A team of Swiss scientists has created a new atomic force microscopy technique that can be used to safely observe various characteristics of living cells without causing them damage. By combining a conventional atomic force microscope (AFM) with a microfluidic circuit, the scientists created a way to observe objects in a fluid environment, something that was previously impossible. The new device, based on hollow force-controlled AFM cantilevers, is aptly called FluidFM.
Zambelli [Dr. Tomaso Zambelli –ed.] originally realized that the technology of the atomic force microscope that is normally used only to image cells could be transformed into a microinjection system. The result of the development by Zambelli and his colleagues in the Laboratory of Biosensors and Bioelectronics at the Institute of Biomedical Technology at ETH Zurich and in the Swiss Center for Electronics and Microtechnology (CSEM) in Neuchâtel was the "fluid force microscope", currently the smallest automated nanosyringe currently in existence.
"Our FluidFM even operates under water or in other liquids – a precondition for being able to use the instrument to study cells" says Zambelli.
The force detection system of the FluidFM is so sensitive that the interactions between tip and sample can be reduced to the piconewton range, thereby allowing to bring the hollow cantilever into gentle but close contact with cells without puncturing or damaging the cell membrane.
On the other hand, if membrane perforation for intracellular injection is desired, this is simply achieved by selecting a higher force set point taking advantage of the extremely sharp tip (radius of curvature on the order of tens of nanometers).
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Image: Staining living neuroblastoma cells by gentle contact on the cell membrane. (a) Diagram showing the staining procedure by gentle contact (not to scale). The hollow tip is maintained in contact with the cell membrane thanks to the force feedback (set point of less than 1 nN). The active agents dissolved in the solution of the microchannel spontaneously diffuse across the membrane into the cytoplasm. (b) Superposition of a differential interference contrast image and of the corresponding fluorescent one of a cell after staining with CellTracker green. The microchannelled cantilever filled with CellTracker green is positioned over the cell in the red circle using the optical microscope. The tip is then brought into gentle contact with the cell membrane by the AFM force feedback system and left there for 15 min, before taking the fluorescent and phase contrast image.