This guide covers what fluid cells are, why they're essential for biological and electrochemical research, the key differences between open and closed designs, how to select the right cell for your AFM system, and best practices for bubble-free, drift-stable operation.
Key Takeaways
- Fluid cells eliminate capillary forces and surface tension that damage soft samples in air
- Open cells give fast liquid access; closed cells support flow, gas control, and long runs
- Verify AFM model, scanner type, and sample geometry compatibility before you buy
- Sub-pN force stability needs the right cantilever, laser alignment, and thermal equilibrium
- Molecular Imaging supplies liquid cell modules, flow systems, and cantilevers for 5500 and 5420 AFMs
What Are Fluid Cells for AFM?
Fluid cells are specialized hardware components that keep both the AFM probe and sample submerged in liquid during scanning. They include a liquid container, a probe holder with optical access for laser alignment and cantilever deflection detection, and seals that prevent leaks.
Basic construction includes:
- A sample chamber that holds the liquid and sample
- A modified cantilever holder with a glass window or port so the laser can reach the cantilever and return to the photodiode
- Seals, ports, or flow-through connections for liquid addition or exchange
Fluid cells work with standard AFM systems, but the laser path needs adjustment for the refractive index change from air to liquid. Bruker training materials note that switching to liquid shifts the apparent laser focus behind the cantilever, changes camera focus, and makes the tip and sample appear farther apart.
Operators must recalibrate the optical path before imaging.
Optical setup is only half the story. Air vs. liquid forces: In air, an adsorbed fluid layer creates surface tension and meniscus forces that raise vertical contact force and lateral shear. Full immersion removes that layer, cutting force on the sample and lowering damage risk.
Why Use Fluid Cells in AFM Imaging?
Fluid cells let you run AFM in liquid instead of air. That shift cuts damaging tip–sample forces, keeps hydrated samples intact, and opens experiments you cannot do in ambient conditions.
Key reasons labs switch to fluid-cell imaging:
- Suppress capillary forces that spike contact load in air
- Image cells, DNA, and bilayers in native buffer
- Run in-situ electrochemical AFM during potential sweeps
- Reach sub-100 pN (and sub-pN noise) force control
- Limit dust and hydrocarbon contamination on the surface
Eliminates Capillary Forces and Surface Tension
In air, an adsorbed liquid layer creates surface tension that raises vertical tip–sample force, and lateral shear can damage soft samples (Bruker foundational training). Liquid immersion suppresses meniscus formation, so contact stays gentler.
Preserves Biological Samples in Native Conditions
AFM in physiologically relevant solution supports native-state imaging and real-time DNA studies (research in PMC).
Nanoscale live-bacteria imaging in water, buffer, or culture medium reaches nanometer resolution without ensemble averaging. That result is impossible in air, where dehydration collapses structures.
A supported-lipid-bilayer protocol notes that full evaporation or air contact destroys the bilayer, so continuous liquid coverage is required.
Enables Electrochemical AFM
A 2018 JACS study ran electrochemical AFM (EC-AFM) in 0.1 M H₂SO₄ with a platinum working electrode, Ag/AgCl reference, and platinum counter electrode. Tapping-mode images taken during cyclic voltammetry showed platinum nanoparticles disappear above 1.35 V and reappear below 0.95 V. Researchers could watch dissolution and redeposition in real time.
Achieves Sub-100 pN Force Imaging
Force control tightens in liquid. A DNA study found that about 200 pN caused excessive deformation and lost submolecular resolution, while 40 pN barely deformed plasmids.
A 2013 Cypher study demonstrated 0.5 pN precision in liquid at room temperature. Within 30 minutes, 60% of tested uncoated BioLevers reached 0.54 ± 0.02 pN integrated noise.
Reduces Contamination Buildup
Closed fluid cells are easy to clean and help block contamination (Oxford Instruments). Sealed systems keep atmospheric dust off the sample and cut surface adsorption of airborne hydrocarbons.
Types of Fluid Cells: Open vs. Closed Systems
Fluid cells for AFM fall into two main designs: open and closed. The right choice depends on experiment length, solvent volatility, and whether you need flow, gas control, or temperature stability.
Open Cell Design (Microcells)
Construction: A small vessel holds limited liquid volume, with the probe mounted on a holder featuring a glass window for laser access.
