The manipulation of fluids in channels with dimensions of tens of micrometres--microfluidics--has emerged as a distinct new field. Microfluidics has the potential to influence subject areas from chemical synthesis and biological analysis to optics and information technology. But the field is still at an early stage of development. Even as the basic science and technological demonstrations develop, other problems must be addressed: choosing and focusing on initial applications, and developing strategies to complete the cycle of development, including commercialization. The solutions to these problems will require imagination and ingenuity.

The origins and the future of microfluidics

This paper describes a procedure that makes it possible to design and fabricate (including sealing) microfluidic systems in an elastomeric materialpoly(dimethylsiloxane) (PDMS)in less than 24 h. A network of microfluidic channels (with width >20 μm) is designed in a CAD program. This design is converted into a transparency by a high-resolution printer; this transparency is used as a mask in photolithography to create a master in positive relief photoresist. PDMS cast against the master yields a polymeric replica containing a network of channels. The surface of this replica, and that of a flat slab of PDMS, are oxidized in an oxygen plasma. These oxidized surfaces seal tightly and irreversibly when brought into conformal contact. Oxidized PDMS also seals irreversibly to other materials used in microfluidic systems, such as glass, silicon, silicon oxide, and oxidized polystyrene; a number of substrates for devices are, therefore, practical options. Oxidation of the PDMS has the additional advantage that it ...

Rapid prototyping of microfluidic systems in poly(dimethylsiloxane)

Microfabricated integrated circuits revolutionized computation by vastly reducing the space, labor, and time required for calculations. Microfluidic systems hold similar promise for the large-scale automation of chemistry and biology, suggesting the possibility of numerous experiments performed rapidly and in parallel, while consuming little reagent. While it is too early to tell whether such a vision will be realized, significant progress has been achieved, and various applications of significant scientific and practical interest have been developed. Here a review of the physics of small volumes (nanoliters) of fluids is presented, as parametrized by a series of dimensionless numbers expressing the relative importance of various physical phenomena. Specifically, this review explores the Reynolds number Re, addressing inertial effects; the Peclet number Pe, which concerns convective and diffusive transport; the capillary number Ca expressing the importance of interfacial tension; the Deborah, Weissenberg, and elasticity numbers De, Wi, and El, describing elastic effects due to deformable microstructural elements like polymers; the Grashof and Rayleigh numbers Gr and Ra, describing density-driven flows; and the Knudsen number, describing the importance of noncontinuum molecular effects. Furthermore, the long-range nature of viscous flows and the small device dimensions inherent in microfluidics mean that the influence of boundaries is typically significant. A variety of strategies have been developed to manipulate fluids by exploiting boundary effects; among these are electrokinetic effects, acoustic streaming, and fluid-structure interactions. The goal is to describe the physics behind the rich variety of fluid phenomena occurring on the nanoliter scale using simple scaling arguments, with the hopes of developing an intuitive sense for this occasionally counterintuitive world.

/pdf/microfluidics-fluid-physics-at-the-nanoliter-scale-4bpahtd8qa.pdf

Microfluidics: Fluid physics at the nanoliter scale

Microfluidic devices are finding increasing application as analytical systems, biomedical devices, tools for chemistry and biochemistry, and systems for fundamental research. Conventional methods of fabricating microfluidic devices have centered on etching in glass and silicon. Fabrication of microfluidic devices in poly(dimethylsiloxane) (PDMS) by soft lithography provides faster, less expensive routes than these conventional methods to devices that handle aqueous solutions. These soft-lithographic methods are based on rapid prototyping and replica molding and are more accessible to chemists and biologists working under benchtop conditions than are the microelectronics-derived methods because, in soft lithography, devices do not need to be fabricated in a cleanroom. This paper describes devices fabricated in PDMS for separations, patterning of biological and nonbiological material, and components for integrated systems.

Fabrication of microfluidic systems in poly(dimethylsiloxane)

This Account summarizes techniques for fabrication and applications in biomedicine of microfluidic devices fabricated in poly(dimethylsiloxane) (PDMS). The methods and applications described focus on the exploitation of the physical and chemical properties of PDMS in the fabrication or actuation of the devices. Fabrication of channels in PDMS is simple, and it can be used to incorporate other materials and structures through encapsulation or sealing (both reversible and irreversible).

