1: Nanoengineering: At the Center of It All Free

All areas of learning are interconnected. You cannot have chemistry without physics, and you cannot have biology without chemistry. Although nanoengineering is a new field, it stands at the intersection of several disciplines that we are already familiar with. The significance of learning about nanoengineering early—or really at any point—in your education is that it allows you to visualize how the knowledge acquired in other classes manifests in the real world. It also represents the forefront of nearly all fields of engineering. Moreover, a considerable portion of the discoveries in basic sciences that result in commercially viable products achieve this through some form of nanoengineering application. For example, information processing using microchips with transistors made on the nanoscale, drug delivery vehicles for vaccination and cancer therapy based on nanoparticles, composite materials for ultralightweight aircraft that incorporate nanofibers, and new materials for batteries and solar cells can only be understood through the “nano” perspective. For a video primer to this chapter, visit https://youtu.be/Rzm8gqknP70 or scan the QR code:

When I was in high school, my beat-up, loaner textbook which belonged to the school was titled Chemistry: The Central Science. “Central,” I wondered, relative to what? Apparently, central, in relation to physics on one side and biology on the other. That is, physics—with its focus on atoms, electrons, photons, and thermodynamics—underlies the rules of chemistry, just as chemistry—with its focus on bonding, reactivity, and interactions between molecules—provides the basis for biology.

The biologist Edward O. Wilson described such connectedness between areas of science as consilience. Consilience literally means the “jumping together”—or ultimately the unity—of knowledge. The chain of relatedness of scientific fields is often discussed in terms of a discipline and an antediscipline. An antediscipline is the discipline that “comes before,” that is, the field of learning that provides the foundation for the next field. For example, physics is the antediscipline of chemistry, and chemistry is the antediscipline of biology.

Given that few universities offer degrees in nanoengineering, what is the relationship between nanoengineering and other, more established, fields? Which fields provide the basis for nanoengineering, and which fields, in turn, does nanoengineering provide the basis for? How is nanoengineering related to the natural sciences and engineering? And, what is the difference between the similar-sounding words of nanoengineering, nanoscience, and nanotechnology?

The antedisciplines of nanoengineering are certainly each of the “big three” of the natural sciences: physics, chemistry, and biology.^† However, the relationship between nanoengineering and the other engineering disciplines is different. It is not a linear relationship but rather a convergence based on the scale of the physical system. See Figure 1.1.

So, I no longer believe that chemistry can be considered the “central science.”^‡ I have instead come to believe that the field that is truly at the center of everything is nanoengineering. Nanoengineering is the understanding and use of materials and phenomena that occur on the scale of around 100 nm or less. Implicit in the word “engi-neering” is the use of these structures for the benefit of society. Nanoengineered products appear in microelectronics (integrated circuits), medicine (nanoparticles for drug delivery), energy conversion (solar cells) and storage (lithium ion batteries), and chemical manufacturing and environmental remediation (in the form of catalysts).

Nanoengineering exists at the frontiers of most traditional engineering disciplines—certainly chemical, mechanical, electrical, and biomedical engineering—in two distinct senses. The first sense pertains to the size scale: when structures considered by these kinds of engineers are shrunken to dimensions of 100 nm or less, they are best viewed through the lens of nanoengineering. The second sense involves the exploitation of new physical effects to solve problems in the real world. Classical engineering, based on the laws of Newton, work effectively when treating objects as if they have no internal structure. Consider a block on an inclined plane from high school physics. In this scenario, the simplification of the block and the plane as solid objects with no internal structure works very well for objects that you can see with your eyes. Indeed, much of what needs to be known about mechanics and materials science to produce “macroscopic goods” (e.g., bridges, automobile engines, dishwashers, and radar antennae) is already known. On the other hand, the frontier of research in these areas—which are likely to uncover new physical effects and thus technologies that could transform everyday life—lie at the nanoscale.

There is often some confusion among students (and professors) regarding the terms nanoengineering, nanoscience, and nanotechnology. Our working definition of nanoengineering is the development and use of materials and systems whose properties are derived from physical effects that occur when matter is constrained in one or more dimensions to 100 nm or less. The study of these physical effects, driven not necessarily by application but by curiosity, is nanoscience. Finally, devices and commercially sold systems that are the products of engineering are examples of nanotechnology. We regret if there are likely instances of these terms in this very book which do not align very closely with these definitions. For such instances, we are sorry.^§

Now is as good a time as any to admit how controversial the above definitions of “nano” are, even among people who work in “nano” throughout their day. Indeed, words with this prefix mean different things to different people. These differences have led to some comical interactions in my journeys as a professional nanoengineer. For example, it is very common for professors to make a few trips per year to different universities to give talks about their research. During this type of trip, the speaker visits with multiple faculty members in their offices to discuss research or education, or merely to reminisce about old times. During one such visit several years ago, a professor I had never met was adamant that nanoengineering was simply colloid science^¶ with a new name. Furthermore, they asserted that there was nothing novel about nanoengineering, and that it was merely a form of “marketing,” designed to recruit students and to attract research funding. I found this point of view unsettling and bizarrely confrontational.^‖

My interrogator was correct that colloid science describes the forces between suspensions of nanoparticles, such as those found in paint, fat globules in milk, and nanoparticles containing mRNA vaccines.^** However, colloid science, as venerable and as important a field as it is, is only a part of nanoengineering. You see, my exposure to nanoengineering came from a completely different perspective. In my PhD research, I developed some techniques to make arrays of nanostructures with controlled dimensions. These structures were made on flat, two-dimensional surfaces for applications in chemical sensors, light filters, and solar cells. In this respect, my work was more akin to the fabrication of microchips than it was to colloid science. Nevertheless, I was so taken aback by the stridency of my interrogator that I could not articulate my views. Having served as a professional professor in a nanoengineering department for more than a decade, I now have a better idea of how I would have responded to my inquisitor, who was so sure that there was only one kind of “nano.”

In fact, there are two kinds of “nano”: “nano” in a flask and “nano” on a wafer, see Figure 1.2. “Nano” in a flask is synonymous with colloid science, while “nano” on a wafer is akin to microelectronics. “Flask nano” is also closely related to chemistry. That is, in chemistry, you synthesize things in a flask. Chemistry becomes colloid science when the substances you synthesized assemble into particles and arrangements of particles in a solution. “Wafer nano,” on the other hand, is closely associated with electrical engineering. You start with a silicon wafer, pattern your transistors, capacitors, and conductive traces, and dice it up into microchips. The other way to think about this type of application is to take a circuit board and shrink it down to nanoscale dimensions.

