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Macroscopic experiments yield time and population averages of the individual characteristics of each
molecule. At the level of individual molecules, the picture is quite different: individual molecules are
found in states far from population average, and their velocity dynamics are seemingly random. Whenever
unusual states or rapid, random motions of a molecule are important, the macroscopic picture fails, and a
microscopic description becomes necessary. Single-molecule experiments differ from macroscopic measurements
in two fundamental ways: First, the fluctuations in both the system and in the measuring instrument are
important, and second, in the relative importance of force and displacement as variables under experimental
control and subject to direct experimental measurements. In single-molecule experiments using atomic force
microscopy or optical tweezers the crucial parts of the measurement instruments themselves are small and
subject to the same fluctuations as the system under study. Sensing at this experimental level thus, gives
access to some of the microscopic dynamics that are hidden in macroscopic experiments.
Label-free investigations on macro systems require measurement tools which allow parallel assessment of
various parameters. An important fact to be considered is the possibility to use an in situ reference probe
which allows compensation for parasitic or convoluting effects, which influence the measurements on a small
scale (e.g. temperature, chemical environment affecting the surface chemistry of the sensor, etc.).
Cantilever array sensors are successfully applied in the field of genomics, gas-sensing, and proteomics and
microorganism susceptibility testing. The elegance of these sensing methods is that the detection of an
analyte does not require any labeling, as well as the various application fields only differ in the functional
layers on the cantilever interface. The detection scheme remains common for all the different applications.
Molecular recognition processes or mechanical changes taking place at a sensor interface are transduced into
mechanical motion or induce shifts in physical parameters (e.g. resonance frequency), which are easily
detected with nanometer – or in case of resonance - frequency shifts in Hz precision (in liquid).
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