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Many of the microscopes are housed together in the Imaging and Analysis Center (IAC), a wonderland of cutting-edge instrumentation available to all Princeton researchers, from undergraduates to senior scientists. Part of the Princeton Materials Institute, the IAC is located on the lowest level of the Andlinger Center for Energy and the Environment, where picture windows on both sides of a long hallway reveal instrument rooms containing microscopes that range in size from a toaster to an industrial freezer.

Corning produces some of the world's purest glass through a process that, for a while, doesn't seem to involve glass at all. It's called vapor deposition.

Several scientists noted the importance of training undergraduates and graduate students to use these instruments so that they are prepared to lead their own research labs and accelerate the rate of discovery.

Corning's proprietary "fusion" process has been a big key to Corning's innovation success over the past two decades. Here's a quick breakdown on how the process works and why it's so important for Corning.

“They’ll say, ‘I care about my health.’ ‘I care that I don’t lose my memories.’ ‘I care that the water’s clean.’ ‘I care that my phone works.’

Jimah, who is Nwokeji’s advisor, continued: “Microscopy is a fast-moving field, and Princeton continues to invest in it. To keep making world-class contributions to research, we and our trainees need to use world-class equipment, both for discoveries and to bring those discoveries out to the wider world.”

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Corning's proprietary "fusion" process has been a big key to Corning's innovation success over the past two decades. Here's a quick breakdown on how the process works and why it's so important for Corning.

It is an all-too-common and annoying problem, but one that Corning scientists are tackling head-on with an anti-reflective solution.

In recognition of the IAC’s unique capabilities, Nature co-leads a “Frontiers in Electron Microscopy for Physical and Life Sciences” conference with Princeton every two years.

“There are so many different flavors of microscopy,” said Brangwynne. “There’s huge difference whether you’re imaging materials, electronic devices or living systems, or whether you’re using an instrument to observe or to manipulate materials. Do you need to see a single cell? Is it a small cell or a big cell? Or is it the 10 million cells making up lung tissue? Microscopy comes in thousands of different flavors, and each has specific needs and preferences.”

For her work exploring bacterial communication, Bassler uses a microscope custom-built for her lab. “Bacteria are really tiny,” she said. “It's hard to image even individual bacteria. It's really hard to image single-gene mRNA transcripts inside bacteria. They’re smaller than small.”

“The ready availability of these tools enables our researchers to make advances that lead their fields,” said Schiffer, a professor of physics. “Furthermore, world-class facilities attract other top scholars, who in turn share their expertise and insights, leading to more progress, which attracts more excellent researchers, creating a virtuous cycle.”

Corning® Gorilla® Glass redefined the toughness and durability of consumer electronics. Gorilla Glass gets its damage resistance from Corning's ion-exchange process. But, how does that work?

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Princeton researchers and engineers are peering into living cells, newly discovered materials, and many more things at impossibly small scales.

“But all these things are dictated by microscopic processes that we cannot see with the naked eye,” said Brangwynne, who is also Princeton’s June K. Wu '92 Professor of Chemical and Biological Engineering. “Fundamentally, microscopy is a window into the underlying drivers of things that matter to everyone.”

Their search for a naturally occurring quasicrystal took more than a decade, but Yao and Steinhardt eventually found the world’s first, and then second, naturally occurring quasicrystals. “Without electron imaging and diffraction, this would have been impossible,” Yao said. “The crystal sample we had was so small, no other technique could have detected its detailed structures.”

The University’s extraordinary microscopic and nanoscopic instruments include atomic force microscopes, transmission electron microscopes, X-ray diffraction and 3D X-ray microscopes, cryo-electron microscopes, ion and electron dual-beam scanning microscopes, and many others. Scientists and engineers use them to see inside human cells and map out the structures of matter, genes and proteins, building an understanding of microscopic processes that leads to new medicines, new tools and new materials.

