Credit: Gabriela Hasbun | Researchers worldwide use A. Paul Alivisatos's chemical methods for synthesizing nanoparticles and customizing their properties.
A version of this essay will be presented at the American Chemical Society Fall 2021 meeting by 2021 Priestley Medal winner A. Paul Alivisatos—the executive vice chancellor and provost, the Samsung Distinguished Professor of Nanoscience and Nanotechnology, and a professor of chemistry and materials science and engineering at the University of California, Berkeley.
Here I will share with you a glimpse into the beauty of a type of object that is too small to see and yet provides illumination in a palette of colors every bit as rich as those we can experience in nature. I speak of nanocrystals, a type of material consisting of the regular spatial arrangements of a small number of atoms. The number is so small that a person just might be able to count them and track the atoms. Let’s say between hundreds and some tens of thousands of them.
Creating nanocrystals, shaping them, learning about them, and seeing how they might be used have been the focus of my research life. Their study offers renewed insight into the laws of physics and principles of chemistry and demonstrates the challenges of materials science and the pitfalls and joys on the road from discovery to their uses today in medical diagnostics and color displays. These tiny crystals have brought a sense of wonder, not just to me but also to thousands of scientists and engineers from around the world who study them.
Think of this essay as a mini bildungsroman, a coming-of-age story of the little nanocrystal, which has grown from a neophyte to a new type of macromolecule, sitting alongside polymers and proteins. Following the Priestley tradition, I will pair the story of the protagonist nanocrystal with a few brief autobiographical interludes.
Let’s start this journey by visualizing a tiny crystal—sadly, getting a bit too hot and melting. The regular arrangement of its atoms gives way under thermal agitation to the freer motions characteristic of atoms in a liquid.
I once had to step in as the substitute teacher for our daughter Clara’s kindergarten science class. The prescribed topic was the states of matter—solid, liquid, and gas. How could I explain this idea to people still sensible enough to prefer explanations in the form of seeing and touching? We headed to the playground, and I asked the children to link arms in the ordered arrangement of a solid. Enthusiasm followed when I asked them to imagine that they were at sea on a boat in calm waters when a storm arrives, pitching them to and fro. Under this agitation, their crystalline arrangement gave way to ceaseless rearrangements amongst them, links forming and breaking even as they stayed in bumpy contact, as in a liquid. True joy broke out when the temperature went up and they could run about freely like gas molecules. Within the time of one recess, they practiced transitioning from solid to liquid to gas and back over. It wasn’t a very quiet class, but Clara confirmed recently that they all remember it to this day.
This leads us to the first fundamental property of nanocrystals: smaller ones melt at lower temperatures. Atoms on the edges of a crystal always have the fewest links with other atoms, so they are easier to dislodge during heating. The smaller the crystal, the more edges there are, making them easier to melt. This was first imagined in the early 1900s and verified decades later by Philippe Buffat and Jean-Pierre Borel with clusters of gold atoms suspended in a gas. My coworkers and I extended their observations to semiconductor nanocrystals early in my research career.
I am starting the nanocrystal’s journey with melting for three reasons. First, it is a good example of a scaling law, a rule of thumb for qualitatively guessing how a given property will change with the size of an object. In this case, the decrease in the melting temperature can be estimated as being proportional to the ratio of the surface area to the volume, or one over the radius of the nanocrystal.
Second, for the size of semiconductors we will be discussing, on the order of 2–10 nm, the decrease in melting temperature can be quite significant, the total being as much as half the temperature for the bulk solid. This difference is crucial because it means that we can expect to grow many useful semiconductors as nanocrystals in hot liquids rather than in the hot gases required for large crystal growth. This will change the whole technology, transitioning electronic material growth from the vacuum chamber to the chemist’s flask and the chemical engineer’s batch reactor vessel and making the process more scalable for commercial applications.