Flask nano produces structures in random locations in a flask or reactor but it does so at a high volume. In contrast, wafer nano produces structures in precise locations but it does so at a low volume. That is, in flask nano you can generate copious amounts of stuff in a three-dimensional “soup” made of chemical reagents (the ingredients) in a solvent medium (the broth). Usually, such particles are used “as-is,” in this liquid environment. That is, they are used in suspension: as in milk, a bucket of paint, or a formulation of vaccine. However, if you want to deposit the particles you have made onto a surface, it is very difficult to arrange them into precise geometries (doing so is often called “deterministic assembly”). In other words, you have very little control over where the final particles are arranged on a 2D substrate.

In wafer nano, in contrast, you can make almost any type of 2D pattern on a flat surface, like silicon (think microchips) or glass. It is also possible to make 3D structures by building up layer upon layer of 2D structures, like laying bricks to make a house. Such control can be achieved with outstanding precision using a process called photolithography. Photolithography, in our opinion, is the most sophisticated process ever employed for the manufacturing of commercial devices.^††

The products of flask nano and wafer nano are quite different in appearance, but the rules which govern their behavior are the same. For example, electrostatic forces, including van der Waals forces, partially determine whether you get a stable suspension of particles or a solid clump. At the same time, these forces are responsible for the stickiness of metals, ceramics, and semiconductors to each other in solid, planar devices. Moreover, the optical and electronic effects of confining materials to nanoscale dimensions are equally applicable to both “flask” and “wafer” forms of nanotechnology. For example, the nanoscale processes responsible for the fluorescence of semiconducting nanocrystals in a flask (or perhaps some day in the bloodstream) are the same as what happens in the diffuser panels in quantum LED (“QLED”) high-definition TVs. Finally, the physical effects of size confinement are ubiquitous. We will find many consequences of the fact that when the critical dimensions of an object approach the atomic scale, materials have a significantly larger proportion of their atoms on the surface. That is, as objects shrink, the fraction of atoms on the surface increases.^‡‡

The consequences of size confinement are profound. Consider the example of chemical reactivity. In solid catalysts with nanoscale dimensions, there are many more active sites for chemical transformation than there would be if the catalyst were a big chunk with smooth sides. For applications in sensing, chemical and biochemical analytes can attach and detatch more quickly from the surface of the sensing material if it has a lot of surface area relative to its mass or volume. Moreover, the signals arising from the binding and de-binding of the analytes to the sensor material are produced more strongly and more immediately. All of these effects are common to materials produced through both flask nano and wafer nano, and thus all fit under the umbrella term of nanotechnology, understood by nanoscience, and produced by nanoengineering.

Nanoengineering draws inspiration from—and has an effect on—essentially all areas of science and engineering.^§§ By learning about nanoengineering as an independent discipline and your native “STEM language,” you get to learn about the good stuff first. That is, you get to take a supersonic journey directly to the frontiers of science and technology, without the need to retrace the steps of centuries of work carried out by generations of scientists and engineers. For example, what required mechanical, chemical, and electrical engineers decades to incorporate into world-transforming technologies—e.g., the strength of carbon nanotubes, the biocompatibility of lipid-based nanoparticles for drug delivery, and light emission from quantum dots—serves as the starting point for nanoengineers. Purists will say “you have to learn the fundamentals first!” And you will learn them. But asking a nanoengineer to get all the way through a physics, chemistry, or engineering degree before learning the good stuff would be like asking a sociologist to first learn everything about neuroscience and psychology before the first semester of sociology course, which is normally undertaken during the first year of undergraduate studies.

When we started the Department of NanoEngineering at UC San Diego in 2007, we recognized that the frontiers of most engineering fields lay in nanostructured materials. Consider a few examples: microprocessors in which the transistors have dimensions of less than 10 nm; composite materials for aircraft which incorporate nanocarbon fibers; lipid nanoparticles for the delivery of mRNA vaccines; and display technologies utilizing semiconductor nanocrystals—i.e., quantum dots—for increased vibrancy of the images. Ask yourself, at what point in an undergraduate curriculum did the individuals who engineered these marvels of technology learn how to do this? The answer is nowhere. They learned how to accomplish these feats on the job, or by accident. In this book, we will teach you how to “skip to the end.” That is, learn how to arrive at the frontier of science and engineering without having to earn a degree in a discipline which is only somewhat related to what you want to do after graduation. That is the power of nanoengineering that we are going to share with you.

The traditional science disciplines, sometimes called the natural sciences,^¶¶ include physics, chemistry, and biology. Just as biology is linked to physics through chemistry, nanoengineering is a product of chemistry, understood using physics, and often has applications in biology, or at least the biomedical sciences.

Nanomaterials derive their unique properties from their small sizes and the physical effects that result from this confinement. These effects often arise from the fact that a material sample with nanoscale dimensions has a large fraction of its atoms on its surface. The atoms at the surface have unsatisfied valencies, or bonds that they could form or would like to form, but have not done so. Visualize molecules at the surface of a thin puddle of water. When these surface molecules look up, toward the air, they find that they lack stabilizing electrostatic interactions with other molecules like them. That is, they are deprived of around half the “bonds” that are experienced by atoms deeper in the bulk of the material.^‖‖ Effects arising from the missing interactions of atoms or molecules near the surface give rise to several properties of nanoscale materials. Such surface-associated properties include greater chemical reactivity, lower surface tension (for liquids only), reduced melting points (for solids only), and other effects. Collections of nanoparticles also organize themselves into dynamic systems based on principles of electrostatics and entropy. For example, nanoparticles—just like gas molecules in a container—like to spread out. These osmotic or entropic forces give rise to a range of important physical effects that occur on the nanoscale but have consequences that can be measured on the macroscopic scale.^***

Matter is the substance of which all things are made. In turn, matter is made of atoms and molecules, and can be found in one of the three basic phases (i.e., solids, liquids, and gases), along with a few other kinds that are important for various reasons (e.g., plasmas and supercritical fluids). The properties of matter depend not only on the properties of atoms and molecules (size, charge, etc.), but also on the way in which these atoms and molecules interact.

