Nanocavity-based Low Frequency Dielectric Spectroscopy

We have developed a unique dielectric permittivity based sensor using simple CMOS fabrication to create capacitors with nanoscale gaps. These nanogap devices are being used to study various important biochemical reactions including DNA hybridization, protein folding, antigen-antibody interaction, and water structure in confinement. The nanogaps we have fabricated have widths ranging from 10 nm to 300 nm, and these dimensions are not only significant because they are on a scale equivalent to many biomolecules, but also because of the unique way in which dielectric spectroscopy works on these scales. We can achieve extremely high electric fields using standard equipment which can be advantageous in looking at various physical limits of biopolymers. Also, the small scales allow us to study the intriguing situation where the electrical double layer interacts when the electrodes are charged, creating a completely polarized fluid. There is also a significant decrease in solution resistance simply due to the small distance between electrodes. This allows us to get more information about the capacitance of the solution than possible with larger setups.

AC electric fields can be induced across the nanogaps, and the resulting behavior of the material in between the electrodes can be studied. By alternating the frequencies of the AC field, we can learn about the properties of the material, an example of which is DNA. Using surface chemistry, we can selectively attach single stranded DNA to the surfaces of the nanogap electrodes. We can then study how DNA hybridizes by observing the change in dielectric permittivity when complementary DNA is introduced. The shape and extent of folding can also be studied by altering the environment and monitoring the changes.

Another application for these devices is protemics. The hydrodynamic radius and dipole moment of various biopolymers can be determined using dielectric spectroscopy. These properties are tools that can be used to study how proteins package themselves.

Water structure is a very powerful topic, and studying how water behaves within nanoscale structures is fundamental in understanding the role of water in biology. Protein folding, DNA hybridization, and enzyme substrate interactions are just a few areas where the structure and position of water is paramount. Water molecules tend to orient themselves in a given direction when interrogated with an electric field. The rate at which the molecules are polarized is a function of the structure they are confined in. By looking at how water rotates under an alternating electric field inside nanoscale structures, we can begin to understand how water molecules might behave within a folded protein or next to a cell membrane, for example.

References:

1. J. Tanner Nevill, Ki-Hun Jeong, and Luke P. Lee, "Ultrasensitive Nanogap Biosensor to Detect Changes in Structure of Water and Ice," Proc. Transducers, Seoul, Korea, pp. 1577-1580, June 5-9, 2005.
2. J. Tanner Nevill, Dino Di Carlo, Peng Liu, Ki-Hun Jeong, and Luke P. Lee, "Detection of Protein Conformational Changes with a Nanogap Biosensor," Proc. Transducers, Seoul, Korea, pp. 1668-1671, June 5-9, 2005.
3. Bonincontro, A. et al. "Dielectric Behavior of Lysozyme and Ferricytochrome-c in Water/Ethylene-Glycol Solutions" Biophysical Journal 86:1118-1123 (2004)
4. Levinger, N. E. "Water in Confinement" Science 298:1722-3 (2002)