The research is published in Science Advances.

“This research combines breakthroughs in artificial muscle technology with metalens technology to create a tunable metalens that can change its focus in real time, just like the human eye,” said Alan She, a graduate student at SEAS and first author of the paper. “We go one step further to build the capability of dynamically correcting for aberrations such as astigmatism and image shift, which the human eye cannot naturally do.”

“This demonstrates the feasibility of embedded optical zoom and autofocus for a wide range of applications including cell phone cameras, eyeglasses and virtual and augmented reality hardware,” said Federico Capasso, Robert L. Wallace Professor of Applied Physics and Vinton Hayes Senior Research Fellow in Electrical Engineering at SEAS and senior author of the paper. “It also shows the possibility of future optical microscopes, which operate fully electronically and can correct many aberrations simultaneously.”

The Harvard Office of Technology Development has protected the intellectual property relating to this project and is exploring commercialization opportunities.

To build the artificial eye, the researchers first needed to scale-up the metalens.

Prior metalenses were about the size of a single piece of glitter. They focus light and eliminate spherical aberrations through a dense pattern of nanostructures, each smaller than a wavelength of light.

“Because the nanostructures are so small, the density of information in each lens is incredibly high,” said She. “If you go from a 100 micron-sized lens to a centimeter sized lens, you will have increased the information required to describe the lens by ten thousand. Whenever we tried to scale-up the lens, the file size of the design alone would balloon up to gigabytes or even terabytes.”

To solve this problem, the researchers developed a new algorithm to shrink the file size to make the metalens compatible with the technology currently used to fabricate integrated circuits. In a paper recently published in Optics Express, the researchers demonstrated the design and fabrication of metalenses up to centimeters or more in diameter.

“This research provides the possibility of unifying two industries: semiconductor manufacturing and lens-making, whereby the same technology used to make computer chips will be used to make metasurface-based optical components, such as lenses,” said Capasso.

Next, the researchers needed to adhere the large metalens to an artificial muscle without compromising its ability to focus light. In the human eye, the lens is surrounded by ciliary muscle, which stretches or compresses the lens, changing its shape to adjust its focal length. Capasso and his team collaborated with David Clarke, Extended Tarr Family Professor of Materials at SEAS and a pioneer in the field of engineering applications of dielectric elastomer actuators, also known as artificial muscles.

The researchers chose a thin, transparent dielectic elastomer with low loss — meaning light travels through the material with little scattering — to attach to the lens. To do so, they needed to developed a platform to transfer and adhere the lens to the soft surface.

“Elastomers are so different in almost every way from semiconductors that the challenge has been how to marry their attributes to create a novel multi-functional device and, especially how to devise a manufacturing route,” said Clarke. “As someone who worked on one of the first scanning electron microscopes (SEMs) in the mid 1960’s, it is exhilarating to be a part of creating an optical microscope with the capabilities of an SEM, such as real-time aberration control.”

The elastomer is controlled by applying voltage. As it stretches, the position of nanopillars on the surface of the lens shift. The metalens can be tuned by controlling both the position of the pillars in relation to their neighbors and the total displacement of the structures. The researchers also demonstrated that the lens can simultaneously focus, control aberrations caused by astigmatisms, as well as perform image shift.

Together, the lens and muscle are only 30 microns thick.

“All optical systems with multiple components — from cameras to microscopes and telescopes — have slight misalignments or mechanical stresses on their components, depending on the way they were built and their current environment, that will always cause small amounts of astigmatism and other aberrations, which could be corrected by an adaptive optical element,” said She. “Because the adaptive metalens is flat, you can correct those aberrations and integrate different optical capabilities onto a single plane of control.”

Next, the researchers aim to further improve the functionality of the lens and decrease the voltage required to control it.

The research was co-authored by Shuyan Zhang and Samuel Shian. The research was supported in part by the Air Force Office of Scientific Research and by the National Science Foundation. This work was performed in part at the Center for Nanoscale Systems (CNS), which is supported by the National Science Foundation.