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“The problem starts with the cover glass on your device,” said Corning’s Dr. Odessa Petzold, who has researched light management surface engineering innovations for more than five years. “Light reflects off of the glass which then makes the display appear dark or dull.”

“That’s the beauty of biology,” said Kang, who is the Warner-Lambert/Parke-Davis Professor of Molecular Biology at Princeton University, a founding member of the Ludwig Institute for Cancer Research Princeton Branch, and an associate director of Rutgers Cancer Institute of New Jersey. “Crystal structures give you a crystal-clear vision about how, at the atomic level, biology works. Seeing the crystal structure gave us the insight to develop the compound, and then we imaged it again and saw that it binds to the pocket exactly as we had hoped and predicted it would do.” That compound is now making its way through the FDA’s drug development process.

“The beauty of Princeton is that we combine both physical sciences and life sciences together in the IAC, so researchers come here, talk to each other, and start interdisciplinary collaborations,” Yao said.

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“If you grab somebody on the street and say, ‘What do you care about?’, they’re not going to say ‘Microscopy!’,” said Cliff Brangwynne, a pioneer in the molecular forces behind neurodegenerative diseases and director of Princeton’s Omenn-Darling Bioengineering Institute.

Designing the instrument makes all the difference, said mosquito researcher Lindy McBride, an associate professor of ecology and evolutionary biology (EEB) and neuroscience. Key to her team’s discovery of how mosquitoes target humans, she said, was an instrument built by Thiberge to image the neurons inside a mosquito’s brain. “We could walk over to the Bezos Center and say we want to image this, at this resolution, with this orientation, and a few months later, the microscope was built,” she said. “We could have bought an off-the-shelf microscope, but it would have been so much slower and so much less powerful.”

Essentially, Corning’s anti-reflective solution greatly reduces the intensity and magnitude of light reflecting off a device.

These multi-user facilities also serve as a focal point of interaction with industry. Companies with research questions pay to use many of the facilities, which speeds innovation while injecting ideas from real-world uses into teaching and research.

Federal grant support for the Princeton researchers included in this story comes from agencies including the National Science Foundation, the National Institutes of Health, the National Cancer Institute, the Department of Energy and the Department of Defense.

Fibrance technology is basically a glass optical fiber that unleashes colorful lighting. Yet, to really understand it, you have to go back to the beginning to learn how it works.

Bonnie Bassler, chair of the Department of Molecular Biology, was instrumental in bringing the cryo-electron microscopes to Princeton. “For half a century, X-ray crystallography reigned supreme as the best tool available to peer into the world of the small,” said Bassler, who is also Princeton’s Squibb Professor in Molecular Biology and a Howard Hughes Medical Institute Investigator. “It’s what Rosalind Franklin used to discover the structure of DNA. It is great for seeing an individual protein, or even maybe two. But cryo-EM shows us whole enormous machines inside a cell.”

The conference brings together top microscopists from around the world to share discoveries, approaches and insights with Princeton’s own microscopy community — the hundreds of undergraduates, graduate students, postdoctoral researchers, staff researchers and faculty members whose advances depend on observing the smallest realms.

You’re enjoying a sunshiny day when your smartphone rings. The bright light makes your screen nearly invisible, forcing you to squint and strainto figure out who is calling. It is an all-too-common problem, but Corning scientists have come up with an anti-reflective solution.

Today's connections are made possible by beams of light constantly bouncing through hair-thin strands of optical fiber. So, how does fiber actually work? Let’s take a look.

These exquisitely sensitive instruments need to be located underground, spiked into bedrock and isolated from even the smallest vibrations. Many of the microscopes require water chillers and noisy air quality handlers, all hidden behind sound-proofed walls. The entire facility is in encased in 3/8” thick aluminum to shield it from errant electromagnetic waves, and the heating and cooling systems are designed to move air in smooth sheets so as not to cause even an atom-sized jiggle.