The third reason to start this story with melting is because I felt like a melting crystal when my mother died when I was 10. Until then, I had grown up in the Chicago area in a stable environment provided to me by my mother, a child of immigrants from Greece and Austria, and by my father, a refugee from the civil war unleashed in Greece in the aftermath of World War II. Her untimely death exposed the instability of our situation, as my father, unable to hold us together, sent my sister, Regina, who is 4 years older, and me back to Greece.
This was a kind of liquid environment. Even as familiar and vital bonds were irretrievably disrupted, the potential for new and enduring ones appeared. In Greece, I was supported and stimulated by my extended family; a strong boarding school, Athens College; and a kaleidoscope of new language and culture. I was exposed to the tough reality of a horrible military dictatorship eventually overthrown with much loss of life by a people-power revolution.
Just as I reestablished stable bonds, so do nanocrystals. And much can be learned from how they do that. The first guess for a good temperature for growing a crystal is somewhere around one-third to one-half of its melting temperature. This brings us to the joyful science of growing tiny, tiny crystals. It’s a lot like when you let a supersaturated solution cool down to form big crystals in science class.
To form nanocrystals, there is a very organized approach to supersaturating precursors to a semiconductor in a very hot liquid. Once the crystallites nucleate, scientists program a cooling protocol, first to a suitable growth temperature and then to a temperature where the crystals can be isolated and collected. This is a little oversimplified. With the contributions of Mike Steigerwald, Moungi Bawendi, and Chris Murray, to name a few, this process is now practiced at high levels in labs around the world and commercially at the multi-metric-ton scale.
During this process, atoms need to be able to come on and off the growing crystals at a certain rate for the crystals to grow well. But something has to protect the tiny, just-forming crystallites from colliding and fusing. That protector is a surfactant, or a layer of amphiphilic molecules chosen so that they will reversibly bind to the crystal surface at the growth temperature. These surfactants fluctuate, transiently opening up little windows for atoms to still be able to add to the crystal.
But the hardest thing is to get the growing crystals to all be the same size. The properties of nanocrystals often depend on their size. So controlling how big the crystals grow is important if you want to study and use those size effects.
We demonstrated and used an approach for creating narrow distributions of crystal sizes that we called size-distribution focusing. It was first imagined by Howard Reiss well before I was born. Here is how it works: At a given concentration of precursor atoms in a liquid, crystals will grow at very different rates depending on their size. Large crystals are more stable and will accrete atoms, while small ones are less stable and tend to lose atoms to the big ones. In crystal growth, that’s called Ostwald ripening, after the turn-of-the-20th-century figure who might have nearly invented nanoscience if only he had an electron microscope.
In the chemical flask, we can regulate this process. By abruptly increasing the concentration of atoms available for growth, we can shift the critical size for crystals—where they are just big enough not to shrink but not big enough to grow—to a much smaller value. A funny thing happens next. Because they have a higher surface energy, the smaller crystals start to grow faster than the big ones, and the size distribution abruptly narrows, at least until that pulse of extra feed atoms is depleted. If you cool the solution, you can trap a narrow distribution of crystal sizes for subsequent studies and uses. It’s cool to see it in action. Ton-scale reactors sometimes use this process to make nanocrystals commercially, although there are many variations and other approaches.
After my personal melting period as a child, I was far, far behind others in school, a bit like a smaller crystal in solution. Fortunately, I soon found myself in a sequence of caring growth environments. As an undergraduate at the University of Chicago, the core curriculum (a broad liberal arts curriculum that aims to teach students how to think, not what to think) taught me how to grapple with the kinds of open-ended but deep questions that are at the heart of true discovery. This helped me transition to the University of California, Berkeley, where the deepest assumptions are always questioned relentlessly. That campus also first exposed me to the ethos of seeking knowledge for the sake of serving the public good, which guides me to this day. At Bell Labs, working with Louis Brus, I discovered my first scientific love, the little nanocrystal. It took a while, but with so much help, I eventually did catch up in my growth. Think of this time as my personal example of sustained focusing and annealing.
