Microfluidics in Detection Science: Lab-on-a-chip Technologies: Volume 5 (Detection Science Series) - Hardcover

Hardcover

ISBN 10: 1849736383 ISBN 13: 9781849736381

Publisher: Royal Society of Chemistry, 2014

Synopsis

With insights into LOC applications, and presenting scaled-down versions of existing technology alongside unique approaches that exploit the physics of the micro and nano-scale, this book will appeal to newcomers to the field and practitioners requiring a convenient reference.

About this title

About the Author

Dr. Sub Reddy (C.Chem. MRSC) obtained his first class degree in Chemistry from the University of Manchester. He received his Ph.D. in Membrane-based Electrochemical Biosensing from the same University (1996). His post-doctoral research interests have included the development of quartz crystal-based biosensors, operating in the liquid phase (University of Wales, Bangor; 1994-1997) and the development of application-specific odour sensors (UMIST, Manchester; 1997-1998). Dr. Reddy was Senior Lecturer in Applied Analytical Chemistry at the University of Surrey and recently moved to the University of Central Lancashire as Senior Lecturer in Analytical Chemistry. Current research interests include the development of smart, permselective and biocompatible molecular imprinted polymers and membrane materials for the sensor/sample interface and the advancement of smart materials-based electrochemical, quartz crystal and optical sensors for medical, food and environmental applications. He is particularly interested in developing hydrogel-based molecularly imprinted polymers (HydroMIPs) for the determination of protein markers and other biomarkers and construction of biosensors.

From the Back Cover

The concept of a miniaturised laboratory on a disposable chip is now a reality, and in everyday use in industry, medicine and defence. New devices are launched all the time, prompting the need for a straightforward guide to the design and manufacture of lab-on-a-chip (LOC) devices.

This book presents a modular approach to the construction and integration of LOC components in detection science. The editors have brought together some of the leading experts from academia and industry to present an accessible guide to the technology available and its potential. Several chapters are devoted to applications, presenting both the sampling regime and detection methods needed. Further chapters describe the integration of LOC devices, not only with each other but also into existing technologies.

With insights into LOC applications, from biosensing to molecular and chemical analysis, and presenting scaled-down versions of existing technology alongside unique approaches that exploit the physics of the micro and nano-scale, this book will appeal to newcomers to the field and practitioners requiring a convenient reference.

From the Inside Flap

The concept of a miniaturised laboratory on a disposable chip is now a reality, and in everyday use in industry, medicine and defence. New devices are launched all the time, prompting the need for a straightforward guide to the design and manufacture of lab-on-a-chip (LOC) devices.

This book presents a modular approach to the construction and integration of LOC components in detection science. The editors have brought together some of the leading experts from academia and industry to present an accessible guide to the technology available and its potential. Several chapters are devoted to applications, presenting both the sampling regime and detection methods needed. Further chapters describe the integration of LOC devices, not only with each other but also into existing technologies.

With insights into LOC applications, from biosensing to molecular and chemical analysis, and presenting scaled-down versions of existing technology alongside unique approaches that exploit the physics of the micro and nano-scale, this book will appeal to newcomers to the field and practitioners requiring a convenient reference.

Excerpt. © Reprinted by permission. All rights reserved.

Microfluidics in Detection Science

Lab-on-a-chip Technologies

By Fatima H Labeed, Henry O Fatoyinbo

The Royal Society of Chemistry

Copyright © 2015 The Royal Society of Chemistry
All rights reserved.

ISBN: 978-1-84973-638-1

Contents

Chapter 1 Materials and Fabrication Techniques for Nano- and Microfluidic Devices Kin Fong Lei, 1, 
Chapter 2 Microfluidics Theory in Practice Matthew J. Davies, Marco P. C. Marques, and Anand N. P. Radhakrishnan, 29, 
Chapter 3 Electrokinetics and Rare-Cell Detection Alireza Salamanzadeh and Rafael V. Davalos, 61, 
Chapter 4 Digital Microfluidics Kailiang Wang and Henry O. Fatoyinbo, 84, 
Chapter 5 Manipulation of Micro-/Nano-Objects via Surface Acoustic Waves Peng Li, Feng Guo, Kevin Lin, and Tony Jun Huang, 136, 
Chapter 6 Introduction to Optofluidics for LOC Systems Henry O. Fatoyinbo, 153, 
Chapter 7 Applications of Dielectrophoresis in Microfluidics Blanca H. Lapizco-Encinas, 192, 
Chapter 8 Novel Lab-on-a-Chip Sensing Systems: Applications of Optical, Electrochemical, and Piezoelectric Transduction in Bioanalysis Anthony J. Tavares, Samer Doughan, M. Omair Noora, Matthew V. DaCosta, Paul A. E. Piunno, and Ulrich J. Krull, 224, 
Subject Index, 270, 

CHAPTER 1

Materials and Fabrication Techniques for Nano- and Microfluidic Devices

KIN FONG LEI

1.1 Introduction

Microfluidic technology has enabled the realisation of a vast range of miniaturised analytical devices. Microfluidic devices are commonly associated with lab-on-chip (LOC) systems or micrototal-analysis system ((μTAS), when scaled-down operations are performed on miniaturised versions of conventional laboratory bench top instruments. One of the main objectives of microfluidic technologies is to provide a total solution, from sample input to display of the analysed results. Complete analytical protocols, from sample pretreatment through to sample/reagent manipulation, separation, reaction, and detection, can be performed automatically on well-designed and integrated miniaturised devices.

