FluidFM Probes: Where It All Begins
At the heart of every FluidFM system is the FluidFM probe: a hollow cantilever with a microscopic channel running through it to an aperture at the tip. By connecting this channel to a pressure controller, you can dispense or aspirate femtoliter volumes while simultaneously sensing interaction forces down to the piconewton range.
Every FluidFM probe consists of two parts: a polymer adapter (tailored to your specific system) and a FluidFM chip that integrates microfluidics and hollow cantilever. Probes come pre-assembled and are ready to use within minutes — simply pipette your solution into the reservoir, connect the probe, and apply a small positive pressure to fill the channel.
Figure 2. How the FluidFM probes are built up.
Probes are available in three standard types, each designed for specific tasks:
FluidFM Micropipette
The largest aperture in the range (2, 4, or 8 µm aperture). Its wide opening makes it ideal for reversibly immobilizing individual cells or micro-sized objects using suction. Best suited for pick and place of cells and dispensing and nanoprinting (e.g., for printing of large spots).
FluidFM Nanosyringe
A sharp tip designed to gently penetrate cell membranes under precise force control (550 or 800 nm aperture). Inject into or extract from the cytoplasm or nucleus. Best suited for injection and extraction (SC Biopsy).
FluidFM Nanopipette
The smallest aperture in the standard range (300 nm), enabling highly localized liquid dispensing with exceptional spatial precision. Best suited for pick and place of bacteria and dispensing and nanoprinting (for printing of detailed patterns).
Main Advantages
FluidFM offers distinct benefits over traditional micropipette or AFM methods:
Gentle & Non-Damaging
The force feedback allows you to approach cells with nanometer precision without killing them.
Universal Versatility
A single system can perform multiple tasks — injection, isolation, adhesion measurement, and printing — simply by changing the probe or the pressure mode.
Easy & Ready-to-Use
FluidFM probes come pre-assembled on a convenient adapter tailored to your system. No complex setup — get started within minutes.
Precise Liquid Handling
The system can control volumes down to the femtoliter scale, enabling extremely localized delivery of drugs or extraction of intracellular content.
Strong & Reversible Grip
By applying negative pressure (suction), the probe can hold onto objects firmly (like a vacuum gripper) and release them instantly by switching to positive pressure.
Key Applications & Modes
FluidFM is used in three main modes, each enabled by a specific probe type. Depending on your research goal, you can switch between modes simply by changing the probe or the applied pressure.
Injection and Sampling:
How it works
The nanosyringe approaches a target cell and penetrates the membrane under precise force control, gentle enough to keep the cell alive. Inject a solution into the cytoplasm or nucleus, or extract cytoplasmic content as a biopsy, with sub-picoliter precision.
Why FluidFM?
Unlike bulk transfection or electroporation, FluidFM delivers reagents with spatial and volumetric precision to a single, chosen cell. Force-feedback ensures membrane penetration without cell damage, critical for hard-to-transfect or sensitive cell types.
Recommended probe
Nanosyringe with an aperture of 550 or 800 nm (for extraction or injection respectively)
Key Applications:
- CRISPR Cell Line Engineering
Vector-free, intra-nuclear delivery of CRISPR complexes into individual cells, including hard-to-transfect cancer and primary cell lines (Antony, J.S. et al., Biotechnol. J., 2024). Simultaneous delivery of all components minimizes off-target effects. - Temporal Single-Cell Profiling
Cytoplasmic biopsies enable single-cell RNA sequencing (scRNA-seq) while keeping the cell alive — known as Live-seq (Chen, W. et al., Nature, 2022). The same cell can be sequenced multiple times, transforming scRNA-seq from a snapshot into a temporal, longitudinal analysis — something no other method offers.
Pick and Place:
How it works
Using the micropipette, you can approach a target cell or particle, apply gentle suction to grab it, lift it, and move it to a new location, with full visual control under the microscope. The same suction-based attachment also allows you to pull cells away from a surface in a controlled manner, directly measuring the force required to detach them.
Why FluidFM?
The reversible vacuum grip means you can hold objects firmly during transport and release them instantly on demand — with no risk of mechanical damage. This makes it far more reliable than optical tweezers or manual micromanipulation when working with fragile biological samples. Combined with the built-in force feedback, FluidFM is uniquely positioned to perform both cell isolation and quantitative adhesion measurements in a single workflow.
Recommended probe
Micropipette (2, 4, or 8 µm aperture) or Nanopipette (300 nm aperture), depending on the size of the target objects.
Key Applications
- Cell Isolation
Isolating single cells for downstream analysis, separating specific clones from a mixed culture, or repositioning cells to build defined 3D structures (Connolly, S. et al, 2024). - Single-Cell Force Spectroscopy
Measuring cell adhesion forces to evaluate how strongly cells bind to surfaces or coatings (Habli, Z. et al, Lab on a Chip, 2024), or other cells (Yang, A. et al, Sci Advance, 2024).
Dispense and Nanoprinting:
How it works
Using the nanopipette or micropipette, you can dispense precise, femtoliter-scale volumes of liquid directly onto a surface or in a defined pattern — in air or in liquid immersion.
Why FluidFM?
The ability to deposit femtoliter volumes at defined positions with nanometer-scale spatial control is unmatched by conventional spotting or inkjet technologies, making it ideal for high-resolution surface patterning.
Recommended probe
Nanopipette (300 nm aperture) or micropipette (2, 4, or 8 µm aperture).
Key Applications
Nanoprinting of biomolecules (Huang, Y. et al, Chemistry, 2024), localized surface modification, or depositing reagents at precise positions on a substrate (Saftics, A. et al, Langmuir, 2019).
