Springer Handbook of Nanotechnology

A biological system can be exceedingly small. Many of the cells are very tiny, but they are very active; they manufacture various substances; they walk around; they wiggle; and they do all kinds of marvelous things – all on a very small scale. Also, they store information. Consider the possibility that we too can make a thing very small which does what we want – that we can manufacture an object that maneuvers at that level.

(From the talk

Thereʼs Plenty of Room at the Bottom

, delivered by Richard P. Feynman at the annual meeting of the American Physical Society at the California Institute of Technology; Pasadena, December 29, 1959).

The constituent components of conventional devices are carved out of larger materials relying on physical methods. This top-down approach to engineered building blocks becomes increasingly challenging as the dimensions of the target structures approach the nanoscale. Nature, on the other hand, relies on chemical strategies to assemble nanoscaled biomolecules. Small molecular building blocks are joined to produce nanostructures with defined geometries and specific functions. It is becoming apparent that natureʼs bottom-up approach to functional nanostructures can be mimicked to produce artificial molecules with nanoscaled dimensions and engineered properties. Indeed, examples of artificial nanohelices, nanotubes, and molecular motors are starting to be developed. Some of these fascinating chemical systems have intriguing electrochemical and photochemical properties that can be exploited to manipulate chemical, electrical, and optical signals at the molecular level. This tremendous opportunity has led to the development of the molecular equivalent of conventional logic gates. Simple logic operations, for example, can be reproduced with collections of molecules operating in solution. Most of these chemical systems, however, rely on bulk addressing to execute combinational and sequential logic operations. It is essential to devise methods to reproduce these useful functions in solid-state configurations and, eventually, with single molecules. These challenging objectives are stimulating the design of clever devices that interface small assemblies of organic molecules with macroscaled and nanoscaled electrodes. These strategies have already produced rudimentary examples of diodes, switches, and transistors based on functional molecular components. The rapid and continuous progress of this exploratory research will, we hope, lead to an entire generation of molecule-based devices that might ultimately find useful applications in a variety of fields, ranging from biomedical research to information technology.

Carbon nanotubes are remarkable objects that look set to revolutionize the technological landscape in the near future. Tomorrowʼs society will be shaped by nanotube applications, just as silicon-based technologies dominate society today. Space elevators tethered by the strongest of cables; hydrogen-powered vehicles; artificial muscles: these are just a few of the technological marvels that may be made possible by the emerging science of carbon nanotubes.

Of course, this prediction is still some way from becoming reality; we are still at the stage of evaluating possibilities and potential. Consider the recent example of fullerenes – molecules closely related to nanotubes. The anticipation surrounding these molecules, first reported in 1985, resulted in the bestowment of a Nobel Prize for their discovery in 1996. However, a decade later, few applications of fullerenes have reached the market, suggesting that similarly enthusiastic predictions about nanotubes should be approached with caution.

There is no denying, however, that the expectations surrounding carbon nanotubes are very high. One of the main reasons for this is the anticipated application of nanotubes to electronics. Many believe that current techniques for miniaturizing microchips are about to reach their lowest limits, and that nanotube-based technologies are the best hope for further miniaturization. Carbon nanotubes may therefore provide the building blocks for further technological progress, enhancing our standards of living.

In this chapter, we first describe the structures, syntheses, growth mechanisms and properties of carbon nanotubes. Then we discuss nanotube-related nano-objects, including those formed by reactions and associations of all-carbon nanotubes with foreign atoms, molecules and compounds, which may provide the path to hybrid materials with even better properties than

pristine

nanotubes. Finally, we will describe the most important current and potential applications of carbon nanotubes, which suggest that the future for the carbon nanotube industry looks very promising indeed.

This chapter provides an overview of recent research on inorganic nanowires, particularly metallic and semiconducting nanowires. Nanowires are

one-dimensional (1-D)

system

one-dimensional, anisotropic structures, small in diameter, and large in surface-to-volume ratio. Thus, their physical properties are different than those of structures of different scale and dimensionality. While the study of nanowires is particularly challenging, scientists have made immense progress in both developing synthetic methodologies for the fabrication of nanowires, and developing instrumentation for their characterization. The chapter is divided into three main sections: Sect.

4.1

the synthesis, Sect.

4.2

the characterization and physical properties, and Sect.

4.3

the applications of nanowires. Yet, the reader will discover many links that make these aspects of nanoscience intimately interdepent.

This chapter introduces the fundamentals of and various technical approaches developed for template-based synthesis of nanorod arrays. After a brief introduction to various concepts associated with the growth of nanorods, nanowires and nanobelts, the chapter focuses mainly on the most widely used and well established techniques for the template-based growth of nanorod arrays: electrochemical deposition, electrophoretic deposition, template filling via capillary force and centrifugation, and chemical conversion. In each section, the relevant fundamentals are first introduced, and then examples are given to illustrate the specific details of each technique.

Nanoparticles are frequently immobilized on substrates to use them as functional elements. In the resulting layer, the particles are accessible, so that their useful properties can be exploited, but their positions are fixed, so that their behavior is stable and reproducible. Frequently, the particlesʼ positions have to be well defined. Templated assembly can position particles even in the low-nanometer size regime, and it can do so efficiently for many particles in parallel. Thus,

building block

nanoparticles become building blocks, capable of forming complex superstructures.

Templated assembly is based on a simple idea: particles are brought to a surface that has binding sites which strongly interact with the particles. Ideally, the particles adsorb solely at the predefined binding sites, thus creating the desired arrangement. In reality, it is often a challenge to reach good yields, high precision, and good specificity, in particular for very small particles. Since the method is very general, particles of various materials such as oxides, metals, semiconductors, and polymers can be arranged for applications ranging from microelectronics to optics and biochemistry.

In this chapter, we describe three-dimensional nanostructure fabrication using 30 keV

focused ion beam chemical vapor deposition (FIB-CVD)

Ga

+

focused ion beam chemical vapor deposition (FIB-CVD) and a

phenanthrene

(C

14

H

10

) source as a precursor. We also consider microstructure plastic art, which is a new field that has been made possible by microbeam technology, and we present examples of such art, including a

micro wine glass

with an external diameter of 2.75 μm and height of 12 μm. The film deposited during such a process is diamond-like amorphous carbon, which has a Youngʼs modulus exceeding 600 GPa, appearing to make it highly desirable for various applications. The production of three-dimensional nanostructure is discussed. The fabrication of microcoils, nanoelectrostatic actuators, and 0.1 μm nanowiring – all potential components of nanomechanical systems – is explained. The chapter ends by describing the realization of nanoinjectors and nanomanipulators, novel nanotools for manipulation and analyzing subcellular organelles.

This chapter outlines and discusses important micro- and nanofabrication techniques. We start with the

integrated

circuit (IC)

most basic methods borrowed from the integrated circuit (IC) industry, such as thin-film deposition, lithography and etching, and then move on to look at microelectromechanical systems (MEMS) and nanofabrication technologies. We cover a broad range of dimensions, from the micron to the nanometer scale. Although most of the current research is geared towards the nanodomain, a good understanding of top-down methods for fabricating micron-sized objects can aid our understanding of this research. Due to space constraints, we focus here on the most important technologies; in the microdomain these include surface, bulk, and high-aspect-ratio micromachining; in the nanodomain we concentrate on e-beam lithography, epitaxial growth, template manufacturing, and self-assembly. MEMS technology is maturing rapidly, with some new technologies displacing older ones that have proven to be unsuited to manufacture on a commercial scale. However, the jury is still out on methods used in the nanodomain, although it appears that bottom-up methods are the most feasible, and these will have a major impact in a variety of application areas such as biology, medicine, environmental monitoring, and nanoelectronics.

Nanoimprint lithography (NIL) is an emerging high-resolution parallel patterning method, mainly aimed

nanoimprint

lithography (NIL)

photolithography (PL)

towards fields in which electron-beam and high-end photolithography are costly and do not provide sufficient resolution at reasonable throughput. In a top-down approach, a surface pattern of a stamp is replicated into a material by mechanical contact and three-dimensional material displacement. This can be done by shaping a liquid followed by a curing process for hardening, by variation of the thermomechanical properties of a film by heating and cooling, or by any other kind of shaping process using the difference in hardness of a mold and a moldable material. The local thickness contrast of the resulting thin molded film can be used as a means to pattern an underlying substrate at the wafer level by standard pattern transfer methods, but also directly in applications where a bulk modified functional layer is needed. This makes NIL a promising technique for volume manufacture of nanostructured components. At present, structures with feature sizes down to 5 nm have been realized, and the resolution is limited by the ability to manufacture the stamp relief. For historical

thermal

NIL

hot embossing

reasons, the term nanoimprint lithography refers to a hot embossing process (thermal NIL). In

UV-NIL

ultraviolet (UV)-NIL,

resin

UV-transparent stamp

a photopolymerizable resin is used together with a UV-transparent stamp. In both processes thin-film squeeze flow and capillary action play a central role in understanding the NIL process. In this chapter we will give an overview of NIL, with emphasis on general principles and concepts rather than specific process issues and state-of-the-art tools and processes. Material aspects of stamps and resists are discussed. We discuss specific applications where imprint methods have significant advantages over other structuring methods. We conclude by discussing areas where further development in this field is required.

