Optical Measurement of Neural Activity Using Surface Plasmon Resonance

We demonstrate that surface plasmon resonance (SPR) is applicable to the optical detection of neural signals. A low-noise SPR sensor was developed as a label- and artifact-free method for the extracellular recording of neural activity. The optical responses obtained from a rat sciatic nerve were highly correlated with simultaneously recorded electrical responses. Additional studies with stimulation intensity and lidocaine further confirmed that the optically measured signals originated from neural activities.The authors acknowledge the support of the Nano- Bioelectronics and Systems Research Center of Seoul National University, which is an Engineering Research Center sponsored by the Korean Science and Engineering Foundation (R11-2000-075-01001-1). The authors also thank Hyung Chul Shin and Woo Taek Oh for their helpful advice and Inter-university Semiconductor Research Center for providing a laboratory space

The topographical guidance of neurons cultured on holographic photo-responsive polymer

Neuronal cells to respond to submicron-scale groove structure. On the grooved structure of particular dimension, it has been reported that neuronal cells grew perpendicular to the groove direction. We used holographic photo-responsive polymer to form a submicron-scale surface relief grating structure. A sinusoidal groove pattern is built up by holographic interference of 488 nm Ar ion laser beams. The primary hippocampal neurons cultured on the surface of the polymer film grew extending their neurites in a perpendicular orientation to the groove direction. This suggests that laser holography can be used to control the neurites orientation and growth. The holographic grating and photo-responsive polymer will raise the possibility of controlling neural network formation between living cells by light.This work was supported by Korea Science and Engineering Foundation (KOSEF) through Nano Bioelectronics and Systems Research Center (NBS-ERC) in Seoul National University

Antibody-Based Surface Plasmon Resonance Detection of Intact Viral Pathogen

Surface plasmon resonance (SPR) technique was used to directly detect an intact form of insect pathogen: the baculovirus, Autographa californica multiple nuclear polyhedrosis virus (AcMNPV). An SPR sensor chip with three bio-functional layerswasusedto detect the intact AcMNPV: amine-reactive crosslinker with a disulfide bond that chemisorbs to gold film, Protein A, and a mouse IgG monoclonal antibody raised against a surface protein of the target viral pathogen. A two-channel (reference & test) micro-fluidic SPR system is used for reliable measurement. Bio-specific response to the AcMNPV is compared with the response for tobacco mosaic virus (TMV) as control. Successive exposure of the sensor chip to both viruses verifies a specific response to AcMNPV. This serves as a prerequisite to the development of a new type of viral pathogen detection sensors.The authors are grateful to Dr. Mandy Esch (Cornell Nanoscale Facility, Cornell University) for valuable advice on fabrication and surface chemistry, Dr. Gary Blissard (Boyce Thompson Institute, Cornell University) for kindly providing AcMNPV baculovirus and AcV1 monoclonal antibody producing hybridoma cell line, and Dr. Milton Zaitlin (Department of Plant Pathology, Cornell University) for kindly providing tobacco mosaic virus. This work was partly supported by DARPA through CBOM, and also partly by joint research program of Cornell Biomedical Engineering Program and Nano Bioelectronics and Systems Research Center of Seoul National University through KOSEF. M.L.S. acknowledges support as a NYSTAR Distinguished Professor through the New York State Office of Science, Technology and Academic Research

GUIDING NEURONS AND FIBROBLAST CELLS USING MICROFIBRICATION ON PHOTOPOLYMER FOR IN-SITU NAVIGATON OF CELLULAR PATTERNING

Cellular patterning has diverse and potential applications in scientific research and engineering. We used laser holographic fabrication to construct the cellular patterning. By the interference of two laser beam on the polymer micro and nanoscale grooves were generated on the photoresponsive polymer. The growth of rat hippocampal neurons were controlled with the microfabricated structure. The directions of neurites were predominant in the perpendicular direction of the grooves and the growth rates of the neurites were also stimulated. Two dimensional cellular patterning of fibroblast cells was constructed along the patterned microstructures on the polymer. These results indicate the feasibility of guiding neurons and fibroblast cells with laser holography, opening the possibility for in-situ navigation in living cells

Extracellular Optical Recording Configuration for Neuronal Action Potential Detection by using Surface Plasmon Resonance: Preliminary Experiment

