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Über dieses Buch

This book describes automatic methods for the design of droplet microfluidic networks. The authors discuss simulation and design methods which support the design process of droplet microfluidics in general, as well as design methods for a dedicated droplet routing mechanism, namely passive droplet routing. The methods discussed allow for simulating a microfluidic design on a high-abstraction level, which facilitates early validation of whether a design works as intended, automatically dimensioning a microfluidic design, so that constraints like flow conditions are satisfied, and automatically generating meander designs for the respective needs and fabrication settings. Dedicated methods for passive droplet routing are discussed and allow for designing application-specific architectures for a given set of experiments, as well as generating droplet sequences realizing the respective experiments. Together, these methods provide a comprehensive “toolbox" for designers working on droplet microfluidic networks in general and an integrated design flow for the passive droplet routing mechanism in particular.Provides both a comprehensive “toolbox" for designers working on droplet microfluidic networks in general and an integrated design flow for the passive droplet routing mechanism in particular;Describes for the first time CAD methods for droplet microfluidic networks, along with the first integrated design process;Includes open source implementations, in order to reach the largest possible user group within the domain of microfluidics.

Inhaltsverzeichnis

Frontmatter

Introduction and Background

Frontmatter

Chapter 1. Introduction

Abstract
This chapter provides an introduction into microfluidics in general and droplet microfluidic networks in particular. It briefly reviews the state-of-the-art design process for such devices and discusses the contributions made in this book to improve it. By this, the chapter gives an overview of the book and its contributions.
Andreas Grimmer, Robert Wille

Chapter 2. Background

Abstract
Microfluidics deals with the manipulation and control of small amounts of fluids and is frequently applied for Lab-on-a-Chip devices. In this chapter, the background on microfluidics including an overview of possible platforms is reviewed. Afterwards, this chapter focuses on droplet microfluidic networks, which are considered in this book. Finally, details on the hardware and software setup are provided, which has been applied for implementing and evaluating the proposed design methods.
Andreas Grimmer, Robert Wille

Design Methods for Droplet Microfluidic Networks in General

Frontmatter

Chapter 3. Simulating Droplet Microfluidic Networks

Abstract
When designing a droplet microfluidic network, a huge number of parameters have to be considered, which finally have to implement the desired functionality. This results in a complex task as design parameters often depend on and affect each other. In order to handle this complex task, models and simulation methods can be employed in the design process. These models and simulation methods allow for deriving the design, for validating the functionality of the design, and for exploring alternative designs.
However, state-of-the-art simulation tools come with severe limitations, which prevent their utilization for practically relevant applications. More precisely, they are often not dedicated to droplet microfluidics, cannot handle the required physical phenomena, are not publicly available, and can hardly be extended. To address these shortcomings, this chapter introduces an advanced simulation framework at the one-dimensional analysis model, which, eventually, allows to simulate practically relevant applications.
In order to describe the advanced simulation framework, this chapter first reviews abstraction levels—especially the one-dimensional analysis model. Based on that, an advanced simulation framework is proposed, which is finally applied for the design of a practically relevant microfluidic network. A case study demonstrates that using the proposed simulation framework allows to reduce the manual design time and costs, e.g., of a drug screening device from one person month and USD 1200, respectively, to just a fraction of that.
Andreas Grimmer, Robert Wille

Chapter 4. Dimensioning Droplet Microfluidic Networks

Abstract
In a droplet microfluidic network, all used components have to be properly chosen. This includes the specifications of the used pumps, modules, sorters, and channels—i.e., the microfluidic network needs to be dimensioned. The specifications of all components and how they are connected eventually will determine the flow of droplets. Here, especially the specification of channels (i.e., their resistances) can be varied in a broad bandwidth and, by this, their proper dimensioning constitutes a significant challenge. In fact, improper specifications can cause the flow in channels/modules to be in the wrong direction or the time a droplet requires to pass a channel/module to be too long/short. However, no dedicated tool support exists yet for completing this specification. Hence, designers are usually left alone during this crucial step, which frequently yields specifications that do not work as intended.
In this chapter, these problems are addressed by introducing first automatic methods that aid designers in the specification of droplet microfluidic networks—especially in the dimensioning of channels. More precisely, methods are proposed which automatically allow to (1) validate whether a manually derived specification indeed works as intended, i.e. fulfills certain objectives as well as (2) conduct the dimensioning to obtain a proper specification.
Case studies show that both methods significantly aid the designer in the process of determining a precise specification for droplet microfluidic networks. To this end, a designer having expert knowledge was provided with these two methods. They enabled him/her to quickly check and refine initial specifications as well as to efficiently determine a specification which works as intended.
Andreas Grimmer, Robert Wille

