A new generation of monodisperse magnetic beads produced by advanced microtechnology methods.

Diagnostic tests are an important part of healthcare and early diagnosis worldwide, reducing costs and saving millions of lives each year. Covid 19 testing is an excellent example of this. Magnetic Ugelstad beads are marketed under the name Dynabeads and produced in Norway by Thermo Fisher Scientific. Dynabeads is an important component of diagnostic tests in hospital analyzers and are used in the diagnosis of infectious diseases, hormones and biomarkers for cancer. Vital decisions regarding patient care are based on these tests. The current generation of magnetic spheres has some limitations eg complex and time-consuming production processes. During the project period, the EU proposed measures to limit emissions of microplastics. The measures will most probably lead to magnetic particles being covered by requirements for the collection and control of emissions. Thermo Fisher Scientific therefore expects the market to demand particles that are not covered by such restrictions. As the content of microplastics in our particles has its origins in the Ugelstad technology, the development of new technology, competence and production methods is necessary to launch new particle platforms. Together with national and international leading research partners and start-up companies, we have developed magnetic spheres that are compatible with the proposed requirements from ECHA. We have worked on three new platforms. One of these has given excellent results in both protein and nucleic acid isolation and we plan to launch the new article platform as the company's new environmentally friendly alternative. Another platform has provided excellent monodisperse non-microplastic products, very fast isolation time and satisfactory results in in vitro immunodiagnostics. This platform still requires more development before a decision is made on the launch of new products and will continue after the research council-supported part of the project has been completed. A third technical solution has been stopped.

Increased knowledge about magnetic bead design outside of the Ugelstad method we have used until now. Through the collaboration with iSpheres and own work, Thermo Fisher has gained knowledge about microfluidics: the advantages but also the challenges. Specific learning about droplet formation, flow and droplet stability, but also magnetic beads resulting from such a process, compatibility with starting and raw materials, glass chip design, production and cost. Knowledge about biodegradability of polymers and chemicals and methods to measure biodegradability. Detailed knowledge about self assembling nanocluster and how to coat them. Sintef has gained knowledge around biocompatible chemical coatings and in vitro diagnostics requirements for non-specific adsorption. The anticipated future impact is the launching of a green, polymer free magnetic bead product line with significantly lower production cost protein capacity, and nucleic acid isolation yield.

Magnetic beads are easy to automate and are the preferred solution for in vitro diagnostic analyzers in hospital and centralized labs worldwide. Dynabeads produced by Life Technologies are the leading solid support and 2,5 billion blood samples are annually analyzed using Dynabeads. Major decisions regarding treatment of patients are based on these analyses. Improvement of Dynabeads will therefore improve health care worlwide. Dynabeads are based on the famous Ugelstad invention from 1985 and are still the leading magnetic bead technology, but have design challenges that are difficult to overcome without using new advanced technologies. Three serious drawbacks of Ugelstads hydrophobic porous styrene beads are: 1) hydrophobic interaction even after coating with a hydrophilic polymer 2) the relatively large variation of the surface area after polymer coating of the beads 3) high autofluorescence caused by the use of aromatic styrene based monomers. Microchannel emulsification have the advantage that all components including the magnetic material may be mixed before emulsification, avoiding a high number of consecutive reactions in bead production. The devices may have more than 1000 channels that produce beads continuously for months. The microchannel emulsification yields compact beads with a high surface area reproducibility and acrylate monomers may be used to avoid autofluorescence. Since the iron is embedded in the polymer, iron oxide interference is avoided. The second tehcnical solution is an inverse Ugelstad process. Here water soluble monomers can be used in a water-in-oil process to produce hydrophilic monosized beads that may be further magnetized and coated to avoid hydrophobic interference. The two above technologies require development of new competence and funding by the Norwegian Research Council will enable research collaboration with SINTEF and École Supérieure de Physique et de Chimie Industrielles in Paris. Pelitex inc have developed a new stable magnetic material based on magnetic iron instead of iron oxide. The material is more magnetic than iron oxide and may enable us to produce smaller beads than we do today.