Soft-lithographic techniques that use rubber stamps and molds provide simple means to generate patterns with lateral dimensions that can be much smaller than 1 μm and can even extend into the single nanometer regime. These methods rely on the use of soft elastomeric elements typically made out of the polymer poly(dimethylsiloxane). The first section of this chapter presents the fabrication techniques for these elements together with data and experiments that provide insights into the fundamental resolution limits. Next, several representative soft-lithography techniques based on the use of these elements are presented: (i) microcontact printing, which uses molecular

inks

that form self-assembled monolayers, (ii) near- and proximity-field photolithography for producing two- and three-dimensional structures with subwavelength resolution features, and (iii) nanotransfer printing, where soft or hard stamps print single or multiple layers of solid inks with feature sizes down to 100 nm. The chapter concludes with descriptions of some device-level applications that highlight the patterning capabilities and potential commercial uses of these techniques.

One of the more significant technological achievements during the last 20 years has been the development of MEMS and its new offshoot, NEMS. These developments were made possible by significant advancements in the materials and processing technologies used in the fabrication of MEMS and NEMS devices. While initial developments capitalized on a mature Si infrastructure built for the integrated circuit (IC) industry, recent advances have come about using materials and processes not associated with IC fabrication, a trend that is likely to continue as new application areas emerge.

A well-rounded understanding of MEMS and NEMS technology requires a basic knowledge of the materials used to construct the devices, since material properties often govern device performance and dictate fabrication approaches. An understanding of the materials used in MEMS and NEMS involves an understanding of material systems, since such devices are rarely constructed of a single material but rather a collection of materials working in conjunction with each other to provide critical functions. It is from this perspective that the following chapter is constructed. A preview of the materials selected for inclusion in this chapter is presented in Table

11.1

. It should be clear from this table that this chapter is not a summary of all materials used in MEMS and NEMS, as such a work would itself constitute a text of significant size. It does, however, present a selection of some of the more important material systems, and especially those that illustrate the importance of viewing MEMS and NEMS in terms of material systems.

Material

Distinguishing characteristics

Application examples

Single-crystal silicon (Si)

High-quality electronic material, selective anisotropic etching

Bulk micromachining, piezoresistive sensing

Polycrystalline Si (polysilicon)

Doped Si films on sacrificial layers

Surface micromachining, electrostatic actuation

Silicon dioxide (SiO

2

)

Insulating, etched by HF, compatible with polysilicon

Sacrificial layer in polysilicon surface micromachining, passivation layer for devices

Silicon nitride (Si

3

N

4

, Si

x

N

y

)

Insulating, chemically resistant, mechanically durable

Isolation layer for electrostatic devices, membrane and bridge material

Polycrystalline germanium (polyGe), Polycrystalline silicon-germanium (poly SiGe)

Deposited at low temperatures

Integrated surface micromachined MEMS

Gold (Au), aluminum (Al)

Conductive thin films, flexible deposition techniques

Innerconnect layers, masking layers, electromechanical switches

Bulk Ti

High strength, corrosion resistant

Optical MEMS

Nickel-iron (NiFe)

Magnetic alloy

Magnetic actuation

Titanium-nickel (TiNi)

Shape-memory alloy

Thermal actuation

Silicon carbide (SiC) diamond

Electrically and mechanically stable at high temperatures, chemically inert, high Young's modulus to density ratio

Harsh-environment MEMS, high-frequency MEMS/NEMS

Gallium arsenide (GaAs), indium phosphide (InP), indium arsenide (InAs) and related materials

Wide bandgap, epitaxial growth on related ternary compounds

RF MEMS, optoelectronic devices, single-crystal bulk and surface micromachining

Lead zirconate titanate (PZT)

Piezoelectric material

Mechanical sensors and actuators

Polyimide

Chemically resistant, high-temperature polymer

Mechanically flexible MEMS, bioMEMS

SU-8

Thick, photodefinable resist

Micromolding, High-aspect-ratio structures

Parylene

Biocompatible polymer, deposited at room temperature by CVD

Protective coatings, molded polymer structures

Liquid crystal polymer

Chemically resistant, low moisture permeability, insulating

bioMEMS, RF MEMS

Table 11.1

Distinguishing characteristics and application examples of selected materials for MEMS and NEMS

Microelectromechanical

microelectromechanical system (MEMS)

systems (MEMS) have played key roles in many important areas, for example transportation, communication, automated manufacturing, environmental monitoring, health care, defense systems, and a wide range of consumer products. MEMS are inherently small, thus offering attractive characteristics such as reduced size, weight, and power dissipation and improved speed and precision compared to their macroscopic counterparts. Integrated

integrated

circuit (IC)

integrated

circuit (IC)

circuit (IC) fabrication technology has been the primary enabling technology for MEMS besides a few special etching, bonding and assembly techniques. Microfabrication provides a powerful tool for batch processing and miniaturizing electromechanical devices and systems to a dimensional scale that is not accessible by conventional machining techniques. As IC

fabrication

technology

fabrication technology continues to scale toward deep submicrometer and nanometer feature sizes, a variety of

nanoelectromechanical system (NEMS)

nanoelectromechanical systems (NEMS) can be envisioned in the foreseeable future. Nanoscale mechanical devices and systems integrated with nanoelectronics will open a vast number of new exploratory research areas in science and engineering. NEMS

NEMS

will most likely serve as an enabling technology, merging engineering with the life sciences in ways that are not currently feasible with microscale tools and technologies.

MEMS has been applied to a wide range of fields. Hundreds of microdevices have been developed for specific applications. It is thus difficult to provide an overview covering every aspect of the topic. In this chapter, key aspects of

MEMS

MEMS technology and applications are illustrated by selecting a few demonstrative device examples, such as pressure sensors, inertial sensors, optical and wireless communication devices. Microstructure examples with dimensions on the order of submicrometer are presented with fabrication technologies for future NEMS applications.

Although MEMS has experienced significant growth over the past decade, many challenges still remain. In broad terms, these challenges can be grouped into three general categories: (1) fabrication challenges; (2) packaging challenges; and (3) application challenges. Challenges in these areas will, in large measure, determine the commercial success of a particular MEMS device in both technical and economic terms. This chapter presents a brief discussion of some of these challenges as well as possible approaches to addressing them.

The new era of nanotechnology

nanotechnology

presents many challenges and opportunities. One area of considerable challenge is nanofabrication, in particular the development of fabrication technologies that can evolve into viable manufacturing processes. Considerable efforts are being expended to refine classical top-down

top-down

approaches, such as photolithography, to produce silicon-based electronics with nanometer-scale features. So-called bottom-up

bottom-up

or self-assembly

self-assembly

processes are also being researched and developed as new ways of producing heterogeneous nanostructures, nanomaterials and nanodevices. It is also hoped that there are novel ways to combine the best aspects of both top-down and bottom-up processes to create a totally unique paradigm change for the integration of heterogeneous molecules and nanocomponents into higher order structures. Over the past decade, sophisticated microelectrode

microelectrode

array devices produced by the top-down process (photolithography)

photolithography (PL)

have been developed and commercialized for DNA diagnostic genotyping applications. These devices have the ability to produce electric field geometries on their surfaces that allow DNA molecules to be transported to or from any site on the surface of the array. Such devices are also able to assist in the self-assembly (via hybridization)

hybridization

of DNA molecules at specific locations on the array surface. Now a new generation of these microarray devices are available that contain integrated CMOS

CMOS

components within their underlying silicon structure. The integrated CMOS allows more precise control over the voltages and currents sourced to the individual microelectrode

microelectrode

sites. While such microelectronic array devices have been used primarily for DNA diagnostic applications, they do have the intrinsic ability to transport almost any type of charged molecule or other entity to or from any site on the surface of the array. These include other molecules with self-assembling properties such as peptides and proteins, as well as nanoparticles, cells and even micron-scale semiconductor components. Microelectronic arrays thus have the potential to be used in a highly parallel electric field

pick and place

pick and place

fabrication process allowing a variety of molecules and nanostructures to be organized into higher order two- and three-dimensional structures. This truly represents a synergy of combining the best aspects of

top-down

and

bottom-up

technologies into a novel nanomanufacturing process.

Carbon nanotubes are nanocomponents par excellence that offer unique properties to be exploited in

sensor

concept

next-generation devices. Sensing applications are perhaps the class that has most to gain from

single-wall carbon nanotube (SWNT)

single-walled carbon nanotubes (SWNTs); virtually any property of SWNTs (e.g., electronic, electrical, mechanical, and optical) can result or has already resulted in sensor concept demonstrators. The basic questions that this chapter will attempt to address are:

why

use SWNTs, and

how

can SWNTs be used in sensing applications? A tour through the gallery of basic nanotube properties is used to reveal the richness and uniqueness of this materialʼs intrinsic properties. Together with examples from the literature showing performance of SWNT-based sensors at least comparable to (and sometimes surpassing) that of state-of-the-art micro- or macrodevices, these nanotube properties should explain

why

so much effort is currently being invested in this field. Because nanotubes, like any other nanoobject, are not easy to probe, a versatile strategy for accessing their

carbon nanotube field-effect transistor (CNFET)

properties, via the carbon nanotube field-effect transistor (CNFET) concept, will be described in this chapter. Fabricating CNFET devices, together with examples of SWNT sensor demonstrators utilizing the CNFET principle, will outline a proposal for

how

nanotubes can

carbon nanotube (CNT)

sensor

be utilized in sensors.

In Sect.

14.1

design considerations for SWNT sensors are brought into attention, starting with a brief survey of SWNT properties useful for sensing. The CNFET is introduced in Sect.