Historically, developmental advances of microfluidic devices originated from the microelectronics manufacturing sector. Silicon has been used as the base substrate material for fabricating microfluidic devices for various applications. Well-established silicon processing and extensive studies of silicon properties have contributed to the rapid evolution of microfluidic technologies. The fabrication process for silicon-based microfluidic devices involve substrate cleaning, photolithography, metal deposition, and wet/dry etching. However, silicon substrate is relatively expensive and optically opaque to certain electromagnetic wavelengths, limiting its applications in optical detection. To combat these shortcomings, glass and polymeric materials have been used to fabricate microfluidic devices. Compared with silicon, glass and polymer materials are inexpensive and optically transparent. Polymer materials include polymethylmethacrylate (PMMA), polystyrene (PS), polycarbonate (PC), and polydimethylsiloxane (PDMS). Amongst these polymer materials, PDMS has been one of the most widely used materials for fabricating microfluidic devices in recent years due to its flexibility in moulding and stamping, optical transparency, and biocompati-bility. Recently, paper has been proposed to be an alternative material used as a substrate of microfluidic devices. Paper is inexpensive, lightweight, available in a wide range of thickness, and is disposable. Aqueous solutions can be transported by wicking, thus realising passive pumping. In addition, well-defined pore sizes in paper can be manufactured and suspended solids within samples can be separated based on size exclusion before an assay is performed. Paper is biocompatible with various biological samples and can thus be modified with a wide range of functional groups to enable covalent bonding of proteins, DNA, or small molecules creating bespoke biochemical sensing systems.

In this chapter, materials used in the fabrication of microfluidic devices are grouped for discussing microfabrication techniques and applications. Moreover, the ability of system integration, cost of processing, and suitability for specific applications will be highlighted. An up-to-date and systematic approach for fabricating nano- and microfluidic devices will be presented.

1.2 Traditional Silicon-Based Microfluidic Devices

From the beginning of the 20th century, continual rapid development of microelectronic technologies made computing processors fast and inexpensive. In 1965, Gordon Moore observed that the number of transistors per unit area would double every two years. This extraordinary growth rate led to the realisation of current personal computers that run on the computing power of millions of transistors within a centimetre scale environment. In the 1980s, microelectromechanical systems (MEMS) were inspired by microelectronic technologies and were developed from microelectronic fabrication processes to build machines on the order of micrometres. The majority of MEMS devices are made from single-crystal silicon wafers and their fabrication processes include deposition of poly-crystalline silicon for resistive elements, metal deposition for conductors, silicon oxide for insulation and as a sacrificial layer, and silicon nitride and titanium nitride for electrical insulation and passivation. Sensors, actuators, and control functions can also be cofabricated on standard silicon wafers. There has since been remarkable progress in research in MEMS technologies, under strong capital promotions from both national governments and industry.

Microfluidic technology is one of the branches of MEMS that handles fluids within submillimetre environments, i.e. typically microlitres, nano-litres, or even picolitres. Fluids are manipulated, mixed, or separated on a compact platform for various biomedical, biochemical and chemical analytical applications. One of the objectives of the development of microfluidic devices is to provide a total solution (i.e. sample-to-answer) in low-cost and rapid systems. For instance, point-of-care (POC) diagnostic applications can be realised based on the advantages of miniaturisation, integration, and automation of the microfluidic system. Microfluidic devices can, and are often modelled as miniaturised versions of conventional laboratory devices, with early developments of microfluidic technologies being based predominantly on silicon as the substrate of choice for many microfluidic devices.

1.2.1 Microfabrication with Silicon

Silicon microfabrication is the process for the production of devices on silicon wafers in the submicrometre to millimetre range. Normally, structures in microfluidic devices have relatively high aspect ratios compared to those in microelectronic devices, which are fabricated to within the top few micrometres of the substrate material. Microfluidic devices may require the whole substrate thickness, utilise both sides of the substrate, or require bonding multiple substrates together. Besides the conventional microelectronic fabrication techniques, such as photolithography, thin-film deposition, and etching, some newer processes were introduced to fulfill the fabrication requirement of microfluidic devices. Since there is a plethora of silicon microfabrication techniques, only the important processes in fabricating microfluidic devices are discussed. For a more comprehensive over-view of further techniques refer to ref. 15.

