## Measuring neural activity using surface plasmons

In the May 1st issue of Optics Letters, a Korean research group has demonstrated another interesting application of surface plasmon resonances: the optical measurement of neural activity. Though I’m not sure how useful this technique will be in the long run, it shows that surface excitations can be used in sensors in many situations when an ordinary optical wave is not sensitive enough. A description after the fold…

To understand this research one requires a small understanding of the biological processes to be studied (biologists, feel free to correct any inaccurate statements I make in the comments). Even a non-biologist such as myself can appreciate that there is a great deal of interest and importance in the study of neural activity. Biological neurons “communicate” using electrical signals, and a study of neuron function is a measurement of the electrical behavior of cells. On the largest scale, one can study neurological behavior using animal experimentation, in essence studying how the “whole package” is put together and responds. On the smallest scale, one can study the electrical response of a single cell using the so-called “patch-clamp” technique.

On an intermediate size scale, in which one wishes to study small but functional collections of cells, other techniques are required. A standard one is the use of planar microelectrode arrays (pMEAs; see F.O. Morin, Y. Takamura, and E. Tamiya, J. Biosci. Bioeng. 100, 131 (2005)), in which a series of electrical probes are applied for both generation and detection of electrical signals in a planar distribution of neurons. A major difficulty in such techniques, however, is that the probes only detect current, and cannot distinguish between the excitation current and the signal current produced by the cells. The difficulty is comparable to someone trying to study the combustion of a match by igniting it with a torch: the torch flame is significantly larger than the match flame and tends to mask it.

Another alternative is optical measurement of the excitation. The propagation of the electrical signal across the cell (in particular, the axon of the nerve cell) corresponds to a physical change of the cell structure, which results in a change of the refractive index. In principle, this change should be detectable through optical scattering experiments, but in practice the change is very weak and hard to detect. Fluorescent dyes can be used to enhance the optical signal, but such dyes are toxic and in general hard to properly apply.

Enter the use of surface plasmons! As I have discussed in a previous post, a surface plasmon is a traveling wave oscillation of electrons which can propagate in the surface of a metal with the proper material properties. Because the plasmon consists of oscillating charges, there is also an electromagnetic wave associated with it which is of extremely high intensity and is extremely localized to the surface. My ‘stock illustration’ of a surface plasmon is shown below:

The image on the left schematically illustrates the behavior of the charge density, electric and magnetic fields of a surface plasmon propagating to the right along the surface of the metal. The image on the right describes the field intensity as a function of distance from the surface: it decays exponentially over a distance typically on the order of the wavelength of light of the same frequency. Right near the surface of the metal, the field intensity is extremely high, significantly higher than the optical field which first excited it. This arises, in a sense, because the 3-dimensional exciting field is ‘squished’ into a 2-dimensional plasmonic field.

The properties of the surface plasmon are highly sensitive to the dielectric properties on both sides of the interface. A small change in the refractive index of a cell on a surface supporting plasmons can translate into a proportionally larger change in the plasmonic signal. The Korean research group has taken advantage of this sensitivity to use surface plasmons to measure neural activity optically.

A simplified schematic (adapted from their paper) of their experimental apparatus is illustrated below.

A rat sciatic nerve is adhered to a 50 nm thick gold film. Electrodes are attached at the ends of the nerve for stimulus and conventional pMEA measurement. A laser diode of wavelength 635 nm and 5 mW output power is used as illumination. After beam expansion, the field is focused into a glass prism and is refracted into the gold film, at which surface plasmons are excited, using what is known as the Kretschmann configuration. Surface plasmons have a different wavelength than light of the same frequency, which means that the momentum of an excited plasmon is higher than that of a comparable photon. The Kretschmann configuration uses the phenomenon of total internal reflection to provide the missing momentum: light is passed into a prism at an angle at which it would be in principle completely reflected. In fact, an ‘evanescent wave’ is produced in the space past the prism, and this evanescent wave has a higher momentum than a freely traveling photon. The evanescent wave can couple into a surface plasmon, and vice versa.

The reflected energy in the light beam depends on the strength of the coupling of light to plasmon, which in turn depends on the refractive index of the nerve. The reflected beam passes out of the prism and the intensity is measured by a photodetector.

The system performed well, measuring refractive index variations on the order of $1.5\times 10^{-5}$. The signals measured correlated well with the excitations and the measured electrical response, but possessed none of the artifacts of the electrical system. This is to be expected, as the optical changes to the nerve are only created by the actual nerve signal. To further demonstrate that the plasmonic system was detecting the actual nerve action, lidocaine was used to block the nerve response: the optical signal decreased as expected.

Numerous researchers have been investigating the use of surface plasmons as the active component of a highly-sensitive biosensor; this paper illustrates, to the best of my knowledge, the first use of plasmons to study the functionality of biological systems. The system avoids the artifacts of the existing electrical systems and, furthermore, does not require the use of toxic fluorescent dyes that other optical detection systems require. The technique seems to hold promise for future studies of neural activity.

Ae Kim, S., Min Byun, K., Lee, J., Hoon Kim, J., Albert Kim, D., Baac, H., Shuler, M.L., June Kim, S. (2008). Optical measurement of neural activity using surface plasmon resonance. Optics Letters, 33(9), 914. DOI: 10.1364/OL.33.000914

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