Operation: The cantilever is submerged in a small drop held by surface tension. Park Systems specifies 2.3 cm³ (2.3 mL) capacity for its open cell, though pre-wetting procedures may use only 50 µL.
Advantages:
- Simplest to learn and use
- Quick liquid addition and sample access
- Minimal assembly steps
Limitations:
- Exposed liquid evaporates over time
- Not suitable for volatile solvents
- Limited experiment duration without refilling
Closed Cell Design (Environmental Cells)
Construction: A sealed chamber with glass top plate and rubber diaphragm or coverslip bottom, forming an enclosed environment.
Capabilities: Closed cells support static liquid or continuous perfusion in a sealed chamber. Implementations vary by platform:
- Oxford MFP-3D closed cell: fully enclosed, ten access ports, glove-box assembly for air-sensitive work
- Bruker NanoWizard BioCell: quick-exchange coverslip, liquid perfusion, CO₂ flow, temperature control from 15–60°C
Advantages:
- Flow-through liquid exchange during imaging
- Inert gas environments
- Temperature and humidity control
- Extended experiment duration
Limitations:
- Steeper learning curve
- More interfaces and seals to manage
- Requires careful bubble elimination
Comparison Table
| Feature | Open Cell | Closed Cell |
|---|---|---|
| Ease of use | Simple; hours to learn | Complex; requires training |
| Liquid volume | 2.3 mL typical | Variable; flow-through capable |
| Evaporation control | Minimal; refill required | Sealed; negligible evaporation |
| Flow capability | None | Yes; perfusion and exchange |
| Typical applications | Short experiments, quick tests, buffer imaging | Long experiments, electrochemistry, live-cell culture, gas control |
| Learning curve | Low | Moderate to high |
Selection guidance: Match the cell type to session length and environmental needs:
- Open cells — short biological imaging, method development, or frequent sample changes
- Closed cells — runs over one hour, electrochemistry, live-cell CO₂ work, or air-sensitive samples
Selecting the Right Fluid Cell for Your Research
Choosing a fluid cell comes down to three checks: whether it fits your AFM, whether it handles your sample and liquid, and whether it can run for the full length of the experiment.
Verify AFM Compatibility
Bruker lists dedicated fluid-cell holders for MultiMode, Dimension, BioScope Resolve, Innova, and CP-II systems. Oxford's closed cell is specifically designed for MFP-3D AFMs. Molecular Imaging offers liquid cell and sample module designs for its 5500 PicoPlus AFM+STM, 5500 ILM PicoPlus BioAFM, and 5420 PicoAFM systems, with compatibility across its modular scanner platforms.
Before purchasing, confirm:
- AFM model and scanner type (contact Molecular Imaging at 1-888-644-0389 for compatibility with 5500 and 5420 platforms)
- Sample dimensions and mounting method
- Optical path clearance for laser alignment
Match Cell to Sample and Liquid Type
Park Systems specifies 4–70°C temperature range and acid/base resistance for its universal cell, while offering PEEK construction for corrosive electrochemistry. Oxford's Cypher ES electrochemistry cell is compatible with most common solvents, electrolytes, and electrode materials.
Consider:
- Aqueous buffers (standard for biological work)
- Organic solvents (require special seals)
- Corrosive solutions (need chemically resistant materials)
- Temperature requirements (systems vary: Bruker BioCell 15–60°C, Park 4–70°C)
Account for Experiment Duration and Evaporation
Sample evaporation limited a sub-pN force study, which is a common constraint in liquid AFM. Short experiments (under 1 hour) may tolerate open cells with periodic liquid addition. Long runs, time-lapse imaging, or low-drift work need closed or Lite designs that keep exposed surface area to a minimum.
Best Practices for Fluid Cell AFM Operation
Sample Preparation and Substrates
Substrate selection:
- Freshly cleaved mica (atomically flat, hydrophilic)
- Borosilicate glass or fused silica
- Oxidized silicon wafers
A 2016 protocol uses freshly cleaved mica bonded to a steel disk with approximately 10 µL of thoroughly mixed epoxy. Molecular Imaging sells 2 cm mica substrates and Au gold thin-film on mica substrates (large and small formats) suited to liquid-cell sample preparation.