1.2.1.1 Photolithography

Photolithography is the transfer of a pattern on to a material and is arguably the most important step in the microfabrication process. It predominantly utilises ultraviolet (UV) light to transfer a geometric pattern from a photomask to a light-sensitive chemical photoresist, e.g., AZ1500-series resists, on the substrate. For higher-resolution patterns, expensive technologies such as X-ray, electron beams, or ion beams are used in the photolithographic process. Generally, a series of steps are included in the photolithographic process, such as photomask creation, wafer cleaning, photoresist application, UV exposure, and development (for exact steps and specification/tolerances, refer to the photoresist manufacturer's datasheet). A brief overview of the steps involved is discussed below.

A photomask is a glass or quartz plate with a chromium geometric pattern, which can be designed by computer software, e.g., Tanner EDA L-Edit. The creation of the photomask begins from a square glass or quartz plate covered with a full layer of chromium. A laser beam or electron beam is used to travel over the photoresist on the chromium surface for exposure of the pattern defined by the computer software. Where the photoresist is exposed, the chromium can be etched away. A transparent path is left for the illuminating light to penetrate through. The glass or quartz plate is trans-parent to UV light and chromium blocks the light. Therefore, a photomask can define the geometric pattern over the entire wafer in a single step of UV exposure.

To obtain highly reliable devices and improve the yield rate, contaminants present on the surface of silicon wafer must be removed before micro-fabrication. RCA clean is the industrial standard cleaning procedure. Werner Kern developed the basic procedure in 1965 while working for RCA (Radio Corporation of America). The RCA clean procedure has three major sequential steps: (1) Mixing one part NH4OH with five parts deionised water, heating to 80 °C, then adding one part H2O2, immersing the wafer for 10 min to remove organic contaminants (Note: A thin silicon dioxide layer along with metallic contamination on the silicon surface is formed and has to be removed in subsequent steps). (2) A short immersion in a 1 : 50 solution of HF and H2O at 25 °C in order to remove the thin oxide layer. (3) Mixing one part HCl and six parts deionised water, heating to 80 °C, then adding one part H2O2, and immersing the wafer for 10 min to remove metal ions.

Photoresist application is followed to create a thin-film photoresist on the wafer surface. Photoresist is a solution of a light-sensitive polymer. Either positive or negative resists can be selected, depending on whether it is desirable to have the opaque regions of the photomask for the protection of the resist during UV exposure, or vice versa. Application of the photoresist layer on the silicon wafer is normally accomplished via a spin-coating process. The photoresist is carefully dispensed onto the wafer surface, avoiding bubble formations, and spun at high speeds, i.e. 3000 rpm. The spinning speed determines the photoresist film thickness. The wafer is then "soft baked" at 75-100 °C for about 1 min to remove solvents and improve adhesion. This process can create a uniform and smooth photoresist film on the wafer surface. The exact values of the parameters including spinning speed, baking temperature, and baking duration can be determined from the manufacturer's datasheet.

After photoresist application, the photoresist is exposed under UV light for the definition of the geometric pattern based on the photomask. The photomask and the photoresist-coated wafer are respectively placed into the UV exposure machine. The machine has micrometre manipulators and a microscope that allow for precise alignment of the fiducial markers located on the photomask and the wafer. The alignment process is critical for fabricating multilayer structures. The photomask is placed in direct contact or proximity contact (10-20 μm) above the photoresist-coated surface. The photoresist is then exposed to UV light under programmed time duration, which is determined by the energy adsorption of the photoresist.

The photoresist is then developed to remove the undesired regions. With positive photoresist, the regions that are exposed by UV light become soluble in the developer. The converse is true for negative photoresist. Control of development time is critical for fabricating high-resolution patterns. Photoresist stripping can be accomplished by etching. Both an oxygen plasma etching process or Piranha solution, i.e. 3 : 1 mixture of H2SO4 and H22, at around 120 °C can remove photoresist.

An example of the photolithography process to fabricate metal patterns on a silicon wafer is illustrated in Figure 1.1. It shows the fabrication process from wafer cleaning, photoresist application through to UV exposure and development. The patterned photoresist on the wafer is thus created. Then, thin-film metal is deposited on the entire wafer surface (see Section 1.2.1.2). Photoresist stripping is performed and the metal pattern is left on the wafer surface. This process is called lift-off and is commonly used for the fabrication of metal electrodes on wafers.

