Scanning probe microscopy.

During the past year, scanning probe microscopy, especially atomic force microscopy (AFM), has taken root in the biological sciences community, as is evident from the large number of publications and from the variety of specialized journals in which these papers appear. Furthermore, there is a strong indication that the technique is evolving from a qualitative imaging tool to a probe of the critical dimensions and properties of biomolecules and living cells. The next stage of the evolution involves the development of microinstruments for process control and sensing applications. Recent advances have been reported in AFM instrumentation and method. For example, the tapping mode of operation is becoming the method of choice to image biological molecules; work to extend tapping-mode operation in liquids has been reported. Biological molecules can also be imaged at low temperature in a cryo-AFM with improved resolution. The measurement of recognition forces between individual molecules continues to attract much attention and has spawned new concepts for ultra-sensitive biosensors. The AFM is being used increasingly for property measurements such as determining the viscoelastic properties of biological molecules. Finally, structural studies using the AFM abound. Some specific highlights include the mapping of DNA using restriction enzymes, imaging during DNA transcription and determining the mode of drug binding to DNA.