14.1.2

as a platform enabling access to individual SWNT properties during the sensing process. The current status of CNFET-based sensor characterization is captured in Sect.

14.1.3

. Methods for fabricating, or supporting the fabrication of, SWNT FETs are reviewed in Sect.

14.2

. Finally, Sect.

14.3

will be devoted to examples of CNT-based sensors, encompassing three main case studies, namely (bio)chemical, piezoresistive, and resonator sensors.

Microfabricated cantilever sensors have attracted much interest in recent years as devices for the fast and reliable detection of small concentrations of molecules in air and solution. In addition to application of such sensors for gas and chemical-vapor sensing, for example as an artificial nose, they have also been employed to measure physical properties of tiny amounts of materials in miniaturized versions of conventional standard techniques such as calorimetry, thermogravimetry, weighing, photothermal spectroscopy, as well as for monitoring chemical reactions such as catalysis on small surfaces. In the past few years, the cantilever-sensor concept has been extended to biochemical applications and as an analytical device for measurements of biomaterials. Because of the label-free detection principle of cantilever sensors, their small size and scalability, this kind of device is advantageous for diagnostic applications and disease monitoring, as well as for genomics or proteomics purposes. The use of microcantilever arrays enables detection of several analytes simultaneously and solves the inherent problem of thermal drift often present when using single microcantilever sensors, as some of the cantilevers can be used as sensor cantilevers for detection, and other cantilevers serve as passivated reference cantilevers that do not exhibit affinity to the molecules to be detected.

In this chapter, we discuss the incorporation of molecules into

therapeutic nanodevice

nanodevices as functional device components. Our primary focus is on biological molecules, although we also discuss the use of organic molecules

nanodevice

supramolecular

as functional components of supramolecular nanodevices. Our primary device interest is in devices used in human therapy and diagnosis, though when it is informative, we discuss other nontherapeutic nanodevices containing biomolecular components. We discuss design challenges associated with devices built from prefabricated components (biological macromolecules) but that are not as frequently associated with fully synthetic nanodevices. Some design challenges (abstraction of device object properties, inputs, and outputs) can be addressed using existing systems engineering approaches and tools (including unified modeling language), whereas others (selection of optimal biological macromolecules from the billions available) have not been fully addressed. We discuss various assembly strategies applicable to biological macromolecules and organic molecules (self-assembly, chemoselective conjugation) and their advantages and disadvantages. We provide an example of a functional mesoscale

FET

protein sensor

device, a planar field-effect transistor (FET) protein sensor, that depends on nanoscale components for its function. We also

molecular

engineering

use the sensor platform to illustrate how protein and other molecular engineering approaches can address nanoscale technological problems, and argue that protein engineering is a legitimate nanotechnology in this application. In developing the functional FET sensor, both direct adsorption of protein analyte receptors as well as linkage of receptors to the sensing surface through a polymer layer were tested. However, in the realized FET sensor, interfaces consist of a polymer layer linked to the semiconductor surface and to an analyte receptor (a protein). Nanotribology and other surface-science investigations of the interfaces revealed phenomena not previously documented for nanoscale

nanoscale

protein interface

protein interfaces (lubrication by directly adsorbed proteins, increases in friction force associated with polymer-mediated increases in sample compliance). Furthermore, the studies revealed wear of polymer and receptor proteins from semiconductor surfaces by an atomic force microscopy (AFM) tip which was not a concerted process, but rather depth of wear increased with increasing load on the cantilever. These studies also revealed that the polymer–protein interfaces were disturbed by nanonewton forces, suggesting that

protein

sensor

interfaces of immunoFET protein sensors translated to in vivo use must likely be protected from, or hardened to endure, abrasion from tissue. The results demonstrate that nanoscience (in this case,

planar immunoFET

nanotribology) is needed to design and characterize functional planar immunoFET sensors, even though the sensors themselves are mesoscale devices. The results further suggest that modifications made to the sensor interfaces to address these nanoscale challenges may be best accomplished by protein and

interfacial

engineering

interfacial engineering approaches.

Signal transduction by G-protein coupled receptors (GPCRs) underpins a multitude of physiological processes. Ligand recognition by these receptors leads to activation of a generic molecular switch involving heterotrimeric G-proteins and guanine nucleotides. With growing interest

G-protein coupled receptor (GPCR)

drug

target

and commercial investment in GPCRs in areas such as drug targets, orphan receptors, high-throughput

high-throughput screening (HTS)

biosensor

screening of drugs, biosensors etc., greater attention will focus on assay development to allow for

microarray

biochip assay

miniaturization, ultrahigh throughput, and eventually, microarray/biochip assay formats that will require nanotechnology-based approaches. Stable, robust, cell-free signaling assemblies comprising

protein

receptor and appropriate molecular switching components will form the basis of future GPCR/G-protein platforms which should be adaptable for such applications as microarrays and biosensors. This chapter focuses on cell-free GPCR assay nanotechnologies and describes some molecular biological approaches for the construction of more sophisticated, surface-immobilized, homogeneous, functional GPCR sensors. The latter points should greatly extend the range of applications to which technologies based on GPCRs could be applied.

Various microfluidic components and their characteristics, along with the demonstration of two recent achievements of lab-on-chip systems are reviewed and discussed. Many microfluidic devices and components have been developed during the past few decades, as introduced earlier for various applications. The design and development of microfluidic devices still depend on the specific purposes of the devices (actuation and sensing) due to a wide variety of application areas, which encourages researchers to develop novel, purpose-specific microfluidic devices and systems. Microfluidics is the multidisciplinary research field that requires basic knowledge in fluidics, micromachining, electromagnetics, materials, and chemistry for various applications.

Among the various application areas of microfluidics, one of the most important is the lab-on-a-chip system. Lab-on-a-chip is becoming a revolutionary tool for many different applications in chemical and biological analyses due to its fascinating advantages (fast speed and low cost) over conventional chemical or biological laboratories. Furthermore, the simplicity of lab-on-a-chip systems will enable self-testing capability for patients or health consumers by overcoming space limitations.

In this chapter centrifuge-based microfluidic platforms are reviewed and compared with other popular microfluidic propulsion methods. The underlying physical principles of centrifugal pumping in microfluidic systems are presented and the various centrifuge fluidic functions such as valving, decanting, calibration, mixing, metering, heating, sample splitting, and separation are introduced. Those fluidic functions have been combined with analytical measurements techniques such as optical imaging, absorbance and fluorescence spectroscopy and mass spectrometry to make the centrifugal platform a powerful solution for medical and clinical diagnostics and high-throughput screening (HTS) in drug discovery. Applications of a compact disc (CD)-based centrifuge platform analyzed in this review include: two-point calibration of an optode-based ion sensor, an automated immunoassay platform, multiple parallel screening assays and cellular-based assays. The use of modified commercial CD drives for high-resolution optical imaging is discussed as well. From a broader perspective, we compare the technical barriers involved in applying microfluidics for sensing and diagnostic as opposed to applying such techniques to HTS. The latter poses less challenges and explains why HTS products based on a CD fluidic platform are already commercially available, while we might have to wait longer to see commercial CD-based diagnostics.

Fluid is often transported in the form of droplets in nature. From the formation of clouds to the condensation of dew on leaves, droplets are formed spontaneously in the air, on solids, and in immiscible fluids. In biological systems, droplets with lipid bilayer membranes are used to transport subnanoliter amounts of reagents between organelles, between cells, and between organs, in processes that control our day-to-day metabolic activities. The precision of such systems is self-evident and proves that droplet-based systems provide intrinsically efficient ways to perform controlled transport, reactions, and signaling.

This precision and efficiency can be utilized in many lab-on-chip applications by manipulating individual droplets using microfabricated force gradients. Complex segmented flow processes involving generating, fusing, splitting, and sorting droplets have been developed to digitally control fluid volumes and concentrations to nanoliter levels. In this chapter, microfluidic techniques for manipulating droplets are reviewed and analyzed.

Since the introduction of the STM in 1981 and the AFM in 1985, many variations of probe-based microscopies, referred to as SPMs, have been developed. While the pure imaging capabilities of SPM techniques initially dominated applications of these methods, the physics of probe–sample interactions and quantitative analyses of tribological, electronic, magnetic, biological, and chemical surfaces using SPMs have become of increasing interest in recent years. SPMs are often associated with nanoscale science and technology, since they allow investigation and manipulation of surfaces down to the atomic scale. As our understanding of the underlying interaction mechanisms has grown, SPMs have increasingly found application in many fields beyond basic research fields. In addition, various derivatives of all these methods have been developed for special applications, some of them intended for areas other than microscopy.

This chapter presents an overview of STM and AFM and various probes (tips) used in these instruments, followed by details on AFM instrumentation and analyses.

scanning

probe microscopy (SPM)

Scanning probe microscopy (SPM) provides nanometer-scale mapping of numerous sample properties in essentially any environment. This unique combination of high resolution and broad applicability has led to the application of SPM to many areas of science and technology, especially those interested in the structure and properties of materials at the nanometer scale. SPM images are generated through measurements of a tip–sample interaction. A well-characterized tip is the key element to data interpretation and is typically the limiting factor.

atomic force microscopy (AFM)

Commercially available atomic force microscopy (AFM) tips, integrated with force-sensing cantilevers, are microfabricated from silicon and silicon nitride by lithographic and anisotropic etching techniques. The performance of these tips can be characterized by imaging nanometer-scale standards of known dimension, and the resolution is found to roughly correspond to the tip radius of curvature, the tip aspect ratio, and the sample height. Although silicon and silicon nitride tips have a somewhat large radius of curvature, low aspect ratio, and limited lifetime due to wear, the widespread use of AFM today is due in large part to the broad availability of these tips. In some special cases, small asperities on the tip can provide resolution much higher than the tip radius of curvature for low-

Z

samples such as crystal surfaces and ordered protein arrays.

