Background

It has long been known that the human body is colonized by a diversified microbiota consisting of bacteria, archaea and fungi. It has only recently been noticed that viruses are also included in this microbiota, which is very important for our health. Published studies also show that certain physiological effects previously attributed to colonizing bacteria instead stem directly from replicating viruses.

All in all, there seems to be a complex interplay between different viruses and the microorganisms on our skin in the construction and maintenance of our microbiota, which in turn plays a crucial role in both good health and disease. Therefore, hygiene products for professional and private use should be designed so that pathogenic viruses, bacteria and fungi are eliminated while the impact on the composition of the microbiota is limited.

Challenge

The use of quantitative PCR and large-scale sequencing over the past ten years has revolutionized our understanding of both individual pathogenic bacteria and the communities of microorganisms in which they are included. The degree of innovation in this area has been high and the knowledge and technology that has been developed is now used successfully in both the pharmaceutical and food industries. In comparison with bacteriology, the development of our understanding of viruses and how they interact with our body has been more modest during the same time period. However, as a result of a number of major investments and recent technical innovations, the development and degree of innovation in virology is forecast to increase sharply in the coming years.

Objectives

The primary objective of the project was to develop and adapt PCR technology and whole genome sequencing for mapping and quantification of viruses and microorganisms on hands, surfaces and soft materials. In addition, the total microbiota on the hands was mapped and quantified before and after application of two different hand wash / disinfection methods on subjects.

Background

There are major socio-economic gains to be made from reducing the spread of disease-causing viruses and microorganisms in the home and public environment. In addition, reducing the spread of infection is a strategic priority area in the WHO's work to limit unnecessary antibiotic use and the development of resistance in society. Effective hygiene products and disinfectants for professional and private use are crucial in this work.

In order to be long-term effective against the spread of infection in society, it is of great importance that repeated use of these products does not harm the natural microbiota present on our skin, as the skin's normal microbiota is an important protection against infections. These products should also not cause resistance selection, as resistance to disinfectants may also give rise to increased resistance to antibiotics.

Challenge

Given the extensive societal challenges we face globally linked to increased problems with antibiotic and biocide resistance, there is today a great need for broader knowledge regarding the development of resistance. As a result of the rapid development that is now taking place in microbiology and virology in terms of tools for whole-genome sequencing and bioinformatics, there are today great opportunities to build new crucial knowledge and actively work to reduce the spread of resistance in society.

Methods

The project further develops and adapts a methodology for whole genome sequencing that is suitable for mapping resistance genes to antibiotics and biocides in microorganisms. This methodology was adapted for studies of the microflora on both hands, surfaces and in complex biological samples. In a study consisting of twelve subjects, the presence of resistance genes in the normal flora of the hands was mapped and quantified before, during and after a long-term use of long-acting disinfectants. 

Culture-based methodology was established and applied for studies of links between biocide resistance and antibiotic resistance, so-called cross-resistance. Specifically, in vitro studies were performed on how skin bacteria's resistance to the biocide benzalkonium chloride can arise, and how the cross-resistance to certain antibiotics then increases. To evaluate the societal relevance of the induced resistance, the most resistant bacteria were completely sequenced and the DNA code was compared with resistance genes identified in hospital samples.

Background

Pandemics and outbreaks of infectious diseases are significant threats to the economy and public health in Sweden and globally. In line with the Government's overall goal for COVID-19, both Swedish authorities and companies are working intensively to develop and verify effective products and preventive measures against SARS-CoV-2. The importance of effective action and products against the spread of infection and viruses also extends beyond the current pandemic, for example, Norovirus causes an estimated annual global social cost of $ 60.3 billion.

Needs

All in all, there are both acute and long-term needs for research and method development concerning effective infection control measures against SARS-CoV-2 as well as other disease-causing viruses and future pandemics. Specifically, there is a lack of capacity in Sweden and actors who can meet the industry's need for laboratory work with viruses and virus inactivation. In addition, data for virus inactivation are incomplete or completely missing, which makes risk assessment of virus inactivation very difficult to do reliably, which is needed when evaluating manufacturing processes and products such as biocides.