You’re enjoying a sunshiny day when your smartphone rings. The bright light makes your screen nearly invisible, forcing you to squint and strainto figure out who is calling. It is an all-too-common problem, but Corning scientists have come up with an anti-reflective solution.

The IAC eagerly welcomes undergraduates into the community and supports their scientific inquiry. “Within two weeks, I went from not knowing much about what an electron microscope even is to using one for my own data acquisition,” said sophomore Maria Karakousis.

Corning produces some of the world's purest glass through a process that, for a while, doesn't seem to involve glass at all. It's called vapor deposition.

John Jimah, an assistant professor of molecular biology who studies malaria and related parasites and has contributed to the development of a transmission- and infection-blocking malaria vaccine candidate, said, “One reason I chose to come here was that I could see that the environment was very interested in training and mentoring the next generation of scientists.”

“Corning continues to push the boundary on how glass, along with other companion coatings or technologies, can help solve tough problems for consumers and their devices,” said Petzold.

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While many of the University’s largest instruments are in the IAC, many more microscopes are located in shared facilities or in individual labs around campus. One of the newest, a multi-million-dollar instrument being built by Herschel Rabitz, the Charles Phelps Smyth ’16 *17 Professor of Chemistry, and Martin Jonikas, associate professor of molecular biology, will be housed in Frick Chemistry Laboratory. This recently funded project aims to develop an instrument that provides unprecedented views of chemicals and small molecules at nanometer resolution.

Princeton’s microscopes and its commitment to making them accessible both played a role in recruiting several recent hires in molecular biology and engineering and applied sciences, including two who were renowned cryo-electron microscopists before coming to the University.

“One of the beauties of the IAC is that this is not just a research center, but also an education center,” Yao said. Yao teaches two award-winning microscopy classes for undergraduate and graduate students. In addition, he and his team lead a two- to four-hour workshop every month on various microscopy techniques on all 33 instruments. Thousands of students have learned and practiced microscopy in the IAC.

The microscope is as big as a walk-in closet, and one of two cryo-EMs in the IAC. It offers an unparalleled view inside cells and will help her build a 3-D model of the attacking protein. “For proteins, structure dictates function,” Nwokeji said. “Once we have the structure, future research can see what it binds to, what it does and ultimately, how to design a drug to stop it.”

Customers are beginning to test-drive this thin-film application for their next-generation devices. In the meantime, Corning scientists are developing a version of the anti-reflective, thin-film coating that is tough enough to withstand the harsh handling of mobile devices.

So, stay tuned. Corning’s pursuit of anti-reflective coatings could soon put an end to the blinding light bouncing off your smartphone.

For his work on metastatic breast cancer, for example, Yibin Kang connected with colleagues who used X-rays to visualize metadherin, a protein that Kang knew was vital to the spread of deadly cancers. The imaging revealed that the protein has two finger-like projections that stick into two pockets on another protein, SND1. Kang’s team had had little success disabling metadherin itself, but after seeing the interconnection, they used high-throughput screening assays to identify a molecule that fills one of SND1’s pockets. They modified that molecule, changing it into a compound that prevents the proteins from intertwining.

Yao has run the IAC since its inception and helped it grow from housing a single instrument to establishing Princeton as a world leader in microscopy. “Of all the top-notch papers published by Princeton authors in Science, Nature and similarly high-impact journals, fully half are associated with the Imaging and Analysis Center,” he said. “Either an author was our user or they used imaging data collected here. This facility is a very important investment for the University.”

Additionally, “here at Princeton, the people who do the analysis talk with the people who think about instrument design and the people who write the algorithms. That sets us apart,” said Joshua Shaevitz, a professor of physics and the Lewis-Sigler Institute for Integrative Genomics, the director of the graduate program in biophysics, and a longtime leader in microscopy at Princeton. “Our goal is not just to push the resolution smaller and smaller, it’s about driving discovery.”

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“By adding a special anti-reflective coating to the cover glass, the light reflection is reduced by more than 75 percent, resulting in a device that’s easier to read in the sun.”