Forces between atoms and molecules—the so-called interatomic or intermolecular forces—are hugely important. These non-covalent bonds^††† are interactions that underlie biology, materials science, and everyday phenomena (see Chapters 2 and 3). For example, the strength of these intermolecular forces determines whether the molecules in a given substance will form a solid, liquid, or gas, at a given temperature and pressure. Intermolecular forces, in turn, can be predicted by understanding the potential energies with which the atoms or molecules interact, but only if we know how this potential energy changes as the atoms, molecules, or nanoparticles get closer together or move farther apart. To illustrate with a familiar example, we know that the gravitational force is attractive because your potential energy increases as you climb a hill, and decreases as you climb down. Indeed, we will learn that the numerical value of the energy of the system holds no physical significance except in its relationship to a reference state (see Figure 1.3). In the case of the gravitational potential energy of a system comprising you and the earth, the energy of the reference state (you standing on the ground) is set to zero, by convention. In other systems, like those consisting of atoms, molecules, or nanoparticles, the reference state is chosen such that the interacting objects are as far apart as possible.

In other words, the amount of force between molecules, nanoparticles, and objects is equal to the rate of change of the potential energy between them. Thus, to say that the potential energy of a system is <0 or negative—usually treated as favorable—does not mean anything unless we know what the energy was before that state emerged. That is, the “before” state: the state with all the atoms held apart at infinite separation, at the farthest corners of the universe. This artificial reference state ensures that there is no energy of interaction at all—i.e., the potential energy of interaction is zero. Thus, by convention, this arrangement means that when objects are stuck together, their potential energy of interaction is a large negative number.

One of the defining features of materials with nanoscale dimensions is that they interact with light differently than do materials with macroscopic dimensions. Such properties of matter at the nanoscale are a consequence of the physical confinement of electronic states, or the “places” an electron either lives or is allowed to live. In other words, the available energy levels and/or the physical locations which an electron may occupy when confined within a nanoscale structure. Interactions between light and matter are dictated by a branch of physics called quantum mechanics. Quantum in this case just means that quantities like energy, wavelength, frequency, momentum, and so forth can only have certain values and not others. This property is called quantization and means that properties can have only discrete values and not a continuous range of values.

The interaction of light and nanoparticles is a branch of nanoscience called nanophotonics, which is the basis of many fields of physics and modern technology. For example, optical signals confined to optical fibers under the oceans mediate much of the transfer of digital information, globally. Light–matter interactions can also be used to glean the properties, shapes, and energies of particles of matter: when a photon—a tiny particle of light—strikes a molecule, nanoparticle, or surface, one of many different things can happen. The photon may be scattered or absorbed by the particle, or it may pass directly through the particle. To a large extent, the fate of the photon which interacts with a particle of matter depends on the energy of the photon and the size of the particle. For one thing, as stated above, the size of the particle determines the energy that electrons which reside in the particle can have. The energies of photons that can be absorbed often correspond to the energy gaps between these energy levels for electrons. Absorption occurs when an electron gets promoted from a lower energy state to a higher energy state. Photons—which consist of oscillating electromagnetic waves—can transfer energy to these electrons. The size of the particles determines the allowable energies of electrons, and thus which photons can be absorbed. When an electron falls from a higher energy state to a lower energy state, a photon may be emitted. This process, emission, can be either fluorescent, which is usually bright and instantaneous, or phosphorescent, which is usually dim and occurs over a long time (think glow-in-the-dark stars or stickers, possibly on the walls of your childhood bedroom).

For nanoparticles made of metal, there is a special type of phenomenon called localized surface plasmon resonance (LSPR). The LSPR involves the periodic oscillation (sloshing back and forth) of the loosely held conduction electrons at the surface of the particle. Particles that are highly symmetric like cubes and spheres exhibit LSPR at only one frequency. However, those with oblong shapes (e.g., like cylinders or grains of rice) exhibit two distinct LSPRs: one for the long dimension and another for the short one.^‡‡‡ Thus, if you can collect and analyze the absorbed, scattered, and emitted photons, and plot the intensity as a function of energy (or equivalently as a function of wavelength or frequency), you can learn a lot about the size, shape and composition of a nanoparticle. This group of techniques, collectively called spectroscopy, is among the most powerful types of research tools available to a nanoengineer (or chemist, materials scientist, or astronomer). The power of spectroscopy is that it reveals aspects of the structure and the composition of a material, even if the sample is too small to see using a microscope. In this book, we will discuss many examples of the use of spectroscopy to elucidate (shed light on, pun intended) the structures of nanoparticles.

In order to engineer nanostructured materials, the initial step is to have the capability to make them. The ability to synthesize materials, including nanomaterials, is the realm of chemistry. That is why chemistry forms the basis of a significant portion of nanoengineering.^§§§ For example, semiconductor nanocrystals (quantum dots), metallic nanoparticles, and polymer nanoparticles are all synthesized using techniques common to chemistry. In fact, the manufacturing of microprocessors using techniques such as photolithography was enabled by chemical inventions such as chemically amplified photoresists.^¶¶¶

A molecule is a collection of atoms which are bound to each other in a precise 3D arrangement. The bonds between these atoms are covalent, meaning that they share electrons. What differentiates a molecule from any old material is that a molecule has finite extent and size (a few tens of nanometers, maximum). Moreover, every other molecule of the same type has exactly the same structure, and is therefore interchangeable. Due to the unique bonding properties of carbon and the ways in which it can bond with itself, the skeletal structures of molecules mainly consist of carbon atoms. Thus, the chemistry of molecules is synonymous with organic chemistry. Organic—i.e., carbon-based—structures are named so because they are the basic building blocks of life: proteins, nucleic acids, carbohydrates, fats, and other molecules like hormones and neurotransmitters are all organic molecules. Synthetic compounds like fuels and other combustibles, some pharmaceuticals, and plastics represent extremely important areas of industrial manufacturing and engineering.^‖‖‖

Organic structures, specifically organic nanostructures, are everywhere. Look around you, particularly the objects and surfaces of objects in your current environment. Whether you are in an office, classroom, library, desert, or beach, it would be challenging to find any object that is not made of or covered with organic or molecular materials. Even desert sand and rocks have a surface microbiome (the “biocrust”) made of many types of microorganisms, lichens, and fungi. As you are likely indoors, consider that the window, although its bulk structure is silicon dioxide glass, is covered with either polymeric coatings or adventitiously (not inherent to the material, accidentally) absorbed organic substances from the air—possibly even from your breath! Thus, the ability to engineer materials at the nanoscale requires, at the very least, a functional understanding of molecular species.

