Biomedical Engineering Reference
In-Depth Information
2.7 Conclusions
The combination of optical tweezers with solid-state nanopores represents a
versatile system for the study of biomolecules. The use of an optical tweezer to
deliver bead-conjugated target molecules to the nanopore allows measurements
similar to those measured with pure translocation (size and length discrimination)
but additionally presents new capabilities unattainable in traditional systems (arbi-
trary position control, force spectroscopy). We have demonstrated that measure-
ments on conductance change and dwell time with the combination of technologies
allow bare dsDNA to be differentiated from RecA-coated dsDNA, comparable to
translocations. However, we have also shown that force curves can be measured on
both types molecules, demonstrating the ability to differentiate molecules through a
second method in the same system. The dependence of measured force curves on
both nanopore dimension and ionic concentration can be described well by a model
incorporating both electrophoresis and electroosmosis. This provides a foundation
with which to understand the results of forthcoming studies.
Future studies will exploit the position control inherent in the optical tweezer
system to allow for this measurement technique to be performed on local structures.
Simultaneous detection of both conductance and applied force will allow for a
multi-faceted approach to detect small features along an individual biomolecule.
This opens the door to, for example, epigenetic footprinting at the molecular scale.
Acknowledgments We acknowledge U. Keyser, J. van der Does and D. Krapf for contributions
to system development. M. van den Hout performed the calculations shown in Fig.
2.8b
. We also
wish to thank S. Lemay, U. Keyser, S. van Dorp and S. Kowalczyk for useful discussions. This
work was supported financially by NWO, FOM, and the EC project READNA.
References
1. D. Branton, D. W. Deamer, A. Marziali, H. Bayley, S. A. Benner, T. Butler, M. Di Ventra,
S. Garaj, A. Hibbs, X. H. Huang, S. B. Jovanovich, P. S. Krstic, S. Lindsay, X. S. S. Ling,
C. H. Mastrangelo, A. Meller, J. S. Oliver, Y. V. Pershin, J. M. Ramsey, R. Riehn, G. V. Soni,
V. Tabard-Cossa, M. Wanunu, M. Wiggin and J. A. Schloss, Nature Biotechnology 26 (10),
1146-1153 (2008).
2. C. Dekker, Nature Nanotechnology 2 (4), 209-215 (2007).
3. A. J. Storm, J. H. Chen, X. S. Ling, H. W. Zandbergen and C. Dekker, Nature Materials 2 (8),
537-540 (2003).
4. J. Li, D. Stein, C. McMullan, D. Branton, M. J. Aziz and J. A. Golovchenko, Nature 412
(6843), 166-169 (2001).
5. A. J. Storm, C. Storm, J. H. Chen, H. Zandbergen, J. F. Joanny and C. Dekker, Nano Letters
5 (7), 1193-1197 (2005).
6. U. F. Keyser, B. N. Koeleman, S. Van Dorp, D. Krapf, R. M. M. Smeets, S. G. Lemay,
N. H. Dekker and C. Dekker, Nature Physics 2 (7), 473-477 (2006).
7. D. Krapf, M. Y. Wu, R. M. M. Smeets, H. W. Zandbergen, C. Dekker and S. G. Lemay, Nano
Letters 6 (1), 105-109 (2006).
Search WWH ::
Custom Search