Several strategies have been developed to improve AFM tip performance. Oxide sharpening improves tip sharpness and enhances tip asperities. For high-aspect-ratio samples such as integrated circuits,

focused ion beam (FIB)

silicon AFM tips can be modified by focused ion beam (FIB) milling. FIB tips reach 3° cone angles over lengths of several microns and can be fabricated at arbitrary angles.

electron beam deposition (EBD)

Other high resolution and high-aspect-ratio tips are produced by electron-beam deposition (EBD), in which a carbon spike is deposited onto the tip apex from the background gases in an electron microscope. Finally, carbon nanotubes have been employed as AFM tips. Their nanometer-scale diameter, long length, high stiffness, and elastic buckling properties make them possibly the ultimate tip material for AFM. Nanotubes can be manually attached to silicon or

chemical vapor deposition (CVD)

silicon nitride AFM tips or

grown

onto tips by chemical vapor deposition (CVD), which should soon make them widely available. In scanning tunneling microscopy

scanning

tunneling microscopy (STM)

(STM), the electron tunneling signal decays exponentially with tip–sample separation, so that in principle only the last few atoms contribute to the signal. STM tips are, therefore, not as sensitive to the nanoscale tip geometry and can be made by simple mechanical cutting or electrochemical etching of metal wires. In choosing tip materials, one prefers hard, stiff metals that will not oxidize or corrode in the imaging environment.

Scanning probe microscopy (SPM) methods such as scanning tunneling microscopy (STM) and noncontact atomic force microscopy (NC-AFM) are the basic technologies for nanotechnology and also for future bottom-up processes. In Sect.

23.1

, the principles of AFM such as its operating modes and the NC-AFM frequency-modulation method are fully explained. Then, in Sect.

23.2

, applications of NC-AFM to semiconductors, which make clear its potential in terms of spatial resolution and function, are introduced. Next, in Sect.

23.3

, applications of NC-AFM to insulators such as alkali halides, fluorides and transition-metal oxides are introduced. Lastly, in Sect.

23.4

, applications of NC-AFM to molecules such as carboxylate (RCOO

–

) with R = H, CH

3

, C(CH

3

)

3

and CF

3

are introduced. Thus, NC-AFM can observe atoms and molecules on various kinds of surfaces such as semiconductors, insulators and metal oxides with atomic or molecular resolution. These sections are essential to understand the state of the art and future possibilities for NC-AFM, which is the second generation of atom/molecule technology.

This chapter is dedicated to scanning probe microscopy (SPM) operated at cryogenic temperatures, where the more fundamental aspects of phenomena important in the field of nanotechnology can be investigated with high sensitivity under well-defined conditions. In general, scanning probe techniques allow the measurement of physical properties down to the nanometer scale. Some techniques, such as scanning tunneling microscopy and scanning force microscopy, even go down to the atomic scale. Various properties are accessible. Most importantly, one can image the arrangement of atoms on conducting surfaces by scanning tunneling microscopy and on insulating substrates by scanning force microscopy. However, the arrangement of electrons (scanning tunneling spectroscopy), the force interaction between different atoms (scanning force spectroscopy), magnetic domains (magnetic force microscopy), the local capacitance (scanning capacitance microscopy), the local temperature (scanning thermo microscopy), and local light-induced excitations (scanning near-field microscopy) can also be measured with high spatial resolution. In addition, some techniques even allow the manipulation of atomic configurations.

Probably the most important advantage of the low-temperature operation of scanning probe techniques is that they lead to a significantly better signal-to-noise ratio than measuring at room temperature. This is why many researchers work below 100 K. However, there are also physical reasons to use low-temperature equipment. For example, the manipulation of atoms or scanning tunneling spectroscopy with high energy resolution can only be realized at low temperatures. Moreover, some physical effects such as superconductivity or the Kondo effect are restricted to low temperatures. Here, we describe the design criteria of low-temperature scanning probe equipment and summarize some of the most spectacular results achieved since the invention of the method about 30 years ago. We first focus on the scanning tunneling microscope, giving examples of atomic manipulation and the analysis of electronic properties in different material arrangements. Afterwards, we describe results obtained by scanning force microscopy, showing atomic-scale imaging on insulators, as well as force spectroscopy analysis. Finally, the magnetic force microscope, which images domain patterns in ferromagnets and vortex patterns in superconductors, is discussed. Although this list is far from complete, we feel that it gives an adequate impression of the fascinating possibilities of low-temperature scanning probe instruments.

In this chapter low temperatures are defined as lower than about 100 K and are normally achieved by cooling with liquid nitrogen or liquid helium. Applications in which SPMs are operated close to 0 °C are not covered in this chapter.

In

time-varying force detection

dynamic force microscopy (DFM)

atomic force

atomic force microscopy (AFM)

microscopy, a force-sensing

cantilever

force-sensing

cantilever probes a sample and thereby creates a topographic image of its surface. The simplest implementation uses the static deflection of the cantilever to probe the forces. More recently, dynamic operation modes have been introduced, which either work at a constant oscillation frequency and sense the amplitude variations caused by tip–sample forces (amplitude modulation or tapping mode) or operate at constant amplitude and varying frequency (frequency modulation mode). Here, we report about new operational concepts capturing the higher harmonics in either amplitude modulation or frequency modulation mode. Higher-harmonic detection in atomic force microscopy allows us to measure time-varying tip–sample forces that contain detailed information about the material characteristics of the sample, while higher-harmonic detection in small-amplitude frequency modulation mode allows a significant improvement in spatial resolution, in particular when operating in vacuum at low temperatures. The most widely used mode of operation of

atomic force microscopy (AFM)

atomic force microscopy (AFM) is tapping mode, because in this mode lateral tip–sample interaction forces are minimized. The gentle interaction between the AFM tip and the sample under test reduces wear on the sample and localizes the deformations to give nanometer, or even molecular, resolution [

25.1

,

2

].

In tapping mode,

AFM (atomic force microscope)

cantilever

the AFM cantilever is vibrated at resonance in the vicinity of the sample so that the tip makes contact with the sample once during each cycle. The tip–sample forces reduce the vibration amplitude of the cantilever. The vibrating cantilever is scanned across the surface while a feedback mechanism adjusts the height of the cantilever base to maintain the vibration amplitude at a constant setpoint value. The topography of the surface is then obtained by recording the feedback signal.

Tapping-mode AFM has the potential to measure much more than simply the topography of a surface, however. As can be seen from Fig.

25.1

, the tip–sample interaction forces as the AFM tip approaches, interacts with, and retracts from the surface has a complex time dependence. This time dependence reflects the attractive and repulsive forces that act between the tip and the sample, and contains information about the chemical and physical properties of the sample.

Fig. 25.1

Calculated tip–sample distance

(a)

and tip–sample interaction forces

(b)

over two cycles of cantilever oscillation. Negative displacements correspond to sample indentation. Attractive (negative) and repulsive (positive) forces appear during the

tip–sample interaction

tip–sample interaction. The magnitude and duration of these forces depend on the physical properties of the sample

In the remaining sections of this chapter we describe methods that enable measurements of the time-varying tip–sample force waveforms in tapping-mode AFM. We first present a simple model to calculate time-varying tip–sample force waveforms and show how these forces depend on sample properties. Then we will present two strategies to engineer the force-sensing cantilever to measure the tip–sample force waveform and its frequency components. As application examples we present: (1) time-varying force measurements that allow quantitative comparisons of material stiffness, and (2) observation of the glass transition of polymer blends with nanometer-scale lateral resolution.

After the discussion of time-varying force measurements in standard AFM tapping mode, we introduce higher-harmonic imaging in AFM with small vibration amplitudes. In small-amplitude AFM imaging, the tip is in the force field of the sample during most of its vibration cycle. Relatively low-order harmonics of the tip–sample force then contain information about the higher-order gradients of the tip–sample interaction force field. These low-order harmonics in small-amplitude dynamic AFM imaging can be measured directly, yielding excellent spatial resolution.

This

atomic force microscope (AFM)

dynamic atomic force microscope (dynamic AFM)

chapter presents an introduction to the concept of the dynamic operational modes of the atomic force microscope (dynamic AFM). While the static (or contact-mode) AFM is a widespread technique to obtain nanometer-resolution images on a wide variety of surfaces, true atomic-resolution imaging is routinely observed only in the dynamic mode. We will explain the jump-to-contact phenomenon encountered in static AFM and present the dynamic operational mode as a solution to avoid this effect. The dynamic force microscope is modeled as a harmonic oscillator to gain a basic understanding of the underlying physics in this mode.

On closer inspection, the dynamic AFM comprises a whole family of operational modes. A systematic overview of the different modes typically found in force microscopy is presented with special attention paid to the distinct features of each mode. Two modes of operation dominate the application of dynamic AFM. First, the amplitude modulation mode (also called tapping mode) is shown to exhibit an instability, which separates the purely attractive force interaction regime from the attractive–repulsive regime. Second, the self-excitation mode is derived and its experimental realization is outlined. While the tapping mode is primarily used for imaging in air and liquid, the self-excitation mode is typically used under

ultrahigh vacuum (UHV)

ultrahigh vacuum (UHV) conditions for atomic-resolution imaging. In particular, we explain the influence of different forces on spectroscopy curves obtained in dynamic force microscopy. A quantitative link between the experimental spectroscopy curves and the interaction forces is established.

