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)

Soft lithography is an alternative to silicon-based micromachining that uses replica molding of nontraditional elastomeric materials to fabricate stamps and microfluidic channels. We describe here an extension to the soft lithography paradigm, multilayer soft lithography, with which devices consisting of multiple layers may be fabricated from soft materials. We used this technique to build active microfluidic systems containing on-off valves, switching valves, and pumps entirely out of elastomer. The softness of these materials allows the device areas to be reduced by more than two orders of magnitude compared with silicon-based devices. The other advantages of soft lithography, such as rapid prototyping, ease of fabrication, and biocompatibility, are retained.

http://science.sciencemag.org/content/sci/288/5463/113.full.pdf

Monolithic microfabricated valves and pumps by multilayer soft lithography

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)

Multicolor optical coding for biological assays has been achieved by embedding different-sized quantum dots (zinc sulfide-capped cadmium selenide nanocrystals) into polymeric microbeads at precisely controlled ratios. Their novel optical properties (e.g., size-tunable emission and simultaneous excitation) render these highly luminescent quantum dots (QDs) ideal fluorophores for wavelength-and-intensity multiplexing. The use of 10 intensity levels and 6 colors could theoretically code one million nucleic acid or protein sequences. Imaging and spectroscopic measurements indicate that the QD-tagged beads are highly uniform and reproducible, yielding bead identification accuracies as high as 99.99% under favorable conditions. DNA hybridization studies demonstrate that the coding and target signals can be simultaneously read at the single-bead level. This spectral coding technology is expected to open new opportunities in gene expression studies, high-throughput screening, and medical diagnostics.

https://faculty.washington.edu/xgao/Images/QD-beads.pdf

Quantum-dot-tagged microbeads for multiplexed optical coding of biomolecules.

Micromachining technology was used to prepare chemical analysis systems on glass chips (1 centimeter by 2 centimeters or larger) that utilize electroosmotic pumping to drive fluid flow and electrophoretic separation to distinguish sample components. Capillaries 1 to 10 centimeters long etched in the glass (cross section, 10 micrometers by 30 micrometers) allow for capillary electrophoresis-based separations of amino acids with up to 75,000 theoretical plates in about 15 seconds, and separations of about 600 plates can be effected within 4 seconds. Sample treatment steps within a manifold of intersecting capillaries were demonstrated for a simple sample dilution process. Manipulation of the applied voltages controlled the directions of fluid flow within the manifold. The principles demonstrated in this study can be used to develop a miniaturized system for sample handling and separation with no moving parts.

https://science.sciencemag.org/content/sci/261/5123/895.full.pdf

Micromachining a Miniaturized Capillary Electrophoresis-Based Chemical Analysis System on a Chip

Electroosmotic pumping is highly efficient in capillaries of less than 100 mu m inner diameter bearing an immobilized surface charge. Electric fields in the kV cm-1 range allow for liquid motion of several mm s-1 in the case of an aqueous electrolyte. This pumping mechanism is used for miniaturized chemical analysis systems. Flow and mixing behaviour in branched channels are characterized. A capillary electrophoresis device allows for repetitive, electroosmotic injections of 100 pL samples, for efficiencies of up to 200000 theoretical plates in less than a minute, and for external laser induced fluorescence detection at any capillary length of choice between 5 and 50 mm.

https://iopscience.iop.org/article/10.1088/0960-1317/4/4/010/pdf

Electroosmotic pumping and electrophoretic separations for miniaturized chemical analysis systems

Fluid flow was driven within a network of intersecting capillaries integrated on a glass chip using electroosmotic pumping. Potentials could be applied to several capillaries simultaneously to quantitatively control the amount of each reagent stream delivered to an intersection of capillaries. An example of a simple dilution of sample with buffer is shown. Kirchhoff's rules for resistive networks were found to predict the currents and fluid flow within the capillaries. Leakage of sample from one channel to another at an intersection was shown to arise from both diffusive and hydrodynamic effects. Application of potentials to the intersecting channels could fully arrest such leakage

Electroosmotic Pumping and Valveless Control of Fluid Flow within a Manifold of Capillaries on a Glass Chip

Methods to fabricate planar capillary electrophoresis devices integrated with a postcolumn reactor in fused silica (quartz) and Pyrex glass are presented. Quartz is etched at ∼1 μm/min with a 2.1:1 width-to-depth ratio using a Cr/Au/Cr metal mask and concentrated HF/HNO(3). On-chip postcolumn reaction of o-phthaldialdehyde (OPA) and amino acids gave theoretical plate numbers up to 83 000 and ∼90 ms peak widths, corresponding to 14 plates/V and a 0.5 μm theoretical plate height. The reactor geometry caused only a 10% degradation in efficiency.

Integrated capillary electrophoresis devices with an efficient postcolumn reactor in planar quartz and glass chips.

The simplified amperometric detection scheme demonstrated is 
based on the amperometric working and electrophoretic ground electrodes 
only. The latter serves as counter and pseudo-reference as well. It is 
shown via the successful determination of neurotransmitters, 
ascorbic acid and phenols on gold or platinum working electrodes that this 
approach is feasible for detection on a channel based electrophoretic 
separation device. Also presented is the detection of carbohydrates and 
amino acids with copper electrodes. The results were found to be similar to 
those obtained with conventional capillary systems with amperometric 
detection, albeit at much reduced analysis times.

Karl Fluri

Papers

Micromachining a Miniaturized Capillary Electrophoresis-Based Chemical Analysis System on a Chip

Electroosmotic pumping and electrophoretic separations for miniaturized chemical analysis systems

Electroosmotic Pumping and Valveless Control of Fluid Flow within a Manifold of Capillaries on a Glass Chip

Integrated capillary electrophoresis devices with an efficient postcolumn reactor in planar quartz and glass chips.

A two-electrode configuration for simplified amperometric detection in a microfabricated electrophoretic separation device.