Chapter 1 Introduction to Microfluidics
Keith Herold and Avraham Rasooly
This short overview discusses the fundamental elements of moving fluids in lab-on-a-chip (LOC) systems. Liquid flow in such systems is usually either single-phase channel flow or droplet flow on a surface (or between two surfaces). A primary characteristic of all flows considered here is that they are laminar flows, which provide a series of benefits as well as some challenges. Some of such basic elements described in this chapter are channel flows, pressure driven flow, electroosmotic driven flow, capillary effects, surface forces, mixing and two-phase flow.
Part I: Fabrication Technologies
Chapter 2 Fabricating PDMS Microfluidic Channels Using a Vinyl Sign Plotter
Michael Armani, Roland Probst and Benjamin Shapiro
A novel technique is presented for creating PDMS microchannels from molds produced by a sign plotter, which can be done quickly, cheaply, and in-house. To do this a vinyl template is made using a sign plotter, a negative template is made from the vinyl using an epoxy mold, and a final PDMS mold is made using the epoxy template. This method allows for microchannel design and fabrication in less than 2 hr, without the need for clean room lithography or a chrome mask, and eliminates the poor transparency, poor sealing, and adhesive residues of microchannels made directly from vinyl cutouts. This fabrication process was used to create channels to demonstrate microfluidic flow control of particles.
Chapter 3 Functionalized Glass Coating for PDMS Microfluidic Devices
Adam R. Abate, Daeyeon Lee, Christian Holtze, Amber Krummel, Thao Do and David A. Weitz
Microfluidic devices can perform multiple laboratory functions on a single, compact, and fully integrated chip. However, fabrication of microfluidic devices is difficult, and current methods, such as glass-etching or soft-lithography in PDMS, are either expensive or yield devices with poor chemical robustness. We introduce a simple method that combines the simple fabrication of PDMS with superior robustness and control of glass. We coat PDMS channels with a functionalized glass layer. The glass coating greatly increases the chemical robustness of the PDMS devices. As a demonstration, we produce emulsions in coated channels using organic solvents. The glass coating also enables surface properties to be spatially controlled. As a demonstration of this control, we spatially pattern the wettability of coated PDMS channels and use the devices to produce double emulsions with fluorocarbon oil.
Chapter 4 Fabrication of Lab-on-a-Chip Devices Using Microscale Plasma Activated Templating (µPLAT)
Robert Carlson, Shih-hui Chao and John Koschwanez
This chapter presents an integrated package of techniques, microscale PLasma Activated Templating (µPLAT), that enable rapid bench-top microfabrication. µPLAT can be used to quickly fabricate low-cost lab-on-a-chip devices that contain features that are difficult to achieve using photolithography-based methods. For applications with resolution requirements above 50 µm, functioning devices can be made without the use of cleanroom operations, photolithography, and intensive chemistry. We present devices fabricated using µPLAT that contain components for on-chip heating, temperature measurement, pumping, and single-cell level trapping.
Chapter 5 Bonding Techniques for Thermoplastic Microfluidics
Chia-Wen Tsao and Don L. DeVoe
The use of thermoplastic polymers as microfluidic substrates is a robust and growing area of research, with important implications for the development of low cost disposable microfluidic devices for a host of bioanalytical applications. Substrate bonding is a critical step required for the formation of sealed microchannels within thermoplastic chips. Unlike silicon and glass, the diverse material properties of thermoplastics opens the door to an extensive array of substrate bonding options, together with a set of unique challenges which must be addressed to achieve optimal sealing results. This chapter reviews the range of techniques developed for sealing thermoplastic microfluidics. In addition to summarizing and discussing practical issues surrounding these various bonding methods, detailed process descriptions for selected sealing techniques are provided.
Chapter 6 Xurography: Microfluidic Prototyping with a Cutting Plotter
Daniel A. Bartholomeusz, Ronald W. Boutté and Bruce K. Gale
Prototyping is necessary to show proof-of-concept for microfluidic applications and to develop and optimize functional microfluidic features unique to each LOC application. Each microfluidic feature depends on the application's chemistry, sample, purpose, detection method, and desired functionality. Inexpensive and rapid prototyping will accelerate the product-to-market and results-to-publication, whether you are developing a novel Lab-on-a-Chip (LOC) for a particular application or using a previously developed LOC technology to test the feasibility of a particular assay.
