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Applications of AFM in Pharmaceutical Sciences

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Analytical Techniques in the Pharmaceutical Sciences

Part of the book series: Advances in Delivery Science and Technology ((ADST))

Abstract

Atomic force microscopy (AFM) is a high-resolution imaging technique that uses a small probe (tip and cantilever) to provide topographical information on surfaces in air or in liquid media. By pushing the tip into the surface or by pulling it away, nanomechanical data such as compliance (stiffness, Young’s Modulus) or adhesion, respectively, may be obtained and can also be presented visually in the form of maps displayed alongside topography images. This chapter outlines the principles of operation of AFM, describing some of the important imaging modes and then focuses on the use of the technique for pharmaceutical research. Areas include tablet coating and dissolution, crystal growth and polymorphism, particles and fibres, nanomedicine, nanotoxicology, drug-protein and protein-protein interactions, live cells, bacterial biofilms and viruses. Specific examples include mapping of ligand-receptor binding on cell surfaces, studies of protein-protein interactions to provide kinetic information and the potential of AFM to be used as an early diagnostic tool for cancer and other diseases. Many of these reported investigations are from 2011 to 2014, both from the literature and a few selected studies from the authors’ laboratories.

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Author information

Authors and Affiliations

  1. Strathclyde Institute of Pharmacy and Biomedical Sciences (SIPBS), University of Strathclyde, 161 Cathedral Street, Glasgow, G4 0RE, UK

    Dimitrios A. Lamprou

  2. School of Pharmacy and Biomedical Sciences, University of Portsmouth, St Michael’s Building, White Swan Road, Portsmouth, PO1 2DT, UK

    James R. Smith

Authors
  1. Dimitrios A. Lamprou
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  2. James R. Smith
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Corresponding author

Correspondence to Dimitrios A. Lamprou .

Editor information

Editors and Affiliations

  1. Bioneer: FARMA Department of Pharmacy, University of Copenhagen, Copenhagen Ø, Denmark

    Anette Müllertz

  2. Strathclyde Institute of Pharmacy and Biomedical Sciences, Glasgow, Seychelles

    Yvonne Perrie

  3. Department of Pharmacy, University of Copenhagen, Copenhagen Ø, Denmark

    Thomas Rades

Appendix: Obtaining an AFM Contact Mode Image in Air

Appendix: Obtaining an AFM Contact Mode Image in Air

As a practical demonstration, this section outlines a typical sequence of the steps necessary for the acquisition of the simplest of AFM operations: a contact mode image to be obtained in air. Most of the details that make the sequence particularly relevant for a specific instrument have been excluded deliberately. Bacteria on a mica surface has been chosen as an example. Mica is an ideal substrate for many AFM studies since it is atomically flat (glass coverslips can appear quite rough for many high-resolution studies); fresh, uncontaminated surfaces can be also prepared, without the need for cleaning, by simply attaching adhesive tape and peeling away the top layer from this layered material (Morris et al. 2001). Mica is negatively charged and so improved adhesion to often negatively charged biological specimens, such as DNA, can be achieved by derivatising the mica surface with a suitable polycation, e.g., poly-l-lysine (Eaton and West 2010).

  1. 1.

    Turn on the AFM instrument and computer, and open the software.

  2. 2.

    Place a piece of mica (1 cm2, cut with scissors) on a nickel stub (1.2 cm2) using double-sided adhesive tape. Press it on firmly.

  3. 3.

    Cleave the mica with adhesive tape. Derivatise the mica, if required.

  4. 4.

    Add an aliquot (10 μL) of the solution containing bacteria to the mica surface. Leave the drop of solution in place for 2 min.

  5. 5.

    Carefully rinse the treated mica plate with distilled water to remove buffer salts, which might mask any biological sample features.

  6. 6.

    Allow to air-dry or carefully use a jet of nitrogen gas.

  7. 7.

    Place the sample on top of the AFM scanner; the magnet will hold the nickel disc of the sample in place.

  8. 8.

    Select a contact mode probe (of low spring constant k, ca. 0.06 N m−1) and fix into the AFM head above the sample.

  9. 9.

    Line up the laser (according to manufacturer’s instructions).

  10. 10.

    Move the sample and/or probe to select imaging region of interest.

  11. 11.

    Select a required scan range (say, 20 μm) and set the scan rate to 1 Hz. Use an image resolution size of at least 512 × 512 pixels. Select the integral, proportional and derivative (PID, external scanner feedback; Eaton and West 2010) settings outlined by the manufacturer (these will depend mostly on the scanner being used and whether air or liquid is the medium).

  12. 12.

    Lower the probe to just above the sample surface and use the automated approach.

  13. 13.

    Slowly increase the PID settings to maximise image contrast to just below the level that produces noise (piezo ringing). It should also be possible to reduce the applied load (reduce deflection) on the cantilever to improve image quality.

  14. 14.

    Once image settings are optimised, obtain a complete image and save (capture) it.

  15. 15.

    The next typical options will either be to zoom in, move to a different area or change the sample.

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Lamprou, D.A., Smith, J.R. (2016). Applications of AFM in Pharmaceutical Sciences. In: Müllertz, A., Perrie, Y., Rades, T. (eds) Analytical Techniques in the Pharmaceutical Sciences. Advances in Delivery Science and Technology. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-4029-5_20

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