124 V. Bazargan and B. Stoeber
reported to lead to complete cell death within 5 days
68
; however, addition of
hydrocortisone led to a significant improvement in cell viability. In a different
study, Wasan et al. showed that high concentration of Pluronic F127 led to notable
toxicity after intraperitoneal injection in rats.
59
Since Pluronic gels release drugs
within periods rarely exceeding several days, they can still be considered a good
material for drug delivery.
52
6.5 FLOW CONTROL USING THERMALLY RESPONSIVE FLUIDS
The following simple and effective microflow control concepts use thermally
responsive fluids, in particular aqueous solutions of Pluronic, as the transport
medium for the fluid or solid sample of interest. That means that the thermally
responsive fluid is present as the carrier fluid in all channels of the microfluidic
system.
6.5.1 Active Valving
6.5.1.1 Principle of an Active Thermal Hydrogel Valve
In a very simple valving approach, a flow conduit is blocked by transforming the
thermally responsive fluid into a hydrogel within the microchannel. Heaters can
be integrated into the channel network so that selective activation of a particular
heater locally generates heat, which increases the fluid temperature beyond the
gel formation temperature of the thermally responsive fluid. This then leads to
localized gel formation as illustrated in Fig. 6.5. As the fluid is present everywhere
in the microfluidic network, localized heating and subsequent gel formation can be
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'Ğů
>ŝƋƵŝĚ
Ɛ͕Đƌŝƚ
Figure 6.4. Phase diagram for a 15 wt% Pluronic F127 solution in water and sodium
phosphate.
110
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Flow Control in Biomedical Microdevices using Thermally Responsive Fluids 125
Figure 6.5. A schematic illustration of the principle of an active valve using a thermally
responsive fluid in a microfluidic network. (a) Fluid from one channel is diverted into two
channels at a channel bifurcation; (b) activating an integrated heater leads to localized gel
formation in the corresponding microchannel, which subsequently blocks this channel to
flow. For color reference, see page 266.
achieved in an arbitrary location and at any time in the microfluidic system.
72
As
gel formation of Pluronic solutions is completely reversible, the hydrogel returns
to its liquid phase upon cooling, and the gel block disappears, opening the channel
again to flow.
6.5.1.2 Microdevice Design and Fabrication
The device shown in Fig. 6.6 was fabricated using standard MEMS technology.
The fabrication process for this test device should be considered as one possible
example process. When designing a specific process for a given application,
process compatibility will other devices of a mictoTAS needs to be considered as
well.
Figure 6.7 shows the schematic of the cross section of the device in Fig. 6.6. The
silicon substrate with the heaters and the glass substrate with the flow channels are
fabricated separately, and bonded together using anodic bonding. A silicon wafer
is coated with a thin film (0.2 μm) of silicon nitride using low pressure chemical
vapor deposition (LPCVD). This film is patterned by photolithography and plasma
etching to open areas that will be used for routing of electrical leads and heaters.
A subsequent silicon wet etch forms 4.5 μm deep recesses in the silicon substrate,
following which the silicon nitride hard mask is removed by plasma etching.
Another silicon nitride layer for electric insulation is deposited onto the substrate
using LPCVD, followed by an LPCVD thin film of doped polysilicon with a sheet
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126 V. Bazargan and B. Stoeber
Figure 6.6. (a) Top view (through the transparent glass lid) of a microfluidic channel
system with heaters integrated into recesses in the channel bottom (silicon substrate). All
flow channels are 10 μm deep and 200 μm wide. (b) Detailed view of an integrated heater
with aluminum leads and several parallel polysilicon heating elements.
Figure 6.7. A schematic cross-section of the microfluidic device shown in Fig. 6.6. The left-
hand side shows the cross-section across a heater in the channel, while the right-hand side
shows a cross-section further away from the channel, through an aluminum lead. For color
reference, see page 267.
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