Professor Nobuyuki Zettsu from the Center for Energy and Environmental Science in the Department of Materials Chemistry of Shinshu University in Japan and the director of the center, Professor Katsuya Teshima, led the research.

The authors published their results online in January this year in Scientific Reports.

“Owing to some intrinsic characteristics of liquid electrolytes, such as low lithium transport number, complex reaction at the solid/liquid interface, and thermal instability, it has not been possible to simultaneously achieve high energy and power in any of the current electrochemical devices,” said Nobuyuki Zettsu, as first author on the paper.

Lithium ion batteries are rechargeable and power such devices as cell phones, laptops, power tools, and even store power for the electrical grid. They’re particularly sensitive to temperature fluxes, and have been known to cause fires or even explosions. In response to the problems with liquid electrolytes, scientists are working toward developing a better all-solid-state battery without liquid.

“Despite the expected advantages of all-solid-state batteries, their power characteristic and energy densities must be improved to allow their application in such technologies as long-range electric vehicles,” Zettsu said. “The low rate capabilities and low energy densities of the all-solid-state batteries are partly due to a lack of suitable solid-solid heterogeneous interface formation technologies that exhibit high iconic conductivity comparable to liquid electrolyte systems.”

Zettsu and his team grew garnet-type oxide solid electrolyte crystals in molten LiOH used as a solvent (flux) on a substrate that bonded the electrode into a solid state as they grew. A specific crystal compound known to grow cubically allowed the researchers to control the thickness and connection area within the layer, which acts as a ceramic separator.

“Electron microscopy observations revealed that the surface is densely covered with well-defined polyhedral crystals. Each crystal is connected to neighboring ones,” wrote Zettsu.

Zettsu also said that the newly grown crystal layer could be the ideal ceramic separator when stacking the electrolyte layer on the electrode layer.

“We believe that our approach having robustness against side reactions at the interface could possibly lead to the production of ideal ceramic separators with a thin and dense interface,” wrote Zettsu, noting that the ceramics used in this particular experiment were too thick to be used in solid batteries. “However, as long as the electrode layer can be made as thin as 100 microns, the stacking layer will operate as a solid battery.”

One hundred microns is about the width of a human hair, and slightly less than twice the thickness of a standard electrode layer in contemporary lithium-ion batteries.

“All-solid-state batteries are promising candidates for energy storage devices,” Zettsu said, noting that several collaborations between researchers and private companies are already underway with the ultimate goal of displaying all-solid-state battery samples at the 2020 Olympic games in Tokyo.

Zettsu and other researchers plan to fabricate prototype cells for electric vehicle use and for wearable devices by 2022.

Other collaborators on this project include researchers from the Institute for Materials Research at Tohoku University, Frontier Research Institute for Materials Science at Nagoya Institute of Technology, and the National Institute for Materials Science.

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Until now, paclitaxel has only been used to target rapidly dividing cancer cells. The team was successful in getting the drug to piggyback on 123B9, an agent they devised to target an oncogene called EphA2 (ephrin type-A receptor 2). EphA2 spreads cancer by allowing malignant cells to migrate from the primary tumor into circulation and eventually to adhere to other tissues.

“Once this novel tumor-homing agent binds to the EphA2 receptor, the oncogene functions as a cancer-specific molecular Trojan horse for paclitaxel, carrying the drug inside the cancel cell, killing the cell, and thwarting metastasis,” said Maurizio Pellecchia, a professor of biomedical sciences at UCR’s School of Medicine who led the research. “Without the targeting agent, paclitaxel cannot hitch a ride on EphA2.”

Study results appear in the Journal of Medicinal Chemistry.

Tumor metastasis is a leading cause of patient morbidity and mortality, and no treatments are currently available that specifically target metastasis formation. Cancer cells depend on a number of oncogenes, like EphA2, to form metastasis, the medical term for cancer spreading from the primary site to other regions in the body, accomplished when cancer cells break away from the primary site, travel through the blood or lymph system, and form new tumors elsewhere in the body.

