Microfluidic Devices for Biomedical Applications

Xiujun (James) Li, Yu Zhou, Xiujun James Li

• Publisher: Woodhead Publishing
• Year: 2013
• eBook ISBN: 9780857097040
• Topic: Physical Sciences
• Subtopic: Medical Technology & Supplies

Microfluidics or lab-on-a-chip (LOC) is an important technology suitable for numerous applications from drug delivery to tissue engineering. Microfluidic devices for biomedical applications discusses the fundamentals of microfluidics and explores in detail a wide range of medical applications.The first part of the book reviews the fundamentals of microfluidic technologies for biomedical applications with chapters focussing on the materials and methods for microfabrication, microfluidic actuation mechanisms and digital microfluidic technologies. Chapters in part two examine applications in drug discovery and controlled-delivery including micro needles. Part three considers applications of microfluidic devices in cellular analysis and manipulation, tissue engineering and their role in developing tissue scaffolds and stem cell engineering. The final part of the book covers the applications of microfluidic devices in diagnostic sensing, including genetic analysis, low-cost bioassays, viral detection, and radio chemical synthesis.Microfluidic devices for biomedical applications is an essential reference for medical device manufacturers, scientists and researchers concerned with microfluidics in the field of biomedical applications and life-science industries.- Discusses the fundamentals of microfluidics or lab-on-a-chip (LOC) and explores in detail a wide range of medical applications- Considers materials and methods for microfabrication, microfluidic actuation mechanisms and digital microfluidic technologies- Considers applications of microfluidic devices in cellular analysis and manipulation, tissue engineering and their role in developing tissue scaffolds and stem cell engineering

Part I

Fundamentals of microfluidic technologies for biomedical applications

1

Materials and methods for the microfabrication of microfluidic biomedical devices

W.I. Wu, P. Rezai, H.H. Hsu and P.R. Selvaganapathy, McMaster University, Canada

Abstract:

The materials that have been employed for the construction of microfluidic devices have been diverse, ranging from traditional materials, such as silicon and glass, to newer polymeric materials. Similarly, the methods for microfabrication have included lithography, casting, injection molding and hot embossing, to name a few. In this chapter, we provide an overview of the various materials and methods that have been used in a diverse range of microfluidic applications. Details on the physical and chemical properties of the materials, as well as the performance characteristics of the microfabrication methods, are provided.

Key words

microfabrication

soft lithography

injection molding

hot embossing stereo lithography

parylene

PDMS

Su-8

paper

glass

silicon

polycarbonate

polyimide

PMMA

CoC/CoP

polyurethane

1.1 Introduction

Advanced microfluidic and lab-on-a-chip devices have been extensively studied and developed over the last two decades, due to their inherent advantages such as low consumption of chemicals, rapid analysis, biocompatibility, low cost and automation in biological, biomedical and analytical chemistry studies. Since the technology for developing these devices was initially adapted from the conventional semiconductor microelectronic industry, initial devices were primarily made from silicon and glass. Many commercially available microfluidic devices are made using this technology. However, these materials are expensive, require high cost fabrication methods; newer polymeric materials have been investigated and fabrication processes have developed, especially in the context of rapid prototyping and disposable applications. Polymers are macromolecules polymerized from smaller molecules called monomers through a series of chemical reactions. They can be categorized on the basis of their structures and behaviors (Nicholson, 1997), but are mostly classified in accordance with their response to thermal treatment. They have a low cost (suited for disposable devices), can be easily mass-produced by various rapid prototyping techniques, have a wide range of material properties (chemical inertness, low electrical, thermal conductivity, etc.), can also be tailored (using surface modification techniques) appropriately for the analyte under consideration and, more importantly, have been already used in tools and laboratory equipment where conventional biological and chemical assays have been conducted. The devices made of polymers are very amenable to automation and high throughput screening. This chapter describes some of the materials widely used in biomicrofluidic and manufacture of microelectromechanical systems (MEMS), their properties, and their fabrication methods.

