Chapter Four · failure evidence
What Atomic Force Microscopy (AFM) got wrong, from 28 dissertations
Atomic force microscopy investigations encounter challenges ranging from cantilever fabrication flaws and optical reflection loss to severe tip adhesion and sample dragging. Furthermore, surface imaging and mechanical sensing frequently fail due to extreme sample roughness, feedback instabilities, and inadequate resolution for chemical or structural features. These records come from PhD theses at 13 institutions, 2021 to 2026. Each links to its thesis. They were extracted by language models reading the full text, so treat each as a lead to read, not a verdict.
Atomic force microscopy lacks resolution, chemical specificity, or reproducibility for delicate targets
Cantilever imaging failed to resolve subtle DNA bending angles and lacked the step edges needed to verify protein functionalization layers. Techniques were also rejected when spatial resolution was constrained by tip geometry, when single-cell measurements showed high variability, or when chemical bonding states could not be non-destructively identified.
Tried and failed
atomic force microscopy on mica surfaces applied to detecting intrinsic sequence-dependent nucleic acid curvature. Outcome: no signal. Reason: surface deposition and imaging resolution lacked sensitivity to resolve subtle mismatch-induced bending angles
Characterizing the bending and twisting mechanics of DNA and its mismatches · Georgia Tech
Considered and rejected
Considered and rejected: Rejected AM-KPFM in favor of FM-KPFM because AM-KPFM spatial resolution is limited by both tip radius and cantilever, whereas FM-KPFM force gradient sensitivity provides higher spatial resolution.
Characterization of InAs Quantum Dots in InP Nanowires Using a Kelvin Probe Force Microscopy · TXST Digital Repository
Tried and failed
atomic force microscopy for layer thickness verification applied to surface protein functionalization monitoring. Outcome: no signal. Reason: lack of distinct step edges prevented clear confirmation of layer attachment
Optimization of Surface-Protein Interactions for Next Generation Biosensors · Georgia Tech
Considered and rejected
Considered and rejected: Rejected single-cell atomic force microscopy for measuring intestinal smooth muscle cell stiffness due to high measurement variability, choosing whole-tissue microprobe indentation instead.
Considered and rejected
Considered and rejected: Rejected atomic force microscopy (AFM) in favor of XPS and Raman microscopy to directly probe chemical bonding and functional group states non-destructively
Investigating the sorption phenomena of free fatty acids using the quartz crystal microbalance · Imperial
Cantilever fabrication and coating defects compromise mechanical sensing and optical readout
Microcantilever manufacturing methods suffered from mechanical breakage during anisotropic wet etching, as well as curling that hid nanoscale deflections. Alternative material cantilevers achieved poor tip deflection compared to baseline piezoelectric designs, and parasitic backside vapor deposition degraded optical lever reflection.
Tried and failed
atomic layer deposition of nanoscale cantilevers applied to mechanical deflection sensing. Outcome: unstable. Reason: out-of-plane twisting and curling obscured deflections below one hundred nanometers
Design and development of magneto-mechanical systems for actuation in haptic devices · Cornell
Tried and failed
anisotropic chemical etching for free-standing microstructures applied to flexible thin-film cantilever fabrication. Reason: free-standing cantilever structures suffered mechanical failure during anisotropic wet etching inside square mask windows
A flexible interconnection for integrated circuits · Iowa State
Tried and failed
physical vapor deposition coating on microcantilevers applied to atomic force microscopy probes. Outcome: no signal. Reason: parasitic backside deposition disrupted optical lever laser reflection despite ion beam stripping attempts
Lost to a baseline
Electrostrictive α-phase PVDF cantilevers achieved only 1/3.4 (approx. 30%) of the scaled tip deflection of baseline piezoelectric β-phase PVDF-TrFE cantilevers (150 nm @ 30 V vs 1.2 µm @ 30 V).
Flexoelectricity in PVDF and TiOx thin films : material characterization for MEMS applications · DSpace-CRIS at TU Wien
High surface roughness and irregular topography exceed scanner deflection and oscillation limits
Highly rough and irregular sample surfaces caused mechanical vibrations and exceeded the vertical travel limits of the cantilever. Additionally, porous and rough topographies restricted cantilever oscillation amplitude, causing image blurring and ghosting artifacts.
Tried and failed
tapping-mode atomic force microscopy applied to rough porous mineral surfaces. Reason: insufficient cantilever oscillation amplitude caused image blurring and ghosting artifacts
Tried and failed
Atomic force microscopy applied to irregular polymer weld line surface morphology. Outcome: no signal. Reason: Irregular sample geometry and induced mechanical vibrations prevented stable surface measurement.
NONDESTRUCTIVE TESTING AND MATERIAL CHARACTERIZATION BY TERAHERTZ PULSED IMAGING AND TIME-DOMAIN SPECTROSCOPY · Georgia Tech
Tried and failed
High-speed atomic force microscopy topographic scanning applied to rough fracture surfaces. Reason: Z-axis cantilever deflection range limits prevented scanning on highly rough topography
Environmentally assisted cracking on titanium alloys · Imperial
Strong tip-sample adhesion and mechanical interference damage samples and obscure features
Excessive adhesion between the probe and viscous films prevented cantilever detachment during retraction cycles or dragged surface coatings across the substrate. Mechanical cell lysis with cantilevers also produced cell wall fragments that covered the surface features being tracked.
