause of organ transplant rejections. Currently available diagnostic methods to detect transplant-relevant donor-specific HLA antibodies (DSA) are complicated, time-consuming, costly, or lack sensitivity.
The Safe Transplant Analytics research project aims at the development of a novel system capable of the multiplex detection of different antibodies in a single sample and thus paving the way for a periodic, secure DSA monitoring. The project will be realized by an analysis system, the universal filter array, in which a multi-parameter analysis in microarray format is performed on special, preferably transparent membranes. SCIENION works on developing methods specifically for microarray spotting on filter membranes, which allow for depositing detection points in a minimal space – with minimal use of expensive antigens or antibodies for multiple analytes. Achieving a high immobilization efficiency while preserving the biofunctionality of the antibodies plays an important role in our work. By printing universal hapten antibodies, the arrays can be adapted to different panels of hapten labeled antigens for specific HLA antibody detection.
Due to its platform character the analysis system has the potential of versatile application options in other medical fields. The ultimate goal is to develop a reliable and cost-effective test system that improves diagnostic accuracy and that can be easily integrated into the routine of medical standard laboratories.
Duration: 09/2017 – 08/2020
Program type: Zentrales Innovationsprogramm Mittelstand (ZIM)