Research to Business

Technology of KIT is used for Corona testing

PCR tests have been part of everyday laboratory life since the beginning of the pandemic. The test procedure detects the genetic material of the SARS-CoV-2 virus in patients infected with Covid-19. For the separation of viral RNA from a throat-nasal swab, a technology for handling magnetic microparticles from KIT is used. This technology is widely used in the commercial laboratory systems of PerkinElmer chemagen Technologie GmbH.

The PCR test requires a swab from the nasal or throat cavity from which the SARS-CoV-2 genome can be isolated. By using the KIT magnetic separation principle in PerkinElmer chemagen's chemagic™ instruments, more than 4,000 samples can be purified in one working day. (Image: SeventyFour / Shutterstock)
The PCR test requires a swab from the nasal or throat cavity from which the SARS-CoV-2 genome can be isolated. By using the KIT magnetic separation principle in PerkinElmer chemagen's chemagic™ instruments, more than 4,000 samples can be purified in one working day. (Image: SeventyFour / Shutterstock)

The current statistics of the Robert Koch Institute in Germany alone put the amount of tests for the spreading coronaviruses at over 1 million per week. This immense number of tests can only be managed in the more than 250 registered laboratories with high-throughput diagnostics. Modern analytical instruments facilitate the tests by automating and parallelizing the individual testing steps in the shortest possible time. A principle for magnetic separation developed at KIT and brought to series production stage by PerkinElmer chemagen Technologie GmbH allows efficient preparation of patient samples in the laboratory, which is always necessary prior to corona testing. Many samples can be isolated simultaneously and fully automated in high throughput. The chemistry developed and used by PerkinElmer chemagen ensures the success of the nucleic acid isolation and the necessary high purity.

PCR test routine

The PCR test is considered to be the safest and most reliable test method for direct pathogen detection: In suspected cases, fragments of the viral genetic material (RNA) are detected in a swab taken from the patient's nose or throat, also known as genome detection. However, only about one-millionth of a gram of genetic material can be obtained from such swabs, which are difficult to detect in these volumes. Therefore, the tiny strands of genetic material are reproduced using polymerase chain reaction (PCR) to make the pathogen visible and measurable to spectroscopic laboratory equipment using fluorescent substances. If the genetic material is detected in the swab, a corona infection is indicated.

Prof. Dr. Matthias Franzreb and Jonas Wohlgemuth invented the principle of magnetic separation and, together with PerkinElmer chemagen, have developed it into a process for laboratory systems. In this procedure, magnetizable metal rods separate the viral genetic substances from the swab samples in an automated and parallelized process. (Image: KIT)

More efficiency through automated purification

A prerequisite for the PCR reaction and laboratory analysis is the clean isolation of the genetic material from the throat-nose swab. The contained genetic material has to be separated, purified from impurities and concentrated. One possible method for this is the separation with magnetic beads. For this purpose, specially coated, small magnetic particles are used to bond the RNA. From the initial solution, only the RNA is bound by the magnetic particles, while the impurities remain in the solution. The magnetic particles with the bonded RNA then have to be separated and washed several times through special buffer solutions. An invention by Prof. Matthias Franzreb and Jonas Wohlgemuth, both from the Institute for Functional Interfaces (IFG) at KIT, makes the sub-process of separating the magnetic particles much more efficient during the different process steps of purification.

The Karlsruhe principle relies on the separation of magnetic particles by means of special, magnetizable metal rods whose magnetic force can be easily switched on and off from the outside. This enables to transfer the bonded RNA for the purification step into a new vessel, in order to redistribute the genetic fragments there after switching off the magnetic force by rotation of the metal rods, comparable to small stirrers. "The whole process is fully automated, not only with one rod, but with an array of 96 rods simultaneously. A single instrument can thus isolate and concentrate the existing genetic material from more than 4,000 samples in one working day using our principle and the chemistry of PerkinElmer chemagen," Wohlgemuth, the inventor, points out. The principle for manipulating and redistributing the particles allows a reproducible and independently running purification procedure, which is integrated in the chemagic™ systems from PerkinElmer chemagen.

The chemagic™ 360 instrument from PerkinElmer chemagen, which uses the principle for manipulation and redistribution of magnetic particles from KIT, is used worldwide for the isolation of nucleic acids from a wide variety of samples such as blood, saliva, swabs, plasma or serum. With the onset of the pandemic and the necessary PCR tests, the demand for such systems increased. (Image: PerkinElmer chemagen Technologie GmbH)

In cooperation to the product

In the 2000s, KIT already applied for a patent for the process for automated handling of magnetic microparticles. "The efficiency of our process very quickly also convinced the company chemagen, which secured the rights of use from KIT," remembers co-inventor Prof. Franzreb. chemagen succeeded to parallelize and further accelerate the procedure and to optimize it for laboratory diagnostics, so that the biotechnology company launched the principle developed at KIT in their "chemagic™" systems. The developed devices were quickly successful with the chemistry developed by PerkinElmer chemagen and have established themselves as a globally used system for the isolation of nucleic acids from a wide variety of samples (blood, saliva, swabs, plasma, serum). In 2011, chemagen was acquired by PerkinElmer, Inc. and the license was sold with it. More than 900 chemagic™ 360 instruments were sold worldwide in 2020, and the market share of sample preparation in Germany was approximately 25 percent.

 

Research for the future

For Prof. Christof Wöll, Institutional Director of IFG, there is no question about the benefits: "New technologies come to bear especially when faced with new challenges. Corona has far-reaching consequences for the entire society. Therefore, the current situation calls for particularly efficient solutions. As a result, the high demand also brings KIT considerable royalty income, which can be reinvested in further solutions." The further development of the process for separating magnetic particles remains a central goal of research at IFG, not least because of the current challenges. KIT researchers are working on further reduction of the amount of chemical reagents required and further acceleration of the process. In this context, the simulation of material properties plays a central role in the Joint Laboratory Virtual Materials Design (VMD), in which KIT is involved as part of the Helmholtz program Materials Systems Engineering (MSE).

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