Pellecchia and his colleagues found that when 123B9 binds to the extracellular region of the EphA2 receptor expressed in cancer cells, it causes the oncogene to internalize and degrade inside the cell, thus preventing cancer cells from entering circulation and metastasizing.

“Because this binding causes EphA2 internalization, we also sought to conjugate 123B9 with paclitaxel and thus direct the drug to migrating cancer cells,” said Pellecchia, who holds the Daniel Hays Chair in Cancer Research at UCR.

Recent collaborative work between UCR and Cedars-Sinai Medical Center in Los Angeles demonstrated that in animal models of human breast cancer, mice treated with 123B9 that was conjugated with paclitaxel had significantly fewer circulating cancer cells in the blood compared to mice that were not treated or even treated with paclitaxel alone.

“Our work predicts that reducing the number of circulating cancer cells produces less metastasis,” Pellecchia said. “Indeed, in a second tumor model of metastatic breast cancer, we demonstrated that mice treated with the EphA2-targeting paclitaxel conjugate presented nearly no lung metastases, while a large numbers of lesions were observed in both untreated mice and in mice treated with just paclitaxel.”

Pellecchia said the road to a therapeutic for human trials is still long and includes the iterative design and synthesis of more potent and selective agents.

“Nonetheless, the proof of concept studies we have obtained thus far are extremely encouraging, and we are confident that with proper support and efforts we could translate our findings into experimental therapeutics for a variety of solid tumors that are driven by EphA2 overexpression, including breast, lung, prostate, pancreatic, and ovarian cancers,” said Pellecchia, who serves as the founding director of the Center for Molecular and Translational Medicine at UCR.

He noted that while these studies solidify UCR’s partnership with Cedars-Sinai Medical Center, the research team moving forward is expanding. Already, it includes UCR’s Jikui Song, an assistant professor of biochemistry, and Dr. Samar Nahas, an assistant clinical professor of gynecology and oncology in the School of Medicine.

The study was supported by grants from the National Cancer Institute at the National Institutes of Health.

Pellecchia was joined in the research by Ahmed F. Salem (first author), Parima Udompholkul, Luca Gambini, and Carlo Baggio at UCR; Si Wang at the Sanford-Burnham-Prebys Medical Discovery Institute, La Jolla, Calif.; Sandrine Billet, Jie-Fu Chen, Edwin M. Posadas, and Neil A. Bhowmick at Cedars-Sinai Medical Center; and Hsian-Rong Tseng at the Department of Molecular and Medical Pharmacology at UCLA. Salem, Wang, and Billet made equal contributions to the research.

Spreading through the Americas, one lizard group, the anoles, evolved like Darwin’s finches, adapting to different islands and different habitats on the mainland. Today there are more than 400 species.

Constructing a family tree for three lizard species collected in Panama at the Smithsonian Tropical Research Institute (STRI) and a fourth from the southeastern U.S., scientists at Arizona State University compared lizard genomes — their entire DNA code — to those of other animals.

The researchers discovered that changes in genes involved in the interbrain (the site of the pineal gland and other endocrine glands), for color vision, hormones and the colorful dewlap that males bob to attract females, may contribute to the formation of boundaries between species. Genes regulating limb development also evolved especially quickly.

“While some reptiles such as tortoises changed remarkably little over millions of years, anole lizards evolved quickly, generating a diversity of shapes and behaviors,” said Kenro Kusumi, corresponding author and professor at ASU School of Life Sciences. “Now that sequencing entire genomes is cheaper and easier, we discovered molecular genetic evidence for rapid evolution that may account for striking differences between bodies of animals living in different environments.”

Kusumi’s lab, working with colleagues at the University of Arizona College of Medicine-Phoenix, is especially interested in how reptiles’ genomes shape their ability to regenerate and to develop a diversity of body forms.

“This is the first time the complete genetic code — the genome — of any vertebrate species from Panama has been sequenced and analyzed,” said Oris Sanjur, co-author and Associate Director for Science Administration at STRI. “Information from these three species is an important contribution to our understanding of biodiversity and the evolution of new species.”

