Micromachining a Miniaturized Capillary Electrophoresis-Based Chemical Analysis System on a Chip
13 Aug 1993-Science (American Association for the Advancement of Science)-Vol. 261, Iss: 5123, pp 895-897
TL;DR: In this article, the authors demonstrated a miniaturized system for sample handling and separation using electrophoresis-based separations of amino acids with up to 75,000 theoretical plates in about 15 seconds.
Abstract: 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.
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TL;DR: A procedure that makes it possible to design and fabricate microfluidic systems in an elastomeric material poly(dimethylsiloxane) (PDMS) in less than 24 h by fabricating a miniaturized capillary electrophoresis system is described.
Abstract: 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 ...
5,491 citations
TL;DR: An extension to the soft lithography paradigm, multilayersoft lithography, with which devices consisting of multiple layers may be fabricated from soft materials is described, to build active microfluidic systems containing on-off valves, switching valves, and pumps entirely out of elastomer.
Abstract: 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.
4,218 citations
TL;DR: 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 as mentioned in this paper.
Abstract: 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.
4,044 citations
TL;DR: Fabrication of microfluidic devices in poly(dimethylsiloxane) (PDMS) by soft lithography provides faster, less expensive routes to devices that handle aqueous solutions.
Abstract: 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.
3,344 citations
TL;DR: Investigation 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.
Abstract: 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.
2,722 citations
References
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TL;DR: In this paper, a modular construction of a miniaturized "total chemical analysis system" is proposed, and theoretical performances of such systems based on flow injection analysis, chromatography and electrophoresis are compared with those of existing chemical sensors and analysis systems.
Abstract: Following the trend towards smaller channel inner diameter for better separation performance and shorter channel length for shorter transport time, a modular construction of a miniaturized 'total chemical analysis system' is proposed. The theoretical performances of such systems based on flow injection analysis, chromatography and electrophoresis, are compared with those of existing chemical sensors and analysis systems.
3,017 citations
01 May 1982
TL;DR: This review describes the advantages of employing silicon as a mechanical material, the relevant mechanical characteristics of silicon, and the processing techniques which are specific to micromechanical structures.
Abstract: Single-crystal silicon is being increasingly employed in a variety of new commercial products not because of its well-established electronic properties, but rather because of its excellent mechanical properties. In addition, recent trends in the engineering literature indicate a growing interest in the use of silicon as a mechanical material with the ultimate goal of developing a broad range of inexpensive, batch-fabricated, high-performance sensors and transducers which are easily interfaced with the rapidly proliferating microprocessor. This review describes the advantages of employing silicon as a mechanical material, the relevant mechanical characteristics of silicon, and the processing techniques which are specific to micromechanical structures. Finally, the potentials of this new technology are illustrated by numerous detailed examples from the literature. It is clear that silicon will continue to be aggressively exploited in a wide variety of mechanical applications complementary to its traditional role as an electronic material. Furthermore, these multidisciplinary uses of silicon will significantly alter the way we think about all types of miniature mechanical devices and components.
2,723 citations
2,065 citations
TL;DR: In this article, a miniature gas analysis system based on the principles of gas chromatography (GC) has been built in silicon using photolithography and chemical etching techniques, which allows size reductions of nearly three orders of magnitude compared to conventional laboratory instruments.
Abstract: A miniature gas analysis system has been built based on the principles of gas chromatography (GC). The major components are fabricated in silicon using photolithography and chemical etching techniques, which allows size reductions of nearly three orders of magnitude compared to conventional laboratory instruments. The chromatography system consists of a sample injection valve and a 1.5-m-long separating capillary column, which are fabricated on a substrate silicon wafer. The output thermal conductivity detector is separately batch fabricated and integrably mounted on the substrate wafer. The theory of gas chromatography has been used to optimize the performance of the sensor so that separations of gaseous hydrocarbon mixtures are performed in less than 10 s. The system is expected to find application in the areas of portable ambient air quality monitors, implanted biological experiments, and planetary probes.
1,414 citations
TL;DR: In this article, a complex manifold of capillary channels has been fabricated in a planar glass substrate and the separation of a mixture of fluorescein and calcein within the channels was achieved using electrophoresis.
Abstract: The feasibillity of miniaturizing a chemical analysis system on a planar substrate has been demonstrated for a system utilizing electrokinetic phenomena for sample separation and solvent pumping. Using micromachining techniques, a complex manifold of capillary channels has been fabricated in a planar glass substrate and the separation of a mixture of fluorescein and calcein within the channels was achieved using electrophoresis. The maximum number of theoretical piates abtained was about 35 000 for calcein, with 5000 V applied, corresponding to 2100 V between the injection and fluorescence detection points in the channels
1,300 citations