Like all forms of matter, nanostructures are made of atoms and molecules, and thus have the potential for reactivity. Thus, they are subject to change and can also be engineered to bring about changes in their environments. In the field of catalysis, which often uses nanoparticles or nanostructured surfaces of larger samples to induce chemical changes, reactivity is their primary function. However, sometimes it is necessary to create a nanoparticle and suppress its reactivity. For example, you would not want a nanoengineered drug delivery system to damage cells or internal organs. Knowledge of chemical reactivity also plays a role in the synthesis of nanostructures in a flask. Many tried-and-true methods for the synthesis of nanoparticles made from semiconductors (e.g., silicon, cadium telluride, lead sulfide, etc.) and metals (e.g., gold, silver, copper, palladium, platinum, etc.) exist in the literature with procedures that are relatively easy to follow. Like the wheel or the multiplication table, such methods do not need to be invented again. While this book will not cover chemical reactivity to the same extent a course in organic or inorganic chemistry, it is important nonetheless to know some key aspects. Such instances will be covered in this book where appropriate, for example, in the sections on catalysis and the synthesis of nanoparticles. However, there will not be a separate section on reactivity.

Some of the most exciting potential applications of nanoengineering are found in biology or biomedical technology. One only needs to consider the success of the mRNA vaccines against the coronavirus that causes COVID-19 to realize the impact of, in this case, nanoscale organic vehicles that deliver mRNA. Nanoscale drug-delivery vehicles have been around for decades, but their sophistication is rapidly increasing. In the case of delivering mRNA molecules, the justification for using nanoparticles is manifold. For one thing, mRNA vaccines cannot function without a vehicle to deliver them into the bloodstream and to the cells of the host. One reason is that mRNA molecules are unstable and would be hydrolyzed instantly in the bloodstream if not encapsulated. Moreover, if they were encapsulated in some random particle, the immune system would recognize them immediately and destroy them. So, structures called lipid nanoparticles or liposomes, which have polymeric or molecular components, were engineered so as to both encapsulate the mRNA molecules and to target them to the appropriate cells.

Nanoengineers often draw inspiration from biology. Biological systems are full of examples of functional nanostructures. For example, molecular motors spin bacterial flagella, viruses are quasi-living nanoparticles, and geckos stick to walls using a mechanism that arises inherently from nanoscale phenomena. Although there was much hype in the 1980s and 1990s about hypothesized “molecular assemblers”—little robots that put molecules together atom by atom—biology already accomplishes this. For example, enzymes and ribozymes are basically automated nanoscale robots. These automatons can affect chemical reactions to generate molecular and nanostructures from simpler components. Engineers often attempt to borrow from the design principles that permit such exquisite control over molecular structures by these natural molecular assemblers.

Engineering is the use of scientific principles and physical effects to solve problems. My whole life, I have been interested in science fiction. I loved Star Trek and Star Wars,^**** and the magic of other worldly devices: the transporter, warp speed, and light sabers. Who, among those reading this book, has not been inspired by sci-fi and fantasy fiction? However, it was not until I started majoring in science that I learned that science itself—the process of pure discovery for its own sake—involved much more patience and bookkeeping than I could handle. Moreover, the products of science I wanted to help create—light sabers and the rest—would not come directly as a result of scientific discovery but due to a closely related realm of human learning, engineering.

Unlike many professional scientists and engineers, I do not make a sharp distinction between science and engineering. For example, there is no engineering without science, and you cannot do good science without tools created by engineering. Moreover, inventing a new material or device or algorithm—i.e., engineering—only gets you so far if you do not know how it works. So to learn how your invention works, you again need science. So, while there may be a dictionary difference, most of us working in technical research are at some level practicing both science and engineering. We pass between one frame of mind and the other, without even thinking about it. In any case, engineering, just like science, comes in many different flavors with broad zones of overlap. Below, I briefly mention how nanoengineering learns from and contributes to the most common fields of engineering.

In a way, all nanoengineering is materials science, because nanoscale systems are, of course, made of materials. However, the two fields have different intellectual roots. Historically, materials science arose from metallurgy: the production of metals from oxidized minerals by smelting, and subsequent casting, forging, or machining of the base metal into useful parts. In particular, how these processes lead to the internal structure that determines the properties (e.g., hardness, strength, flexibility, etc.) of the finished object. Thus, the arrangement of atoms, sizes of grains, kinetics of processes, and thermodynamics of phase changes, are the bread and butter of materials science. These structures and processes are probed with X-ray diffraction techniques, electron microscopy, and calorimetry. To be sure, nanoengineering uses many of the same tools. However, broadly speaking, compared to materials science, nanoengineering is often concerned with the surfaces of such structures and the properties which emerge from size confinement. Nevertheless, you will still find materials scientists doing nanoengineering, and vice versa. It is not that there is no overlap, rather, the center of the bullseye is somewhat different for the two fields.

One major point of divergence, however, between classical materials science and nanoengineering is how they treat soft materials—polymers, gels, biological tissue, and self-assembled structures like micelles and liposomes. Indeed, materials science did not subsume the study of polymeric materials until relatively recently. Polymers, however, play a central role within nanoengineering, given the criticality of photolithography^†††† and photoresist^‡‡‡‡ chemistry as the central technique of manufacturing on the nanoscale. Moreover, organic molecules of the type that form micelles and lipid nanoparticles are the basic building blocks of solution-based nanotechnology.

