Biomedical Engineering Reference
In-Depth Information
when studying the interaction between biomolecules which, in their native state, are
located at the cell surface. In a DFS experiment, the application of an external force
to a biomolecular system offers moreover the possibility to elucidate the molecular
mechanisms in living organisms that operate, in physiological conditions, under the
action of a mechanical force (such as in the presence of the bloodstream shear force
of or in molecular motors).
The single molecule detection sensitivity coupled to the need of only a tiny
amount of sample to carry out reliable experiments may endow DFS with the
remarkable potentiality to drive the development of force/biorecognition-based nano-
biosensors for applications in the field of early diagnostics. Either in this connec-
tion or for biorecognition research in general, the efforts toward implementation of
efficient and reliable automatic procedures to analyze DFS results have enormously
increased with some success (see Chapter 5).
More recent results witness that DFS applications to biorecognition processes
are susceptible to undergo significant developments in the near future, even boosted
by the improvements of AFM equipments (see Chapter 2). Quite recently devel-
oped low-drift AFM apparatus could lend higher potentialities to DFS experiments,
making possible to perform measurements for longer times, allowing thus to fol-
low processes at near equilibrium. On the other hand, new high-speed AFM equip-
ments make accessible monitoring even faster biological events in real time. Further-
more, the combination of DFS with high-resolution AFM imaging allows both real-
time topographical imaging and characterization of the binding properties of single
biomolecular partners to visualize, identify, and quantify local receptor binding sites
by assigning their locations to the topographical features of surfaces. Such a kind of
combined approach is expected to become progressively more and more used since
it offers the possibility to extract simultaneous dynamical and spatial information on
the interacting systems at single molecule level. The use of conductive surfaces (tip
and substrate) in DFS experiments would make feasible to combine DFS with con-
ductive measurements (e.g., by scanning tunneling microscopy [STM] or conductive
AFM) either to elucidate the interplay between electron transfer and biorecognition
processes in electron transfer complexes, or to implement multisensing detection.
Finally, coupling DFS with ultra-sensitive optical techniques, such as advanced
fluorescence and Raman-SERS (surface-enhanced Raman spectroscopy), could
deserve a great promise for both a deeper study of biorecognition, enriched with
chemical information, and the design of innovative nanobiosensors for early detec-
tion of biomarkers.