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)

Nanotechnology is a multidisciplinary field, which covers a vast and diverse array of devices derived from engineering, biology, physics and chemistry. These devices include nanovectors for the targeted delivery of anticancer drugs and imaging contrast agents. Nanowires and nanocantilever arrays are among the leading approaches under development for the early detection of precancerous and malignant lesions from biological fluids. These and other nanodevices can provide essential breakthroughs in the fight against cancer.

Cancer nanotechnology: opportunities and challenges.

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.

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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)

Microfluidic devices for manipulating fluids are widespread and finding uses in many scientific and industrial contexts. Their design often requires unusual geometries and the interplay of multiple physical effects such as pressure gradients, electrokinetics, and capillarity. These circumstances lead to interesting variants of well-studied fluid dynamical problems and some new fluid responses. We provide an overview of flows in microdevices with focus on electrokinetics, mixing and dispersion, and multiphase flows. We highlight topics important for the description of the fluid dynamics: driving forces, geometry, and the chemical characteristics of surfaces.

Engineering flows in small devices

We describe the formation and control of nanoscale, submerged fluid jets. The focusing process necessary to achieve these small length scales is characterized experimentally and theoretically. Fast mixing is one important application of nanoscale fluid control: We demonstrate this with a continuous-flow mixer capable of mix times of less than $10\ensuremath{\mu}\mathrm{s}$ and sample consumption rates of nanoliters per second. This new technique facilitates the study of fast reaction kinetics on time scales unattainable with conventional mixing technology.

Hydrodynamic Focusing on a Silicon Chip: Mixing Nanoliters in Microseconds

https://www.cell.com/biophysj/pdf/S0006-3495(96)79538-3.pdf

Biotechnology at low Reynolds numbers

A channel-cell system is provided for detecting the presence and/or measuring the presence of analyte particles in a sample stream comprising a laminar flow channel (100), two inlet means (30, 20) in fluid connection with said laminar flow channel (100) for respectively conducting into the laminar flow channel (100) an indicator stream (70) which may comprise an indicator substance which indicates the presence of said analyte particles by a detectable change in property when contacted with said analyte particles, and the sample stream (80), wherein the laminar flow channel (100) has a depth sufficiently small to allow laminar flow of the streams and a length sufficient to allow particles of the analyte to diffuse into said indicator stream (70) to the substantial exclusion of said larger particles in the sample stream (80) to form a detection area; and outlet means (60) for conducting the streams out of the laminar flow channel (100) to form a single mixed stream.

Microfabricated diffusion-based chemical sensor

This invention provides a microfabricated extraction system and methods for extracting desired particles from a sample stream containing desired and undesired particles. The sample stream is placed in laminar flow contact with an extraction stream under conditions in which inertial effects are negligible. The contact between the two streams is maintained for a sufficient period of time to allow differential transport of the desired particles from the sample stream into the extraction stream. In a preferred embodiment the differential transport mechanism is diffusion. The extraction system of this invention coupled to a microfabricated diffusion-based mixing device and/or sensing means allows picoliter quantities of fluid to be processed or analyzed on devices no larger than silicon wafers.

Microfabricated differential extraction device and method

Microfabricated fluid systems allow complex chemical analyses to be performed on sub-nanoliter volumes. However, many common laboratory procedures, including filtration, have yet to be robustly implemented in micro-fluid systems. A device has been developed to separate particles and molecules based on their diffusion coefficients; the process is demonstrated using a micromachined device with fluid channels as small as 20 μm. A simple model predicts exponential dependence of the output concentration on diffusion coefficient in certain regimes. Experiments confirm the model.

James P. Brody

Papers

Hydrodynamic Focusing on a Silicon Chip: Mixing Nanoliters in Microseconds

Biotechnology at low Reynolds numbers

Microfabricated diffusion-based chemical sensor

Microfabricated differential extraction device and method

Diffusion-based extraction in a microfabricated device