1.2 Microfabrication methods

The microfabrication techniques used in construction of microfluidic devices can be broadly classified into two types. These are (1) photolithography-based, and (2) replication based. In photolithographic microfabrication, light is used to define patterns on a photosensitive material, and its wavelength determines the resolution that can be achieved. The final resolution of the pattern also depends on the limitation of optical components, and material properties such as numerical aperture and the polarity of photoresist. The photosensitive material itself can be used as a structural feature of the device, or this pattern can be transferred onto another structural material. In the replication method, a master mold is made using either the photolithographic process or traditional machining processes. This mold, which could be of any material, can withstand the operating conditions of the process, and is used to replicate the pattern or feature onto another softer material through direct physical contact. The choice of the fabrication method in any application depends on various factors such as the desired substrate, cost, speed, feature size, and profile. The following sections will briefly describe existing microfabrication technologies and materials used in microfluidic applications, along with their advantages and limitations.

1.2.1 Photolithography-based microfabrication

Photolithography is the technique of using light to define features on a photo-definable material. This technique, along with the established semiconductor manufacturing process of thin film deposition and etching, was initially adapted to produce the first microfluidic devices on silicon (Manz et al., 1991; Terry et al., 1979) and glass (Fan et al., 1992; Jacobson et al., 1994) substrates. New methods to fabricate high-aspect-ratio open microchannel structures in silicon or glass substrate using various etching techniques such as reactive ion etching, HF wet etching, or KOH wet etching, were simultaneously developed. Subsequently, the microchannels were enclosed using bonding techniques such as electromagnetic induction heating (Thompson et al., 2002), hydrophobic silicon bonding (Tong et al., 1994), fusion bonding (Harendt et al., 1992), and anodic bonding (Kutchoukov et al., 2003). Although these processes are well developed, the cost of the substrates and of microfabrication in a clean room facility makes them unsuitable for disposable microfluidic devices. These microfabrication techniques have been extensively reviewed in review articles (Bustillo et al., 1998; Gad-El-Hak, 2002; Hoffmann and Voges, 2002; Judy, 2001a, 2001b; Lang, 1996; Maluf, 2002; Miki, 2005; Petersen, 1982; Rai-Choudhury, 1997; Stokes and Palmer, 2006).

The cost consideration led to the investigation and use of photo-definable polymers such as conventional photoresists that have been used for patterning in the microelectronics industry as structural elements in microfluidic devices. For instance, these photoresists were applied to create manifolds for microfluidic devices (Burns et al., 1998), though channel height is limited to < 3 μm due to their physical parameters. Even earlier, X-rays were used to define features in photoresist using a process known as lithographie, galvanoformung, abformung (LIGA) to obtain > 350 μm microstructures with an aspect ratio of > 100:1 (Becker et al., 1986). Later, the photoresist SU-8, which requires no complex X-ray facility, was developed for high microstructures using the standard photolithography process (Lin et al., 2002; Sikanen et al., 2005; Yang, 2004). A channel height of 100 μm and aspect ratio of > 10:1 is achievable, according its manufacturer (MICROCHEM, 2012).

Various methods have been adopted for fabrication of photoresist-based microfluidic devices. The first method shown in Fig. 1.1c begins with a spincoating of photoresist onto a substrate, and patterning with a photomask (Metz et al., 2004; Tay et al., 2001). Once the open microchannels are created, a sacrificial material is filled into the space of the microchannel. Subsequently, a second layer of photoresist is spin-coated and patterned on top to define the access holes for inlet and outlet. Finally, the sacrificial layer is dissolved to create the closed microchannels. The major disadvantage in this process is the slow dissolution, therefore only short microchannels are applicable. The second method shown in Fig. 1.1b laminates a dry SU-8 or Kapton film on top of the open microchannels (Agirregabiria et al., 2005). Although this process is relatively simple, the alignment and the bonding strength of lamination could be challenging. The third method shown in Fig. 1.1a uses two exposures at different wavelengths to create the embedded microchann...

Table of contents

• Cover image
• Title page
• Table of Contents
• Copyright
• Contributor contact details
• Woodhead Publishing Series in Biomaterials
• About the editors
• Preface
• Part I: Fundamentals of microfluidic technologies for biomedical applications
• Part II: Applications of microfluidic devices for drug delivery and discovery
• Part III: Applications of microfluidic devices for cellular analysis and tissue engineering
• Part IV: Applications of microfluidic devices in diagnostic sensing
• Index