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Journal ArticleDOI

Soft Lithography in Biology and Biochemistry

01 Jan 2001-Annual Review of Biomedical Engineering (Annual Reviews 4139 El Camino Way, P.O. Box 10139, Palo Alto, CA 94303-0139, USA)-Vol. 3, Iss: 1, pp 335-373
TL;DR: Soft lithography offers the ability to control the molecular structure of surfaces and to pattern the complex molecules relevant to biology, to fabricate channel structures appropriate for microfluidics, and topattern and manipulate cells.
Abstract: ▪ Abstract Soft lithography, a set of techniques for microfabrication, is based on printing and molding using elastomeric stamps with the patterns of interest in bas-relief. As a technique for fabricating microstructures for biological applications, soft lithography overcomes many of the shortcomings of photolithography. In particular, soft lithography offers the ability to control the molecular structure of surfaces and to pattern the complex molecules relevant to biology, to fabricate channel structures appropriate for microfluidics, and to pattern and manipulate cells. For the relatively large feature sizes used in biology (≥50 μm), production of prototype patterns and structures is convenient, inexpensive, and rapid. Self-assembled monolayers of alkanethiolates on gold are particularly easy to pattern by soft lithography, and they provide exquisite control over surface biochemistry.

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Citations
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Journal ArticleDOI
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


Cites background from "Soft Lithography in Biology and Bio..."

  • ...The advantages and applications of soft rather than silicon microfluidics have been reviewed McDonald et al., 2000; Quake and Scherer, 2000; Whitesides and Stroock, 2001; Whitesides et al., 2001; Ng et al., 2002; Sia and Whitesides, 2003 ....

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Journal ArticleDOI
TL;DR: This work highlights recent developments in engineering uncrosslinked and crosslinked hydrophilic polymers for biomedical and biological applications and shows how such systems' intelligent behavior can be used in sensors, microarrays, and imaging.
Abstract: Hydrophilic polymers are the center of research emphasis in nanotechnology because of their perceived “intelligence”. They can be used as thin films, scaffolds, or nanoparticles in a wide range of biomedical and biological applications. Here we highlight recent developments in engineering uncrosslinked and crosslinked hydrophilic polymers for these applications. Natural, biohybrid, and synthetic hydrophilic polymers and hydrogels are analyzed and their thermodynamic responses are discussed. In addition, examples of the use of hydrogels for various therapeutic applications are given. We show how such systems’ intelligent behavior can be used in sensors, microarrays, and imaging. Finally, we outline challenges for the future in integrating hydrogels into biomedical applications.

3,524 citations

Journal ArticleDOI
25 Jun 2010-Science
TL;DR: Mechanically active “organ-on-a-chip” microdevices that reconstitute tissue-tissue interfaces critical to organ function may expand the capabilities of cell culture models and provide low-cost alternatives to animal and clinical studies for drug screening and toxicology applications.
Abstract: Here, we describe a biomimetic microsystem that reconstitutes the critical functional alveolar-capillary interface of the human lung. This bioinspired microdevice reproduces complex integrated organ-level responses to bacteria and inflammatory cytokines introduced into the alveolar space. In nanotoxicology studies, this lung mimic revealed that cyclic mechanical strain accentuates toxic and inflammatory responses of the lung to silica nanoparticles. Mechanical strain also enhances epithelial and endothelial uptake of nanoparticulates and stimulates their transport into the underlying microvascular channel. Similar effects of physiological breathing on nanoparticle absorption are observed in whole mouse lung. Mechanically active "organ-on-a-chip" microdevices that reconstitute tissue-tissue interfaces critical to organ function may therefore expand the capabilities of cell culture models and provide low-cost alternatives to animal and clinical studies for drug screening and toxicology applications.

3,081 citations

Journal ArticleDOI
10 Sep 2004-Science
TL;DR: Investigating the persistence of single cells of Escherichia coli with the use of microfluidic devices found phenotypic switching occurred between normally growing cells and persister cells having reduced growth rates, leading to a simple mathematical description of the persistence switch.
Abstract: A fraction of a genetically homogeneous microbial population may survive exposure to stress such as antibiotic treatment. Unlike resistant mutants, cells regrown from such persistent bacteria remain sensitive to the antibiotic. We investigated the persistence of single cells of Escherichia coli with the use of microfluidic devices. Persistence was linked to preexisting heterogeneity in bacterial populations because phenotypic switching occurred between normally growing cells and persister cells having reduced growth rates. Quantitative measurements led to a simple mathematical description of the persistence switch. Inherent heterogeneity of bacterial populations may be important in adaptation to fluctuating environments and in the persistence of bacterial infections.

2,599 citations

PatentDOI
24 Sep 2003-Science
TL;DR: The fluidic multiplexor as discussed by the authors is a combinatorial array of binary valve patterns that exponentially increases the processing power of a network by allowing complex fluid manipulations with a minimal number of inputs.
Abstract: High-density microfluidic chips contain plumbing networks with thousands of micromechanical valves and hundreds of individually addressable chambers. These fluidic devices are analogous to electronic integrated circuits fabricated using large scale integration (LSI). A component of these networks is the fluidic multiplexor, which is a combinatorial array of binary valve patterns that exponentially increases the processing power of a network by allowing complex fluid manipulations with a minimal number of inputs. These integrated microfluidic networks can be used to construct a variety of highly complex microfluidic devices, for example the microfluidic analog of a comparator array, and a microfluidic memory storage device resembling electronic random access memories.

