21 research outputs found
Hydrogel-coated microelectrode array for neural interface
Recently, hydrogel has been extensively used in various biomedical applications including soft contact
lenses, wound healing materials and as a means for controlled drug delivery and release. In this
study, we propose to use hydrogel as a novel neural interface. Planar microelectrode arrays were
coated with hydrogel in order to improve the quality of the interface and to aid in drug delivery to cells
on microelectrode arrays (MEAs).This work was supported by the International
Collaboration Program, NBS-ERC (Nano Bioelectronics
and Systems Engineering Research Center)/
KOSEF (Korea Science and Engineering Foundation)
and also supported in part by the Nanobiotechnology
Center (NBTC), an STC Program of the
National Science Foundation under Agreement No.
ECS-9876771
Optical Monitoring of Neural Network Connectivity Using FM1-43-Evoked Activity from Focal Stimulation of Microelectrode Arrays
This work was supported by the International Collaboration Program NBS-ERC/KOSEF (S.J.K) and by the National Institute of Biomedical Imaging and Bioengineering under Agreement Number R21-EB007782 (M.R.H)
Development of Hybrid Neural Prosthetic Devices
This work was supported by the National Institute of Biomedical Imaging and Bioengineering under Agreement Number R21-EB007782 (M.R.H)
Identification of synaptic activities in microelectrode array-based neural networks
The Microelectrode Arrays (MEAs) have been used for several decades to investigate neuronal networks
in vitro. In most of the studies, the neuronal networks have been studied statistically due to
complexity of cultured neuronal networks. However, in order to understand the behaviours of neuronal
networks dynamically, the identification of synaptic activities of individual neurons is crucial. In this
study, we observed individual synaptic activities by utilizing low density neuronal networks arranged
orthogonally on MEAs.This work was supported by the International
Collaboration Program, NBS-ERC (Nano Bioelectronics
and Systems Engineering Research Center)/
KOSEF (Korea Science and Engineering Foundation)
and NIH, NS-044287, NSF, ECS-9876771
Modulation of Cultured Neural Networks Using Neurotrophin Release
Polyacrylamide and poly(ethylene glycol) diacrylate hydrogels were synthesized and
characterized for use as drug release and substrates for neuron cell culture. Protein release
kinetics was determined by incorporating bovine serum albumin (BSA) into hydrogels during
polymerization. To determine if hydrogel incorporation and release affect bioactivity, alkaline
phosphatase was incorporated into hydrogels and a released enzyme activity determined using
the fluorescence-based ELF-97 assay. Hydrogels were then used to deliver a brain-derived
neurotrophic factor (BDNF) from hydrogels polymerized over planar microelectrode arrays
(MEAs). Primary hippocampal neurons were cultured on both control and
neurotrophin-containing hydrogel-coated MEAs. The effect of released BDNF on neurite
length and process arborization was investigated using automated image analysis. An
increased spontaneous activity as a response to the released BDNF was recorded from the
neurons cultured on the top of hydrogel layers. These results demonstrate that proteins of
biological interest can be incorporated into hydrogels to modulate development and function of
cultured neural networks. These results also set the stage for development of hydrogel-coated
neural prosthetic devices for local delivery of various biologically active molecules.This work was supported by the International Collaboration
Program, Nano Bioelectronics and Systems Engineering
Research Center/Korea Science and Engineering Foundation
(R11-2000-075-00002-0), by the Nanobiotechnology Center
(NBTC), an STC Program of the National Science Foundation
under agreement no. ECS-9876771, the National Institutes
of Health under agreement no. R01-NS044287 (WS)
and by the National Institute of Biomedical Imaging and Bioengineering under agreement no. R21EB007782 (MRH).
The computational image analysiswas supported by the Center
for Subsurface Sensing and Imaging Systems (NSF EEC-
9986821). The authors acknowledge use of the Wadsworth
Center Advanced Light Microscopy & Image Analysis Core
Facility. They would also like to thank Shirley Madewell and
Adriana Verschoor for critical review of the manuscript
Electrical Stimulation-Induced Cell Clustering in Cultured Neural Networks
Planar microelectrode arrays (MEAs) are
widely used to record electrical activity from neural networks.
However, only a small number of functional
recording sites frequently show electrical activity. One
contributing factor may be that neurons in vitro receive
insufficient synaptic input to develop into fully functional
networks. In this study, electrical stimulation was applied
to neurons mimicking synaptic input. Various stimulation
paradigms were examined. Stimulation amplitude and
frequency were tailored to prevent cell death. Two effects
of stimulation were observed when 3-week-old cultures
were stimulated: (1) clusters of neural cells were observed
adjacent to stimulating electrodes and (2) an increase in
spontaneous neuronal activity was recorded at stimulating
electrodes. Immunocytochemical analysis indicates that
stimulation may cause both new neuron process growth as
well as astrocyte activation. These data indicate that electrical
stimulation can be used as a tool to modify neural
networks at specific electrode sites and promote electrical
activity.This work was supported by the International
Collaboration Program, NBS-ERC (Nano Bioelectronics and Systems
Engineering Research Center)/KOSEF (Korea Science and Engineering
Foundation), NIH, NS-044287 and the Nanobiotechnology
Centre (NBTC), an STC program of the National Science Foundation
under Agreement Number ECS-9876771. The authors also
acknowledge use of the Wadsworth Center Advanced Light Microscopy
& Image Analysis Core Facility for the work presented herein
Low-density neuronal networks cultured using patterned poly-l-lysine on microelectrode arrays
Synaptic activity recorded from low-density networks of cultured rat hippocampal neurons was monitored using microelectrode arrays (MEAs).
Neuronal networks were patterned with poly-l-lysine (PLL) using microcontact printing ( CP). Polydimethysiloxane (PDMS) stamps were
fabricated with relief structures resulting in patterns of 2 m-wide lines for directing process growth and 20 m-diameter circles for cell soma
attachment. These circles were aligned to electrode sites. Different densities of neurons were plated in order to assess the minimal neuron density
required for development of an active network. Spontaneous activity was observed at 10โ14 days in networks using neuron densities as low as
200 cells/mm2. Immunocytochemistry demonstrated the distribution of dendrites along the lines and the location of foci of the presynaptic protein,
synaptophysin, on neuron somas and dendrites. Scanning electron microscopy demonstrated that single fluorescent tracks contained multiple
processes. Evoked responses of selected portions of the networks were produced by stimulation of specific electrode sites. In addition, the neuronal
excitability of the network was increased by the bath application of high K+ (10โ12 mM). Application of DNQX, an AMPA antagonist, blocked
all spontaneous activity, suggesting that the activity is excitatory and mediated through glutamate receptors.This work was supported by the International Collaboration
Program, NBS-ERC (Nano Bioelectronics and Systems Engineering
Research Center)/KOSEF(Korea Science and Engineering
Foundation) and NIH, R01NS-044287, NSF, ECS-9876771.
Authors also appreciate help from T.H. Lee and J.K. Lee for
assistance in the fabrication of MEAs and stamp masters