Methodology

Both cellular and molecular quantitative methods will be applied in the project. Initially, standard methods for laboratory evaluation of virucidal effects (i.e. methods for measuring virus inactivation) should be established and adapted; both model viruses and pathogenic viruses should be used. In addition, methodology for detection and mapping of existing viruses shall be tested exploratively in environments where hygiene products are used. The established methodology must also be able to be used for the production of reliable and supplementary data regarding chemical and thermal inactivation of disease-causing viruses, thereby contributing to future risk assessments being safer and more accurate.

Objectives

Overall, after the implementation of the project, there will be better capacity to meet Swedish industry's needs for studies of viruses and virucidal effects, which promotes the development of effective preventive measures, processes and products. In addition, knowledge about virus inactivation has been strengthened.

Optical analysis using fluorescence in the ultraviolet part of the spectrum (UVF) is a well-known method that is particularly suitable for the detection of biological substances. Trace amounts of oil is one common substance where UVF is used.

Ultraviolet fluorescence analysis

The UVF technology is relatively simple in theory: a sample is illuminated with UV radiation. The sample is first absorbing the light (excited) and then emitting light (emission via fluorescence). The fluorescence is detected and analysed. 

The fluorescence is shifted towards longer wavelengths than the incident light, which makes it easier to separate scattered light from the light source from the fluorescence being measured.

Sensors based on UVF have been developed since the 1970s and there are commercial instruments on the market. The technology is characterized by a high sensitivity, but a complication is that common biological substances such as bacteria and algae have fluorescence spectra that can overlap with spectra of the substance that you want to detect. UVF instrumentations therefore need to either have narrow specifications on the type of water or other media in which they operate effectively, or allow multispectral detection, ie emission detection and / or excitation takes place at a number of different adjustable wavelengths.

In its most general form (a so-called fluorometer), a UVF instrument becomes expensive and less suitable as an autonomous sensor in the field. This means that a product for a specific application area can often not be used for another.

Tailor-made systems for analysis directly in processes

RISE develops tailor-made systems based on multispectral UVF for analysis for field use, e.g. to detect oil in water. The development takes place together with the metal research institute Swerim.

UVF can provide a relatively high sensitivity (e.g. micrograms of oil per liter of raw water) and can also be used for distinction between different substances, if accurately  calibrated. In many cases, several spectrum are needed to ensure a reliable result. The technology is also very interesting for 'early warning systems' and to indicate is a process or sample volume needs further investigation and / or immediate action.

RISE' systems are built to contribute to the digitalisation of the processes involved. We strive for non-contact measurements that are:

• continuous,
• connected to the system, and
• used inline in the production flow.

The generic UVF technology at RISE is adapted to the customers' area of ​​application and packaged in robust prototypes that can be evaluated in the field for further product development.

RISE system for UVF

The basic components included in the RISE UVF system are shown in the picture: excitation takes place with a replaceable UV-LED and detection of the emission is done via a monochromator. The analysis system can be set to filter any wavelength in the ultraviolet and visible part of the spectrum.

Where do you need to measure?

Contact us to discuss more about what UVF can do for your particular application!

LIBS, laser-induced breakdown spectroscopy, is a method for quick and non-contact analysis of the chemical composition of a material, without time-consuming sample preparation. The method is also often referred to as non-destructive since such an extremely small amount of the material is needed for the analysis.

The method relies on the fact that a material that is heated to extremely high temperatures emits light that is specific to the atoms included in the material. In LIBS, a high-energy laser pulse is focused on a sample. The material then becomes so hot that the material decomposes into excited ions and atoms, into a plasma. By analyzing the light of the plasma, the characteristic atomic emission lines can be identified, giving information of the elements in the material. 