Adhesive considerations:
- Use epoxy or optical glue that resists leaching into the imaging buffer
- Ensure adhesive is fully cured before liquid addition
- Avoid adhesives that release solvents or plasticizers
Bubble Management
Bruker guidance warns that bubbles can disrupt the laser path or bend the cantilever, and lipid-bilayer work shows air contact can destroy fragile films. Pre-wet the cantilever and tip with about 50 µL of imaging solution before approach to limit trapped air.
Bubble elimination techniques:
- Degas buffers under vacuum or by sonication before use
- Fill cells slowly to avoid trapping air
- Flush systems with degassed liquid to purge bubbles from tubing and ports
- Verify the laser spot is visible and stable on the photodiode before engaging
Cantilever Selection for Liquid Environments
NIST reports that air operation typically uses cantilevers around 40 N/m, while liquid requires cantilevers below 1.0 N/m. For damage reduction, NIST gives below 0.2 N/m as an example of a compliant cantilever, cautioning that damage is reduced but not eliminated.
Molecular Imaging offers:
- Si-L-10 silicon liquid-tapping cantilever for biological samples, proteins, and soft materials in aqueous or physiological solutions
- Si3N4-L-10 silicon-nitride liquid-tapping cantilever for robust biological and polymer imaging with durability suited to extended aqueous sessions
- FM-10 low-frequency soft tapping cantilever optimized for delicate biological samples and soft materials, minimizing perturbation
Drift Minimization
Liquid-AFM drift is commonly thermal or driven by rapid evaporation, and it falls off once the system reaches thermal equilibrium. Bruker training flags temperature mismatch between the liquid and the microscope as a primary source. Coating choice matters too: over three hours, gold-coated BioLevers drifted 900 nm rms versus 70 nm rms for uncoated levers, so removing gold cut drift by more than tenfold.
Drift reduction strategies:
- Equilibrate sample, liquid, and microscope to the same temperature
- Allow 30–60 minutes for thermal stabilization before imaging
- Use uncoated or minimally coated cantilevers when possible
- Minimize exposed liquid surface area to reduce evaporation
Tip Contamination Prevention
Bruker guidance permits UV cleaning of cantilevers before use. Pair that with routine hygiene controls:
- Swap in fresh probes often during long sessions
- Keep imaging buffers clean and filtered
- Clean all wetted hardware before assembly
- Use clean substrates and disciplined sample-prep protocols so loose material does not transfer to the tip during scanning
Frequently Asked Questions
What is AFM and how does it work?
Atomic force microscopy (AFM) is a scanning probe technique that uses a sharp tip on a cantilever to measure surface topography at nanometer resolution. The tip senses tip-sample interaction forces; feedback maintains constant interaction while raster scanning, producing 3D topographic maps.
How much does an AFM microscope cost?
AFM systems range from $20,000 to $300,000 depending on capabilities, with research-grade instruments at the high end. Fluid cell accessories vary by design—contact Molecular Imaging at 1-888-644-0389 for current pricing.
What is AFM spectroscopy?
AFM spectroscopy (force spectroscopy) measures force-distance curves by recording cantilever deflection as the tip approaches and retracts from surfaces. This reveals mechanical properties such as adhesion, elasticity, and molecular unfolding forces at the piconewton scale.
Can I use any liquid with AFM fluid cells?
Most aqueous buffers work well for biological applications. Some cells support common solvents and electrolytes, and corrosion-resistant designs handle acids or bases. Compatibility depends on the cell, seals, tubing, and temperature—always confirm with the manufacturer before using organic solvents or corrosives.
What causes image drift in fluid cell AFM?
Common causes include thermal disequilibrium between liquid and microscope, solvent evaporation changing fluid volume, cantilever coating stress, and mechanical instability. Drift becomes negligible at thermal equilibrium, so stabilize temperature and minimize evaporation by using closed or low-evaporation cells for long experiments.
How do I prevent tip contamination in liquid environments?
Use fresh probes frequently, maintain clean buffer solutions, and consider UV cleaning of cantilevers before use. Bruker permits UV cleaning as an approved method. Freshly cleaved substrates, clean hardware, and proper sample-preparation protocols also reduce contamination risk.
Need help selecting a fluid cell for your AFM system? Molecular Imaging offers liquid cell modules, flow systems, environmental control accessories, and dedicated liquid-environment cantilevers for the 5500 and 5420 AFM platforms. Contact the team at 1-888-644-0389 or songxu@nanocuetech.com to verify compatibility and configure your system for biological, electrochemical, or materials-science imaging in liquid.