Force microscopy in air suffers from small quality factors of the force sensor (i.e., the cantilever beam), which are shown to limit the resolution. Also, the above-mentioned instability in the amplitude modulation mode often hinders imaging of soft and fragile samples. A combination of the amplitude modulation with the self-excitation mode is shown to increase the quality, or

Q

-factor, and extend the regime of stable operation. This so-called

Q

-control module allows one to increase as well as decrease the

Q

-factor. Apart from the advantages of dynamic force microscopy as a nondestructive, high-resolution imaging method, it can also be used to obtain information about energy-dissipation phenomena at the nanometer scale. This measurement channel can provide crucial information on electric and magnetic surface properties. Even atomic-resolution imaging has been obtained in the dissipation mode. Therefore, in the last section, the quantitative relation between the experimental measurement channels and the dissipated power is derived.

Atomic force microscopy (AFM),

atomic force microscopy (AFM)

developed in the late 1980s to explore atomic details on hard material surfaces, has evolved into a method capable of imaging fine structural details of biological samples. Its particular advantage in biology is that measurements can be carried out in aqueous and physiological environments, which opens the possibility to study the dynamics of biological processes in vivo. The additional potential of the AFM to measure ultralow forces at high lateral resolution has paved the way for measuring inter- and intramolecular forces of biomolecules on the single-molecule level. Molecular recognition studies using AFM open the possibility to detect specific ligand–receptor interaction forces and to observe molecular recognition of a single ligand–receptor pair. Applications include biotin–avidin, antibody–antigen, nitrilotriacetate (NTA)–hexahistidine 6, and cellular proteins, either isolated or in cell membranes.

The general strategy is to bind ligands to AFM tips and receptors to probe surfaces (or vice versa). In a force–distance cycle, the tip is first approached towards the surface, whereupon a single receptor–ligand complex is formed due to the specific ligand receptor recognition. During subsequent tip–surface retraction a temporarily increasing force is exerted on the ligand–receptor connection, thus reducing its lifetime until the interaction bond breaks at a critical (unbinding) force. Such experiments allow for estimation of affinity, rate constants, and structural data of the binding pocket. Comparing them with values obtained from ensemble-average techniques and binding energies is of particular interest. The dependences of unbinding force on the rate of load increase exerted on the

receptor–ligand

bond

receptor–ligand bond reveal details of the molecular dynamics of the recognition process and energy landscapes. Similar experimental strategies have also been used for studying intramolecular force properties of polymers and unfolding–refolding kinetics of filamentous proteins. Recognition

recognition

imaging

imaging, developed by combing dynamic

force

microscopy

force microscopy with force spectroscopy, allows for localization of receptor sites on surfaces with nanometer positional accuracy.

Nanotribology and nanomechanics studies are needed to develop a fundamental understanding of interfacial phenomena on a small scale and to study interfacial phenomena in

micro-/nanoelectromechanical system (MEMS/NEMS)

micro-/nanoelectromechanical systems (MEMS/NEMS), magnetic storage devices, and other applications. Friction and wear of lightly loaded micro-/nanocomponents are highly dependent on surface interactions (few atomic layers). These structures are generally coated with molecularly thin films. Nanotribology and nanomechanics studies are also valuable in the fundamental understanding of interfacial phenomena in macrostructures and provide a bridge between science and engineering. An

atomic force microscope (AFM)

atomic force microscope (AFM) tip is used to simulate a single-asperity contact with a solid or lubricated surface. AFMs are used to study the various tribological phenomena, which include surface roughness, adhesion, friction, scratching, wear, detection of material transfer, and boundary lubrication. In situ surface characterization of local deformation of materials and thin coatings can be carried out using a tensile stage inside an AFM. Mechanical properties such as hardness,

Youngʼs modulus

of elasticity

Youngʼs modulus of elasticity, and creep/relaxation behavior can be determined on micro- to picoscales using

depth-sensing indentation

a depth-sensing indentation system in an AFM. Localized surface elasticity and viscoelastic mapping of near-surface regions can be obtained with nanoscale lateral resolution. Finally, an AFM can be used for

nanofabrication

nanomachining

nanofabrication/nanomachining.

In this chapter, we describe the static and dynamic normal forces that occur between surfaces in vacuum or liquids and the different modes of friction that can be observed between: (i) bare surfaces in contact (dry or interfacial friction), (ii) surfaces separated by a thin liquid film (lubricated friction), and (iii) surfaces coated with organic monolayers (boundary friction).

force

surface

friction

force

measuring technique

Experimental methods suitable for measuring normal surface forces, adhesion and friction (lateral or shear) forces of different magnitude at the molecular level are described. We explain the molecular origin of van der Waals, electrostatic, solvation and polymer-mediated interactions, and basic models for the contact mechanics of adhesive and nonadhesive elastically deforming bodies. The effects of interaction forces, molecular shape, surface structure and roughness on adhesion and friction are discussed.

Simple models for the contributions of the adhesion force and external load to interfacial friction are illustrated with experimental data on both unlubricated and lubricated systems, as measured with the surface forces apparatus. We discuss rate-dependent adhesion (adhesion hysteresis) and how this is related to friction. Some examples of the transition from wearless friction to friction with wear are shown.

Lubrication in different lubricant thickness regimes is described together with explanations of nanorheological concepts. The occurrence of and transitions between smooth and stick–slip sliding in various types of dry (unlubricated and solid boundary lubricated) and liquid lubricated systems are discussed based on recent experimental results and models for stick–slip involving memory distance and dilatancy.

Friction

friction

has long been the subject of research: the empirical da Vinci–Amontons friction laws have been common knowledge for centuries. Macroscopic experiments performed by the school of

Bowden

and

Tabor

revealed that macroscopic friction can be related to the collective action of small asperities. Over the last 15 years, experiments performed with the atomic force microscope have provided new insights into the physics of single asperities sliding over surfaces. This development, together with the results from complementary experiments using surface force apparatus and the quartz microbalance, have led to the new field of

nanotribology

. At the same time, increasing computing power has permitted the simulation of processes that occur during sliding contact involving several hundreds of atoms. It has become clear that atomic processes cannot be neglected when interpreting nanotribology experiments. Even on well-defined surfaces, experiments have revealed that atomic structure is directly linked to friction force. This chapter will describe friction force microscopy

friction force

microscopy (FFM)

experiments that reveal, more or less directly, atomic processes during sliding contact.

We will begin by introducing friction force microscopy, including the calibration of cantilever force sensors and special aspects of the ultrahigh vacuum environment. The empirical Tomlinson model

Tomlinson model

often used to describe atomic stick-slip results is therefore presented in detail. We review experimental results regarding atomic friction, including thermal activation, velocity dependence and temperature dependence. The geometry of the contact is crucial to the interpretation of experimental results, such as the calculation of the lateral contact

lateral

contact stiffness

stiffness, as we shall see. The onset of wear on the atomic scale has recently been studied experimentally and it is described here. In order to compare results, we present molecular dynamics simulations

molecular

dynamics simulation (MDS)

that are directly related to atomic friction experiments. The chapter ends with a discussion of dissipation measurements

dissipation

measurement

performed in noncontact force microscopy, which may become an important complementary tool for the study of mechanical dissipation in

mechanical

dissipation in nanoscopic device

nanoscopic devices.

Engines and other machines with moving parts are often limited in their design and operational lifetime by friction and wear. This limitation has motivated the study of fundamental tribological processes with the ultimate aim of controlling and minimizing their impact. The recent development of miniature apparatus, such as

microelectromechanical system (MEMS)

microelectromechanical systems (MEMS) and

nanometer-scale

device

nanometer-scale devices, has increased interest in

atomic-scale

friction

atomic-scale friction, which has been found to, in some cases, be due to mechanisms that are distinct from the mechanisms that dominate in macroscale friction.

Presented in this chapter is a review of

computational study

tribological process

computational studies of tribological processes at the atomic and nanometer

nanometer

scale. In particular, a review of the findings of computational studies of

nanometer-scale

indentation

nanometer-scale indentation,

nanometer-scale

friction

friction and lubrication

nanometer-scale

lubrication

is presented, along with a review of the salient computational methods that are used in these studies, and the conditions under which they are best applied.

An optical tweezer is a scientific instrument that uses a focused

laser

beam to provide an attractive or repulsive force, depending on the index mismatch, to physically hold and move microscopic

dielectric

objects [

33.1

]:

Since their invention just over 20 years ago, optical traps have emerged as a powerful tool with broad-reaching applications in biology and physics. Capabilities have evolved from simple manipulation to the application of calibrated forces on – and the measurement of nanometer-level displacements of – optically trapped objects.

The ability to apply forces in the piconewton range to micrometer-sized particles while simultaneously measuring displacement with nanometer resolution is now routinely adopted for the study of molecular motors at the single-molecule level [

33.2

], the physics of colloids and mesoscopic systems [

33.3

,

4

], and the mechanical properties of polymers and biopolymers [

33.5

,

6

,

7

]. In parallel with the widespread use of optical trapping, theoretical and experimental work on fundamental aspects of optical trapping is being actively pursued [

33.8

,

9

,

10

]. In this chapter we will give a short overview of the principles of trapping and detection; different calibration methods, as well as the influence of surfaces and viscosity, will be discussed. The chapter ends with a short insight into the application of optical tweezers to cell biology.