When I was a student, I used to think that chemical engineering was a synonym for chemical manufacturing. I realized much later in my academic career that while chemical engineers are employed in chemical manufacturing, the design of large-scale chemical synthetic sequences is indeed still carried out by chemists.^§§§§ Chemical engineers, in contrast, are concerned first and foremost with the continuum properties of fluid media^¶¶¶¶ that may or may not have reactions going on within them. That is, how to induce a chemical change on the large scale while making it as safe and as profitable as possible. While chemical engineering has matured, the frontier of research in the field has gone from phenomena that occur on a continuum scale—i.e., where you can ignore molecular details—to the molecular scale—where you cannot. Chemical engineering interfaces with nanoengineering in many areas, but especially in polymer science. Not only is the manufacturing of polymers a hugely important area for chemical manufacturing, but polymers themselves are a highly important intermediate in other manufacturing processes.^‖‖‖‖

Transport phenomena—including the transport of heat and mass—are the bedrock of chemical engineering, and many of the tools used to treat these phenomena on the macroscopic scale also apply to the nanoscale. Indeed, nanoscale processes are subject to heat transfer by convection, conduction, and radiation, and more or less follow the rules of continuum fluid mechanics. One example of an effect of size confinement is the greater probability of laminar flow^***** between adjacent layers in a microfluidic channel.^{†††††} Indeed, the field of microfluidics^{‡‡‡‡‡} involves a suite of tools and techniques for transporting liquids and generating droplets and even nanoparticles. Often, such lab-on-a-chip type devices are used in analysis of small samples or generating particles for therapies. The lipid nanoparticles used as delivery vehicles for mRNA vaccines and chemotherapeutic agents are famous examples. We will find that the transport of nanoparticles is often driven by entropic or osmotic effects. Namely, gradients in concentration or differences in the number of available statistical microstates between one state and another. The entropic or osmotic driving force propels the system to evolve in a manner that maximizes the number of states available under given conditions.

Separations comprise a range of industrial processes, from distillation of ethanol in the production of whisky to water purification by reverse osmosis. A key technology which enables separations in fluids is a often a nanoporous membrane, and thus the design and synthesis of such membranes involve nanoengineering. At the very least, they involve the use of a polymeric structure whose system of pores may allow for the transmission of some types of molecules but the exclusion of others. Separation is most often carried out on the basis of size, but could also be based on charge or chemical functionality. Consider the case of dialysis bags used in management of kidney disease.

Catalysts are chemical species that speed up a reaction but which are not part of the reactants or products. They work by lowering the activation barrier—or the potential energy—embodied by the transition state, which is a short-lived molecule halfway between reactants and products. If the barrier (hill) is lowered by the involvement of a catalyst, the reactants can get over the hill much, much more quickly. In fact, many reactions do not occur within any reasonable time frame because there is no catalyst present. Catalysts thus make the impossible possible. They are used ubiquitously (everywhere) in the manufacturing of chemicals, materials, and fuels.

Examples of catalysts are small organic molecules, metal atoms or ions surrounded by organic ligands,^§§§§§ biological enzymes, and surfaces. When we say “surfaces” we are usually talking about surfaces that have some kind of nanoscale features, often roughened or having pores throughout their bulk (like a type of mineral known as zeolite). Alternatively, catalysts can exist in the particulate form. The advantage of using surfaces and particles as catalysts is that they can be easily removed from the reaction mixture and reused later. The importance of catalysts has turned them into a lucrative industry: the market for catalysts is in the tens of billions of dollars annually, while the value of chemical manufacturing enabled by catalysts is many trillions, worldwide.

The purview of mechanical engineering is the forces, movements, heat flow and energy flow, usually within or between solid structures.^¶¶¶¶¶ Most of the time, classically, mechanical engineers treat such processes using continuum theories. Continuum theories ignore the atoms and molecules of which matter is made. That is, such theories lack granularity. Classically, for most systems obeying Newton’s laws of motion, atoms, electrons, and molecules can be ignored. However, as the frontiers of mechanical engineering have touched on kinetics, heat flow, kinematics, and forces in more sophisticated, modern systems, it has become impossible to ignore molecular effects. A good example is the theory surrounding microelectromechanical systems (MEMS). In such systems, the effects of size confinement are ever-present. Moreover, it is not uncommon to find mechanical engineers at work in explicitly the nanoscale domain. Indeed, one does not even need to consider the existence of atoms and molecules to arrive at one of the most prevalent or striking consequences of size confinement, that is, scaling laws.

Some of the most import consequences that result from shrinking the dimensions of materials comes not from any quantum phenomenon but simply from math. That is, scaling laws. Scaling laws refer to the fact that certain dimensions or aspects of a block of material become larger or smaller relative to others as the system shrinks. For example, consider the ratio of surface area to volume of a sphere. The volume of the sphere, $V= 4 3 π R 3$ ⁠, scales with the cube of the radius. Its surface area, A_surface = 4πR², however, scales with its square. Thus, as a sphere shrinks, the surface area shrinks less slowly than does the volume. To put it differently, the surface area scales with volume in proportion to $1 R$ ⁠. Small R values give you a big surface area, relative to the volume.

Scaling laws such as the relationship between the surface area and volume are true whether we are talking about objects the size of planets or of tennis balls. But, the physical effects of downscaling do not really become profound until you reach sizes of micrometers (“microns”) and less. One example from the field of nanomedicine (see Chapter 13), is the concept of burst release (Figure 1.4). Consider the problem of encapsulating drug molecules inside a spherical nanoparticle. The maximum achievable loading will depend on the interior volume of the nanoparticle, along with the drug’s solubility. However, given the strength of van der Waals forces on the small scale, you can also expect some fraction of the drug molecules to stick to the surface of the nanoparticles. These molecules will be the first to escape into the bloodstream as soon as the nanoparticles are injected. The smaller the nanoparticles, the greater the surface area compared to the volume, and thus the greater proportion of drug molecules would be released in such a “burst” mechanism. Therefore, one must carefully engineer the nanoparticles system, such that the appropriate amount of drug is released at the appropriate time.

Scaling effects occur whenever you shrink an object, whether or not you consider the atomic structure of the material specimen. However, the existence of atoms and molecules leads to a new set of phenomena that are also a consequence of scaling. For example, in the field of catalysis, it is often the case that atoms closest to the surface are the ones that are the most reactive. Remember, these surface atoms have unfilled capacity to bond to other atoms, whether they are of the same kind in the bulk, or atoms of reactants. Moreover, the smaller the catalytic particle gets—considering the particle as a whole or as bumps on a catalytic surface—the more atoms we have at the surfaces and edges, the more effective the catalytic process. In contrast, a very large sphere, when zoomed in, appears to have atoms arranged in a two dimensional sheet without significant opportunity for molecules to bind and react at the catalyst surface.

