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

▪ 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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Soft Lithography in Biology and Biochemistry

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Micro Total Analysis Systems. 1. Introduction, Theory, and Technology

We survey progress over the past 25 years in the development of microscale devices for pumping fluids. We attempt to provide both a reference for micropump researchers and a resource for those outside the field who wish to identify the best micropump for a particular application. Reciprocating displacement micropumps have been the subject of extensive research in both academia and the private sector and have been produced with a wide range of actuators, valve configurations and materials. Aperiodic displacement micropumps based on mechanisms such as localized phase change have been shown to be suitable for specialized applications. Electroosmotic micropumps exhibit favorable scaling and are promising for a variety of applications requiring high flow rates and pressures. Dynamic micropumps based on electrohydrodynamic and magnetohydrodynamic effects have also been developed. Much progress has been made, but with micropumps suitable for important applications still not available, this remains a fertile area for future research.

https://microfluidics.stanford.edu/Publications/Micropumps_Cooling/Laser%20Review%20of%20Micropumps%20in%20JMM.pdf

A review of micropumps

Fundamental and applied research in chemistry and biology benefits from opportunities provided by droplet-based microfluidic systems. These systems enable the miniaturization of reactions by compartmentalizing reactions in droplets of femoliter to microliter volumes. Compartmentalization in droplets provides rapid mixing of reagents, control of the timing of reactions on timescales from milliseconds to months, control of interfacial properties, and the ability to synthesize and transport solid reagents and products. Droplet-based microfluidics can help to enhance and accelerate chemical and biochemical screening, protein crystallization, enzymatic kinetics, and assays. Moreover, the control provided by droplets in microfluidic devices can lead to new scientific methods and insights.

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Reactions in Droplets in Microfluidic Channels

Nanoliter-sized liquid drops can be accurately metered inside hydrophilic microchannels using a combination of hydrophobic surface treatment and air pressure. The technique involves spontaneously filling the microchannels up to a hydrophobic region and splitting a liquid drop by injecting air through a hydrophobic side channel. The hydrophobic regions are fabricated by using a patterned metal mask on a substrate. The patterned substrate is immersed in an isooctane solution containing 1H,1H,2H,2H-per-fluorodecyltrichlorosilane to form hydrophobic patches on the exposed surface. Stripping the metal mask leaves the hydrophobic patches and restores the hydrophilic substrate surface. Precise and accurate liquid volumes, ranging from 0.5 to 125 nanoliters, have been metered using this technique. Theoretical predictions of the pressure needed to meter drops compare well with the experimental values.

Nanoliter liquid metering in microchannels using hydrophobic patterns

A class of “lab-on-a-chip” devices use external air pressure for pumping discrete drops in a microchannel network. External air connectors can be cumbersome and are real-estate intensive. We have developed an on-chip technique to generate pressures required for metering and pumping of nanoliter-volume discrete drops. This is achieved by heating of trapped air in a pressure-generating chamber. The pressure-generating chamber is connected to the point of pressure application in the liquid-conveying microchannel through an air-delivery channel. The trapped air volume on the order of 100 nL is heated by resistive metal heaters by tens of degrees celcius to generate air pressures on the order of 7.5 kN/m2. The rate of discrete drop pumping is electronically controlled in the microchannel device by controlling the rate of air heating. Flow rates on the order of 20 nL/s are obtained in the microchannel (300 μm × 30 μm) by heating the air chamber at the rate of ∼6 °C/s. In this paper, we describe the design, fabr...

On-chip thermopneumatic pressure for discrete drop pumping.

Fast solute mixing can be achieved in a microchannel by rapid unidirectional displacement of a discrete liquid drop. The recirculation streamlines created within the liquid during the drop’s motion cause the solute to interlayer across the channel depth, provided the interlayer diffusion of the solute is small. Uniform interlayering appears when the drop is displaced by more than three drop lengths in a slit-type microchannel, thereby reducing the solute diffusion distances to a fraction of the channel depth. By fabricating the microchannel to a depth of less than 50 µm even large molecules with a low diffusivity ( D< 10 −8 cm 2 s −1 ) can be mixed in seconds. The above strategy is shown by modeling the mixing of solutes present in a drop moving in a slit-type microchannel.

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Mathematical modeling of drop mixing in a slit-type microchannel

We have developed a method to pattern self assembled monolayer films of n-octadecyltrichlorosilane on silicon and glass substrates using a simple lift-off procedure. By defining hydrophobic regions at definite locations in microchannels and using an external pressure source, we can split off precise nanoliter volume liquid drops and control the motion of those drops through the microchannels. We have also constructed an on-chip pressure source for drop splitting and motion by heating air trapped in a micromachined chamber. Both techniques can produce and move drops on the order of 50 nl.

Microfluidic flow control using selective hydrophobic patterning

The movement and mixing of microdroplets through microchannels is described employing microscale device. Sample and reagent are injected into the device through entry ports (A) and they are transported as discrete droplets through channels (B) to a reaction chamber, such as a thermally controlled reactor where mixing and reactions (e.g., restriction enzyme digestion or nucleic acid amplification) occur (C). The biochemical products are then moved by the same method to an electrophoresis module (D) where migration data is collected by a detector (E) and transmitted to a recording instrument. Importantly, the fluidic and electronic components are designed to be fully compatible in function and construction with the biological reactions and reagents.

Kalyan Handique

Papers

Nanoliter liquid metering in microchannels using hydrophobic patterns

On-chip thermopneumatic pressure for discrete drop pumping.

Mathematical modeling of drop mixing in a slit-type microchannel

Microfluidic flow control using selective hydrophobic patterning

Moving and mixing of microdroplets through microchannels