Scientists estimate that there are 40 species of anolid lizards living in Panama, compared to only one in the U.S. A team from ASU collected three species with permission from the Ministry of the Environment, MiAmbiente: the Central American giant anole, Anolis frenatus, lives high on tree trunks; the grass anole, A. auratus, perches on bushes or on grassy vegetation and the slender anole, A. apletophallus, found only in Panama, hangs out lower on tree trunks or on the ground.

Researchers at ASU’s School of Life Sciences lined up the DNA sequences of the lizards with the DNA sequences of 31 other animals: the lobe-finned fish and the four-legged animal groups that evolved from them. They also took a careful look at genes that code for proteins: more than 22,000 genes in the green anole, A. carolinensis, versus approximately 20,000 identified each in A. auratus and A. frenatus and 13,000 in A. apletophallus.

One obvious explanation for a faster rate of evolution is the anole lizards’ faster rate of reproduction. Anoles typically mate in their first year of life, while other reptiles take much longer to reach sexual maturity. They also breed with many other individuals so mutations that make it difficult for individuals to survive are eliminated fairly quickly.

The first and only other anole lizard to be sequenced previously was the green anole, A. carolinensis, the only anole species resident in the U.S. In that study from MIT, the A. carolinensis genome held evidence of more recent evolution and the loss of ancient repeated elements in the part of the DNA that does not code for proteins. In this sense, it was important to sequence the three Panamanian species, because the U.S. species may not be the most representative of the diverse anole group.

“For 15 years, an impressive amount of time and money poured into discovering the genomes of mammals, motivated by our drive to understand human evolution and to look for cures for disease. Even though the squamate reptiles include more than 10,000 species — almost double the number of mammal species — a single genome was not enough to understand the variability within this group,” said the first author of the report, Marc Tollis, a post-doctoral fellow at ASU.

“By comparing these four anole lizard genomes, we’re beginning to understand how one of the most diverse groups of vertebrates regenerate, develop and diversify,” he added.

The scientists, led by Tahar Amari, an astrophysicist at the Center for Theoretical Physics at the École Polytechnique in Palaiseau Cedex, France, considered solar flares, which are intense bursts of radiation and light. Many strong solar flares are followed by a coronal mass ejection, or CME, a massive, bubble-shaped eruption of solar material and magnetic field, but some are not — what differentiates the two situations is not clearly understood.

Using data from NASA’s Solar Dynamics Observatory, or SDO, the scientists examined an October 2014 Jupiter-sized sunspot group, an area of complex magnetic fields, often the site of solar activity. This was the biggest group in the past two solar cycles and a highly active region. Though conditions seemed ripe for an eruption, the region never produced a major CME on its journey across the Sun. It did, however, emit a powerful X-class flare, the most intense class of flares. What determines, the scientists wondered, whether a flare is associated with a CME?

The team of scientists included SDO’s observations of magnetic fields at the Sun’s surface in powerful models that calculate the magnetic field of the Sun’s corona, or upper atmosphere, and examined how it evolved in the time just before the flare. The model reveals a battle between two key magnetic structures: a twisted magnetic rope — known to be associated with the onset of CMEs — and a dense cage of magnetic fields overlying the rope.

The scientists found that this magnetic cage physically prevented a CME from erupting that day. Just hours before the flare, the sunspot’s natural rotation contorted the magnetic rope and it grew increasingly twisted and unstable, like a tightly coiled rubber band. But the rope never erupted from the surface: Their model demonstrates it didn’t have enough energy to break through the cage. It was, however, volatile enough that it lashed through part of the cage, triggering the strong solar flare.

By changing the conditions of the cage in their model, the scientists found that if the cage were weaker that day, a major CME would have erupted on Oct. 24, 2014. The group is interested in further developing their model to study how the conflict between the magnetic cage and rope plays out in other eruptions. Their findings are summarized in a paper published in Nature on Feb. 8, 2018.

“We were able to follow the evolution of an active region, predict how likely it was to erupt, and calculate the maximum amount of energy the eruption can release,” Amari said. “This is a practical method that could become important in space weather forecasting as computational capabilities increase.”

