© 2008 OSA / CLEO/QELS 2008 a2892_1.pdf CWM3.pdf Detection of Neural Cell Activity Using Plasmonic Gold Nanoparticles Jiayi Zhang, Tolga Atay, Arto Nurmikko Department of Physics and Division of Engineering, Brown University, Providence, Rhode Island02912, USA Jiayi_Zhang@brown.edu Abstract: Metal nanoparticles have been studied intensively for their applications using localized surface plasmon polariton (SPP) resonance. We have demonstrated for the first time that using gold nanoparticles, one can detect electrical activities from the neurons. ©2008 Optical Society of America OCIS Codes: (240.6680) Surface plasmons; (170.0170) Medical optics and biotechnology 1. Introduction Applications of metal nanoparticles are often based on their SPP resonance, which leads to a strong enhancement of local electromagnetic field. Such resonance also makes it possible to detect a shift in the extinction spectra when the nanoparticles are exposed to a change of local electric field. On the other hand, the essence of the neuroscience is to study the neuron activity from single cell to network level, which requires detecting the transient electric field change in the vicinity of the cell membranes. During the last few decades, different recording techniques have been developed, ranging from invasive electrical methods using thin metal wires to non-invasive optical methods using voltage sensitive fluorescent dyes. Having been able to detect neuron activity successfully, these techniques have various drawbacks, e.g. the toxicity and bleaching of the fluorescent dye. Here we report a new non-invasive technique which utilizes the shift in the resonance mode of a gold nanoparticle array to detect the neural cell activity. We first show that applying an external electric field, with similar amplitude to that from an active neuron, across a plasmon/electrolyte interface results in a corresponding transient change in the scattered light from the nanoparticle plasmonic array itself. The neurons are then grown onto the nanoparticle template, and corresponding transient signals are detected when the neurons are stimulated by glutamate, a chemical trigger. 2. Electric field modulated scattering light from the nanoparticle array The shift in SPP resonance is due to the change in the dielectric constant of the metal which results from the variation in the free electron concentration at the metal-electrolyte interface under the external electric field. Slow electric field (of less than 1 Hz) modulated SPP resonance shifts in thin gold films has been reported recently [1]. Yet the “switching” of neural cells happens in a relatively high frequency range of up to 1kHz and over a relatively small area of (10μm)2. We have chosen a gold nanoparticle array to improve both the frequency response and the compatibility of such plasmonic devices in neuroscience applications. It has been shown recently that the fabrication of metal nanoparticles by electron beam lithography provides the flexibility in tuning the resonance by size, shape and layout of the nanoparticle arrays [2]. The parameters of the gold nanoparticles that we fabricated, 160nm of diameter and 400nm of center-to-center distance, are chosen such that, in the presence of an external electric field, the change in the amplitude of the scattered light is maximized at the excitation laser wavelength of 853nm (Fig.1(a)). In the first step of our experiments, a 500Hz external electric field of 5V/mm is applied to the nanoparticle array in a saline solution. Such electric field is typical for the cable model of neuron electrical activity and well simulates the amplitude of the electric field when the neuron “fires” [3]. Shown in Fig.1(b) is the transient scattered light from the array collected by a photodiode and amplified by 200 times. Such measurement confirmed that the change in the scattered light is able to report the electric field change in the vicinity of the nanoparticle. © 2008 OSA / CLEO/QELS 2008 a2892_1.pdf CWM3.pdf Figure 1(a) SEM image and transmission spectrum of the gold nanoparticle array; (b) transient scattered light from the gold nanoparticle array when a 500Hz electric field is applied. 3. Neuron activity detection by plasmons from stimulation by a chemical trigger The dissociated hippocampal neurons are grown directly onto the nanoparticle plasmonic array for two weeks before the measurement. Both the neuron body and the neuron processes grow directly on the nanoparticles, showing the healthiness of the neuron (Fig. 2(a)). Glutamate flux to the neuron causes the neuron activity to temporarily change from single spikes to bursts, which are several consequent spikes. The scattering signals from the plasmonic array both before and after the glutamate flux are shown in Fig. 2(b) &(c). The signal before the glutamate stimulation shows evident single spikes while bursts can be seen in the signal after the glutamate stimulation. Figure 2(a) SEM image of the neuron grown onto the gold nanoparticle array, with traces of neuron body and neuron processes; (b) transient scattered light before the glutamate flux shows single spike activity; (c) transient scattered light after the glutamate flux shows burst activity. 4. Conclusions It is shown for the first time that neuron activity can be detected by the SPP resonance shift in gold nanoparticles. Such recording technique not only opens up the possibility of applying nanoparticles into in vivo systems for optical imaging, but also provides the opportunity of probing local neuron activity on nanometer scale where local membrane ion channels operate. Research supported by the National Science Foundation. [1] V. Lioubimov, A. Kolomenskii, A. Mershin, D.V. Nanopoulos, and H.A. Schuessler, “Effect of varying electric potential on surface-plasmon resonance sensing”, Appl. Optics 43(17), 3426-32(2004). [2] T. Atay, J.H. Song, and A.V. Nurmikko, “Strongly interacting Plasmon nanoparticle paris: from dipole-dipole interaction to conductively coupled regime”, Nano Lett. 4(9), 1627-31(2004). [3] C. Gold, D.A.Henze, C. Koch, and G. Buzsaki, “On the origin of the extracellular action potential waveform: A modeling study”, J. Neurophysio. 95(5), 3113-28(2006).