2,292 citations

References
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Journal ArticleDOI
20 Oct 1995-Science
TL;DR: A high-capacity system was developed to monitor the expression of many genes in parallel by means of simultaneous, two-color fluorescence hybridization, which enabled detection of rare transcripts in probe mixtures derived from 2 micrograms of total cellular messenger RNA.
Abstract: A high-capacity system was developed to monitor the expression of many genes in parallel. Microarrays prepared by high-speed robotic printing of complementary DNAs on glass were used for quantitative expression measurements of the corresponding genes. Because of the small format and high density of the arrays, hybridization volumes of 2 microliters could be used that enabled detection of rare transcripts in probe mixtures derived from 2 micrograms of total cellular messenger RNA. Differential expression measurements of 45 Arabidopsis genes were made by means of simultaneous, two-color fluorescence hybridization.

10,287 citations

Journal ArticleDOI
24 Mar 2000-Science
TL;DR: The nucleotide sequence of nearly all of the approximately 120-megabase euchromatic portion of the Drosophila genome is determined using a whole-genome shotgun sequencing strategy supported by extensive clone-based sequence and a high-quality bacterial artificial chromosome physical map.
Abstract: The fly Drosophila melanogaster is one of the most intensively studied organisms in biology and serves as a model system for the investigation of many developmental and cellular processes common to higher eukaryotes, including humans. We have determined the nucleotide sequence of nearly all of the approximately 120-megabase euchromatic portion of the Drosophila genome using a whole-genome shotgun sequencing strategy supported by extensive clone-based sequence and a high-quality bacterial artificial chromosome physical map. Efforts are under way to close the remaining gaps; however, the sequence is of sufficient accuracy and contiguity to be declared substantially complete and to support an initial analysis of genome structure and preliminary gene annotation and interpretation. The genome encodes approximately 13,600 genes, somewhat fewer than the smaller Caenorhabditis elegans genome, but with comparable functional diversity.

6,180 citations

Journal ArticleDOI
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


"Soft Lithography in Biology and Bio..." refers background or methods in this paper

  • ...We and others have made microfluidic systems to carry out separations with CE by using plasma oxidation to seal PDMS capillaries irreversibly to glass surfaces (97, 199)....

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  • ...The use of plastics (including elastomers such as PDMS) in the fabrication of μTAS is rapidly becoming more common because of the advantages—especially in cost—offered by these materials (13, 97)....

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Journal ArticleDOI
30 May 1997-Science
TL;DR: Human and bovine capillary endothelial cells were switched from growth to apoptosis by using micropatterned substrates that contained extracellular matrix-coated adhesive islands of decreasing size to progressively restrict cell extension.
Abstract: Human and bovine capillary endothelial cells were switched from growth to apoptosis by using micropatterned substrates that contained extracellular matrix-coated adhesive islands of decreasing size to progressively restrict cell extension. Cell spreading also was varied while maintaining the total cell-matrix contact area constant by changing the spacing between multiple focal adhesion-sized islands. Cell shape was found to govern whether individual cells grow or die, regardless of the type of matrix protein or antibody to integrin used to mediate adhesion. Local geometric control of cell growth and viability may therefore represent a fundamental mechanism for developmental regulation within the tissue microenvironment.

4,641 citations


"Soft Lithography in Biology and Bio..." refers background in this paper

  • ...BCE cells attached to surfaces composed of multiple adhesive islands in an inert sea—where each island was too small to allow growth—spread over an area that was larger than the aggregate area of the adhesive spots and entered the growth phase (15)....

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  • ...In a typical experiment, the hydrophobic hexadecanethiol is printed onto a gold-coated surface to generate patterns that promote the adsorption of proteins; the remainder of the surface is covered with an alkanethiol that is terminated with (EG) 3OH groups; this surface resists the adsorption of proteins and the adhesion of cells (15, 17)....

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  • ...BCE cells also attached to patterns consisting of multiple adjacent islands with diameters smaller (3–5 μm) than that of the cell (Figure 8) (15)....

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  • ...Biological processes—for example, adsorption of protein—that occur at the surfaces of SAMs can be studied with surface plasmon resonance (35–39), quartz crystal microbalance (40–42), ellipsometry (43), contact angle (44, 45), infrared spectroscopy (46, 47), atomic force microscopy (48, 49), sum frequency spectroscopy (50), X-ray photoelectron spectroscopy (51), surface acoustic wave and acoustic plate mode devices (52, 53), confocal and optical microscopies (15), low-angle X-ray reflectometry (54, 55), electrochemical methods (56, 57), and scanning elecron microscopy (58, 59)....

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  • ...Approaches to patterning cells generally involve the patterning of proteins in the geometry desired for the cells; proteins and cells are delivered to the patterned surfaces from solutions or suspensions (15, 17)....

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Book
01 Jan 1977
TL;DR: In this article, the polarization of light waves and propagation of polarized light through polarizing optical systems are discussed. But the authors focus on the application of ellipsometry in the field of measurement in ellipsometer systems.
Abstract: Preface. 1. The polarization of light waves. 2. Propagation of polarized light through polarizing optical systems. 3. Theory and analysis of measurements in ellipsometer systems. 4. Reflection and transmission of polarized light by stratified planar structures. 5. Instrumentation and techniques of ellipsometry. 6. Applications of ellipsometry. Appendix. Author index. Subject index.

4,634 citations