brain abscess

The multidisciplinary nature of AFM

Atomic force microscopy (AFM) is utilised in a wide range of disciplines from biology to engineering.

 
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This is possible because of its versatility and high resolution, which make it a powerful tool for imaging the diverse nanoscale world in air, liquid, and vacuum environments. We think the best way to highlight its multidisciplinary nature is by telling you about five of our favourite AFM-related journal articles of 2018:

Biology

Nanoscale mechanics of brain abscess: An atomic force microscopy study

Brain abscess is a life-threatening swelling of part of the brain arising from infection. In this journal article, the viscoelastic properties: Young’s modulus and hysteresis (H) of three layers of brain abscess tissue were measured using atomic force microscopy for the first time.

 
Young’s modulus and hysteresis of three layers of brain abscess tissue. © Minelli et al.

Young’s modulus and hysteresis of three layers of brain abscess tissue. © Minelli et al.

 

The measurements were performed immediately after surgical removal where the tissue was rough and inhomogeneous in terms of thickness. Therefore, an AFM instrument with a large z-range movement had to be used, allowing the researchers to map large areas of the tissue without interruption. In this way, they were able to avoid the preparation steps such as fixation or freezing of the tissue to facilitate measurement, which could affect the mechanical response of the sample.

Nanomechanical characterisation of the abscess is important for understanding how it responds to surgical instruments and for developing precise mechanical models of the brain.

Medicine

Evaluating the efficacy of the anticancer drug cetuximab by atomic force microscopy

In eukaryotic cells, epidermal growth factor receptor (EGFR) is activated by EGF and its abnormal regulation leads to the growth of many cancers. Cetuximab, a monoclonal antibody acts as an anticancer drug by specifically binding to EGFR and inhibiting its activity.

In this journal article, nano-indentation was firstly performed to measure the Young’s modulus of cancer cells without and without cetuximab treatment. It was shown that the rigidity of the cancer cells increased following cetuximab treatment, which decreased their migration and proliferation.

 
Young’s modulus of cancer cells with control, cetuximab, and EGF treatment. © Zhang et al.

Young’s modulus of cancer cells with control, cetuximab, and EGF treatment. © Zhang et al.

 

Secondly, AFM tips functionalised with cetuximab and EGF were brought into contact with cancer cells to allow the molecules to interact with EGFR and subsequently retracted, breaking the interaction. It was demonstrated that the binding strength between EGFR and cetuximab was higher than that between EGRF and EGF. Thus, EGRF more favourably binds to cetuximab, preventing its activation by EGF and leading to the death of cancer cells.

 
Binding forces and probabilities of various interaction combinations between cetuximab, EGF, and EGRF. © Zhang et al.

Binding forces and probabilities of various interaction combinations between cetuximab, EGF, and EGRF. © Zhang et al.

 

This work shows the potential of AFM as a tool for studying the efficiency of anticancer drugs.

Chemistry

Fast and controlled fabrication of porous graphene oxide: application of AFM tapping for mechano-chemistry

Porous graphene oxide is a crucial material in applications such as energy storage and nanofiltration. Pores are commonly formed by etching the material under oxygen plasma. This journal article demonstrates how the evolution of pores in the material can be controlled locally by scanning it with an AFM tip in tapping mode.

The mechanism is as follows. Graphene oxide has both graphene and polar hydroxylated domains. During etching, oxygen species attach and intermediate structures are formed. The unstable nature of these structures means that their carbon-carbon bonds break, releasing volatile products. When the graphene oxide is removed from the plasma chamber to be scanned with an AFM tip, it is exposed to moisture in the air. The water molecules react with the intermediate structures of the hydroxylated domains, forming more stable structures, which leads to a reduction in the etching rate and thus, the ability to control and tune pore formation.

 
The evolution of pores in graphene oxide upon treatment with oxygen plasma and AFM tapping. © Chu et al.

The evolution of pores in graphene oxide upon treatment with oxygen plasma and AFM tapping. © Chu et al.

 

This work represents the first use of AFM as a mechanochemistry tool.

Physics

Light Emission from Plasmonic Nanostructures Enhanced with Fluorescent Nanodiamonds

Metallic nanostructures are known to enhance the light emission from fluorescent emitters in a process known as surface-enhanced fluorescence. However, the effect of fluorescent emitters on metallic nanostructure light emission has not been widely studied because this emission is weak compared to that of the fluorescent emitters and the signals overlap on a photoluminescence spectrum.

In this journal article, a single gold nanoparticle was manipulated to approach a single fluorescent nanodiamond using an atomic force microscope. Since the gold nanoparticle emits light via the anti-stokes process and the fluorescent nanodiamond does not, the emission from both could be separately analysed in the resulting spectra. By measuring emission before and after coupling between the species, it was shown that the emission signal of both was enhanced after coupling.

 
Coupling of the gold nanoparticle and fluorescent nanodiamond using AFM manipulation and the photoluminescence spectra of these particles in the free and coupled state. © Zhao et al.

Coupling of the gold nanoparticle and fluorescent nanodiamond using AFM manipulation and the photoluminescence spectra of these particles in the free and coupled state. © Zhao et al.

 

This work presents the first concrete experimental study of emission enhancement from metallic nanostructures by fluorescent emitters at the single particle level.

Engineering

Design and Realization of 3D Printed AFM Probes

AFM probes are typically fabricated from one base material using micromachining, which involves many lithographic and processing steps. This approach has limitations in terms of usable material and complexity of the final structure given its time-consuming nature. To overcome these limitations, the use of additive manufacturing may be a viable option.

In this journal article, direct laser writing lithography using two-photon polymerization is explored as a potential route for fabricating AFM probes, enabling the 3D structure of the AFM probes to be produced in a single process. Initially, 3D polymer probes were fabricated in a monolithic fashion.

 
Polymeric 3D printed probes and the utilised 3D printing system. © Alsharif et al.

Polymeric 3D printed probes and the utilised 3D printing system. © Alsharif et al.

 

Given their low quality-factor, the bandwidth was about ten times larger than silicon probes. This meant that they were successfully used to perform high-speed AFM where the image quality remained static after 200 scans.

Furthermore, given the ability to 3D-print arbitrary structures of AFM probes using the direct laser writing technique, bisegmented probes were fabricated. These probes allowed the first and second harmonic resonant frequencies to be tuned independently, enabling new types of tip-sample interactions to be investigated.

Overall this article demonstrates the advantages of 3D-printed polymeric probes over conventional silicon probes and how they may open up new AFM imaging capabilities.

What was your favourite AFM-related paper of 2018? We’d love to hear about it in the comments below.

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