A model, which explains scale effects in mechanical properties and tribology is presented. Mechanical properties are scale dependent based on the strain gradient plasticity and the effect of dislocation-assisted sliding. Both single asperity and multiple asperity contacts are considered. The relevant scaling length is the nominal contact length – contact diameter for a single-asperity contact, and scan length for multiple-asperity contacts. For multiple asperity contacts, based on an empirical power-rule for scale dependence of roughness, contact parameters are calculated. The effect of load on the contact parameters and the coefficient of friction is also considered. During sliding, adhesion and two- and three-body deformation, as well as ratchet mechanism, contribute to the dry friction force. These components of the friction force depend on the relevant real areas of contact (dependent on roughness and mechanical properties), average asperity slope, number of trapped particles, and shear strength during sliding. Scale dependence of the components of the coefficient of friction is studied. A scale dependent transition index, which is responsible for transition from predominantly elastic adhesion to plastic deformation has been proposed. Scale dependence of the wet friction, wear, and interface temperature has been also analyzed. The proposed model is used to explain the trends in the experimental data for various materials at nanoscale and microscale, which indicate that nanoscale values of coefficient of friction are lower than the microscale values due to an increase of the three-body deformation and transition from elastic adhesive contact to plastic deformation.

Human hair is a nanocomposite biological fiber. Maintaining the

human hair

nanotribological characterization

human hair

nanoindentation

atomic force microscopy (AFM)

human hair

health, feel, shine, color, softness, and overall esthetics of hair is highly desired. Hair care products such as shampoos and conditioners, along with damaging processes such as chemical dyeing and permanent wave treatments, affect the maintenance and grooming process and are important to study because they alter many hair properties. Nanoscale characterization of the cellular structure, mechanical properties, and morphological, frictional, and adhesive properties (tribological properties) of hair are essential to evaluate and develop better cosmetic products, and to advance the understanding of biological and cosmetic science. The atomic/friction force

atomic force microscope (AFM)

friction force

microscopy (FFM)

microscope (AFM/FFM) and nanoindenter have become important tools for studying the micro/nanoscale properties of human hair. In this chapter, we present a comprehensive review of the structural, mechanical, and tribological properties of various hair and skin as a function of ethnicity, damage, conditioning treatment, and various environments. Various cellular structure of human hair and fine sublamellar structures of the cuticle are identified and studied. Nanomechanical properties such as hardness, elastic modulus, tensile deformation, fatigue, creep, and scratch resistance are discussed. Nanotribological properties such as roughness, friction, and adhesion are presented, as well as investigations of conditioner distribution, thickness, and binding interactions. To study the electrostatic charge build-up on hair, surface potential studies are also presented.

Numerous

nanomechanics

applications of nanotechnology have been developed to probe the unique mechanical properties of cells. In addition, since biological materials exhibit such a wide spectrum of properties, they offer new concepts for nonbiological biomimetic applications. In this chapter, the viscoelastic properties of a cell and its subcellular compartments are described. First, a qualitative picture is presented of the relevant building blocks: the cytoskeleton, cell membrane, nucleus, adhesive complexes, and motor proteins. Next, the various methods used to probe cellular and subcellular mechanics are described, and some of the quantitative results presented. These measurements are then discussed in the context of several theories and computational methods that have been proposed to help interpret the measurements and provide nanomechanical insight into their origin. Finally, current understanding is summarized in the context of directions for future research.

In current biotechnology and biomedicine, cell-based investigations are rapidly gaining importance due to the recognition that molecular research alone does not provide a sufficiently complex insight. The high cost of animal studies and the fact that their results often cannot be directly transferred to humans additionally shifts the focus towards cell-based assays. This current trend triggers the development of more sophisticated laser-based techniques to manipulate and investigate cells. In this rapidly changing field, it is nearly impossible to provide a comprehensive view of all available techniques, since new techniques are constantly developed on nearly a weekly basis. In this chapter, we have made an effort to provide the physical basis for laser-based cell manipulation, complemented by several of the more exceptional applications of

optical

cell manipulation

optical cell manipulation.

NEMS Structural integrity is of paramount importance in all devices. Load applied during the use of devices can result in component failure. Cracks can develop and propagate under tensile stresses, leading to failure. Knowledge of the mechanical properties of nanostructures is necessary for designing realistic micro-/nanoelectromechanial systems (MEMS/NEMS) and biological micro-/nanoelectromechanical systems (bioMEMS/bioNEMS) devices. Elastic and inelastic properties are needed to predict the deformation due to an applied load in the elastic and inelastic regimes, respectively. The strength property is needed to predict the allowable operating limit. Some of the properties of interest are hardness, elastic modulus, bending strength, fracture toughness, and fatigue strength. Many of the mechanical properties are scale dependent; therefore these should be measured at relevant scales. Atomic force microscopy and nanoindenters can be used satisfactorily to evaluate the mechanical properties of micro-/nanoscale structures. Commonly used materials in MEMS/NEMS are single-crystal silicon and silicon-based materials, e.g., SiO

2

and polysilicon films deposited by low-pressure chemical vapor deposition. Single-crystal SiC deposited on large-area silicon substrates is used for high-temperature micro-/nanosensors and actuators. Amorphous alloys can be formed on both metal and silicon substrates by sputtering and plating techniques, providing more flexibility in surface integration. Electroless-deposited Ni-P amorphous thin films have been used to construct

LIGA

technique

microdevice

microdevices, especially using the so-called LIGA (lithography, galvanoformung, abformung) techniques. Micro-/nanodevices need conductors to provide power, as well as electrical/magnetic signals, to make them functional. Electroplated gold films have found wide applications in electronic devices because of their ability to make thin films and be processed simply. Polymers, such as poly(methyl methacrylate)

poly(methyl methacrylate) (PMMA)

poly(dimethylsiloxane) (PDMS)

(PMMA), poly(dimethylsiloxane) (PDMS), and polystyrene are commonly

bioMEMS/bioNEMS

nanofluidic

device

used in bioMEMS/bioNEMS, such as micro-/nanofluidic devices, because of ease of manufacturing and

polymer

biocompatible

biomedical device

reduced cost. Many polymers are biocompatible so they may be integrated into biomedical devices.

This chapter presents a review of mechanical property measurements on the micro-/nanoscale of various

nanostructure

stress and deformation analysis

materials of interest, and stress and deformation analyses of nanostructures.

One of the best materials to use in applications that require very low wear and reduced friction is diamond, especially in the form of a diamond coating. Unfortunately, true diamond coatings can only be deposited at high temperatures and on selected substrates, and they require surface finishing. However, hard amorphous carbon – commonly known as diamond-like carbon or a DLC coating – has similar mechanical, thermal and optical properties to those of diamond. It can also be deposited at a wide range of thicknesses using a variety of deposition processes on various substrates at or near room temperature. The coatings reproduce the topography of the substrate, removing the need for finishing. The friction and wear properties of some DLC coatings make them very attractive for some tribological applications. The most significant current industrial application of DLC coatings is in magnetic storage devices.

In this chapter, the state-of-the-art in the chemical, mechanical and tribological characterization of ultrathin amorphous carbon coatings is presented.

EELS and Raman spectroscopies can be used to characterize amorphous carbon coatings chemically. The prevailing atomic arrangement in the DLC coatings is amorphous or quasi-amorphous, with small diamond (

sp

3

), graphite (

sp

2

) and other unidentifiable micro- or nanocrystallites. Most DLC coatings, except for those produced using a filtered cathodic arc, contain from a few to about

at

.%50 hydrogen. Sometimes hydrogen is deliberately incorporated into the sputtered and ion-plated coatings in order to tailor their properties.

Amorphous carbon coatings deposited by different techniques exhibit different mechanical and tribological properties. Thin coatings deposited by filtered cathodic arc, ion beam and ECR-CVD hold hold much promise for tribological applications. Coatings of 5 nm or even less provide wear protection. A nanoindenter can be used to measure DLC coating hardness, elastic modulus, fracture toughness and fatigue life. Microscratch and microwear tests can be performed on the coatings using either a nanoindenter or an AFM, and along with accelerated wear testing, can be used to screen potential industrial coatings. For the examples shown in this chapter, the trends observed in such tests were similar to those found in functional tests.

nanodevice

Reliability of various micro- and nanodevices requiring relative motion as well as magnetic storage

lubricating

film

adhesion

stiction

devices requires the use of hydrophobic and lubricating films to minimize adhesion, stiction,

friction

wear

friction, and wear. In various applications, surfaces need to be protected from exposure to the operating environment, and hydrophobic films are of interest. The surface films should be molecularly thick, well-organized, chemically bonded to the substrate, and insensitive to environment. Ordered molecular assemblies with high hydrophobicity can be engineered using chemical grafting of various polymer molecules with suitable functional head groups, spacer chains, and nonpolar surface terminal groups.

self-assembled monolayer (SAM)

hydrophobicity

In this chapter, we focus on self-assembled monolayers (SAMs) with high hydrophobicity and good nanotribological properties. SAMs are produced by various organic precursors. We first present a primer to organic chemistry, followed by an overview of selected SAMs with various substrates, spacer chains, and terminal groups in the molecular chains and an overview of

self-assembled monolayer (SAM)

nanotribological property

contact angle (CA)

nanotribological properties of SAMs. The contact angle, adhesion, friction, and wear properties of SAMs having various spacer chains with different surface terminal and head groups (hexadecane thiol, biphenyl thiol, perfluoroalkylsilane, alkylsilane, perfluoroalkylphosphonate, and alkylphosphonate)

chemical

degradation

on various substrates (Au, Si, and Al) are surveyed. Chemical degradation mechanisms and environmental effects are studied. Based on the contact angle and nanotribological properties of various SAM films by atomic force microscopy (AFM) it is found that

atomic force microscopy (AFM)

perfluoroalkylsilane and perfluorophosphonate SAMs exhibit attractive hydrophobic and tribological properties.

