Micro-Drops and Digital Microfluidics

Micro-Drops and Digital Microfluidics

William Andrew

Chapter One

CHAPTER OUTLINE

1.1 The development of microfluidics 1 1.2 The advantages of digital and droplet microfluidics compared to conventional microflows 2 1.2.1 From microflows to microdrops 2 1.2.2 Microdrops: comparison between digital and droplet microfluidics 3 1.3 The respective place of digital and droplet microfluidics in today's microfluidics 5 1.4 Summary 6 References 6

1.1 The development of microfluidics

The development of microfluidics has been remarkable since the 1980s. Historically, in the 1980s, the first applications of microfluidics were triggered by the generalization of ink-jet printing, and also to some extent by space applications, where droplets are used to feed micromotors. Today, the developments are boosted by biotechnology. Indeed, microfluidics is the basis of most biotechnological developments, simply because biological samples are in a liquid state and biological organisms live in an aqueous environment. Compared to conventional techniques, the use of microfluidic devices has many advantages: the volumes of sample and reagents are significantly reduced—which is practical and diminishes the cost of the process; the results (diagnostic) or the products (biochemistry) are obtained in a much shorter time—which also contributes to reducing costs, or can be necessary for medical emergency reasons; the level of sensitivity is increased due to higher precision and selectivity of the process; the risks with the manipulation of toxic or dangerous products are decreased. Besides, miniaturization allows for an increase in automation and parallelization, which opens the way to screening and systematic testing in the domain of drug discovery. Finally, portability is a unique feature that will permit diagnostic and bioanalysis in the field.

However, the revolution that fluidic microsystems brings to biotechnology depends on the response to some challenges, the most important being the integration of all the components of the system on the same chip. Hence, pumps, valves, mixers, etc. must be miniaturized in order to obtain an integrated system, introducing a complicated choice between active methods—efficient, but difficult to miniaturize and requiring energy sources—and passive methods—easier to integrate, but less efficient. Another challenge is the growing complexity of the microfabrication required to support all the functions of the system: it is foreseen that composite materials will have to be assembled and connected. In biotechnology, the volume reduction from the macroscopic environment where the targets are located to the microscopic environment of the microsystem is also a huge challenge. Molecules and/or particles existing in macroscopic volumes have to be concentrated in microvolumes in order to be introduced in a biochip. Miniaturization of the whole chain of treatment is still to be done. Finally, the very large surface/volume ratio of miniaturized systems modifies the physical behavior of the system and some new problems arise, like, for instance, the adherence of target molecules to the solid walls, or the effect of capillary forces that may prevent the fluid from entering microchannels.

1.2 The advantages of digital and droplet microfluidics compared to conventional microflows

1.2.1 From microflows to microdrops

The most common—and historically first—microsystems, such as microelectrical–mechanical systems (MEMS) or lab-on-a-chip (LOC), are using microflows; conceptually, they are more or less derived from macroscopic devices, taking into account the particularities brought by the reduction of the dimensions and the physical modifications due to the influence of the solid walls. In such systems, microfluidics is often combined with electrics, magnetics, optics, acoustics, and chemistry in order to perform adequate functions. These systems have brought considerable progress to biotechnology. A striking example is that of screening that consists in searching for a specific component in a sample. Conventionally, screening is performed in microplates comprising tenth of 10 µL wells. With this format, when screening for 100,000 components, the process can last for about 4 months and require up to 10 L of reagent. Using microflow systems such as the one described in Figure 1.1, the duration of the same screening is reduced to a week and the quantities of sample are reduced by 100 times. However, a week is still a long time; nowadays, the use of droplet or digital microfluidics reduces the time to about 20 min. This is the case for example of the digital microfluidic (DMF) device shown in Figure 1.2. We see here the considerable advantage brought by digital or droplet microfluidics that is closely linked to the dramatic reduction of volume. The working volumes can be reduced down to 50 nL and probably less than that in the near future.

An advantage brought by the use of microdroplets is the reduction of the contact with the solid walls: a large part of the contact surface of the liquid with the solid wall being replaced by a liquid–liquid or liquid–gas interface, the solid contact surface to liquid volume ratio is reduced compared to that of microflow systems; hence, adherence and adhesion problems are reduced (but not suppressed).

1.2.2 Microdrops: comparison between digital and droplet microfluidics

Digital and droplet microfluidics have in common the use of microdrops and the associated reduction of volume (Figure 1.3). However, they differ considerably. Droplet microfluidics is a particular example of two- or multiphase microflows, where droplets are transported by a carrier flow, whereas DMF is based on a totally different approach, inspired by microplate systems where the manipulation robot would be incorporated; in such systems, the microdrops are moved and treated individually as digital entities on a planar surface (hence the other name of DMF is planar microfluidics), allowing for a very reconfigurable system.

Contrary to microflow and droplet microfluidic systems, where pumps and valves are actuated by mechanical, electrical, magnetic, or acoustic forces, pumping and valving functions are inherent in the DMF construction. A unique actuation force (electric or acoustic) performs all the different tasks like pumping, valving, and motioning the liquid samples.

In the conclusions of Chapter 15, it is shown that digital and droplet microfluidic systems are in fact very complementary. DMF can handle extremely small volumes of liquids and realize operations and manipulation in parallel, and with great accuracy, whereas droplet microfluidics is well adapted to perform operations in series, like screening or encapsulation.

1.3 The respective place of digital and droplet microfluidics in today's microfluidics

It seems interesting to position the place of DMF in the global panel of state-of-the-art microfluidics. The different "toolboxes" proposed by today's microfluidics are shown in Figure 1.4. The first and most important toolbox is the "microflow" toolbox (top left in Figure 1.4). It is now mature and has already been the object of a few books and numerous publications. DMF (top right) is a new toolbox that is the subject of this book. It is still at a developing stage, and its possibilities have not all been determined. More recently, new concepts have been developed to complement the possibilities offered by microfluidics: on the one hand, the two toolboxes, constituted by two-phase microflows and droplet microfluidics that will be the object of Chapter 14, are schematized on the bottom right of Figure 1.4; on the other hand, "open" microfluidics, i.e., microflows in partially opened channels, where the flow is stabilized by capillarity forces in the absence of a solid boundary, is at the crossroads between single- and two-phase microflows (bottom left in Figure 1.4). Open microfluidics is probably the less advanced type of microfluidics today.

1.4 Summary

The aim of this book is to provide the reader with the background for the physical behavior of microdrops in general, with a focus on DMF. A profound understanding of the physics of microdrops—subjected only to surface tension and capillary forces, and to a lesser extent to gravity—is required to be able to tackle the study of DMF—in which electric or acoustic forces are involved. In Chapter 14, an introduction to droplet microfluidics has been inserted in order to give a more complete view of the use of droplets in microsystems.

(Continues...)

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Excerpted from Micro-Drops and Digital Microfluidics by Jean Berthier Copyright © 2013 by Elsevier Inc. . Excerpted by permission of William Andrew. All rights reserved. No part of this excerpt may be reproduced or reprinted without permission in writing from the publisher.
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