ABSTRACT

CONTENTS 7.1 Introduction ................................................................................................ 177 7.2 Some Basic Considerations ...................................................................... 178 7.3 Passive Micromixers.................................................................................. 181

7.3.1 Pressure-Driven Passive Micromixers ....................................... 181 7.3.2 Electrically Driven Passive Micromixers................................... 185

7.4 Active Micromixers ................................................................................... 188 7.5 Multiphase Micromixers........................................................................... 191 7.6 Performance Metrics for Microscale Mixer Design

and Evaluation ........................................................................................... 192 7.7 Design Methodology for Optimal Diffusion-Based, Micromixers

for Batch Production Applications ......................................................... 195 References ............................................................................................. 206

The topic of mixing on the microscale has been at the forefront of research and development efforts over roughly the last fifteen years since the technological thrust toward miniaturization of fluidic systems began. Mixing is of significant importance to realizing lab-on-a-chip microscale reactors and bioanalysis systems because the reactions carried out on the micro-or even nanoscale in such devices require the on-chip mixing of samples and reagents. Typical application class examples are thermal-cycling reactors for the popular polymerization chain reaction (PCR)1,2 and the Ligase chain reaction (LCR)3 as well as other similar applications. Fully integrated microfluidic chips performing such reactions require modestly fast mixing in batch mode, should the mixing be performed on-chip. This is so because the

bottleneck in terms of temporal performance usually lies with the thermal cycling reactions themselves, and because a specific volume of mixture is usually needed to be produced. In such an application, the emphasis would be shifted toward low levels of the resource used to drive the chip, that is, low pressure if the device is pressure driven or low voltage if the device is electrokinetically driven. This requirement can be critical for reactions such as PCR and LDR sequences where several levels of on-chip mixing are necessary, and even more so if the chips are multiplexed. A second example application area of microscale mixers is to perform continuous flow fastreaction kinetics experiments. In this case mixing must be faster than reaction rates with timescales down to microseconds. In contrast with the previous application area, the emphasis is on localized mixing with very small timescales and batch volume delivery is not a necessity. Low levels of the driving force to operate the chip are desired, but can be sacrificed in exchange for speed, so long as the chip is not structurally compromised. Yet another possible performance requirement of microscale mixers could demand longer-term continuous production, in which case the emphasis would be on maximizing the mixture flow rate delivered, while keeping the driving force for delivery at low levels. An application that would require such performance would be in situ, designer drug delivery, whereby a particular drug cocktail would be synthesized on-chip from constituents at proportions specific to a particular patient, and directly delivered at the point of care.