Boundary films are formed by physisorption, chemisorption, and chemical reaction. A good boundary

boundary

film

physisorption

chemisorption

lubricant should have a high degree of interaction between its molecules and the solid surface. As a general rule, liquids are good lubricants when they are polar and thus able to grip solid surfaces

perfluoropolyether (PFPE)

(or be adsorbed). In this chapter, we focus on various perfluoropolyethers (PFPEs) and

nanodeformation

ionic liquid films. We present a summary of nanodeformation, molecular conformation, and lubricant

perfluoropolyether (PFPE)

nanotribological property

spreading studies, followed by an overview of the nanotribological properties of polar and nonpolar

atomic force microscopy (AFM)

PFPEs and ionic liquid films studied by atomic force microscopy (AFM), and chemical

tribotest apparatus

degradation studies using a high-vacuum tribotest apparatus. In this chapter, we focus on PFPE and

ionic liquid (IL)

film

nanodeformation

ionic liquid films. We first present a summary of nanodeformation, molecular conformation, and lubricant spreading studies and an overview of nanotribological and electrical studies of commonly used polar and nonpolar PFPE and ionic liquid films using AFM and chemical degradation studies using a high-vacuum tribotest apparatus.

The surfaces of plants represent multifunctional interfaces between the organisms and their biotic

smart

material

plant surface

(living) and the nonbiotic solid, liquid, and gaseous environment. The diversity of plant surface structures has evolved over several hundred million years of evolution. Evolutionary processes have led to a large variety of functional plant surfaces which exhibit, for example, superhydrophobicity, self-cleaning, superhydrophilicity, and reduction of adhesion and light reflection. The primary surface of nearly all parts of land plants is the epidermis. The outer part of epidermal cells is an extracellular membrane called the cuticle. The cuticle, with its associated waxes, is a stabilization element, has a barrier function, and is responsible for various kinds of surface structuring by cuticular folding or deposition of three-dimensional wax crystals on the cuticle. Surface properties, such as superhydrophobicity, self-cleaning, reduction of adhesion and light reflection, and absorption of harmful ultraviolet (UV) radiation, are based on the existence of three-dimensional waxes. Waxes form different morphologies, such as tubules, platelets or rodlets, by self-assembly. The ability of plant waxes to self-assemble into three-dimensional nanostructures can be used to create hierarchical roughness of various kinds of surfaces. The structures and principles which nature uses to develop functional surfaces are of special interest in biomimetics. Hierarchical structures play a key role in surface wetting and are discussed in the context of superhydrophobic and self-cleaning plants and for the development of biomimetic surfaces. Superhydrophobic biomimetic surfaces are introduced and their use for self-cleaning or development of air-retaining surfaces, for, e.g.,

self-cleaning

drag reduction at surfaces moving in water, are discussed. This chapter presents an overview of plant structures, combines the structural basis of plant surfaces with their functions, and introduces

superhydrophobic surface

existing biomimetic superhydrophobic surfaces and their fabrication.

Superhydrophobic surfaces exhibit extreme

superhydrophobicity

self-cleaning

water-repellent properties. These surfaces with high contact angle and low contact angle hysteresis also exhibit a self-cleaning effect and low drag for fluid flow. These surfaces are of interest in various applications, including self-cleaning windows, exterior paints for buildings, navigation ships, textiles, solar panels, and applications requiring antifouling and a reduction in fluid flow, e.g., in micro/nanochannels. Superhydrophobic surfaces can also be used for energy conservation and energy conversion, such as in the development of a microscale capillary engine. Superhydrophobic surfaces prevent the formation of menisci at a contacting interface and can be used to minimize adhesion and stiction. Certain plant leaves, notably lotus leaves, are known to be superhydrophobic and self-cleaning due to hierarchical roughness and the presence of wax

lotus (

Nelumbo nucifera

)

effect

tubules on the leaf surface. This phenomenon is known as the

lotus effect

. Superhydrophobic and self-cleaning surfaces can be produced by using roughness combined with hydrophobic coatings. In this chapter, the theory of roughness-induced superhydrophobicity and self-cleaning is presented, followed by the characterization data of natural leaf surfaces. Micro-, nano-, and hierarchical patterned structures have been fabricated, and the wetting properties and adhesion have been characterized to validate models and provide design guidelines for superhydrophobic and

self-cleaning

surface

surface

self-cleaning

contact angle (CA)

model

self-cleaning surfaces. In addition, a model of contact angle for oleophilic/phobic surfaces is presented. The wetting behavior of fabricated surfaces is investigated. Fundamental physical mechanisms of wetting responsible for the transition between various wetting regimes, contact angle, and contact angle hysteresis are also discussed.

Many

attachment system

attachment system

biologically inspired

plant

species of animals and plants are supplied with diverse attachment devices, which morphology depends on the species biology and on particular function, in which the attachment device is involved. Many functional solutions have evolved independently in different lineages of animals and plants. Based on the original and literature data, we have proposed classification of biological attachment systems according to several principles:

1.

Fundamental physical mechanism, on which the system operates

2.

Biological function of the attachment device

3.

Duration of the contact.

In more detail, we discuss here locomotory attachment devices capable of multiple bonding and debonding cycles. Finally, we show a biomimetic potential of studies on biological attachment devices.

leg attachment pad

gecko foot

smart

adhesion

The leg attachment pads of several creatures, including many insects, spiders, and lizards, are capable of attaching to a variety of surfaces and are used for locomotion. Geckoes, in particular, have

hairy

attachment

the largest mass and have developed the most complex hairy attachment structures capable of smart

smart

adhesion

adhesion – the ability to cling to different smooth and rough surfaces and detach at will. These

microscale

hair

animals make use of about three million microscale hairs (setae) (about 14000 mm

−2

) that

nanoscale

spatula

branch off into hundreds of nanoscale spatulae (about three billion spatula on two feet). This so-called division of contacts provides high dry adhesion. This multiple-level hierarchically structured surface construction provides the gecko with the compliance and adaptability to create a large real area of contact with a variety of surfaces. Modeling of the gecko attachment system as a hierarchical

hierarchical

spring model

spring model has provided insight into the adhesion enhancement generated by this system. van der Waals forces are the primary mechanism utilized to adhere to surfaces, and capillary forces are a secondary effect that can further increase the adhesion force. Preload applied to the setae increases adhesive force. Although a gecko is capable of producing of the order of 20 N of adhesive force, it retains the ability to remove its feet from an attachment surface at will. The adhesive strength of gecko setae is dependent on orientation; maximum adhesion occurs at 30°. During walking, a gecko is able to peel its foot from surfaces by changing the angle at

fibrillar structure

which its setae contact the surface. Manmade fibrillar structures capable of replicating gecko adhesion

superadhesive tape

wall-climbing robot

have the potential for use in dry superadhesive tapes and treads for wall-climbing robots for various applications. These structures can be created using micro/nanofabrication techniques or self-assembly.

The

millipede

concept presented in this chapter is a new approach to storing data at high speed and ultrahigh density. The interesting part is that millipede stores digital information in a completely different way from magnetic hard disks, optical disks, and transistor-based memory chips. The ultimate locality is provided by a tip, and high data rates are a result of massive parallel operation of such tips. As storage medium, polymer films are being considered, although the use of other media, in particular magnetic materials, has not been ruled out. The current effort is focused on demonstrating the millipede concept with areal densities higher than 1 Tb/inch

2

and parallel operation of very large two-dimensional (2-D) (up to 64 × 64) atomic force microscopy (AFM) cantilever arrays with integrated tips and write/read/erase functionality. The fabrication and integration of such a large number of mechanical devices (cantilever beams) will lead to what we envision as the very large-scale integration (VLSI) age of micro- and nanomechanics.

In this chapter, the millipede concept

millipede

system concept

for a microelectromechanical systems (MEMS)-based storage device is described in detail. In particular, various aspects pertaining to AFM thermomechanical read/write/erase functions, 2-D array fabrication and characteristics,

x

, 

y

, 

z

microscanner design, polymer media properties, read channel modeling, servo control and synchronization, as well as modulation coding techniques suitable for probe-based data-storage devices are discussed.

Nanorobotics

nanorobotics

is the study of robotics

robotics

at the nanometer scale, and includes robots that are nanoscale in size and large robots capable of manipulating objects that have dimensions in the nanoscale range with nanometer resolution. With the ability to position and orient nanometer-scale objects, nanorobotic manipulation is a promising way to enable the assembly of nanosystems including nanorobots.

This chapter overviews the state of the art of nanorobotics, outlines nanoactuation, and focuses on nanorobotic manipulation systems and their application in nanoassembly, biotechnology and the construction and characterization of nanoelectromechanical systems (NEMS)

nanoelectromechanical system (NEMS)

through a hybrid approach.

Because of their exceptional properties and unique structures, carbon nanotubes (CNTs)

carbon nanotube (CNT)

and SiGe/Si nanocoils are used to show basic processes of nanorobotic manipulation, structuring and assembly, and for the fabrication of NEMS including nano tools, sensors and actuators.

