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A random Abstract
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Nano-volume drop patterning for rapid on-chip neuronal connect-ability assays.
[22q11.2 deletion syndrome]
The
ability
of
neurons
to
extend
projections
and
to
form
physical
connections
among
them
(
i
.
e
.
,
"
connect-ability
"
)
is
altered
in
several
neuropathologies
.
The
quantification
of
these
alterations
is
an
important
read-out
to
investigate
pathogenic
mechanisms
and
for
research
and
development
of
neuropharmacological
therapies
,
however
current
morphological
analysis
methods
are
very
time-intensive
.
Here
,
we
present
and
characterize
a
novel
on-
chip
approach
that
we
propose
as
a
rapid
assay
.
Our
approach
is
based
on
the
definition
on
a
neuronal
cell
culture
substrate
of
discrete
patterns
of
adhesion
protein
spots
(
poly-d-lysine
,
23
±
5
μm
in
diameter
)
characterized
by
controlled
inter-spot
separations
of
increasing
distance
(
from
40
μm
to
100
μm
)
,
locally
adsorbed
in
an
adhesion-repulsive
agarose
layer
.
Under
these
conditions
,
the
connect-ability
of
wild
type
primary
neurons
from
rodents
is
shown
to
be
strictly
dependent
on
the
inter-spot
distance
,
and
can
be
rapidly
documented
by
simple
optical
read-outs
.
Moreover
,
we
applied
our
approach
to
identify
connect-ability
defects
in
neurons
from
a
mouse
model
of
22
q
11
.
2
deletion
syndrome
/
DiGeorge
syndrome
,
by
comparative
trials
with
wild
type
preparations
.
The
presented
results
demonstrate
the
sensitivity
and
reliability
of
this
novel
on-
chip
-based
connect-ability
approach
and
validate
the
use
of
this
method
for
the
rapid
assessment
of
neuronal
connect-ability
defects
in
neuropathologies
.