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Theoretical research to evaluate the microbial habitability of Europa using data collected from analogous environments on Earth has been conducted by a group of Brazilian researchers linked to the University of São Paulo (USP) that jointly authored an article published in Scientific Reports.

“We studied the possible effects of a biologically usable energy source on Europa based on information obtained from an analogous environment on Earth,” said Douglas Galante, a researcher at Brazil’s National Synchrotron Light Laboratory (LNLS) and the Astrobiology Research Center (NAP-Astrobio) of the University of São Paulo’s Institute of Astronomy, Geophysics & Atmospheric Sciences (IAG-USP).

Galante coordinates the study, supported by the São Paulo Research Foundation — FAPESP through a Master’s fellowship from chemist Thiago Pereira, co-author of the article who has in Galante his supervisor, and through a Thematic Project which aims at investigating places in Brazil and Africa with possible vestiges of geochemical and isotopical transformations related to the emergence of multicelular life in Neoproterozoic Age.

Similarities with primitive earth

In the Mponeng gold mine near Johannesburg, South Africa, at a depth of 2.8 km, the research project not only found traces of major changes linked to history of life on Earth, but also a terrestrial context analogous to Europa. It was recently discovered that the bacterium Candidatus Desulforudis audaxviator survives inside the mine without sunlight by means of water radiolysis, the dissociation of water molecules by ionizing radiation.

“This very deep subterranean mine has water leaking through cracks that contain radioactive uranium,” Galante said. “The uranium breaks down the water molecules to produce free radicals [H+, OH-, and others]. The free radicals attack the surrounding rocks, especially pyrite [iron disulfide, FeS₂], producing sulfate. The bacteria use the sulfate to synthesize ATP [adenosine triphosphate], the nucleotide responsible for energy storage in cells. This is the first time an ecosystem has been found to survive directly on the basis of nuclear energy.”

According to Galante and colleagues, the environment colonized by bacteria in the Mponeng mine is an excellent analogue of the environment assumed to exist at the bottom of Europa’s ocean.

Although the temperature in Europa’s surface is next to absolute zero, there is an enormous amount of thermal energy in its core, as an effect of Europa’s interaction with Jupiter’s powerful gravitational attraction, which causes the satellite’s orbit to be extremely elliptical, meaning Europa finds itself either to close or too far from the Gas Giant. That makes the icy moon to suffer geometrical deformation as it moves at the mercy of Jupiter’s immense tidal force. The energy released by the alternating states of elongation and relaxation makes Europa’s subsurface capable of hosting an ocean of liquid water.

“However, it’s not enough for there to be heated liquid water,” said Galante. According to the researcher, the basis for all biological activity known to Earth are the chemical gradients, i.e., differences in concentrations of molecules, ions or electrons in distinct regions which produce a flow in a certain direction, allowing the occurrence of cellular respiration, photosynthesis, ATP production and other processes common to living beings.

“Hydrothermal emanations — of molecular hydrogen [H₂], hydrogen sulfide [H₂S], sulfuric acid [H₂SO₄], methane [CH₄] and so on — are important sources of chemical imbalance and potential factors of ‘biological transduction’, i.e., transformation of the imbalance into biologically useful energy,” Galante said. “These hydrothermal sources are the most plausible scenario for the origin of life on Earth.”

Investigating conditions in Europa for ATP production

The group evaluated how chemical imbalance in Europa could be initiated through the emanation of water leading to chain reactions between water and chemical elements found in Europa’s crust — however, a total lack of empirical data prevents scientists from unequivocally presuming any of these events (an “Europa Mission” may take place as late as 2030, stated Nasa, the US space agency). “That’s why we looked for a more universal physical effect that was highly likely to occur. That effect was precisely the action of radioactivity,” Galante said.

Celestial bodies in the Solar System with rocky cores share the same radioactive materials, ejected in space by the Supernova explosion that originated the Sun and the planets. Uranium, thorium and potassium are the radioactive elements considered by the research, which estimated the concentrations for these materials in Europa, based on the quantities already observed and measured on Earth, in meteorites and in Mars.