This chapter discusses a rapid and inexpensive micro-fabrication technique using a cutting plotter (a plotter fit with a knife blade) with 10 µm resolution, to directly cut microstructures in thin polymer films that can be laminated into complete microfluidic devices, without photolithographic processes or chemicals. Cutting plotters are ideal for microfluidic prototyping because they can cut micro-features with aspect ratios of 1 - 2 times the material thickness in films ranging from 25 - 1000 µm thick. The plotters also costs less that $5,000 and materials cost much less than a photomask. Multi-layered microfluidic structures cut from pressure sensitive and thermal activated adhesive films can be cut and laminated in less than 30 minutes. This method of using a cutting plotter to prototype is called Xurography, for the Greek root words Xuron and graphe meaning razor and writing, respectively. This inexpensive method can rapidly build microfluidic devices or tertiary fluid connections for higher resolution devices.
We describe xurography in detail, from materials and set-up, to design and fabrication. We also describe a couple of applications where xurography enabled a quick device feasibility study and significantly shorted the design time for a complicated microfluidic device.
Chapter 7 Silicon and Glass Micromachining
Edwin T. Carlen, Johan Bomer, Jan van Nieuwkasteele and Albert van den Berg
The past two decades have seen rapid advancement of Lab on a Chip (LOC) systems with applications ranging from gas chromatography to capillary electrophoresis, and more recently to high-pressure chemistry and single cell analysis. For many applications in clinical medicine, biology and chemistry, silicon and glass may still be the preferred materials. The mechanical rigidity, chemical resistance, and low permeability properties of silicon and glass, combined with the optical transparency of glass, make them a good choice for many demanding LOC applications. The large and well developed silicon and glass micromachining toolbox provide the capability to obtain microstructures with high precision and repeatability. In addition, scaling device dimensions down to the nanometer scale is relatively straight forward using silicon and glass micromachining, which is important for emerging fields, such nanofluidics and nanosensing.
Chapter 8 Flow Lithography for Fabrication of Multi-Component Biocompatible Microstructures
Yuk Kee Cheung, David Shiovtiz and Samuel K. Sia
This chapter details and expands upon the original flow lithography procedure that we have developed to directly pattern multi-component microstructures made up of biocompatible hydrogel. We discuss in detail the relevant experimental parameters for making the fabrication technique work in practice as well as the parameters needed to render the substrates compatible with mammalian cells.
Chapter 9 Microtechnology to Fabricate Lab-on-a-Chip for Biology Applications
Sang-Hoon Lee
Recently, basic experimental techniques and associated equipments and tools in a biology laboratory are changing to handle small quantities of samples more efficiently and 'Lab on a chip (LOC)' is one of the latest emerging technologies. To satisfy the diverse requirements of biologists rapidly, it is recommendable for biologists themselves to design and fabricate LOC; however, it is still difficult for them to start. This chapter is written to introduce the overview of microfabrication technology for LOC and the practical method for fabricating LOCs with three examples.
Chapter 10 Cyclic Olefin Copolymer (COC) Polymer Molding for LOC
Dong Sung Kim and Kwang W. Oh
Cyclic olefin copolymer (COC) draws attention as a primary substrate material for the microfluidic lab on a chip (LOC) applications based on its various advantages with regards to physical and chemical properties. For the replication of small structures (especially less than 10 µm), hot embossing is preferable and provides the simple fabrication process compared to the injection molding technique. However, as far as productivity is concerned, an injection molding process is the most effective replication technique for the polymer based LOC which has microstructures with feature size greater than 10 µm. In this chapter, (i) the fabrication process of silicon and polydimethylsiloxane (PDMS) mold inserts and the hot embossing process, and (ii) the proper processing windows of the injection molding and thermal bonding processes of the COC microfluidic LOC are described and discussed in detail. For the injection molding of the COC LOC, the fabrication process of nickel mold inserts is introduced based on UV-photolithography and subsequent electroplating process. A mold base which enables us to utilize a number of fabricated mold inserts by simple replacement is described to develop various types of injection molded COC LOC. Materials required for the whole fabrication process of the COC microfluidic LOC are also provided. Finally, application examples of the molded COC LOC and the perspective on future trends of the COC polymer molding process are provided.
