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

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.

https://science.sciencemag.org/content/sci/298/5593/580.full.pdf

Microfluidic large scale integration

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.

Micromachining a miniaturized capillary electrophoresis-based chemical analysis system on a chip

Soft materials are finding applications in areas ranging from microfluidic device technology to nanofabrication. We review recent work in these areas, discuss the motivation for device fabrication with soft materials, and describe applications of soft materials. In particular, we discuss active microfluidic devices for cell sorting and biochemical assays, replication-molded optics with subdiffraction limit features, and nanometer-scale resonators and wires formed from single-molecule DNA templates as examples of how the special properties of soft materials address outstanding problems in device fabrication.

https://science.sciencemag.org/content/sci/290/5496/1536.full.pdf

From Micro- to Nanofabrication with Soft Materials

Introduction A Why POC Diagnostics? B Time B Patient Responsibility and Compliance B Cost B Diagnostic Targets C Proteins C Metabolites and Other Small Molecules C Nucleic Acids C Human Cells D Microbes/Pathogens D Drugs and Food Safety D Current Context of POC Assays E POC Glucose Assays E Lateral Flow Assays E Limitations of “Traditional” POC Approaches F Enabling Technologies G Printing and Laminating G Microfluidic Technologies and Approaches: “Unit Operations” for POC Devices G Pumping and Valving H Mixing I Separation I Reagent Storage J Sample Preparation K Surface Chemistry and Device Substrates L Physical Adsorption L Bioaffinity Attachment L Covalent Attachment M Substrate Materials M Detection M Electrochemical Detection N Optical Detection N Magnetic Detection N Label-Free Methods O Enabling Multiplexed Assays O Recent Innovation O Lateral Flow Assay Technologies O Proteins P Antibodies P Protein Expression and Purification Q Nucleic Acids Q Aptamers R Infectious Diseases and Food/Water Safety R Blood Chemistry S Coagulation Markers S Whole Cells S Trends, Unmet Needs, Perspectives T Glucose T Global Health and the Developing World T Personalized Medicine and Home Testing U Technology Trends U Multiplexing V Author Information V Biographies V Acknowledgment W References W

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Point of care diagnostics: Status and future

Electrokinetic forces are emerging as a powerful means to drive microfluidic systems with flow channel cross-sectional dimensions in the tens of micrometers and flow rates in the nanoliter per second range. These systems provide many advantages such as improved analysis speed, improved reproducibility, greatly reduced reagent consumption, and the ability to perform multiple operations in an integrated fashion. Planar microfabrication methods are used to make these analysis chips in materials such as glass or polymers. Many applications of this technology have been demonstrated, such as DNA separations, enzyme assays, immunoassays, and PCR amplification integrated with microfluidic assays. Further development of this technology is expected to yield higher levels of functionality of sample throughput on a single microfluidic analysis chip.

Electrokinetically Controlled Microfluidic Analysis Systems

Laboratory on a chip : A new experimentation format

Phytophthora species are plant pathogens that cause considerable damage to agrosystems and ecosystems, and have a major impact on the economy. Infection occurs when their biflagellate zoospores move and reach a root on which they aggregate. However, the communication between the plant and the zoospores and how this communication modifies the behavior of the swimming zoospores is not yet well characterized. Here we show that using a microfluidic device comprising a growing Arabidopsis thaliana root, we are able to study the kinetics of Phytophthora parasitica zoospores approaching the root and aggregating on a specific area, in real time. We show that the kinetics of zoospores is modified only below a distance of about 300 μm from the center of aggregation, with a decrease in the speed coupled with an increase in the number of turns made. In addition, we show that the rate of aggregation is constant throughout the experiment, approximately one hour, and depends on the density of zoospores. The rate is consistent with a random encounter of zoospores with the root, indicating that no long range signal is evidenced in our set-up.

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Kinetics of zoospores approaching a root using a microfluidic device

Abstract In the present work, a prototype was developed to observe the flow behavior of viscous fluids under free surface shear and determine an adhesion energy in this flow geometry. The geometry consists of an eccentric Couette cell (outer cylinder radius of 89.5 mm, inner cylinder radius of 43.75 mm and minimal gap of 3 mm) that can be used in two modes, where both cylinders can respectively rotate in the same or opposite directions. Cylinders are horizontal and short relatively to their diameters (30 mm long). Transparent windows allow in-situ flow observations. The design, development, and testing of the prototype with a model viscous fluid (silicone fluid with a 2.2 104 Pa.s Newtonian viscosity) are reported in this paper. The flow behavior of small fluid volumes (fill factor smaller than 15%) was investigated under co- and counter-rotating configurations to determine steady-state flow conditions. Stationary conditions were identified in the counter-rotating mode. The velocity conditions and resulting observations are studied and analysed. However, for the used silicone fluid, the bulk dissipative energy is much larger than the work of adhesive forces in the investigated regimes. The adhesion energy contribution could not be detected for this fluid.

C. Cohen

Papers

Electrokinetically Controlled Microfluidic Analysis Systems

Laboratory on a chip : A new experimentation format

Kinetics of zoospores approaching a root using a microfluidic device

Investigation of the interface behavior of a viscous fluid under free surface shear flow using an eccentric transparent Couette cell