Many of the vaccines currently being tested in clinical studies to combat Covid-19 are based on inactivated variants of the novel coronavirus or other viruses that have SARS-CoV-2 characteristics on their surface. Viruses are produced in cell cultures through the use of bio-technology. Professor Thomas Burg, head of the Institute of Integrated Micro-Nano Systems at TU Darmstadt, stresses that “close-knit process control is absolutely essential in order to guarantee consistent and optimum productivity”. Virus concentration plays a key role here. The high demand for vaccines combined with limited production capacity presents a challenge for the industry, with Burg adding: “at present there are no sufficiently fast and inexpensive methods for measuring virus concentrations on a large scale.” The common PCR-based methods take too long because the genetic material of the viruses first has to be replicated using polymerase chain reaction (PCR). Burg and his colleagues therefore want to measure the pathogen directly: “To achieve this, we are developing measurement techniques that are faster than conventional virus analysis and can also be easily automated.”
The researchers in Darmstadt are currently pursuing two concepts: One procedure is a micromechanical method based on a kind of mini-scales, whereas the other uses laser light that interacts with the viruses. Each of the required sample quantities is so small that the samples can be taken continuously during the biotech process without disrupting ongoing production. Only a few nanolitres of sample are required in each case – one nanolitre being equivalent to one millionth of a millilitre.
Burg's team is not only concerned with the actual verification, but also with sample preparation. For this purpose, the Darmstadt researchers have designed microfluidic systems in order to be able to efficiently enrich and count even very low concentrations of virus particles in the future. In addition to the upstream sample preparation, a computer-based evaluation ensures that the measurement is highly sensitive, as Burg explains: “Using special computing methods, we are able to track down the signature of nanoparticles in the relatively noisy raw signals. That should also work very well for viruses.”
The scientists have already successfully used their measurement techniques in other projects, for example to investigate novel materials or bacteria. Burg stresses that some adjustments are now required for virus measurement in vaccine production to enable the pathogens to be detected across a wide range of concentrations and so that they can be differentiated from other particles.