The unusual properties of surface atoms do not stop with those located exactly at the surface. In fact, the bonding of a an atom in a solid or liquid usually extends a few layers beyond those in which it is in physical contact. For example, consider a thin film of liquid with nanoscale dimensions. Say that the liquid film is about 5 nanometers thick. As we will find in Chapter 4, the surface tension of the liquid arises due to the difference in potential energy of a molecule at the surface compared to the energy of the same type molecule deeper in the bulk. If you shrink a liquid sample down to molecular dimensions, there is less of a difference in energy between a molecule on the surface compared to a molecule in the bulk, and thus the overall surface tension is reduced. The examples of surface reactivity, burst release, and surface tension are just three examples of size surface to volume effects that have significant effects which can be used in nanoengineered systems.

Perhaps no field has benefited more from advances in nanoengineering than the fields of electrical and computer engineering. All of modern microelectronics and thus all of modern information technology is based on nanoscale systems and devices. These devices—microprocessors, integrated circuits, graphics processing units (GPUs), memory chips, etc.—are made using fabrication and manufacturing methodologies that are by definition nanoengineering. For example, every integrated circuit in the phone or laptop on which you may be reading the e-version of this book was made by a process called photolithography. Photolithography—meaning, literally, writing in stone with light—is the most sophisticated manufacturing process ever devised for a commercial product. It involves chemical processing, manufacturing engineering, chemistry and polymer engineering, and optical physics. The result of this sophisticated process is to make devices such as transistors and capacitors on silicon microchips. The structures on these chips can be made routinely with sizes significantly less than 10 nanometers. While microchips have had dimensions of less than 1 micrometer (or “micron”) for decades, the process of making these devices has always been called microfabrication. Notwithstanding, the prefix “micro” is a misnomer. Indeed, the features on microprocessors are as “nano” as things get.

No concept in technology is more closely associated with the miniaturization of microelectronic devices than Moore’s Law. Moore’s law, named after Gordon Moore, the co-founder and CEO of Intel during much of its rise, noticed that the density of transistors on a microchip doubles approximately every 18 to 24 months. There are several other formulations of Moore’s law, with some suggesting that the cost of computation approximately halves every 18 months or the sizes of transistors shrink by half every 18 months, but the overall effect is clear: computational power has been on an exponential rise for decades. Moreover, this growth is enabled by advances in nanoengineering. Indeed, essentially all of the processes we will talk about in this book have played a role in this unprecedented technological development.

Processes of mass production by replicating patterns on 2D surfaces are now centuries old. For example, the Gutenberg Bible, the first book manufactured by the printing press, ushered in a cultural transformation. After this invention, it became possible, if not to read the minds of the authors, then to come as close as possible. The printing press used to operate by first creating large metal sheets with raised features—“boilerplates”—that when inked could be pressed into paper over and over again to make many copies of words on a page. Nanofabrication engineering, in the service of microelectronics manufacturing, has taken these basic concepts and elevated them to completely new heights.^{‖‖‖‖‖} Instead of boilerplates, modern techniques of replicating nanoscale patterns use transparency masks made of quartz and covered with an opaque layer of chromium with apertures that let light through. These nanoscopic holes can be etched into the metal using a process that starts with a technique known as electron beam lithography.^****** This mask is akin to a photographic “negative,” a strip of film that contains the image from which the photographic prints are created in a dark room. In nanofabrication processes, we use a modern type of darkroom, called a cleanroom.^{††††††} The room must be clean, because a grain of dust could be orders of magnitude larger than the devices you are trying to make. If this dust came between the mask and the substrate, it might ruin the entire chip.

Electrical engineers at consumer electronics companies like Sony, Samsung, LG, and Philips are doing a lot of nanoengineering. Modern day consumer electronic devices use a wide range of materials which derive their properties from nanoscale phenomena. Take display technologies as an example. Organic light-emitting displays (OLEDs) use molecular semiconductors to emit colored light with high efficiency and with high contrast between adjacent pixels. These nanoscale molecules emit light at particular visible wavelengths which are partly determined by the manner in which their electrons are confined. Even a conventional liquid crystal display (LCD) uses rod-like molecules to increase or decrease the brightness of white light that passes through a red, green, or blue color filter. Moreover, quantum-dot enabled panels (“QLED” displays) use fluorescent light coming from a sheet of semiconductor nanocrystals to generate a color gamut that is warmer^{‡‡‡‡‡‡} and more pleasing to the eye. The exploitation of new optical phenomena arising from nanostructured materials like molecular semiconductors, liquid crystals, and quantum dots is the very essence of nanoengineering.

Compared to the ancient core disciplines of mechanical, electrical, and chemical engineering, bioengineering is a relative newcomer.^§§§§§§ Bioengineering is a vast area comprising disparate fields such as biotechnology (including protein engineering), and biomedical imaging (which has a lot of overlap with electrical engineering), bioinformatics (which involves a lot of computer science), and engineering of orthopedic structures (which shares overlap with mechanical engineering). Like nanoengineering, it is so broad that it can be hard to define, but advances in various areas within bioengineering have already led to marked improvements in human life. As with many of the connections between disciplines we have explored in this chapter, the boundaries between what qualifies as bioengineering and nanoengineering—or even bionanoengineering—are not always distinct. The two examples that I will discuss below, tissue engineering and drug delivery, could just as well be discussed in a book on applications of chemical engineering in the medical sciences. Nevertheless, the nano-centered perspective yields some important insights.

The design and synthesis of implantable scaffolds for wound repair, bone regeneration, and constructs that control the release of drugs is known as tissue engineering.^¶¶¶¶¶¶ When applied in biomedical technology, the use of scaffolds, usually polymers or hydrogels mixed with host-derived cells such as stem cells, is known as regenerative medicine. For these cells to adher to these implantable synthetic scaffolds, such constructs must necessarily have nanoscale features. The constructs must also have a porous internal structure that blends in with the physiology of the host, so that it is not rejected by the immune system. That is to say, a material that enabled the creation of new blood vessels in this artificial milieu must be engineered on the nanoscale.

Perhaps the defining application of the field of nanomedicine is the delivery of drugs using nanoengineered vehicles. The advantages of confining drugs to nanostructures prior to delivery into the bloodstream have been known and exploited for decades. There are many reasons. First of all, naked, unencapsulated drug molecules often have low solubility in the bloodstream. Moreover, they do not always reach the diseased tissue, and have adverse effects when they interact with healthy tissue. Nowhere is this unwanted cellular toxicity more problematic than in cancer therapy. Indeed, tumors are human cells, and thus most chemical agents that kill tumor cells can also kill healthy ones.

