The atomic force microscope is currently the only instrument able to image biological samples (see below - DNA tethered to a surface) with molecular resolution in buffer solution. Not only can the AFM provide topographical images of surfaces, but forces between single molecules and the mechanical properties of biological samples can also be investigated. Since measurements are made while biological samples are in buffer solutions the samples remain alive, and temporal changes in structure can be measured.

     In AFM imaging a fine tip attached to a cantilever spring is scanned over the sample surface. The interaction between the cantilever tip and the sample causes the cantilever to bend, which is detected by the deflection of a laser beam focused on the end of the cantilever. From this bending, a force between the sample and the tip can be calculated. A piezoelectric surface (piezo) is used to measure the x and y direction and to adjust the vertical distance between the tip and sample. Two different AFM modes determine how the vertical distance is determined: 1) Contact Mode: The feedback loop between the laser detector and piezo adjusts the vertical distance from the tip to the sample such that the cantilever is held at a constant deflection. 2) Dynamic Mode: The feedback loop keeps the amplitude of a vibrating cantilever constant by correcting the vertical distance. Other applications of the Atomic Force Microscope include: formation of force-distance curves, measurements of adhesion or elasticity and measurements of the biding and rupture forces of receptor-ligand complexes. Discussions of the applications of AFM can be found in the refernce PDFs at the bottom of the page.  To learn more read Theory Practic and Applications text (large file > ) and try the virtual AFM lab experience.  Those wishing to purchase an AFM may want to read through the Park Systems evaluation guide .  A quick comparison table of microscopy techniques is also available .

Applications:

1. Visualization
2. Physical property maps
   
3. Spacial Metrology: Nanoscience and nanotechnology
   
4. Electrochemistry
   

Pros:

1. Can image conducting or non-conducting surface
2. Little to no sample preparation in many cases
   

Cons:

1. Tip-sample interactions can distort or destroy the sample
2. AFM cannot image all biological samples at atomic resolution
3. Repetative scanning can detach sample
4. Specimen must be firmly attached to a solid support for measurement
5. Information gained is generally restricted to regions of the specimen that are directly exposed to the scanning tip.