Chapter 5. Designing Meanders

Abstract
When drawing physical designs of microfluidic devices, designers often have to handle re-occurring entities. Meander channels are one example, which are frequently used in different platforms but always have to fit the respective application and design rules. This chapter presents a method which is capable of automatically generating user-defined, two-dimensional designs of fluidic meander channels facilitating fluidic hydrodynamic resistances. This method is distributed as an online tool called Meander Designer and implements specific design rules as it considers the user’s needs and fabrication requirements. The compliance of the meanders generated by the Meander Designer is confirmed by fabricating devices using the generated designs and comparing whether the resulting devices indeed realize the desired specification. To this end, two case studies are considered: first, the realization of dedicated fluidic resistances and, second, the realization of dedicated mixing ratios of fluids. The results demonstrate the versatility of the method regarding application and technology. Overall, the freely accessible online tool with its flexibility and simplicity renders manual drawing of meanders obsolete and, hence, allows for a faster, more straightforward design process.
Andreas Grimmer, Robert Wille

Design Methods for Microfluidic Networks Using Passive Droplet Routing

Frontmatter

Chapter 6. Passive Droplet Routing

Abstract
Instead of using valves, switches, or any other active components, passive droplet routing only exploits the hydrodynamic effect that a droplet always enters the channel with the highest instantaneous volumetric flow rate. By exploiting this mechanism, entirely passive microfluidic networks can be designed, which allow to control a droplet to flow through an intended path through a microfluidic network. This supports the execution of multiple different experiments on the same device and, hence, increase the device’s flexibility, effectiveness, as well as reusability. But despite these promises, passive droplet routing requires dedicated design methods, which are proposed in this part of the book. To provide a basis for that, this chapter reviews the underlying physics of passive droplet routing. Therefore, the 1D analysis model is used to describe the passive droplet routing at bifurcations.
Andreas Grimmer, Robert Wille

Chapter 7. Designing Application-Specific Architectures

Abstract
The passive routing mechanism can be used in different architectures, which define how the used modules executing the operations are connected and arranged. Thus far, simple architectures like rings and buses have been considered. But these architectures are often unsuited for the given experiments and suffer from large execution times or require complex droplet re-injections.
This chapter aims to overcome these obstacles by exploring application-specific architectures, which are particularly suited for a given set of experiments to be realized. But designing an application-specific architecture which allows to execute all experiments, considers physical constraints, and is optimized for the designer’s needs is a complex task. In order to handle this complexity and to generate these application-specific architectures, an automatic method is introduced in this chapter. The proposed method automatically generates architectures that are optimized with respect to various physical constraints and/or design objectives such as the number of required modules, connections, and depth. An evaluation demonstrates the performance of the proposed design method and the superiority of the resulting application-specific architectures compared to the ring architecture which is mostly used thus far.
Andreas Grimmer, Robert Wille

Chapter 8. Generating Droplet Sequences

Abstract
The passive droplet routing mechanism allows to route a payload droplet (containing the biological sample) through different paths of a microfluidic network and, by this, allows for executing different experiments on a single device. But in order to establish a routing for the payload, a dedicated orchestration of droplet injections has to be realized. In fact, whenever a payload is supposed to take a non-default successor at any bifurcation in the network, it has to be made sure that another droplet (called header droplet) arrives before and flows through the default successor in order to “block it”. Especially for application-specific architectures, generating the corresponding droplet sequences and injection times is not obvious. To address this problem, this chapter first proposes an abstraction of the flow behavior in the form of a discrete model. Based on this discrete model, the generation for the desired droplet sequence can now be formulated as a combinatorial problem and, hence, allows to use automatic methods for solving it. Based on that, this chapter eventually describes corresponding methods for the generation of droplet sequences realizing the desired experiments.
Andreas Grimmer, Robert Wille

Chapter 9. Integrated Design Process

Abstract
The tasks to design droplet microfluidic networks are often conducted manually using calculations, simplifications, as well as assumptions and require the consideration of a large number of design parameters. Thus far, no integrated design process for this is available. In order to improve this status quo, the chapters of Part II of this book presented a variety of tools for microfluidics in general, which supports designers in single tasks like simulation, dimensioning, or designing meanders. Besides that, the chapters of Part III of this book additionally introduced dedicated methods for microfluidic networks based on passive droplet routing. By this, several automatic methods are available that support the designer in major tasks of the design process of droplet microfluidic networks in general as well as when the networks are based on passive droplet routing in particular. This chapter demonstrates that these methods can even be combined to an integrated design process for designing microfluidic networks based on passive droplet routing.
Andreas Grimmer, Robert Wille

Conclusion

Frontmatter

Chapter 10. Summary and Conclusion

Abstract
In the current design process of droplet microfluidic networks, designers conduct many tasks manually, which requires to consider a large number of design parameters all affecting the functionality. After the design, the functionality is usually validated by fabricating prototypes and conducting experiments. However, this current design process based on multiple iterations of refining and testing the design produces high costs (financially as well as in terms of time).
This book proposed design methods, which support or automate tasks in the design process of droplet microfluidic networks. This resulted in a “toolbox” including methods which are generally applicable for droplet microfluidic networks (Part II) and methods which are dedicated to networks employing passive droplet routing (Part III). Furthermore, this book proposed an integrated design process for microfluidic networks using passive droplet routing by combining the methods from Parts II and III.
Andreas Grimmer, Robert Wille

Backmatter

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