Tried and failed
Atomic force microscopy imaging applied to viscous organic film on mineral substrate. Outcome: unstable. Reason: Excessive tip-surface adhesion prevented probe detachment during retraction cycles
Characterising mineral surfaces and probing the impact of ageing in crude oil using AFM · Imperial
Considered and rejected
Considered and rejected: Directly sputtering onto bare silicon for AFM was rejected in favor of blotted drop-casting because the cantilever tip would pick up/drag the PEG layer during scanning.
Metallic nanocarrier complex targeting neuroendocrine prostate cancel cells. · Cranfield
Tried and failed
cantilever-induced mechanical cell lysis via atomic force microscopy applied to bacterial pole growth tracking. Reason: ruptured cell wall remnants obscured newly formed poles, preventing detection of growth onset
Feedback instabilities and spurious coupling disrupt dynamic cantilever force sensing
Frequency modulation techniques introduced spurious driving artifacts into mechanical resonators and suffered from thermal drift instabilities during coarse approach. Dynamic microrheology measurements also failed due to confounding sensitivities to surface tension and electrostatic charge.
Tried and failed
resonant frequency modulation for cyclic adiabatic inversion applied to ultrasensitive microcantilever force sensing. Reason: frequency modulation directly coupled spurious driving artifacts into the mechanical resonator that could not be subtracted
Advancing a nuclear magnetic resonance force microscopy (NMRFM) probe and simulating NMRFM in thin films · UT Austin
Tried and failed
atomic force microscopy shear microrheology applied to interfacial liquid-liquid nanosheets. Outcome: no signal. Reason: Confounding sensitivities to interfacial surface tension and electrostatic charge.
The biophysical regulation of the cytoskeleton in PDAC · Imperial
Tried and failed
direct frequency shift feedback during coarse approach applied to non-contact atomic force microscopy. Outcome: unstable. Reason: thermal drift and resonance frequency shifts during coarse mechanical steps caused feedback instability
Left open by the authors
Problems the authors named and did not get to.
Left open
Resolve whether morphological domains in polymer-NFA blend films correspond to the polymer or NFA using atomic force microscopy. Blocker: Requires fabricated thin-film samples and an atomic force microscope (AFM)
Photophysics of narrow bandgap organic semiconductors for infrared photodetectors · Imperial
Left open
Perform atomic force microscopy analysis on SD-chitin films to characterise their porosity, surface morphology, and thickness uniformity. Blocker: Requires physical SD-chitin samples and an atomic force microscope (AFM) apparatus.
Automated strategy for probing enzymatic degradation of lipid membranes · Imperial
Left open
Optimize sample concentration, filtration, and mechanical agitation protocols for atomic force microscopy characterization of Janus star polymer micelles. Blocker: Requires wet lab sample preparation and access to atomic force microscopy instrumentation
Precise Synthesis, Characterization, and Applications of Nonlinear Polymers with Varied Architectures · Georgia Tech
Left open
Synthesize cyclic brush polymers with diverse side chains and image their ultra-high molecular weight architectures using atomic force microscopy. Blocker: Requires a wet chemistry synthesis lab and atomic force microscopy (AFM) instrumentation.
Development of Functional Enyne Molecules to Control Degradability and Architecture in Metathesis Polymers · Georgia Tech
Left open
Perform experimental studies to test if higher effective stiffness in higher AFM eigenmodes causes surface damage during contact resonance. Blocker: Requires a specialized atomic force microscopy (AFM) physical laboratory and thin-film samples.
Gradientes de deformación para controlar dominios ferroeléctricos en películas delgadas de Bi-Fe-O · Repositorio Institucional BUAP
Left open
Study trapped interfacial contamination nanobubbles using gated FM-KPFM with band-edge pinning to map strain and piezoelectricity. Blocker: Requires atomic force microscopy / Kelvin probe force microscopy experimental laboratory setup and physical samples.
Electrostatic effects of inhomogeneous strain in monolayer transition metal dichalcogenides · UT Austin
Left open
Test DNA minicircles with weaker poloidal bias and use monomeric avidin markers in AFM imaging to improve resolution. Blocker: Requires wet lab facilities, DNA minicircle synthesis, and atomic force microscopy (AFM) instrumentation.
Investigating Poloidal Bias in DNA Minicircles and Overhang influence on DNA Dehybridization · Georgia Tech
Left open
Compare SPR detection of intact and freeze-thaw lysed extracellular vesicles using AFM to assess vesicular degradation effects on sensitivity. Blocker: Requires a wet lab, SPR biosensor apparatus, atomic force microscopy (AFM), and extracellular vesicle samples
Left open
Combine atomic force microscopy adhesion measurements with X-ray micro-CT to analyze how surface roughness affects fluid surface coverage. Blocker: Requires physical access to atomic force microscopy (AFM) and X-ray micro-CT experimental setups and rock samples.
Wettability characterisation of sandstone and carbonate rocks using X-ray micro-CT imaging · Imperial
Left open
Measure surface forces between microspheres and PDMS molds using atomic force microscopy or a surface force apparatus. Blocker: Requires physical laboratory equipment (AFM or SFA) and physical material samples.
Microneedle Patch Delivery of Controlled-Release Microspheres to the Skin · Georgia Tech
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