Thus, nanoscale particles that serve as delivery vehicles for such drugs which can target the cancer cells have been the subject of intense research for decades. In fact, rudimentary forms of nanoparticles in the form of micelles and liposomes have been used to deliver drugs in chemotherapy infusions since the 1970s. If you or someone you know has undergone chemotherapy, it is very likely that the infusion involved some kind of nanoscale vehicle which delivered the drug. Other functions of such particles include evasion of detection by the host’s immune system and also localization to the site of the cancer tissue. At the time of writing, the COVID-19 pandemic is receding significantly because of the advent of nanoparticle delivery agents. In particular, mRNA molecules used to encode the spike protein of the coronavirus would be broken apart quickly after entering the bloodstream. Thus, nanoparticles based on lipid (fat) molecules, polymers, and detergent-like surfactant molecules are used to encapsulate the mRNA. For these reasons and others that we will discuss in Chapter 13, nanoengineering is expected to continue to increase the power of therapeutics with profound benefits for human health.

Nanoengineering derives its intellectual strength from decades—or even centuries—of learning in the basic sciences. Moreover, we would argue that many of the most exciting challenges in traditional engineering disciplines fall into the category of nanoengineering. While most practitioners in academic and industrial research and development are trained in one of these traditional disciplines, they must learn the principles of nanoengineering on the job. Our goal is to allow you to “skip to the point” and start your education as a nano-minded individual exactly where the action is. Along the way, you will learn deep physical principles—from this course and others—that actually provide a frame of reference for future learning in disciplines which have a more established intellectual history. That is, physics, chemistry, biology, and all the flavors of engineering. This kind of study will be more fun, make more sense, and be highly motivating. We are excited to share our knowledge with you in the next fourteen chapters.

Reflect on what excites you about nanoengineering? Why did you take this course? What do you hope to learn? If you are taking it because “it is required for my degree,” then write a few words as to why you chose this degree program.

How big is a nanometer? How many nanometers thick is a red blood cell? A human hair? A cat’s hair? An optical fiber? A transistor on a microchip?

Give three examples of products around your space right now that were manufactured using nanoengineering.

Consider an enzyme, which is a protein which evolved in biological systems to catalyze a type of reaction. The enzyme contains a pocket called the active site, which binds one or more substrates. Do you suppose that the shape of the active site is most complementary to the shapes of the reactants, the products, or the transition state that resembles the conversion from reactants to products? Why?

Describe at least two consequences of size confinement. These effects can be physical, chemical, or biological.

What are some consequences of the increasing surface-to-volume ratio as objects approach the nanoscale? Consider both mathematically smooth surfaces along with “real” matter consisting of atoms.

In what ways does the field of biology serve as an inspiration for sophisticated nanoengineered systems?

Why are nanoparticles useful as vehicles for drug delivery?

Some people say that the field of nanoengineering began with the speech by Caltech professor Richard Feynman “There’s Plenty of Room at the Bottom.” Look up the text of this speech. What is your reaction? Which of his predictions have come true?

What is your favorite example of nanotechnology or miniaturization from fiction? In what way is it plausible and in what way is it implausible?

What excites us about nanoengineering is its central role in essentially all of modern technology. Moreover, its foundations are derived from every area of the basic sciences, from physics and chemistry to biology. From the nanoscale tools used to design and manufacture microprocessors for information technology and artificial intelligence systems to nanoscale carriers used to deliver vaccines and other drugs, nanostructured materials are everywhere, and they are transforming the world. We are excited to be able to contribute to research and education in this field, and to share our passion with you.

One nanometer (1 nm) is 1 billionth of a meter, or 1 × 10⁻⁹ m. A red blood cell is around 2 µm thick, or 2000 nm. A human hair is around 100 µm or 100 000 nm. On average, a cat hair is at most half the diameter of a human hair, or 50 000 nm. A typical multimodal optical fiber is about the thickness of a human hair, including the inner glass core (where the light actually travels) and outer glass cladding. The minimum feature size that can be patterned through photolithography on a microchip is less than 10 nm, although the actual size of a transistor is somewhat larger than this.

The physical products of nanoengineering are everywhere. Objects that have nanoscale dimensions in one dimension only include myriad thin films of various compositions: metals, ceramics, polymers, and inks. For example, the wrapper on the protein bar I am eating has a shiny aluminum coating that was probably deposited by sputter deposition, as well as multiple layers of polymers engineered for various purposes (protective films, adhesion promotors, ink, etc.). I am looking through eyeglasses that have many coatings, such as anti-reflective polymers. My phone has a layer of a fluorine-decorated polymer that is only one molecule thick! (The purpose is to make it slipperier for scrolling and writing texts without taking your thumb off the screen, and for making it easier to clean.) My computer, phone, and tablet have dozens of integrated circuits each, all of which have nanoscopic circuit elements like transistors, resistors, vias (conductors that travel up and down through the layers), and other conductive traces, all with dimensions in the tens of nanometers. These structures were all manufactured using photolithography, the primary “top-down” tool used for nanoengineering.

The active site is the place in an enzyme where the reaction takes place. A significant portion of the rest of the structure of an enzyme serves to stabilize and/or define the shape of this active site. In order to affect the reaction as rapidly as possible, the active site should have a shape that is complementary to the transition state. A snug fit with the transition state will lower the overall potential energy of the state in which the enzyme and substrate are in physical contact. If the active site of the enzyme were instead designed to fit the reactant(s) instead of the transition state between reactants and products, then the reactants would just sit in the active site like a lazy person watching TV on the couch, with no reason to move toward becoming products. If the active site had a shape which was complementary to the products, the reactants probably would not even bind, and there would be no reaction.

There are many effects or properties of nanostructures that arise from confining matter to one or more dimensions. In the realm of physical size confinement, the ratio of surface area to volume increases as particles become smaller. This effect is purely mathematical; that is, it happens whether or not we consider the fact that matter is made of molecules! Also, when electrons are confined to small particles of semiconductors and metals, such objects exhibit optical absorbance and fluorescence (e.g., in semiconductor quantum dots) and localized surface plasmon resonances (e.g., in metallic nanoparticles) that do not occur in larger samples of these materials. In the realm of chemical effects of size confinement, the increase in surface area relative to volume places a larger fraction of atoms and molecules near the surface, which can lead to increased catalytic activity.