“From these amounts, we were able to estimate the energy released, how this energy interacts with the surrounding water, and the efficiency of the water radiolysis resulting from this interaction in generating free radicals,” Galante said.

According to the study, along with radionuclides, pyrite is a crucial ingredient whose presence is indispensable for life in Europa. “One of the proposals deriving from our study is that traces of pyrite should be looked for as part of any assessment of the habitability of a celestial body,” stated Galante. Chances for finding pyrite in a hypothetical mission to Europa are good, since sulfur (S) and iron (Fe) are elements found in abundance across the Solar System.

“The ocean bed on Europa appears to offer very similar conditions to those that existed on primitive Earth during its first billion years. So studying Europa today is to some extent like looking back at our own planet in the past. In addition to the intrinsic interest of Europa’s habitability and the existence of biological activity there, the study is also a gateway to understanding the origin and evolution of life in the Universe.”

Some cities, such as New York and Chicago, are laid out on a precise grid, like the atoms in a crystal, while others such as Boston or London are arranged more chaotically, like the disordered atoms in a liquid or glass. The researchers found that the “crystalline” cities had a far greater buildup of heat compared to their surroundings than did the “glass-like” ones.

The study, published today in the journal Physical Review Letters, found these differences in city patterns, which they call “texture,” was the most important determinant of a city’s heat island effect. The research was carried out by MIT and National Center for Scientific Research senior research scientist Roland Pellenq, who is also director of a joint MIT/ CNRS/Aix-Marseille University laboratory called <MSE>² (MultiScale Material Science for Energy and Environment); professor of civil and environmental engineering Franz-Josef Ulm; research assistant Jacob Sobstyl; <MSE>² senior research scientist T. Emig; and M.J. Abdolhosseini Qomi, assistant professor of civil and environmental engineering at the University of California at Irvine.

The heat island effect has been known for decades. It essentially results from the fact that urban building materials, such as concrete and asphalt, can absorb heat during the day and radiate it back at night, much more than areas covered with vegetation do. The effect can be quite dramatic, adding as much as 10 degrees Farenheit to night-time temperatures in places such as Phoenix, Arizona. In such places this effect can significantly increase health problems and energy use during hot weather, so a better understanding of what produces it will be important in an era when ever more people are living in cities.

The team found that using mathematical models that were developed to analyze atomic structures in materials provides a useful tool, leading to a straightforward formula to describe the way a city’s design would influence its heat-island effect, Pellenq says.

“We use tools of classical statistical physics,” he explains. The researchers adapted formulas initially devised to describe how individual atoms in a material are affected by forces from the other atoms, and they reduced these complex sets of relationships to much simpler statistical descriptions of the relative distances of nearby buildings to each other. They then applied them to patterns of buildings determined from satellite images of 47 cities in the U.S. and other countries, ultimately ending up with a single index number for each — called the local order parameter — ranging between 0 (total disorder) and 1 (perfect crystalline structure), to provide a statistical description of the cluster of nearest neighbors of any given building.

For each city, they had to collect reliable temperature data, which came from one station within the city and another outside it but nearby, and then determine the difference.

To calculate this local order parameter, physicists typically have to use methods such as bombarding materials with neutrons to locate the positions of atoms within them. But for this project, Pellenq says, “to get the building positions we don’t use neutrons, just Google maps.” Using algorithms they developed to determine the parameter from the city maps, they found that the cities varied from 0.5 to 0.9.

The differences in the heating effect seem to result from the way buildings reradiate heat that can then be reabsorbed by other buildings that face them directly, the team determined.

Especially for places such as China where new cities are rapidly being built, and other regions where existing cities are expanding rapidly, the information could be important to have, he says. In hot locations, cities could be designed to minimize the extra heating, but in colder places the effect might actually be an advantage, and cities could be designed accordingly.