Poly(dimethylsiloxane) as a material for fabricating microfluidic devices.

A method of generating electrospray from solutions emerging from small channels etched on planar substrates is described. The fluids are delivered using electroosmotically induced pressures and are sprayed electrostatically from the terminus of a channel by applying an electrical potential of sufficient amplitude to generate the electrospray between the microchip and a conductor spaced from the channel terminus. No major modification of the microchip is required other than to expose a channel opening. The principles that regulate the fluid delivery are described and demonstrated. A spectrum for a test compound, tetrabutylammonium iodide, that was continuously electrophoresed was obtained by coupling the microchip to an ion trap mass spectrometer.

Generating electrospray from microchip devices using electroosmotic pumping.

A glass microchip having a channel with a cross section of 5.6 [mu]m high and 66 [mu]m wide was fabricated using standard photolithographic and etching techniques. The surface of the channel was chemically modified with octadecylsilane to function as the stationary phase for open channel chromatography. Electroosmotic flow was used to [open quotes]load[close quotes] the sample into the microchip and to [open quotes]pump[close quotes] the mobile phase during the experiments. For electric field strengths in the separation column from 27 to 163 V/cm, the linear velocity for the electroosmotic flow ranged from 0.13 to 0.78 mm/s. Detection was performed using direct fluorescence for separation monitoring and indirect fluorescence for void time measurements. Plate heights as low as 4.1 and 5.0 [mu]m were generated for unretained and retained components, respectively. 28 refs., 6 figs., 2 tabs.

Open channel electrochromatography on a microchip

An integrated monolithic device (8 mm × 10 mm) that performs an automated biochemical procedure is demonstrated. The device mixes a DNA sample with a restriction enzyme in a 0.7-nL reaction chamber and after a digestion period injects the fragments onto a 67-mm-long capillary electrophoresis channel for sizing. Materials are precisely manipulated under computer control within the channel structure using electrokinetic transport. Digestion of the plasmid pBR322 by the enzyme HinfI and fragment analysis are completed in 5 min using 30 amol of DNA and 2.8 × 10-3 unit of enzyme per run.

Integrated Microdevice for DNA Restriction Fragment Analysis

A microfabricated injection valve incorporating a porous membrane structure is reported that enables electrokinetic concentration of DNA samples using homogeneous buffer conditions followed by injection into a channel for electrophoretic analysis. The porous membrane was incorporated in the microchannel manifold by having two channels separated from each other by 3−12 μm and connected by a thin porous silicate layer. This design allows the passage of current to establish an electrical connection between the separated channels but prevents large molecules, e.g., DNA, from traversing the membrane. Concentrated DNA can be injected into the separation channel and electrophoretically analyzed. Experiments exhibit a nonlinear increase in concentration with time, and DNA fragments can be concentrated up to 2 orders of magnitude as shown by comparison of peak intensities for analysis performed with and without concentration.

Microfabricated porous membrane structure for sample concentration and electrophoretic analysis.

A fused quartz microchip with a serpentine column geometry is fabricated to perform rapid microchip electrophoresis of dansylated amino acids. A 67 mm separation column is constructed in a 7 x 10 mm area on a quartz substrate using standard photolithographic, etching and deposition techniques. Buffer and sample flows within the channel manifold are precisely controlled through potentials applied to the reservoirs. To enhance the detection limits, a stacking injection technique is used to concentrate the sample at the inlet of the separation column. The stacked injections exhibit high reproducibility (2.1% relative standard deviation in peak area). Using a separation length of 67 mm and a separation field strength of 1100 V/cm, separations are performed in < or = 15 s generating approximately 40,000 theoretical plates.

John Michael Ramsey

Papers

Generating electrospray from microchip devices using electroosmotic pumping.

Open channel electrochromatography on a microchip

Integrated Microdevice for DNA Restriction Fragment Analysis

Microfabricated porous membrane structure for sample concentration and electrophoretic analysis.

Microchip electrophoresis with sample stacking