188 Bio-MEMS: Technologies and Applications inhomogeneous surface-charge distributions based on the grooved channel configurations used by Stroock et al.36 in a counterpart pressure-driven flow.
T-junction mixers with inhomogeneous surface-charge distributions have been successfully demonstrated on a microchip by Wu and Liu54 in a low- aspect-ratio (0.3) PDMS microchannel on a silicon substrate by implanting patterned electrodes into the silicon substrate. Applying voltage of alternating signs to successive electrodes generated a nonuniform charge distribution on the bottom wall of the channel, resulting in secondary flows during operation and improved mixing performance. Glass T-junction micromixers with vari- ous heterogeneous zeta potential patterns in very low aspect- ratio micro- channels (0.04) have been manufactured by Biddiss et al.55 They used soft lithography techniques to chemically pattern the glass microchannel bottom surface. Both physical realizations54,55 of this very interesting concept achieved significant mixing enhancement relative to their homogeneous counterparts.
Widespread practical usage in integrated chips of these types of enhanced micromixers may be hampered by the manufacturing process complexity and the durability and shelf life of surface modification when the latter is the chosen method of introducing surface-charge nonuniformity. Much like many electrokinetically driven devices, these micromixers are limited to very low flow rates dictated by the requirement of keeping the driving voltages low.
Secondary flows associated with electrohydrodynamic (EHD) instability generated by conductivity gradients in the working fluid have also been shown through simulation and experimentation to enhance mixing by Lin et al.56 and could be promising for a practical mixing device of fluids with inherent or imposed conductivity gradients in the practical environment.
Coupled electrorotation of latex microspheres has been proposed and dem- onstrated by Wilson et al.57 on a glass chip with two electrodes separated by a PDMS wedge, and although intrusive, may be promising for inducing fast local mixing in microfluidic environments.
Micromixers 189 pulsations. The same idea has since been considered in a variety of micro- channel mixers. An early example was that of Volpert et al.59 Following their work, pressure pulsations were also used by Deshmukh et al.,60 who employed a low-aspect-ratio (approximately 0.2) mixer microchannel with a T-junction fabricated in silicon using DRIE. An integrated planar micro- pump was used to pulse the flow in the mixing channel dividing the mixed liquids into small serial segments and making the mixing process indepen- dent of convection. A similar device, with a cross-junction and without integrated pumping, was presented by Lee et al.61 and was also fabricated in silicon using DRIE.
The chaotic-advection behavior and associated mixing enhancement of pulsed flow cross-junction mixers have been studied theoretically by Lee,62 while Niu and Lee63 analyzed a multi-cross-junction variant. Pulsations are in general introduced through the side channels of the cross-junction(s).
Glasgow and Aubry64 demonstrated numerically and experimentally the merits of flow pulsation in a T-junction microchannel mixer. Analysis and realization of pulsed flow T-junction micromixers has been presented more recently by Tabeling et al.65 Their micromixer was realized with glass and PDMS technology and utilized an on-chip microhydraulic actuation system based on microvalves introduced by Unger et al.,66 fabricated using their soft lithography technique. A multi-side-channel (as in Unger et al.66), pulsed flow T-junction mixer was analyzed and evaluated by Bottausci et al.67 They concluded that the multiple side-channel design performs better than the single side-channel one when the pulsations introduced through the side chan- nels are out of phase. A swirl-chamber mixer micromilled in PMMA was proposed by Chung et al.9 in which the swirling of the fluids was achieved by forward and backward pumping. The mixing chamber was fitted with two opposing channels of unit aspect ratio tangent to the circular chamber. Simu- lation indicated up to a twofold mixing improvement compared to that in a straight channel at rather high, yet laminar, Reynolds numbers (20 to 400). In general, the majority of the pulsed flow and pressure micromixers are contin- uous-flow devices and have been shown to improve mixing compared to their steady-state counterparts leading to shorter mixing-channel lengths for Rey- nolds numbers of order one or less. When considering such micromixers for applications, this improvement should be put in perspective of the added complexity, not so much in terms of manufacturing processes, but that result- ing from the need for pressure actuation.