Today, LIBS is used commercially in many applications. Handheld systems are available and the technology is widely used for quality control, sorting, identification and analysis.

RISE develops LIBS equipment and analysis methods into customized solutions in e.g. metal recycling or production, together with the Swedish metals research institute Swerim.

Contact us to discuss what LIBS can do for your application!

Lead is traditionally included as a brass alloying element and provides favourable properties for machining and casting. Many components that come into contact with drinking water, such as water taps, fixtures and couplings, are made of brass. For these products, it will be necessary to phase out lead in the near future owing to stricter limit values for lead in the revised EU Drinking Water Directive.

In the past, lead was also widely used in various types of corrosion protection products, due to its very good corrosion properties.

Expertise in brass and corrosion protection

RISE has extensive experience and knowledge of both brass and corrosion protection, as well as production technology and materials technology, which are necessary to be able to offer assistance at all stages. Phasing out lead from brass is complex and necessitates modifications to the entire value chain from molten metal to the finished product, as well as for verifying the properties of the finished product. RISE has carried out comprehensive work to map and optimise process steps in order to obtain lead-free brass products with the desired properties.  

Regarding corrosion, RISE evaluates corrosion protection by means of accelerated tests as well as in field stations to assess durability and service life, for example. This can be very helpful when you need to replace corrosion protection or surface finishing in order to phase out the use of toxic or environmentally hazardous substances or otherwise introduce more sustainable alternatives. Another important element of our work is the characterisation of corroded surfaces and corrosion products using sophisticated modern technologies, such as microscopy, spectroscopy and electrochemical measurement methods.  

RISE’s offer

• RISE can assist your transition to lead-free brass alloys. We help you identify suitable alternative alloys and assist with the modification of production processes and evaluation of the properties and corrosion resistance of lead-free products.
• RISE provides guidance when choosing corrosion protection based on the prevailing conditions. We perform everything from short, accelerated tests to prolonged exposure tests in a real-world environment in our field stations. We analyse products and carry out various forms of quality control in accordance with current standards or proprietary methods based on existing needs.

Contact us for more information on how RISE canhttps://www.ri.se/en/centre-chemical-substitution help your company to phase out lead and other heavy metals from your products.

Pharmaceutical research and development

Using computational approaches, we can aid early in pharmaceutical development, by predicting properties of active substances such as interaction with the hERG channel, carcinogenicity, mutagenicity and reproductive toxicity (CMR) as well as potential endocrine disruptions. Where kinetic data is available, we offer noncompartmental analysis (NCA) for the drug substances. Additionally, we can perform mutagenicity predictions of impurities according to the ICH M7 guideline using computational software such as Leadscope^® and offer expert evaluations of results.

Chemical safety

We can help you in predicting chemical properties and toxicity using QSAR or QSPR models as well as read-across for REACH registrations of industrial chemicals when no experimental data is available. We can also assist with exposure estimations in both occupational and environmental settings using models. Both human and environmental health can be considered in these estimations.

Safe and sustainable by design (SSbD) work

If you are working within the SSbD framework, we can provide expert decisions based on early screening in order to ensure safe chemicals are considered early in product development. We can assist with computational-aided screening of candidate chemicals within your process and facilitate selection of safer and more sustainable chemicals. Furthermore, we can suggest safer substitutions within your current process or risk management approaches. 

Model development

Our experts use cutting-edge machine learning (ML) techniques such as deep learning, molecular embedding, and multi-task learning. We can construct models using these approaches from your own data where appropriate. Additionally, we can consult on your model development if expert support is required.

Research

At RISE we are also very active in a number of major scientific development programs where in silico approaches are used as part of new approach methodologies (NAMs). We are currently involved in Riskhunt3R, MistraSafeChem, PharmECO and BioSUSTex.

Getting in touch is a good start!

We provide solutions for bringing safe new medicines, chemicals and products to market. If you are unsure whether your needs fit within the above services, please contact us and we can direct you to appropriate experts at RISE or offer tailor-made solutions.