FluidFM® for Virology - Get a unique control over your single virion-single cell in-vitro experiment!
Typically, viral infections are studied in bulk experiments where many cells in culture are exposed to the virus simultaneously, making it difficult to study single virus entry events or the spread of the viral infection between individual cells.
With the gentle, micro-channeled, and force feedback-controlled FluidFM Probes, single virions can be deposited onto selected cells allowing unprecedented control to study viral infections in-vitro. FluidFM can therefore help to illuminate fundamental questions on virulence, virus replication, or host immune response and thereby boost the development of novel antiviral drugs and vaccines.
Precisely deposit a single virion
Single virions can be placed at an exact location on your cell of choice
Inject a single virion
Directly inject a single virion into the cytoplasm or the nucleus of a specific cell
Measure biophysical changes
Measure mass changes, variation in stiffness, and changes in adhesion force
Isolate, extract & analyze
Isolate infected cells - or take single cell biopsies - for further expansion or analysis
Observe & monitor
Continuously monitor the cell and observe the surrounding culture via integrated microscope and tracking software
How the FluidFM technology can boost your virology experiments
Gain unprecedented insights in viral infection
FluidFM introduces new experimental possibilities to virology by allowing full control over how many virions interact with user-selected cells in adherent cell cultures. This promises new insights into:
Cell entry and infection mechanism
Cellular response, virus cooperativity and virus life-cycle stages
Proliferation, spreading rate and cell to cell infection
Working principle of viral manipulation with FluidFM.
Quantify host defense & virus cooperativity
By placing defined numbers of virions onto a cell, the host cell defense against the virus can be quantified. Therefore, infection probability, the host defense limitations, and the cooperation between virions can be studied.
A single virion is being pushed through the hollow cantilever of the FluidFM micropipette. Image courtesy of P. Stiefel, ETH Zurich.
4 virions have been deposited on a selected single cell. Image courtesy of P. Stiefel, ETH Zurich.
Monitor cell-to-cell spread
Thanks to the integrated CO2- and temperature incubation unit as well as the epi-fluorescence microscope, FluidFM operates in a fully cell culture-compatible environment. This preserves the cell culture context of the infected cells and, together with the software-supported automated tracking function, allows long-time observation of the infected or manipulated cell. This allows following in detail how the viral infection spreads from the host cell to its neighbors and onto the rest of the culture.
Introduce single infected cells to healthy cultures or vice-versa
Gently pick up a single cell from adherent or suspension culture and place it into another well plate with micrometer precision, fully preserving the cells’ viability. This enables to study the effect of introducing single infected cells into a healthy culture. The same method can also be used to place healthy cells, resistant cells, or drug-treated cells onto infected cultures.
Isolated single cell.
Isolate cells of interest for further expansion or analysis
Single cells can be isolated from a culture based on morphology or fluorescent markers. Staying fully viable, these cells of interest can then be expanded in a new dish or processed for further proteomic or transcriptomic analysis. It is even possible to take single cell biopsies for analysis.
Gain mechanical insights from single cell infection
The integrated force feedback of FluidFM Probes allows quantifying mechanical interactions with pN force resolution. Measure biophysical changes induced by the infection of single cells, such as variations in stiffness, changes in adhesion force and, depending on the system, even changes in mass. FluidFM thus allows to correlate morphological with mechanical changes induced by the virus onto its host cells.
In this video, a single cell is detached from fully adherent and confluent culture. Courtesy of A. Sancho and J. Groll, Functional Materials for Medicine and Dentistry, University Hospital of Würzburg.
FluidFM technology can help answer fundamental questions on virus virulence, replication, host immune response and can boost development of novel drugs and vaccines via precise bottom-up approaches.
Learn how researchers have benefited from using FluidFM in their virology experiments
Single virion infection study
Millions of people suffer from Leukemia around the world. While treatment drugs exist, cancer regularly develops a resistance against them. Researchers from both the University Hospital Würzburg and the University Würzburg found a new potential approach to overcome resistance to the recently approved Midostaurin drug and even increase the drug activity, also with help of FluidFM cell measurements.
Stents help millions of people every year to overcome arterial blockages, saving many lives in the process. Once implanted, the stent should integrate well and prevent formation of blood clots. In this publication research groups from ETH Zurich investigate stent design optimization by measuring cell adhesion to its surface with FluidFM.
Single cell force spectroscopy offers fundamental insights into many fields yet suffers from low throughput. MTA Budapest tremendously speeds up the acquisition of single cell adhesion data by using FluidFM adhesion measurements to calibrate an optical sensor array. Thus, they are able mechanically monitor more than 1000 adherent cells in parallel.
Viral entry, replication and spread within a host culture is poorly understood at the single virion – single cell level. Researchers from ETH Zurich developed a method to precisely deposit single virions on cells, here with vaccinia (smallpox) viruses. The results implicate cooperation between virions to overcome the host defenses during infection.
This study conducts a two-step approach that combines nondestructive and quantitative withdrawal of intracellular fluid with subpicoliter resolution using fluidic force microscopy, followed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.