When actual nanocrystals come out of their own growing environments, scientists often check their quality. So what level of quality can we expect from a crystal when it is grown in a hot liquid compared with one formed at much higher temperatures in a pristine vacuum environment, like those used to make precision electronics? This isn’t a rhetorical question. One of the most senior theoretical physicists at the renowned and somewhat-scary Bell Labs posed that question to me when I was a postdoc. I visited him, proud of the fact that my colleagues and I had made one of the earliest examples of a colloidal semiconductor nanocrystal, hoping that he would guide me towards great experiments to try next. Alas, he recommended that I find another object to fall in love with. He quickly estimated the number of impurities present in a typical liquid and suggested that my quest to make an electronic-grade material in a liquid was a fool’s errand. He did invite me to return should I come up with a better direction.
After a suitable period of shock, I regrouped and did as I had been taught at Chicago and Berkeley—I questioned his assumptions and soon found they might be faulty. To understand why his assumptions were indeed wrong, think about the finances involved in buying a diamond engagement ring. At some point in life, you may have had the good fortune to meet somebody special and to go to a jewelry store to buy them a diamond, or perhaps you received one. When I met Nicole, my life partner, I sure remember that jewelry store trip. It was tough because of course, I wanted to buy the biggest, most perfect diamond I could. The price of diamonds follows a scaling law, the cost increasing with the square of the volume. This is because larger diamonds of high quality are much rarer. And why is that? Because if a defect does form in a growing diamond crystal, then it takes a while for that defect to be corrected or pushed out to the surface, a process called annealing out. Indeed, in the simplest model, the annealing time increases with the exponent of the volume.
Here’s the beautiful thing: nanocrystals turn this logic upside down and inside out. Since they are small, it is easy to anneal out any mistakes. As it turns out, it is much more forgiving to make a group of tiny crystals close to perfect than to do so with big ones. So a simple flask of hot liquid should do just as fine at making high-quality crystals as a slow, expensive vacuum process.
A little proof was required. My colleagues and I subjected nanocrystals to very high pressures to see if they would change their crystalline forms to ones with more dense packing through a process known as a solid-solid phase transition, or structural transformation. These changes most frequently start at defect sites. We found that well-formed nanocrystals could withstand pressures far above those that produce transitions in larger, bulk crystals. And that’s because the interior defects invariably present in large crystals were absent in the little ones.
This all bodes well, but recall that the greatest strength most often also leads to the greatest weakness. In the nanocrystal, while the interior can be pristine, the surfaces and interfaces require a high level of care.
I’ve emphasized semiconductors as our material class of choice when making nanocrystals without explaining why. I joined Louis Brus at Bell Labs specifically to explore the quantum size effect and how it could manifest in colloidal nanocrystals. To understand this size effect, imagine one of those museum exhibits where a ball is launched around a curved funnel. The ball at first moves almost lazily as it travels around the wide, upper portion of the funnel. But pretty soon it really zings as it drops lower and loops around in ever-tighter radii.
Similarly, the electrons moving around in a semiconductor have a higher kinetic energy in smaller crystals due to how the crystal boundary alters their motion, like the ball whizzing around in the lower parts of the funnel. As a result, to excite an electron in a semiconductor from the bonding environment it normally occupies to a higher, more “free to move about” level, you need more energy when the crystal is smaller to compensate for that increased kinetic energy. When that excited electron returns to the ground state by emitting light, the color of that light will shift to a higher energy, or a bluer color, in smaller crystals. This highly simplified picture is good enough to see that precisely controlled sizes and shapes of colloidal semiconductor nanocrystals could be used to produce an entire palette of light-emitting materials. You can see how the nanocrystal was soon on its way to becoming a fundamental new type of macromolecule and a building block of nanoscience.
