10x FASTER & EASIER.
SINGLE CELL FORCE SPECTROSCOPY
In this video, a single cell is detached from fully adherent and confluent culture. The measured forces both depend on the substrate as well as the bonds to the neighboring cells. Courtesy of A. Sancho and J. Groll, Functional Materials for Medicine and Dentistry, University Hospital of Würzburg.
GET SOUND STATISTICS WITHIN A DAY.
Single cell force spectroscopy offers quality mechanical data on a single cell level. The main drawback so far was its low throughput and complex handling. FluidFM-based single cell force spectroscopy now offers 10 times higher throughput and much easier manipulation of the cells of interest.
Pick a cell with negative pressure, measure, release it again with a positive pressure pulse or by a short cleaning procedure.
20 to 200
CELLS A DAY
THAN STANDARD METHODS
10x HIGHER FORCE RANGE
THAN STANDARD METHODS
FOR CELL MECHANOBIOLOGY & BIOPHYSICS.
Both in biophysics and mechanobiology, the physical study of single cells allows insights into biological phenomenon such as differentiation, growth and proliferation. In cancer research, stem cells, and organoids, the cell mechanical properties and interactions with its environment are key to obtain a deeper understanding. Further, for implant materials there is a clinical need to understand and control how various cells adhere to it.
With each cell being different from its neighbor – also known as cell heterogeneity - one goal is to understand these effects on a single cell level. Single cell force spectroscopy has been established as an insightful method to address such questions using atomic force microscopy (AFM).
The process of gluing a cell to an AFM cantilever is however tedious and time-consuming, limiting the throughput to few cells per day. Yet due to cell-cell heterogeneity many cells are typically needed to meaningfully assess any experimental condition.
Here FluidFM offers a dramatic improvement, by reversibly immobilizing a cell to a FluidFM probe by suction, and subsequent release with pressure. This allows the increase of the throughput by a factor of 10 to 100.
Get sound statistics within one day instead of weeks or months.
A cell is detached from adherent culture with a FluidFM micropipette.
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.
LARGEST FORCE RANGE. HIGHEST FLEXIBILITY.
Reduced preparation time in combination with reusable measurement probes makes FluidFM the perfect tool for all your single cell mechanical studies.
Thanks to the unique properties of FluidFM technology, you can gather solid cell mechanical data in a much shorter time. Gain access to unparalleled measurement ranges, increasing your experimental flexibility. FluidFM gives you the edge.
Measure suspended or fully adherent cell
FluidFM micropipettes allow to either attract a suspended cell from solution or to directly pick it up from fully adherent culture. FluidFM can thus overcome cell adhesion forces of more than 1000 nN.
From pN to µN
Measure forces from tens of pN up to µN by taking advantage of FluidFM probes with various stiffnesses and opening diameters. With spring constants from 0.3 N/m to 4 N/m and available openings from 300 nm to 8 µm, a wide range of cells and mechanics can be covered.
Pick. Measure. Clean. Repeat.
With many mammalian cells having a tendency to adhere quickly to any substrate – also the FluidFM probe – a common approach is to clean the probe after each cell. The procedure takes less than two minutes before picking up the next cell for measurements. For non-adherent cells, this cleaning procedure can be skipped, and the throughput is even higher.
Illustration of a cell being detached from a substrate by FluidFM. The measured force-distance curve can give insights on adhesion strength, energy, distance as well as the involved bio-chemical bonds.
FluidFM has been used in many publications to quantify cell mechanical properties. Below we present 3 highlights; many more can be found in our publications section.
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.
A. Garitano-Trojaola, A. Sancho, R. Goetz, S. Walz, H. Jetani, E. Teufel, N. Rodhes, M. DaVia, L. Haertle, S. Nerreter, C. Vogt, J. Duell, R. Tibes, S. Kraus, A. Rosenwald, L. Rasche, M. Hudecek, M. Sauer, H. Einsele, J. Groll & M. Kortüm. RAC1 Inhibitor EHT1864 and Venetoclax overcome Midostaurin resistance in Acute Myeloid Leukemia. (2019) Blood. doi: 10.1182/blood-2019-129762
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.
E. Potthoff, D. Franco, V.D'Alessandro, C. Starck, V. Falk, T. Zambelli, J.A. Vorholt, D. Poulikakos & A. Ferrari. Toward a rational design of surface textures promoting endothelialization. (2014) Nano Letters, 14(2), 1069 — 1079. doi:10.1021/nl4047398
Calibrating high-throughput devices
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.
M. Sztilkovics, T. Gerecsei, B. Peter, A. Saftics, S. Kurunczi, I. Szekacs, B. Szabo & R. Horvath. Single-cell adhesion force kinetics of cell populations from combined label-free optical biosensor and robotic fluidic force microscopy. (2020) Scientific Reports. doi: 10.1038/s41598-019-56898-7