Single Molecule Sensors

By Harold Craighead

It is clear that a critical need in countering terrorist threats is in the detection of toxic chemical, biological and explosive agents at the lowest possible concentrations. The ultimate in sensitivity is required for remote detection, to detect concealed materials, or for detection and response before concentrations reach dangerous levels. And the ultimate limit on the sensitivity of chemical sensors would be at the single molecule level.

Addressing this challenge is an appropriate direction for the physics community. Physicists would seem to have the proper background to explore and develop new spectroscopic techniques that can effectively identify chemical compounds down to the single molecule level. Physicists also have experience in dealing with signal transduction and developing methods such as electrical, optical, magnetic or other approaches for converting chemical signatures to analyzable signals. The technology for manipulating, sorting, counting and isolating single molecules presents challenges that physicists are already addressing to some degree with nanoscale technology. Issues that become extant when one approaches the quantum or discrete electrical charge limits are also areas of research that can be directed toward sensor technology.

Effective sensor technology is an interdisciplinary effort and is likely to involve systems comprising advanced electronics, chemical engineering approaches, new materials and biological systems. Physicists can provide leadership and contributory roles in these complex systems developments. For example, miniaturization and integrating new materials are areas in which physicists have been effective.

Living systems present possibly the most effective existing systems for ultra-sensitive chemical detection and analysis. The biochemical systems that have evolved in cells are remarkable in their ability to identify individual molecules and create signals to which a cell can respond. Biomimetic approaches may provide guidance to effective high sensitivity chemical and biological sensors. Another approach is literally to connect to the biologically derived systems for sensor components, coupling either to living cells or cellular components as part of a sensor. Extracting biologically derived receptors and coupling those to inorganic signal transduction devices also presents a possible approach to which biophysicists can present unique perspectives and skills.

Dealing with biological threats is a necessity in counter terrorism. Working with and understanding biological systems is therefore important for rapid detection and identification of pathogens, viruses and biological entities. Using single molecule analysis to identify individual biological entities is an important aspect of single molecule sensor utilization. There may be significant value to coupling high-sensitivity or single molecule chemical analysis to the identification of a single cell, spore or virus. Genetic, chemical and physical characteristics can be a component of such analyses. Reading information in a single DNA or RNA molecule is an example of single molecule analysis that could be used in pathogen detection.

Physicists may be able to effectively direct some of the theoretical and experimental efforts in single molecule and nanoscale science into improved sensor technologies. Even though sensors that are deployed in the near term may not operate at the single molecule level, the ideal represents a clear goal that can captivate and focus the attention of physicists. The resulting research and development is likely to generate technologies that can be used even before the single molecule level is attained.