Biomedical Engineering Reference
In-Depth Information
a
b
Teflon tubing
200 µm I.D.
Buffer
PDMS
Chemistrode
Carrier fluid
Membrane
140 µM
fluorescein
Channel:
100 × 100 µm
Site 1
Site 1:
pulsing at
15 µm
spacing
Site 2:
7 cm
downstream
Glass slide
c
0 ms
120 ms
240 ms
360 ms
480 ms
200 µm
3
2
1
3
1
1
2
3
1
2
1
2
0
50
100
150
200
250
80
Calcium
Stimulant marker
d
e
f
70
60
50
40
30
1.5
1.0
0.5
0.0
120
80
40
0
Insulin
Stimulant marker
200
25 µm
Islet of Langerhans
100
0
20
40
60
80
100
120
140
160
180
Plug sequence
FIGURE 6.82
The. “chemistrode.”. (From. Delai. Chen,. Wenbin. Du,. Ying. Liu,. Weishan. Liu,. Andrey.
Kuznetsov,.Felipe.E..Mendez,.Louis.H..Philipson,.and.Rustem.F..Ismagilov,.“The.chemistrode:.A.
droplet-based. microluidic. device. for. stimulation. and. recording. with. high. temporal,. spatial,. and.
chemical.resolution,”.
Proc. Natl. Acad. Sci. U. S. A.
.105,.16843-16848,.2008..Copyright.(2008).
National.Academy.of.Sciences,.U..S..A.)
when there are two lines operating in parallel (otherwise, one line could be capturing some of
the other line's low). he chemistrode allows for exposing cells to pulses of chemicals as short
as a few tens of milliseconds (more than an order of magnitude faster than Orwar's waveform
synthesizer) and spreading in space approximately more than 200 μm (similarly to Owar's wave-
form synthesizer, although it could potentially be improved). he researchers used the chemis-
trode to stimulate a mouse islet of Langerhans on a glass-bottomed dish and recorded insulin
secretion every 1.5 seconds and an increase in intracellular calcium by luorescence microscopy.
An advantage of the chemistrode over Orwar's waveform synthesizer is that it allows for sam-
pling the chemical microenvironment of the cell (the plugs can be analyzed oline); however,
Orwar's patch clamp measurements would be diicult with the chemistrode.
6.10 Summary
In sum, BioMEMS constitutes a set of alternative techniques that are very appealing for basic
cell biology studies because they potentially allow for
a more precise spatiotemporal design
of the
signals (artiicially) delivered to cells than traditional cell culture techniques. BioMEMS enables
biologists to design heterogeneous
substrates
(containing topographical features or micropat-
terns of biomolecules) and heterogeneous
microluidic environments
, even with some temporal
control. In most cases, this increased precision is aimed at creating cell cultures of
increased
physiological relevance
. For example, microluidic systems can be used to mimic the release of