Electrical excitation has also been used as an alternative to pressure pulsa- tions toward improving mixing on the microscale by inducing unsteady sec- ondary flows and chaotic advection. One of the earliest micromixers utilizing unsteady electrical fields was that of Lee et al.61 They demonstrated a pressure- driven, continuous-flow device with periodic electrical excitation introduced in a chamber on the flow path. They used a combination of silicon and SU-8 technology to manufacture this low-aspect-ratio (approximately 0.13) active
190 Bio-MEMS: Technologies and Applications mixer. They took advantage of dielectophoretic forces induced by the inho- mogeneous electrical field to improve mixing of dielectric microparticles.
Shortly after, Oddy et al.68 presented electrical active mixers based on electro- kinetic instability excited by sinusoidal oscillations of the electrical filed. They evaluated a glass-covered PDMS cross-junction mixer and a chamber cross- junction one very similar to that of Lee et al.61 in Borofloat glass. The main flow in both these low-aspect-ratio (0.1 to 0.33) micromixers could be either pressure or electrically driven. Their measurements proved the concept that substantial improvement in mixing can be achieved through the exploitation of electrokinetic instability by applying AC voltages of a few kVolts at frequen- cies of a few Hz. A T-junction active mixer with an array of electrodes installed on either side of a unit aspect ratio, mixing channel was successfully demon- strated by El Moctar et al.69 Unsteady mixing-enhancing flow is generated due to EHD instability under the application of steady electrical fields for fluids that have different electrical properties. This pressure-driven device can also be operated as an active one by applying an unsteady electrical field, which further improves mixing performance at low Reynolds numbers (approxi- mately 0.02). A Ψ-junction and ring-chamber combination active mixer has been simulated by Chen et al.,70 and realized by Zhang et al.,71 on a silicon chip with integrated heavily doped silicon electrodes. Unsteady electrical fields imposed in the ring chamber generate secondary flows, which improve mixing as shown in the simulation results. The device can be pressure or electrokinetically driven. More recently, Shin et al.72 conducted an experimental study of an electrically driven and actuated cross-junction, microchannel mixer realized on glass. Under a steady driving voltage of a few hundred volts, they observed instability developing along the focused middle stream with a fre- quency of a few Hz. Under unsteady conditions with tens of volts peak-to- peak amplitude, they showed modest mixing enhancement at frequencies around the first harmonic of the natural instability mode. Active electrically excited micromixers are attractive for low-flow-rate applications and do not involve fabrication and operational technological complexity superior to that required for their passive counterparts, other than an AC generator. Indeed, they are easier to manufacture than passive mixers employing nonhomoge- neous charge distributions on microchannel walls. They have the standard operational drawbacks of electrically driven microfluidic devices.
Magnetic actuation has also been exploited to produce better micromixing performance. The principle of using magnetohydrodynamic (MHD) forcing to improve mixing on the microscale was nicely demonstrated by Solomon et al.73 They performed experiments comparing long-range chaotic mixing of miscible and immiscible impurities in a time-periodic flow by producing an alternating magnetic field that generated alternating vortex structures due to MHD insta- bility. Chaotic advection created by magnetic forces inducing mixing on flows carrying magnetic microbeads has been demonstrated by Suzuki and Ho74 and Suzuki et al.75 on a low-aspect-ratio serpentine microchannel with a T-junction and an integrated array of copper electrodes normal to the channel length. A glass-covered SU-8 channel was created on a silicon substrate in which the
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Micromixers 191 conductors were embedded. This design succeeded in rapidly dispersing mag- netic microbeads at very low Reynolds numbers (approximately 0.01). Very good performance in mixing using magnetic microbeads was achieved by Rida et al.76 on a micromixer realized in polymethylmethacrylate (PMMA) with integrated ferromagnetic permalloy layers to focus the magnetic field generated by an external electromagnet. In a rather rare design involving moving parts, Lu et al.77 and Ryu et al.78 developed micromixer chips with PDMS or Parylene Ψ-junction microchannels with an integrated permalloy bar rotor on a silicon substrate. When the microrotor was rotated by an external rotating magnetic field, it could act both as a mechanical stirrer and a pumping impeller.