Chapter 11 Laminated Object Manufacturing (LOM) Technology Based Multi-Channel Lab-on-a-Chip for Enzymatic and Chemical Analysis
Steven Sun, Nikolay Sergeev, Jesse Francis, Yordan Kostov, Minghui Yang, Hugh A. Bruck, Keith E. Herold and Avraham Rasooly
Lab-on-a-chip (LOC) technology has the potential to greatly simplify analytical analysis by providing a platform for chemical and biochemical reactions as well as the analysis of such reactions without a laboratory. Prototyping of LOC is critical for rapid and low cost system development. Among the many prototyping methods, Laminated Object Manufacturing (LOM) technology is one of the most rapid and cost effective options. Using this method, it is possible to create 3D microfluidic structures by assembling a stack of polymer sheets, where each layer is fabricated by laser machining of a polymer sheet such as acrylic or polycarbonate and bonding the layers with adhesive. The main elements of LOM using polymer sheets are described here, including LOC design, laser machining, bonding and testing. An example of an eight channel LOC for enzymatic and chemical analysis based on mixing two reagents is provided. The technology, combined with suitable medical assays, has the potential to enhance the quality of health care and to provide care to underserved populations.
Chapter 12 Laser Micromachining
Emanuel Waddell
The use of microfluidic devices is making rapid inroads in the modern analytical laboratory, primarily because of their small physical footprint, speed and efficiency of chemical separations, and reduced reagent consumption. Traditionally, lab-on-a-chip devices have been manufactured in silica due to its well understood surface chemistry and favorable micromachining techniques that are ubiquitous in the microelectronics industry. These techniques are typically based on silica etching which is time consuming, requires specialized resources, and utilizes a large amount of chemical solvents that pose unique safety and environmental hazards. Recently researchers have begun to utilize devices fabricated from polymer substrates as an alternative to glass. Reasons include reducing the total cost and the ability to tailor physical and chemical properties which may include surface roughness, surface charge, optical clarity, and tensile strength. For example, polymer substrates typically have greater impact resistance than glass and when one considers mass production, the cost of polymer substrates are a fraction of the cost of glass which leads to a large amount of savings. However, some of the advantages of using polymers are negated by the traditional microfabrication techniques used to manufacture metal or silicon molds which are subsequently utilized to fabricate polymer devices by imprinting or injection molding. The primary negative associated with manufacturing molds in the laboratory by traditional methods is the time commitment for the production of the original mold and the inability to modify the mold. This proves to be costly and time consuming. In a research and development environment it is important that researchers have access to fabrication techniques that are rapid and easily implemented with a variety of substrates. In addition it is important that changes in the fluidic circuit be implemented with minimal cost and limited time investment. Laser micromachining has been proven to be such a technique and this brief discussion describes the fabrication of simple fluidic circuits in a polymer substrate. In summary, this chapter will examine the practical details involved in laser micromachining provided from the perspective of the novice researcher who desires to utilize the technique for scribing simple microfluidic circuits in readily available polymer substrates.
Chapter 13 Shrinky-Dink Microfluidics
Anthony A. Grimes, Brent D. Rich, Maureen Long, Diep Nguyen and Michelle Khine
Fabricating small and intricate patterns into silicon, glass, or quartz is traditionally expensive as well as manually and time intensive. These setups typically require investments in large specialized equipment, a cleanroom, and costly consumables. To translate from academic prototyping in engineering labs to truly useful analytical tools for researchers from the range of fields that "Lab on a Chip" technologies is predicted to eventually benefit, this field must mature to the point where robust and specifically designed devices can be readily realized. Ideally, researchers can conceive of a specific device design that can uniquely help investigate their hypothesis-driven investigation, and then within minutes, have in their hands a fully functional device. We have recently developed a new technique to circumvent the time and expense of conventional photolithography by leveraging the inherent shrinkage properties of the child's toy Shrinky-Dinks. Shrinky-Dinks are sheets of pre-stressed polystyrene (PS) sheets. By simply patterning these polystyrene sheets, we can create microfabricated patterns. The process we have developed is even faster than soft lithography, the commonly accepted prototyping standard for microfluidics. Furthermore, this technique obviates the high-tooling and consumable costs of photolithography altogether. Using this technique, 3D chips can even be rapidly developed directly in polystyrene (PS). In this review, we characterize the shrinkage performance of these thermoplastics and the tolerances of the patterning. While the tolerances achievable with this thermoplastic cannot yet compete with photolithography, they are sufficient for many applications. In fact, certain applications particularly benefit from the inherent channel geometries (e.g. rou