Single Cell Force Spectroscopy with FluidFM


Dive into Single-Cell Force Spectroscopy with FluidFM.

FluidFM-enabled Single Cell Force Spectroscopy

With the FluidFM technology, live cells can be reversibly immobilized onto the cantilever by applying and maintaining adequate negative pressure of the fluidic channel on the FluidFM probe. This gentle physical, rather than invasive chemical, immobilization allows single cell force spectroscopy measurements to be done in native conditions (without chemical treatment of cells). 

With this ability, FluidFM probes can be used multiple times, hence improving the experimental reproducibility. In addition, once the measurement of a single cell is completed, the FluidFM probe can be controlled to absorb another cell for further measurements.

The FluidFM technology thus increases both throughput and efficiency of single cell force spectroscopy measurements, drastically reducing the time required to obtain statistically relevant data compared to conventional AFM-based SCFS. [1]

Features & Benefits of single cell force spectroscopy measurement with FluidFM

Accelerate your research with a semi-automated single-cell adhesion measurement. The FluidFM OMNIUM platform is a semi-automated system for measuring up to 200 single cells a day. Get reproducible, direct force measurements in high quality and with sound statistics.


High Throughput

Measure up to 200 cells a day using semi-automated workflows.

Many Cell Types & Colloids

For mammalian cells, microbes, and colloids

Broad Force Range

Direct force measurement from pN to µN

Curious about Automated Single Cell Force Spectroscopy with FluidFM?

10x faster measurements compared to standard methods

As objects like cells or colloids can be quickly exchanged through reversible immobilization, measurement throughput is increased more than 10-fold. Up to 200 individual objects can be analyzed in a single day.

FluidFM Mechanobiology - Working principle of single-cell force spectroscopy with FluidFM

Working principle of single cell force spectroscopy with FluidFM.

Simple - no glue needed

The suction method of immobilizing the objects onto the FluidFM cantilever makes it reversible and avoids any glue: Pick. Measure. Release. Repeat.

Switch the probe anytime or reuse to save money

Whether due to degradation, contamination or a required change of probe geometry or chemistry – you can switch the probe at anytime. Just release the object, change the probe, and take up the object again. Our FluidFM Probes typically last for several force spectroscopy measurement days allowing the analysis of several hundred cells.

Many cell types and colloids supported

Cells and colloids come in a wealth of shapes and sizes. FluidFM single-cell force spectroscopy works with adherent or suspension mammalian cells, spheric or rod-shaped microbes, and with colloids, bubbles, and droplets from 0.5 to 100 µm particle size. FluidFM can handle them whether they are hundreds of nm or dozens of µm in diameter. Customers have even analyzed non-colloidal E.coli cells.

 

Cells Microbes Colloids

FluidFM Mechanobiology - Cell

FluidFM Mechanobiology - Microbe

FluidFM Mechanobiology - Colloid

Adherent or suspension cells Spheric or rod shaped. Algae, bacteria, protozoa, and fungi.
Colloids from 0.5 to 100 µm particle size. Also for bubbles, droplets.
Self-centering – means reproducibility

The position of the object on the FluidFM cantilever is given by the position of the aperture. Thus, every colloidal probe will be centered automatically and at the same position – as long as the same FluidFM Probe is used. This results in highly reproducible positioning. 

FluidFM Mechanobiology - Single cell force spectroscopy

1) cell is selected 2) Cell is detached from surface 3) Resulting force spectroscopy. Image courtesy of Bruker.

10x higher force range

The various stiffnesses and opening diameters of FluidFM Probes enable to measure forces from tens of pN up to µN.

Pick from substrate or attract from solution, or even air

Pick-up cells directly from a substrate or attract them from a solution via liquid influx to the aperture of the FluidFM Probe. This method is also recommended when the long-term adhesion of a microbe to a substrate is too strong to quantify, and hence shorter-term interactions are studied. Researchers have also performed particle and microbe measurements in air.

FluidFM Mechanobiology - Single cell force spectroscopy

S. Cerevisiae, also known as baker’s yeast, are picked-up from medium, measured and then deposited in a line with a FluidFM Micropipette. The cells stay fully viable through this procedure. Image courtesy of P. Dörig, ETH Zurich.

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Related Resources

Instrument / Probes

FluidFM ADD-ON FluidFM OMNI­UM
Description Convenient solution to add FluidFM functionality to existing AFM systems
Versatile, automated, stand-alone FluidFM system, optimized for life science applications with large manipulation range
Pre-existing require­ments Needs a compat­ible AFM from third party supplier
No require­ments
Hard­ware FluidFM module as add-on to existing AFM systems
Stand­alone FluidFM system with inte­grated micro­scope and force-control unit
Software Exten­sion to software of AFM supplier
Stand­alone software with dedi­cated work­flows and automa­tion
Automation Limited and depending on AFM system
Automated workflows available as well as full manual control if needed
Compat­ible probes Full range of FluidFM Nano­syringes, Nano­pipettes, and Micro­pipettes
More on FluidFM probes & technology
Probe replace­ment 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)


Single Cell Force Spectroscopy Relevant Specifications

FluidFM ADD-ON FluidFM OMNI­UM
Work­flow automa­tion
Operator guided mea­surement for each cell.
Limited automa­tion available depend­ing on AFM supplier software.
Operator selects cells of interest in software.
Auto­mated mea­surement and release of selected cells.
Auto­mated probe washing proce­dure between two cells.
Through­put
Up to 20 adherent cells per day
Up to 100 adherent cells per day
Force sensitiv­ity and resolu­tion
< 100 pN
< 1 nN
Force range
100 pN to 1 µN
1 nN to 1 µN
Force mapping 
Available as sup­ported by specific AFM
Not available
AFM imaging modes
All modes as sup­ported by specific AFM
Not available
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)
XY-automa­tion
Yes, depend­ing on AFM model
Yes
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.


References

[1] Dehullu, Jérôme, et al. "Fluidic force microscopy captures amyloid bonds between microbial cells." Trends in microbiology 27.9 (2019): 728-730.