Fluid flow at the microscale exhibits unique phenomena that can be leveraged to fabricate devices and components capable of performing functions useful for biological studies. The physics of importance to microfluidics are reviewed. Common methods of fabricating microfluidic devices and systems are described. Components, including valves, mixers, and pumps, capable of controlling fluid flow by utilizing the physics of the microscale are presented. Techniques for sensing flow characteristics are described and examples of devices and systems that perform bioanalysis are presented. The focus of this review is microscale phenomena and the use of the physics of the scale to create devices and systems that provide functionality useful to the life sciences.

The ability to actively manipulate fluid-flow patterns through microfluidic devices is important to many current applications and vital to the development of more complex systems in the future. A typical actively controlled valve developed to date consists of a flexible diaphragm coupled to an electromagnetic, electrostatic, or thermopneumatic actuator.[1]Design of an air-driven membrane valve has also been reported.[2] Despite this progress, there remains a significant need for materials that allow easy and controlled manipulation of valves and actuators in microfabricated devices, and ideally, independent control over multiple components within a single device. Recently, pH-responsive hydrogel materials have been used as valves in microfluidics devices. [3,4] This has allowed control of flow based on local environmental conditions (e.g., pH), which is attractive for some applications due to the simplicity of the system design. This work demonstrated the feasibility of forming hydrogel valves in microfluidic devices via photopolymerization and of utilizing hydrogels that undergo shape changes in response to stimuli as controllable valves or actuators. However, using pH as a control mechanism limits the number of components that can be independently controlled and requires that all components of the system be compatible with the requisite changes in pH. Many microfluidics applications will not be compatible with a wide range of pH conditions. Furthermore, for some applications it would be advantageous to have independent external control of valve operation, which would be difficult to achieve with pH-responsive materials. In the current system, dramatic changes in material size and shape can instead be induced by exposure to specific wavelengths of light. The use of light as a stimulus is particularly attractive as it is easily directed to specific locations within a channel network, possibly allowing further control.To accomplish this, we have developed materials that undergo pronounced and reversible changes in shape and size in response to different wavelengths of light. These materials are composites of a thermally responsive polymer (poly[N-isopropylacrylamide-co-acrylamide] with a 95:5 comonomer ratio) and particles that have distinct and strong optical-absorption profiles (gold colloids and nanoshells). The gold colloid was formed using the method of Duff et al., [5] while gold nanoshells with a 110 nm diameter silica core and 10 nm thick gold shell were synthesized as described by Oldenburg et al. [6] The absorption spectra of these two nanomaterials are shown in Figure 1. The composites were formed by mixing the nanoparticles with the monomer solution, thus entrapping the particles within the hydrogel matrix after polymerization. These nanocomposite materials respond to different wavelengths of light (Fig. 2); in this example, one nanocomposite material collapses in response to green light (gold-colloid nanocomposite hydrogel) while the other collapses in response to near-IR light (gold-nanoshell nanocom...

A microfluidic apparatus capable of creating continuous microscale cylindrical polymeric structures has been developed. This system is able to produce microstructures (e.g. fibers, tubes) by employing 3D multiple stream laminar flow and "on the fly"in-situ photopolymerization. The details of the fabrication process and the characterization of the produced microfibers are described. The apparatus is constructed by merging pulled glass pipettes with PDMS molding technology and used to manufacture the fibers and tubes. By controlling the sample and sheath volume flow rates, the dimensions of the microstructures produced can be altered without re-tooling. The fiber properties including elasticity, stimuli responsiveness, and biosensing are characterized. Responsive woven fabric and biosensing fibers are demonstrated. The fabrication process is simple, cost effective and flexible in materials, geometries, and scales.

A fabrication platform for realizing integrated microfluidic devices is discussed. The platform allows for creating specific microsystems for multistep assays in an ad hoc manner as the components that perform the assay steps can be created at any location inside the device via in situ fabrication. The platform was utilized to create a prototype microsystem for detecting botulinum neurotoxin directly from whole blood. Process steps such as sample preparation by filtration, mixing and incubation with reagents was carried out on the device. Various microfluidic components such as channel network, valves and porous filter were fabricated from prepolymer mixture consisting of monomer, cross-linker and a photoinitiator. For detection of the toxoid, biotinylated antibodies were immobilized on streptavidin-functionalized agarose gel beads. The gel beads were introduced into the device and were used as readouts. Enzymatic reaction between alkaline phosphatase (on secondary antibody) and substrate produced an insoluble, colored precipitate that coated the beads thus making the readout visible to the naked eye. Clinically relevant amounts of the toxin can be detected from whole blood using the portable enzyme-linked immunosorbent assay (ELISA) system. Multiple layers can be realized for effective space utilization and creating a three-dimensional (3-D) chaotic mixer. In addition, external materials such as membranes can be incorporated into the device as components. Individual components that were necessary to perform these steps were characterized, and their mutual compatibility is also discussed.

We present a method for the ultra rapid prototyping of microfluidic systems using liquid phase photopolymerization, requiring less than 5 min from design to prototype. Microfluidic device fabrication is demonstrated in a universal plastic or glass cartridge. The method consists of the following steps: introduction of liquid prepolymer into the cartridge, UV exposure through a mask to define the channel geometry, removal of unpolymerized prepolymer, and a final rinse. Rapidly fabricated masters for polydimethylsiloxane micromolding are also demonstrated. The master making process is compared to SU-8 50 photoresist processes. Press-on connectors are developed and demonstrated. All materials used are commercially available and low cost. An extension of these methods (mix and match) is presented that allows for maximal design flexibility and integration with a variety of existing fluidic geometries, components, and processes.