The final step in this leg of the journey is to deal with that one weakness of nanocrystals, their surfaces and interfaces. In electronic-grade semiconductors, surface atoms pose a challenge. These atoms are bonded only on one side and as a consequence can act as sites known as charge traps, where charged species like electrons are localized and subsequently lost to heat rather than emitting light or producing a current. These sites frustrate light emission and can lead to light degrading the crystal.
The key is to protect against these problem surfaces by making a kind of Russian Matryoshka doll nanocrystal with one material of a larger bandgap wholly surrounding a lower-bandgap core. In the late 1990s, we built on work by many colleagues in the field and grew core-shell nanocrystal quantum dots with as much as 85% light-emission efficiency. With Shimon Weiss, we added layers that rendered quantum dots biocompatible, and we introduced them inside biological cells for imaging. Shuming Nie made the same advance. That was a milestone. It showed that these materials had practical uses and that the nanocrystal could operate as a kind of ambassador of the world of electronic materials to the world of biological science and health.
The little nanocrystal was now ready to be a building block on larger scales, and my research expanded to the study of how to create spatial arrangements of nanocrystals in 3D. This was chemistry on a new scale, where the single nanocrystal represents the atomic building block, and the goal was to assemble them into artificial molecules. We developed two approaches. The first, almost infinitely programmable and simultaneously discovered by Chad Mirkin, uses DNA as a scaffold for nanocrystal arrangements. The second uses inorganic scaffolding through a new sequence of chemical transformations. We learned how to make rods and plates, as well as branched, hollow, nested, and striped nanocrystals. We showed that each of these transformations is modular, and they can be performed in various orders and sequences. For nanoscience, this is akin to the rules that guide organic chemists when they build molecules.
This point marked another transition for me. I shifted from catching up, starting a research program, and looking at small things with great focus to a period of opening, expanded views, and giving back—a shift to sharing with the community at scale. Three such opportunities arose for me, all at about the same time. First, Nano Letters. While I’m credited as being the founding editor of Nano Letters, many talented people from the American Chemical Society Publications team and the community played vital roles. Also, the way I see it, Nano Letters would never have enjoyed the success it did without the devoted and tireless work of my spouse and partner, Nicole Alivisatos. In record time, Nano Letters became the forum where the very best of the new discipline of nanoscience was published and published quickly. We created a forum that erased boundaries between chemistry, physics, materials science, engineering, and many other disciplines that all contributed to this exciting, chaotic, wonderful border zone of discovery.
The second big opportunity was cofounding the Molecular Foundry with colleagues at the Lawrence Berkeley National Laboratory. The idea was to establish a national user facility based on sharing expertise, not a unique instrument. It is a place of energy, joy, and the exuberance of sharing discovery with the community.
The third significant opportunity was commercializing nanocrystals for beneficial uses. I was soon a cofounder of two companies: Quantum Dot Corporation, which first made quantum dot biolabels available for medical research and the clinic, and Nanosys, which pioneered so many aspects of today’s quantum dot displays, bringing a larger gamut of colors to consumers and to artists.
But those opportunities weren’t the last. My engagements in leadership and other roles in the scientific community have branched out and expanded in new ways. I was so honored to serve as director of the Lawrence Berkeley National Lab and now as the provost of the University of California, Berkeley.
And now there is a new chapter opening in my life. I am thrilled to have the opportunity to return this fall as president to the University of Chicago, where I was formed by the core curriculum.
Likewise, my research has also come full circle, back to the most basic study of nanocrystals, but now at previously unimaginable levels of observation and control. My group has joined with scientists like Frances Ross to develop a new tool for nanoscale visualization, the liquid-cell transmission electron microscope, including the graphene liquid cell. Using this tool, we can see nanoparticles at atomic resolution as they move in their native liquid environment, growing and dissolving, and we can even use it to locate the position of every single atom within one specific nanocrystal. Ostwald would have wept.
What a joyful journey the little nanocrystal has brought me on so far. What wonderful opportunities seem just around the corner. I am so grateful.