“If you’re planning a new section of Phoenix,” Pellenq says, “you don’t want to build on a grid, since it’s already a very hot place. But somewhere in Canada, a mayor may say no, we’ll choose to use the grid, to keep the city warmer.”

The effects are significant, he says. The team evaluated all the states individually and found, for example, that in the state of Florida alone urban heat island effects cause an estimated $400 million in excess costs for air conditioning. “This gives a strategy for urban planners,” he says. While in general it’s simpler to follow a grid pattern, in terms of placing utility lines, sewer and water pipes, and transportation systems, in places where heat can be a serious issue, it can be well worth the extra complications for a less linear layout.

This study also suggests that research on construction materials may offer a way forward to properly manage heat interaction between buildings in cities’ historical downtown areas.

The work was partly supported by the Concrete Sustainability Hub at MIT, sponsored by the Portland Cement Association and the Ready-Mixed Concrete Research and Education Foundation.

In the study, the researchers describe the 3D-printed custom device, which, along with its electronic and pneumatic components, can be easily obtained and assembled for a total cost of about $600, a fraction of the cost of comparable commercial systems. The device occupies a small footprint as well, not much larger than a tissue box. “Most commercial microfluidic instruments are very costly; as a result, not every lab has access to exciting technology for single-cell analysis,” said William Stephenson PhD, Senior Research Engineer in the NYGC’s Technology Innovation Lab, who led the development of the instrument and is a lead author on the study. “We designed the instrument to perform droplet microfluidics and in particular Drop-seq, a massively parallel technology for single cell RNA-sequencing.”

In collaboration with researchers and clinicians at HSS, a world leader in rheumatology research and disease treatment, the group used the instrument to profile joint synovial tissue from RA patients. RA is an autoimmune disease that affects 1% of the population and is associated with painful swelling in the joints. The precise cause of RA is undetermined and muddled by the diversity of cells found in the swollen joints of patients.

The portability of the controller permitted patient samples to be processed on-site and immediately after surgery, minimizing handling and transport to optimize sample quality. The researchers collected samples from five RA patients totaling 20,387 cells and looked at the individual gene expression patterns for each cell. “This dataset gave us the opportunity to identify individual subpopulations of cells that could drive the progression of RA, even if they have not been previously characterized,” said Rahul Satija PhD, a Core Faculty Member at NYGC, Assistant Professor of Biology at NYU, and senior author on the study.

By analyzing the complete dataset and searching for clusters of similar cells, the researchers identified 13 groups, representing both infiltrating immune and inflamed stromal populations. Of particular interest were distinct groups of fibroblasts with strikingly different gene expression patterns. “Roughly an hour after surgical excision, individual cells from patient tissues were labeled for single-cell sequencing. From this work, we have classified unrecognized fibroblast subtypes that may prove to be important drug targets for our RA patients,” said Laura Donlin, Co-Director of the HSS Precision Medicine Lab and Assistant Professor at Weill Cornell Medicine, and a lead author on the study. The researchers were able to validate the presence of these multiple groups using flow cytometry, and discovered that they exhibited distinct localization patterns with the joint tissue as well.

The dataset is a step towards creating a comprehensive “cell atlas” for synovial tissue from RA patients. Moving forward, the researchers are compiling data from additional RA patients, and aim to obtain patient samples from other arthritic conditions such as psoriatic arthritis and osteoarthritis. In addition, they plan to use CITE-seq, a technique also developed in the Technology Innovation Lab at the NYGC, to more precisely classify cell types by measuring the presence of surface proteins in addition to the transcriptome. They also envision that technology will be useful for profiling samples that are difficult to study in a standard lab, such as highly infectious samples in biocontainment facilities or samples being collected in field research settings. To facilitate its widespread use in the scientific and medical community, the instrument has been fully “open-sourced.” Instructions and assembly manuals for the instrument can be found online at the popular microfluidics repository Metafluidics (metafluidics.org/devices/minidrops). “We hope that this instrument lowers the hurdles associated with performing single-cell transcriptome profiling experiments in basic research and clinical settings,” Dr. Stephenson said.

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