1.2.1.2 Thin-Film Deposition

Thin-film deposition process is an "additive" process that adds a thin film on the entire surface, such as silicon dioxide, polysilicon, silicon nitride, and metal. Basically, physical vapour deposition (PVD) is a common approach for fabricating microfluidic devices, where a thin film is deposited onto a substrate surface by the condensable vapour of the desired material, through a vacuum or low-pressure gaseous environment. The vapour is physically transported from a target source by various techniques, e.g., evaporation, sputtering, cathodic arc, and pulsed laser. Evaporative deposition and sputter deposition are discussed and compared below.

In general, evaporation is used to deposit metals and some compounds with low fusion temperature, e.g., Au, Al, Ti, Cr, and SiO. Resistive and electron beam heating are the major types of evaporation techniques. In resistive heating, the desired metal is placed in a refractory tungsten "boat" working as an electrically heated filament. When current is applied to the filament, the metal is evaporated and deposited onto the substrate. An illustration of the resistive evaporation is shown in Figure 1.2. In electron-beam heating, an electron beam is scanned over the metal to generate a vapour for deposition. It has high deposition rates and lower substrate heating than resistive evaporation, thus generating less tensile stress in the deposited film on the unheated substrate.

Sputter deposition is based on the bombardment of a sputtering target by accelerated inert ions, e.g., Ar. Ejected clusters of the target material become condensable vapour for deposition. There are several methods to obtain the necessary plasma, such as direct current (DC), radio frequency (RF), magnetron, and reactive sputtering techniques. Most materials can be sputtered if sufficiently high-energy plasma can be generated. Sputtering provides a flux of more energetic atoms than in evaporation, thus, it has better step coverage and stress control. Because sputter deposition is from a spatially distributed source, the molecules maintain some directionality for only roughly their mean free path. Sidewall coating is nearly equal to surface coating because the substrate is immersed in the plasma. Evaporation deposits directionally from the source, and thus has poor step coverage. However, this is very useful for lift-off processes. Illustrations of the step coverage between evaporation and sputtering are shown in Figure 1.3.

1.2.1.3 Etching

Once the substrate has been protected with a photoresist or mask, either a thin-film deposition process or an etching process can be performed to add or remove material. The etching process is a "subtractive" process and is generally divided into wet etching with chemical solutions and dry etching with plasma methods.

In order to fabricate subtractive structures, e.g., holes, trenches, and mesas, on silicon wafer, wet silicon etching is performed with appropriate choice of substrate type, thin-film masking layer, and etchant. Depending on the selection of etchants, silicon wafer can be etched in all directions at nearly the same rate, i.e. isotropic etching, or unequal etch rates for different crystal planes, i.e. anisotropic etching. The most common isotropic etchant is HNA, which is a mixture of hydrofluoric acid (HF), nitric acid (HNO), and acetic acid (CHCOOH). With the SiO mask, microfluidic channels can be etched in the silicon wafer. However, the etch rate is slowed down when the channels are long and narrow due to the diffusion limits of the reaction. Good agitation of the etchant can enhance the etch rate and the etched channel surface (a near perfect hemispherical shape). For anisotropic etching, hydroxides of alkali metals, i.e. KOH, NaOH, CeOH, RbOH, etc., can be used as crystal-orientation-dependent etchants of silicon. They etch much slower on the (111) plane of silicon than other planes. It is also important to note that etching at concave corners on (100) silicon stops at (111) intersections, but convex corners are undercut. Illustrations of isotropic and anisotropic etching are shown in Figure 1.4.

Reactive ion etching (RIE) can be accomplished by chemical reactions under low pressure (a few millitorr) with an RF-generated plasma. Etching at low temperatures (from room temperature to 250 °C) can be achieved by such energetic ions. The reactant gas SF is commonly used for silicon etching. The bulk silicon etching is carried out by the release of the fluorine free radicals through dissociation, ionisation, and attachment reactions. Since the reaction proceeds spontaneously, the etch profiles are nearly isotropic. For fabricating very high-aspect ratio subtractive structures, deep reactive ion etching (DRIE) was introduced. A high-density inductively coupled plasma and an alternating process of etching and protective polymer deposition are used to achieve an aspect ratio of up to 30 : 1. The practical maximum etch depth capability is of the order of 1 mm. The etching step uses SF with a substrate bias of — 5 to — 30 V. The cations generated in the plasma are accelerated nearly vertically into the substrate being etched. After etching for a period of time, polymer deposition using CF is started for coating with a protective polymer layer on all exposed surfaces. Then, the etching step is repeated and the polymer layer on the horizontal surfaces is rapidly removed due to the ion bombardment and the presence of reactive fluorine radicals. With the protective polymer layer on the vertical surfaces, this alternating process can enhance the aspect ratio of the silicon etching.

(Continues...)

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Edition details

• Publisher: Royal Society of Chemistry
• Publication date: 2014
• Language: English
• ISBN 10: 1849736383
• ISBN 13: 9781849736381
• Binding: Hardcover
• Number of pages: 292
• Editor: Fatima H Labeed