Biomedical Engineering Reference
In-Depth Information
(a) E-beam lithography
Silicon
wafer
(b) Photolithography
E-beam resist
Photoresist
2 µm
(d) Assembly
(c) Molding
PDMS replica
1 µm
PDMS slab
Reference
electrode
D
(e) Operation
(f )
nCh IC
nCh d
nCh EC
Cell
nCh EC
ECS
D
µCh in
µCh out
nCh p
ICS
nCh d
µCh in
Cell
nCh IC
Suction
nCh p
µCh out
Signal
D
Reference
electrode
ICS
D
Signal
FIGURE 5.55 A. PDMS. lateral. patch. clamp. design. that. delivers. high-yield. giga-seals.. (From. C..
Chen.and.A..Folch,.“A.high-performance.elastomeric.patch.clamp.chip,”. Lab Chip .6,.1338,.2006..
Reproduced.with.permission.from.The.Royal.Society.of.Chemistry..Figure.contributed.by.Chihchen.
Chen.)
“GLASS OR POLYMER?”: THAT'S THE PATCH CLAMP QUESTION
Polymers (most notably PDMS) provide a route for cheap microfabrication through
replica-molding. However, if the price one has to pay is a suboptimal surface chemistry that
compromises the throughput of the assay (e.g., the percentage of giga-seals), then it may no
longer be the best option. he Yobas design may have found the optimal strategy because it
uses glass (thus far unmatched as a patch clamp material, if we ask any cell type), a micros-
copy-friendly lateral design, and although the processing is expensive, the cost per device can
be brought down using batch fabrication if the device is commercialized.
In 2010, two groups (Micha Spira's from the Hebrew University of Jerusalem and
Nicholas Melosh's from Stanford University, see Section 5.7) report “in-cell” patch
clamp recordings achieved with “self-impaling” nanofabricated electrodes. hese
electrodes can be fabricated by more traditional techniques (e.g., they do not require
microluidic protocols) and their operation does not dyalize the cells, so they are more
benign than traditional perforating electrodes.
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