70 S. Norman and R. Bellamkonda
effectively. Some three-dimensional MEAs attempt to solve this problem by
delivering media to the center of a slice. One type of 3D MEA for cultures contains
500 μm tall towers fabricated out of SU-8 and has functional electrodes and fluid-
delivering capabilities.
13
One way to prevent the center of slice cultures from becoming necrotic is
to force media though the slice, but this does not necessarily have to be done
through towers that traverse the slice; tissue can also be contained in a chamber
and fresh media perfused through. This setup is advantageous because a relatively
large amount of nutrients and fresh media can continually be put in contact with
the brain slice. There are several varieties of microperfusion devices. Some
employ SU-8 towers on glass substrates, and brain slices sit atop the towers while
fresh media is perfused above and below the slice.
14
Similar microtower PDMS
perfusion devices also exist,
15
and some contain multiple pore sites for enhanced
exchange of media and nutrients.
16
4.1.3 Microfluidic Devices
Microfluidic devices allow the researcher to study a particular cell line, collection
of cells, or small organism in a controlled environment while using resources effi-
ciently. Microfluidic devices that house cells are effective for drug screening, and
can also be used to see how cells develop under different chemical and physical
environmental conditions. Microfluidic devices with separate chambers have been
used to study specific neurons involved in the movement and chemosensation
of Caenorhabditis elegans.
17
Neural stem cells and neuron-like cell lines have been
grown in microfluidic chambers made from polyimide, glass, and PDMS.
18
Some
microfluidic devices are capable of creating concentration gradients; this is partic-
ularly important when studying cell development, as gradients supply neurons
and their growth cones with guidance cues and development instructions.
19
Other
devices have employed electroosmosis to expose neuronal cell lines to signaling
molecules.
20
In addition, microfluidic systems capable of exposing cells to tem-
perature gradients have been developed to explore the activity of temperature–
sensitive neurons.
21
An interesting modification of the planar MEA is the compartmental MEA.
These devices are initially fabricated like traditional MEAs, with deposition of
metal for electrodes and leads, and then a covering of an insulating material,
but compartments are added to separate the processes of neurons from their
somas.
22,23
PDMS microfluidic chambers have also been fabricated to create com-
partments when placed over MEAs.
24
This compartmentalization allows inves-
tigators to monitor the effects of different cellular environments on neuronal
cultures.
4.2 IN VIVO DEVICES
Before the widespread microfabrication of silicon electrodes, electrophysiologists
used microwires and glass micropipettes to record signals from brains, spinal
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