Physical effects of the size confinement also include the fact that relatively weak forces can have large effects on small particles. That is, small particles are also much more likely to be under the influence of relatively weak forces like van der Waals forces, which do not have a much effect on macroscopic objects compared to the effects of, for example, gravity. For biological systems, the effects of size confinement are related to the fact that cells are small, viruses are small, bacteria are small, and biological macromolecules are small. For example, drug molecules that are encapsulated in nanoparticles drug delivery vehicles can easily sluice through holes in leaky vasculature—i.e., blood vessels—for delivering particles to tumor tissue. Moreover, nanoparticle-based agents can be used in radiology and medical imaging to enhance contrast. Such particles often have strong optical absorption or fluorescence. Such materials include small structures like quantum dots and metallic nanoparticles, which can be injected into the bloodstream and can thus find their way into tight places. Additionally, some organisms have developed the ability to manipulate the surface energy and/or adhesion of their skin. Such abilities make it possible for certain species of lizards, such as geckos, to either walk on water—e.g., the Brazilian pygmy gecko—or upside down on ceilings—e.g., many other species of gecko.

There are many ways in which the properties of materials change as we approach as we approach the nanoscale. These effects occur whether or not we consider the fact that real material is made of atoms and molecules. For example, the strength of the leg of an elephant scales with the cross-section of its legs, while the weight of an elephant scales with its volume. Also, consider a cube of a catalytic nanoparticle. It has more surface area relative to its linear dimension—independent of its atomic structure—if you scale it down, than does a larger cube. Chemically, what you have with the smaller cube is a greater fraction of its total number of atoms on the surface compared to the bulk. In terms of reactivity, the smaller cube will be more reactive, but its physical properties will also change. For example, the forces between atoms will be decreased because atoms on the surface have fewer van der Waals interactions with other atoms. Thus, the cohesive energy density will be decreased, as will the melting point. These examples point to two kinds of effects that arise from size confinement: (1) effects arising from simple geometry (i.e., math), and (2) effects arising from the fact that the object is made of atoms.

Biological systems serve as a wonderful inspiration for engineers, particularly nanoengineers. The concept of the nanoscale assembler, popularized by K. Eric Drexler, with which atoms can be arranged in precise ways and in large quantities, is already in some sense a reality. That is, biological systems made of macromolecules already perform these sophisticated tasks, particularly the action of metabolism and enzymatic biosynthesis. Also, there are examples of energy dissipating systems in biology that can perform complex, machine-like tasks. These tasks include the action of a ribosome, which can receive instructions from messenger RNA (mRNA) and convert it into protein. Other great examples are in the realm of biological motors, such as the flagella of microorganisms and sperm cells.

There are a number of advantages of nanoparticles as delivery vehicles for drugs. The first advantage is solubility. Many drug molecules are hydrophobic and do not dissolve in the bloodstream, or they dissolve in very low concentrations in the bloodstream. Moreover, a poorly soluble drug molecule can aggregate with itself. The resulting precipitate can form an embolus—a solid particle which circulates in the blood vessels—that can occlude (block) the healthy flow of blood. The second advantage is the ability to precisely target diseased tissue. In the field of anticancer therapeutics, it is the case that drug molecules that kill cancer cells may also be harmful to healthy cells. Thus, a method of administering the drug that reaches all tissue equally well can be highly toxic. For example, it is often the chemotherapy that makes cancer patients feel sick, not just the cancer itself. The third advantage of nanoparticle drug delivery vehicles (from this admittedly incomplete list) is the ability to encapsulate drug molecules. Thus, a nanoengineer has the ability to control the release of a drug molecule over time. Too large of a release all at once could have toxic effects or could not have the kind of sustained therapeutic power as if the drug molecule were slowly released into the system at a controlled rate.

There are many people who believe that the advent of nanotechnology was signaled by the physicist Richard Feynman’s famous lecture delivered in 1959, “There’s Plenty of Room at the Bottom.” In this talk, Feynman made predictions about what might be achievable in a future world based on nanotechnology. For example, a motor with a dimension of a very small fraction of an inch, as well as the prediction that it would be possible to fit a very large amount of information in the form of the text of The Encylcopædia Brittanica on the head of a pin, with a size reduction of $1 25 000$ ⁠. Both of these achievements were achieved by scientists and engineers during this time. For example, the motor was made through a very painstaking assembly of mechanical parts using very fine tools, which, although being very difficult, did not really require any nanoengineering. Writing text on a pinhead took longer but was eventually accomplished by means of writing with an electron beam. Although the entire text of the encyclopedia was not achieved, an equivalent information density was achieved by writing the first page of Dickens’ A Tale of Two Cities.

Darren’s favorites nanotechnology or miniaturization technology comes from the TV show Star Trek: The Next Generation. In this show, the crew of the Enterprise encounters a species known as the Borg. The Borg are half biological, half machine beings that communicate with each other wirelessly and through subspace to create something called The Borg Collective—i.e., a collective consciousness involving millions of beings, which can make decisions instantly and as a group, with disastrous consequences! Famously, the Borg try to “assimilate” other biological species and cultures into their collective.

In the movie Star Trek: First Contact, it has been revealed that the first step toward assimilation is the injection of nanobots into the bloodstream of the victim. These nanoscale terrorists co-opt the biology and metabolism—and even the thoughts!—of the victim and lay the groundwork for the future installation of electrical and mechanical prosthetic devices characteristic of the Borg’s outward appearance (do an image search on Google after you are done with your homework). So, this is certainly a gloomy prediction based on fiction, but it was Darren’s favorite, nonetheless. A number of technological hurdles would be required to achieve this level of sophistication for nanoengineered systems. For example, such a system of nanobots would have to have the ability to control matter, affect chemical reactions, and infiltrate cells while overcoming the effects of van der Waals forces, which are extremely sticky on the nanoscale.

My ideas about consilience originated from Edward O. Wilson’s book of the same name. I read this book after my freshman year in college, in the summer of 2002. To this day, I consider it the most important and inspirational book of scientific philosophy I have ever read. In many ways it has guided the development of my own research trajectory, which now combines nanoengineering and chemistry, with neurobiology and human perception.

• E. O. Wilson, Consilience: The Unity of Knowledge, Vintage, 1999, p. 384.