Sampling of cytoplasmic and nucleoplasmic fractions from single live cells
This approach has uncovered the ability of cells to withstand extraction of up to several picoliters and opens opportunities to study cellular dynamics and cell-cell communication under physiological conditions at the single-cell level.
Guillaume-Gentil, O., Grindberg, R. V., Kooger, R., DorwlingCarter, L., Martinez, V., Ossola, D., Pilhofer, M., Zambelli, T., & Vorholt, J. A. (2016). Tunable Single-Cell Extraction for Molecular Analyses. Cell, 166(2), 506–516.
Single cell isolation via tunable delivery of trypsin
In this report, a versatile approach for isolating single HeLa cells directly from their culture dish is presented. Fluidic force microscopy is first used to detach the targeted cell(s) via the tunable delivery of trypsin, thereby achieving cellular detachment with single-cell resolution.
Industry relevant colloids typically range from 1 nm to 1000 nm, yet the classical colloidal probe technique works with colloids of 1 µm or larger. Here, researchers from the University of Bayreuth and ETH Zurich present a new method using FluidFM which unlocks the use of colloidal probes below 1 µm.
Often colloids can consist of soft biological material. In contrast, the established colloidal probe technique mainly works with hard colloids – mostly due to the high complexity of gluing soft colloids to the cantilever. Here, researchers from the University of Bayreuth describe a universal approach using FluidFM to measure soft colloids.
3D printing has become prevalent in many fields, especially in tissue engineering. Yet so far it was not possible to melt-electrowrite (MEW) hydrogels, limiting print architecture and resolution of this important material in biomedicine. Researchers from The Julius Maximilians University of Würzburg and the University Hospital Würzburg have discovered a way unlocking MEW with promising implications to directly print soft, yet resilient tissues. FluidFM helped to characterize the printed material with its fast colloidal probe technique.
Scientist at ETH Zurich quantified the hydrophobic adhesion properties of 28 bacteria strains taken from leaf isolates. They developed a modular FluidFM approach where colloidal, hydrophobic probes were brought in contact with the isolated bacteria on a PLL coated glass substrate. With 700 individual bacteria measured, this very extensive single cell force spectroscopy study allowed to observe cell-cell heterogeneity. The differences between the strains regarding hydrophobic interactions covered 3 orders of magnitude and correlated well with bacteria retention in planta.
Pascal holds a doctoral degree from ETH Zurich. His passion for entrepreneurship and Startups has led him to the foundation of Cytosurge. He currently serves as CEO of the company and is responsible for all operational and strategic matters of the company.
When away from work, Pascal enjoys spending time at the Rhine river - in summer and in winter. He loves scuba diving and has a passion for the latest tech gadgets.
Management TeamFounders
Stephan is a software architect with over 14 years of experience. As one of the company's first employees he has a profound understanding of the FluidFM technology. In his role as CTO he leads the research and development of our solutions and is responsible for the direction, design and development of Cytosurge's products.
When the sun is shining, Stephan enjoys playing soccer. However, he takes far more pleasure in watching soccer matches from inside a stadion or from the comfort of his living room couch.
Management TeamResearch & Development
Pablo is a trained micro- and nanosystems engineer and won the ETH medal for his outstanding PhD thesis on FluidFM. With a good connection to our customers he brings invaluable experience into our team. In his position, Pablo ensures that our solutions fully meet our customers' needs and expectations.
To relax, he enjoys video games as well as long talks with his family and friends while sipping a glass of wine.
Management TeamResearch & Development
Pascal holds a doctoral degree from ETH Zurich. His passion for entrepreneurship and Startups has led him to the foundation of Cytosurge. He currently serves as CEO of the company and is responsible for all operational and strategic matters of the company.
When away from work, Pascal enjoys spending time at the Rhine river - in summer and in winter. He loves scuba diving and has a passion for the latest tech gadgets.
Management TeamFounders
Stephan is a software architect with over 14 years of experience. As one of the company's first employees he has a profound understanding of the FluidFM technology. In his role as CTO he leads the research and development of our solutions and is responsible for the direction, design and development of Cytosurge's products.
When the sun is shining, Stephan enjoys playing soccer. However, he takes far more pleasure in watching soccer matches from inside a stadion or from the comfort of his living room couch.
Management TeamResearch & Development
Pablo is a trained micro- and nanosystems engineer and won the ETH medal for his outstanding PhD thesis on FluidFM. With a good connection to our customers he brings invaluable experience into our team. In his position, Pablo ensures that our solutions fully meet our customers' needs and expectations.
To relax, he enjoys video games as well as long talks with his family and friends while sipping a glass of wine.
Management TeamResearch & Development
Pascal holds a doctoral degree from ETH Zurich. His passion for entrepreneurship and Startups has led him to the foundation of Cytosurge. He currently serves as CEO of the company and is responsible for all operational and strategic matters of the company.
When away from work, Pascal enjoys spending time at the Rhine river - in summer and in winter. He loves scuba diving and has a passion for the latest tech gadgets.
