High-tech visualisation of biological samples

A transmission electron microscope.

The BioVis research infrastructure provides many instruments for the visualisation of biological samples. Among others, transmission electron microscopy (TEM).

Since 2007, the BioVis platform has been assisting researchers across various disciplines.

As a three-part infrastructure, it offers several tools to aid researchers in the visualisation and analysis of biological samples. BioVis constitutes a coherent infrastructure divided into different nodes: light microscopy, electron microscopy, flow cytometry, and cell sorting.

Guidance is provided by experienced staff, comprising five employees, with Dirk Pacholsky serving as the platform’s manager.

“Our primary customers consist of researchers from Uppsala University, although both now and historically, there has been a focus on researchers from the Department of Immunology, Genetics, and Pathology (IGP). This has occasionally led to the misconception that BioVis exclusively serves IGP researchers, which is not the case. We are open to anyone who sees the need to utilise the instruments at our disposal,” explains Dirk Pacholsky.

Portrait photo of Dirk Pacholsky.

Dirk Pacholsky is Head of BioVis and responsible for flow cytometry within the infrastructure. Photo: Dirk Pacholsky/Gerling.

Full-service or self-service

For researchers seeking assistance with light- or electron microscopy, flow cytometry, or cell sorting at BioVis, two support models are available.

“We typically refer to them as full-service or self-service. In the former, the researchers bring their fully processed samples, and we operate the instruments used for light microscopy or flow cytometry. For electron microscopy, we offer the same service, although we usually assist with sample preparation as well. The alternative is to operate the instruments independently, for which we provide an introductory course once a month, followed by access to run the instruments independently,” Dirk elaborates.

Established in 2007 by Lena Claesson-Welsh, a professor at IGP, BioVis has progressed significantly since its inception, both in terms of the number of instruments and their utilisation.

Lena Claesson-Welsh next to a confocal microscope.

BioVis was started by Lena Claesson-Welsh, Professor at the Department of Immunology, Genetics and Pathology. Photo: Dirk Pacholsky.

“Initially, it was largely a ‘one-man-show’ with my predecessor and only one instrument in each segment. I joined in 2009, and about a year later, it exploded. Over the next six years, we were part of SciLifeLab and reached our highest staff count of six employees in total. From 2017 until now, we have been based at the Rudbeck Laboratory with 12 different instruments distributed across the various nodes. From 2024, we also have a new location at Uppsala Biomedical Centre (BMC),” says Dirk and continues:

“There, we have placed one flow cytometer analyser and plan to follow up with one confocal microscope. The goal of the BMC site is to establish a BioVis extension which offers flow cytometry, light microscopy and cell sorting. In order to make this venture a reality, some structural changes are required in terms of personnel and, last but not least, financing.”

A confocal microscope.

Light microscopy is one of the services offered at BioVis at both the Rudbeck Laboratory and the BMC. Among others, this confocal microscope.

While the majority of funding comes from the Disciplinary Domain of Medicine and Pharmacy, IGP has invested approximately SEK 21 million in the infrastructure over the years. The third source of income comprises fees from the instrument users.

“The majority of our users are researchers at Uppsala University who, thanks to our funding from Medfarm, can utilise our instruments at a subsidised rate. Additionally, we have external users from other universities and companies who pay a higher fee,” Dirk mentions.

Are there any requirements for using the instruments?

“We are an open lab and do not have specific requirements or criteria for access. If one wishes to use our facilities, we are accommodating. However, for independent instrument usage, researchers need to take our introductory course.

“Infrastructures are often led by professors knowledgeable in specific research areas. At BioVis, we instead specialise in the instruments, making us very efficient. Essentially, if one wants space at our facilities, they get it. Cell sorting may have a waiting period of up to two weeks, whereas flow cytometry or light and even electron microscopy has a much higher throughput,” Dirk explains.

Challenges and opportunities

BioVis’ future appears promising, although, as always, there are both challenges and opportunities. These often go hand in hand, says Dirk Pacholsky.

“The challenges we face include attempting to achieve redundancy at the instruments, enabling two staff members at each node. Currently, we have two people at each, except for flow cytometry, where it’s only me. If we accomplish this in the future, it would create ‘free time’, which we could use for method development within BioVis, contributing to developing the infrastructure and its service to our customers.”

Robin Widing

The three parts of BioVis

Electron microscopy

Electron microscopy yields higher magnification and resolution than light microscopy by using an electron beam and a system of electron lenses for imaging. This allows detailed visualisation of the ultrastructures of the specimens.

There are two main types: transmission electron microscopy (TEM), which provides detailed internal images, and scanning electron microscopy (SEM), which offers detailed surface images. This advanced imaging method is crucial in fields such as materials science, biology, and nanotechnology for studying structures at the molecular and atomic levels. BioVis offers a TEM and sample preparation laboratory.

Light microscopy

Light microscopy uses visible light and a system of lenses for the imaging of small samples and their structures. Various methods such as bright-field, phase-contrast, fluorescence microscopy and even super-resolution are available. Each method enhances different aspects of the sample’s features.

Light microscopes are fundamental tools in biology, medicine, and materials science for examining cell structures, microorganisms, and other fine details. BioVis offers slide scanner, confocal microscopy, STED and two-photon microscopy.

Flow cytometry

This method allows for the rapid and simultaneous multiparametric analysis of thousands of particles per second, identifying and quantifying specific cell populations based on markers tagged with fluorescent dyes. Flow cytometry is widely used in research and clinical diagnostics for applications such as immunophenotyping, cell sorting, and measuring cellular functions. BioVis houses two different flow cytometers and two different cell sorters.

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