A series of processes of nanorobotic manipulation, structuring and assembly has been demonstrated experimentally. Manipulation of individual CNTs in 3-D free space has been shown by grasping using dielectrophoresis and placing with both position and orientation control for mechanical and electrical property characterization and assembly of nanostructures and devices. A variety of material property investigations can be performed, including bending, buckling, and pulling to investigate elasticity as well as strength and tribological characterization. Structuring of CNTs can be performed including shape modification, the exposure of nested cores, and connecting CNTs by van der Waals forces, electron-beam-induced deposition and mechanochemical bonding.

Nanorobotics provides novel techniques for exploring the biodomain by manipulation and characterization of nanoscale objects such as cellular membranes, DNA and other biomolecules. Nano tools, sensors and actuators can provide measurements and/or movements that are calculated in nanometers, gigahertz, piconewtons, femtograms, etc., and are promising for molecular machines and bio- and nanorobotics applications. Efforts are focused on developing enabling technologies for nanotubes and other nanomaterials and structures for NEMS and nanorobotics. By combining bottom-up nanorobotic manipulation and top-down nanofabrication

nanofabrication

processes, a hybrid approach is demonstrated for creating complex 3-D nanodevices. Nanomaterial science, bionanotechnology, and nanoelectronics

bionanotechnology

nanoelectronic

will benefit from advances in nanorobotics.

Micro-/nanoelectromechanical systems (MEMS/NEMS)

micro-/nanoelectromechanical system (MEMS/NEMS)

need to be designed to perform expected functions in short durations, typically in the millisecond to picosecond range. The expected life of devices for high-speed contacts can vary from a few hundred thousand to many billions of cycles, e.g., over a hundred billion cycles

micromirror device (DMD)

digital

for digital micromirror devices (DMDs), which puts serious requirements on materials. The surface-area-to-volume ratio in MEMS/NEMS is large, and in systems involving relative motion, surface forces such as adhesion, friction, and meniscus and viscous forces become very large compared with inertial and electromagnetic forces. There is a need for fundamental understanding of adhesion,

friction

friction/stiction,

stiction

wear, lubrication, and the role of surface contamination and environment, all on the nanoscale. Most mechanical properties are known to be scale dependent, therefore the properties of nanoscale structures need to be measured. For bioMEMS/bioNEMS,

bioMEMS/bioNEMS

adhesion between biological

molecular

layer

molecular layers and the substrate, and friction and wear of biological layers, can be important. Component-level studies are required to provide a better understanding of the tribological phenomena occurring in MEMS/NEMS. The emergence of the fields of

nanotribology

nanotribology and

nanomechanics

nanomechanics, and

atomic force microscopy (AFM)

atomic force microscopy (AFM)-based techniques, has provided researchers with a viable approach to address these problems. The emerging field of

biomimetics

biomimetics holds promise for the development of

nanomaterial

biologically inspired

biologically inspired nanomaterials and nanotechnology products. One example is the design of surfaces with

superhydrophobicity

roughness-induced

roughness-induced superhydrophobicity, self-cleaning, and low adhesion based on the so-called lotus effect. This chapter presents an overview of

nanoscale

adhesion

nanoscale adhesion, friction, and

wear

wear studies of materials and

lubrication

lubrication for MEMS/NEMS and bioMEMS/bioNEMS, and component-level studies of stiction phenomena in MEMS/NEMS devices,

MEMS/NEMS

device

as well as hierarchical nano-structured surfaces for superhydrophobicity,

self-cleaning

self-cleaning, and low adhesion.

The prediction and characterization of multi-length-scale tribological phenomena is challenging, yet essential for the advancement of micro- and nanomachine technology. Here, we consider theoretical underpinnings of multiasperity friction, review various approaches to measure micro- and nanoscale friction, and discuss the effect of monolayer coatings to reduce friction. We then focus on test results from a friction-based actuator called a nanotractor. The experimental procedures and data analysis used to

wear

measure friction, adhesion force, and wear are detailed. We observe and discuss a variety of phenomena including nanoscale slip with an associated bifurcation in the transition to motion, contact aging and deaging, a stick–slip/steady sliding bifurcation behavior, and wear. We anticipate great progress towards reliable, contacting micro- and nanomachines by linking theory and experiment to nano- and microscale tribological phenomena and by improving the testing, materials, and processing methods used to characterize these phenomena.

The commercialization of MEMS/NEMS devices is proceeding slower than expected, because the reliability problems of microscopic components differ from macroscopically known behavior. In this chapter, we provide an overview of the state of the art in MEMS/NEMS reliability. We discuss the specific, MEMS-related problems caused by stiction due to surface forces and electric charge. Materials issues such as creep and fatigue are treated as well. Nanoscale wear is covered briefly. MEMS packaging is also discussed, because the reliability of MEMS/NEMS components critically depends on the available protection from the environment.

To be able to accurately design structures and make reliability predictions in any field, it is first necessary to know the mechanical properties

mechanical property

nanostructure

mechanical property

of the materials that make up the structural components. The devices encountered in the fields of microelectromechanical systems (MEMS)

MEMS

and nanoelectromechanical systems (NEMS),

NEMS

stress

strength

Youngʼs modulus

are necessarily very small, and so the processing techniques and the microstructures of the materials used in these devices may differ significantly from bulk structures. Also, the surface-area-to-volume ratios in such structures are much higher than in bulk samples, and so surface properties become much more important. In short, it cannot be assumed that the mechanical properties measured for a bulk specimen of a material will apply when the same material is used in MEMS and NEMS. This chapter will review the techniques that have been used to determine the mechanical properties of micromachined structures, especially residual stress, strength and Youngʼs modulus. Theexperimental measurements that have been performed will then be summarized, in particular the values obtained for polycrystalline silicon (polysilicon).

production of MEMS products

Low-volume micro/nanoelectromechanical systems (MEMS/NEMS) production is practical when an attractive concept is implemented with business, manufacturing, packaging, and test support. Moving beyond this to high-volume production adds requirements on design, process control, quality, product stability, market size, market maturity, capital investment, and business systems. In a broad sense, this chapter uses a case study approach: It describes and compares the silicon-based MEMS accelerometers, pressure sensors, image projection systems, microphones, and gyroscopes that are in high-volume production. Although they serve several markets, these businesses have common characteristics; for example, the manufacturing lines use automated semiconductor equipment and standard material sets to make consistent products in large quantities. Standard well-controlled processes are sometimes modified for a MEMS product. However, novel processes that cannot run with standard equipment and material sets are avoided when possible. This reliance on semiconductor tools, as well as the organizational practices required to manufacture clean, particle-free products, partially explains why the MEMS market leaders are integrated circuit (IC) manufacturers. There are other factors. MEMS and NEMS are enabling technologies, so it can take several years for high-volume applications to develop. Indeed, market size is usually a strong function of price. This becomes a vicious circle, because low price requires low cost – a result that is normally achieved only after a product is in high-volume production. During the early years, IC companies reduce cost and financial risk by using existing facilities for low-volume MEMS production. As a result, product architectures are partially determined by capabilities developed for previous products. This chapter includes a discussion of MEMS product architecture with particular attention to the impact of electronic integration, packaging, and surfaces. Packaging and testing are critical, because they are significant factors in MEMS product cost. MEMS devices have extremely high

MEMS

surface effect

surface-to-volume ratios, so performance and stability may depend on the control of surface characteristics

after packaging

. Looking into the future, the competitive advantage of IC suppliers is decreasing because MEMS foundries are growing and small companies are learning to integrate MEMS/NEMS devices with die from complementary metal–oxide–semiconductor (CMOS) foundries in one package. Packaging challenges still remain, because most MEMS/NEMS products must interact with the environment without degrading stability or reliability.

The potential of MEMS technologies has been viewed as a revolution comparable or even bigger than that of microelectronics. These scientific and engineering advancements in micro-/nano-electromechanical systems (MEMS/NEMS) could bring previously unthinkable applications to reality, from space systems, environmental instruments, to daily-life appliances. As presented in previous chapters, the development of core MEMS processes has already demonstrated a lot of commercial applications as well as future potentials with elaborate functionalities. However, creating a low-cost reliable package for the protection of these MEMS products is still a very difficult task. Without addressing these packaging and reliability issues, no commercial products can be sold on the market. Packaging design and modeling, packaging material selection, packaging process integration, and packaging cost are the main issues to be considered. In this chapter, we will present the fundamentals of MEMS packaging technology, including packaging processes, hermetic and vacuum encapsulations, polymer-MEMS assembly and encapsulation, thermal issues, packaging reliability, and future packaging trends. The future development of MEMS packaging will rely on the success of the implementation of several unique techniques, such as packaging design kits for system and circuit designer, low-cost wafer-level and chip-scale packaging techniques, effective testing techniques, and reliable fabrication of an interposer [

55.1

] with vertical through-interconnects for device integrations.

This chapter is a human-centered survey of nanotechnologyʼs broader implications, reporting on the early phase of work by social scientists, philosophers, and other scholars. It begins with the social science agenda developed by governments, and the heritage of research on technology and organizations that social science brings to this mission. It then outlines current thinking about nanotechnologyʼs economic impacts, health or environmental impacts, and social contributions. It discusses how technology can be regulated by a combination of informal ethics and formal law, then concludes by considering the shape of popular nanotechnology culture, as reflected in science fiction, public perceptions, and education.