Management TeamFounders
Stephan is a software architect with over 14 years of experience. As one of the company's first employees he has a profound understanding of the FluidFM technology. In his role as CTO he leads the research and development of our solutions and is responsible for the direction, design and development of Cytosurge's products.
When the sun is shining, Stephan enjoys playing soccer. However, he takes far more pleasure in watching soccer matches from inside a stadion or from the comfort of his living room couch.
Management TeamResearch & Development
Pablo is a trained micro- and nanosystems engineer and won the ETH medal for his outstanding PhD thesis on FluidFM. With a good connection to our customers he brings invaluable experience into our team. In his position, Pablo ensures that our solutions fully meet our customers' needs and expectations.
To relax, he enjoys video games as well as long talks with his family and friends while sipping a glass of wine.
Management TeamResearch & Development
Pascal holds a doctoral degree from ETH Zurich. His passion for entrepreneurship and Startups has led him to the foundation of Cytosurge. He currently serves as CEO of the company and is responsible for all operational and strategic matters of the company.
When away from work, Pascal enjoys spending time at the Rhine river - in summer and in winter. He loves scuba diving and has a passion for the latest tech gadgets.
Management TeamFounders
Stephan is a software architect with over 14 years of experience. As one of the company's first employees he has a profound understanding of the FluidFM technology. In his role as CTO he leads the research and development of our solutions and is responsible for the direction, design and development of Cytosurge's products.
When the sun is shining, Stephan enjoys playing soccer. However, he takes far more pleasure in watching soccer matches from inside a stadion or from the comfort of his living room couch.
Management TeamResearch & Development
Pablo is a trained micro- and nanosystems engineer and won the ETH medal for his outstanding PhD thesis on FluidFM. With a good connection to our customers he brings invaluable experience into our team. In his position, Pablo ensures that our solutions fully meet our customers' needs and expectations.
To relax, he enjoys video games as well as long talks with his family and friends while sipping a glass of wine.
Management TeamResearch & Development
FluidFM has provided us the chance to detach mammalian cells that were very strongly adhered to the substrate, in a systematic way and without any chemical modification of the cantilever; thus, allowing us to study cell behaviour in their natural state and environment.
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Find the ideal FluidFM system for your virology experiments
Easy click-fix mount of probe pre-assembled on adaptor, no tools needed
Automated probe exchange process
Incubator for CO2 and temperature control
Available (from AFM supplier)
Available, specially tailored to the FluidFM OMNIUM
Compatibility
Nanosurf (CoreAFM, FlexAFM and DriveAFM), Bruker (Bioscope Resolve), JPK (Nanowizard, CellHesion and ForceRobot families)
n.a. (standalone system)
FluidFM ADD-ON
FluidFM OMNIUM
Workflow automation
Operator controlled experiments. Limited automation available depending on AFM supplier software.
Operator selects cells of interest in software. Automated deposition, extra-cellular application or injection. According to user pre-defined parameters. Automated cell pick-up & transfer to user defined positions possible. Automated cell tracking and monitoring integrated in software.
Viral deposition / injection throughput
Up to 10 cells per hour, operator guided.
Up to 300 cells per hour, automated.
Z-movement resolution
< 0.1 nm
< 5 nm
Z- measurement range
10 µm to 200 µm (depending on AFM system)
5 cm
Accessible XY-range during one measurement
100 µm x 100 µm (depending on AFM system)
240 mm x 74 mm (two well plates)
Cell Pick & Place
n.a.
Cells can be transferred to another position in the same well or a well of another plate
Cell Pick & Place throughput
n.a.
Approx. 60 cells/h depending on cell type
Culture plate / slide compatibility
Depending on AFM model, typically low-profile dishes (50mm or 35 mm), not compatible with standard well plates.
Compatible with standard plates (6, 12, 24-well), petri-dishes, glass slides and more.
FluidFM ADD-ON
FluidFM OMNIUM
Injection / application of virions
+
+++
Transfection / genome editing of cells for virus research
+
+++
Cell isolation (Pick & Place)
-
+++
Co-cultivation with other cell types / cell patterning
-
+++
Analysis / omics of single cells
+
+
- Not recommended; + Works but with drawbacks; ++ Works but not optimal in every situation; +++ Method of choice
With the rise of the recent COVID 19 pandemic, the vulnerability of the diverse healthcare systems across the world to highly infectious diseases became apparent. The SARS-CoV2 is just another severe outbreak of a disease that cannot be easily detected and confined within geographical borders.
The unexpected spread of the SARS-CoV2, and its disastrous impact on the strongest economies worldwide, made the political and scientific communities aware that profound understanding and investments are needed in all areas of epidemiology if we want to improve our defenses against future pandemics.
Among other modern techniques that help understanding virus function towards the development of novel vaccines and drugs, FluidFM technology can help answer fundamental questions on virus virulence, replication, host immune response and can boost development of novel drugs and vaccines via precise bottom-up approaches.
Management Team