We propose an extracellular optical recording configuration for neuronal action potential detection by using surface plasmon resonance (SPR). The method does not use fluorescence dyes but still taking advantages of optical recording. As a preliminary experiment, the electrochemical SPR effect without neurons was investigated. This showed that a high resolution SPR setup (10-4~10~5 angular shift or more) is required to overcome noise and improve SPR signal. Several issues for neural signal recording are addressed to modify SPR optical configuration.This work was supported by Korea Science and Engineering Foundation (KOSEF) through Nano Bioelectronics and Systems Research Center (NBS-ERC) in Seoul National University, Nanobiotechnology Center (NBTC), an STC Program of the National Science Foundation (Agreement No. ECS-9876771), and the Cornell Nanoscale Facility (Agreement No. ECS-9731293)

Submicron-scale topographical control of cell growth using holographic surface relief grating

The cell orientation and attachment were controlled by a submicron-scale topographical cue. For achieving the submicron undulation of surface topography, the laser holography on a photo-responsive azobenzene copolymer layer has been employed to produce surface relief grating (SRG) which has a regular sinusoidal shape. Cultured human astrocytes (HA) were preferentially attached onto the SRG surface and highly elongated along the SRG direction. This topographical control scheme would be very efficient to control the cell growth for cellular engineering applications and to understand the interactions of the cells with a submicron-scale topographical surface.This work was supported partly by Overhead Research Fund of S.N.U. and also partly by KOSEF through the Nano-Bioelectronics and Systems Research Center at Seoul National University. One of the authors (SDL) acknowledges the support from KOSEF through CFRM at Korea University

Neural Prosthesis in the Wake of Nanotechnology : Controlled Growth of Neurons Using Surface Nanostructures

Neural prosthesis has been successfully applied to patients with motional or sensory disabilities for clinical purpose. To enhance the performance of the neural prosthetic device, the electrodes for the biosignal recording or electrical stimulation should be located in closer proximity to target neurons than they are now. Instead of revising the prior implanting surgery to improve the electrical contact of neurons, we propose a technique that can bring the neurons closer to the electrode sites. A new method is investigated that can control the direction of neural cell growth using surface nanostructures. We successfully guide the neurons to the position of the microelectrodes by providing a surface topographical cue presented by the surface nanostructure on a photoresponsive polymer material. Because the surface structure formed by laser holography is reversible and repeatable, the geometrical positioning of the neurons to microelectrodes can be adjusted by applying laser treatment during the surgery for the purpose of improving the performance of neural prosthetic device

A new image signal transfer method using laser in artificial retina

A new optical link method for the retinal prosthesis is proposed. A laser diode system was chosen to transfer image into the eye and the new optical system was designed and evaluated in silico and ex vivo. The use of laser diode array in artificial retina system makes system simple by deleting signal processing part inside of the eyeball. The designed optical system is enough to focus laser beam on photodiode array in 20 × 20 application on simulation using Code V program, and about 200 μm focusing of laser beam was possible on experiment with porcine eye.This paper was supported by the Nano Bioelectronics and Systems Research Center of Seoul National University, which is an ERC supported by the Korean Science and Engineering Foundation (KOSEF)

Soft Bio-Integrated Multifunctional Devices Using an Intrinsically Stretchable Conducting Nanomembrane

Soft bioelectronic systems with a unique mechanical property, namely modulus matching between human skin (or tissue) and the device, have gained widespread attention. This is because of their closed-loop strain-insensitive electrical performance ranging from application in the long-term stable measurements of physiological signals and feedback modulation to human skin (or organs). Various materials and integration/fabrication strategies such as buckled, rigid islands, and wavy designs addressed for soft bioelectronic systems require complex device fabrication with time-consuming packaging and integration processes. In this study, we developed a soft bio-integrated multifunctional device (SBMD) fabricated through the simple thermal evaporation and transfer processes. The intrinsically stretchable Au–SEBS film composed of thermally evaporated gold (Au) nanomembranes and an elastomeric substrate was applied to various functional modules that are capable of sensing the strain (up to ~300%), temperature (with a thermal sensitivity of ~0.6 Ω/°C), chemicals (at a concentration of NaCl of ~0.5 wt%), and even electrophysiological cardiac/muscle signals and showing thermal actuations (80 °C at 9 V). Specifically, such multifunctions of the SBMD were stably performed even on skin. Thus, we believe the SBMD would be a promising candidate for realizing soft bioelectronic systems