Funding for these technological marvels comes from federal research grants, donor funding and the University endowment, which has helped purchase what Dean for Research Peter Schiffer calls “some of the best technical equipment in the world, in service of cutting-edge science and engineering research.”

You’re enjoying a sunshiny day when your smartphone rings. However, the bright light makes your screen nearly invisible, forcing you to squint and strain your eyes to figure out who is calling.

“Corning continues to push the boundary on how glass, along with other companion coatings or technologies, can help solve tough problems for consumers and their devices.”

Corning® Gorilla® Glass redefined the toughness and durability of consumer electronics. Gorilla Glass gets its damage resistance from Corning's ion-exchange process. But, how does that work?

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Junior Jennifer Nwokeji is using one of the University’s most sophisticated microscopes, a cryogenic electron microscope (cryo-EM), to try to decode how a protein is burrowing through the membrane wall of a human cell. She hopes to find a cure or treatment for malaria, a disease that still ravages her parents’ home country of Nigeria.

A.J. te Velthuis, an assistant professor of molecular biology and a leading virologist who studies coronaviruses and flu viruses, said he was drawn to Princeton because of its community of instrument users, who meet regularly for scientific discussion and to share insights and ideas. “During my interview, I spoke with students and members of the faculty,” he said. “Getting to work with them and find new ways to look at viruses is really inspiring.”

“The problem starts with the cover glass on your device. Light reflects off of the glass which then makes the display appear dark or dull.”

This process begins with a thin, inorganic film applied to the device’s cover glass. Once in the sun or bright light, the proprietary coating material manipulates incoming light, causing light waves to interfere and cancel each other out.

Princeton scientists are peering into the smallest corners of matter using an exceptional collection of sophisticated microscopes — some so big they fill a room. These remarkable instruments have established the University as a world leader in microscopy and led to countless discoveries.

But Yao and physicist Paul Steinhardt, Princeton’s Albert Einstein Professor in Science, believed that 5-fold symmetry must exist in the natural world, since other scientists had artificially created a quasicrystal in a lab.

“Microscopy is an engine to all kinds of research, from environmental science to bioengineering and quantum physics,” said Nan Yao, the IAC director and the inaugural professor of the practice in the Princeton Materials Institute. “No matter what kind of materials we deal with — polymers, ceramics, glass, graphene, quantum dots, lithium metal oxide, or living cells — we need to see it to analyze it.”

In addition to the room-sized microscopes available in the IAC, many Princeton researchers and engineers design instruments targeted to their specific questions, which are then housed in their own labs.

A way to stop cancer cells from metastasizing. New insight into Alzheimer’s. A revolutionary form of matter with 5-fold symmetry. Exquisitely precise quantum sensors built from diamonds.

Today's connections are made possible by beams of light constantly bouncing through hair-thin strands of optical fiber. So, how does fiber actually work? Let’s take a look.

Princeton microscopes and teamwork also played a key role in a revolutionary contribution to materials science: discovering a natural quasicrystal. For centuries, crystallographers had insisted that crystals could only have 3-fold, 4-fold, or 6-fold symmetry, never 5-fold or 7-fold.

Fibrance technology is basically a glass optical fiber that unleashes colorful lighting. Yet, to really understand it, you have to go back to the beginning to learn how it works.

Also, rather than dulling colors like some other commercial anti-reflective coatings, Corning's solution enhances color fidelity. This means that your phone’s imagery and text would be sharp and legible even in sunlight.

Princeton undergraduates who take advantage of the IAC training and resources go on to graduate school with a clear edge, he said. At most peer universities, he said, only graduate students and postdocs have access to the most cutting-edge tools.

Stéphan Thiberge, director of microscopy facilities at the Bezos Center for Neural Circuit Dynamics at the Princeton Neuroscience Institute, is like a modern-day clockmaker, assembling novel microscopes with tiny screwdrivers — with help from computer-assisted design software and the physics department’s machine shop.