A crystal shape conundrum is finally solved

Rice theorists’ method can predict shapes of crystals that lack symmetry

Peer-Reviewed Publication

RICE UNIVERSITY

 

IMAGE: RICE UNIVERSITY RESEARCHERS HAVE DEVELOPED A METHOD TO PREDICT HOW CRYSTALS TAKE SHAPE FROM THEIR INTERNAL CHEMISTRY, EVEN WHEN THE CRYSTAL LACKS SYMMETRY. THIS REPRESENTATION OF A SILVER NITRATE CRYSTAL HAS EIGHT EDGES, NONE OF WHICH MATCH THE OTHERS. THE RICE TEAM’S ALGORITHM WAS STILL ABLE TO PREDICT ITS SHAPE. view more 

CREDIT: ILLUSTRATION BY LUQING WANG/RICE UNIVERSITY

HOUSTON – (Nov. 28, 2022) – A crystal’s shape is determined by its inherent chemistry, a characteristic that ultimately determines its final form from the most basic of details. But sometimes the lack of symmetry in a crystal makes the surface energies of its facets unknowable, confounding any theoretical prediction of its shape.

Theorists at Rice University say they’ve found a way around this conundrum by assigning arbitrary latent energies to its surfaces or, in the case of two-dimensional materials, its edges.

Yes, it seems like cheating, but in the same way a magician finds a select card in a deck by narrowing the possibilities, a little algebraic sleight-of-hand goes a long way to solve the problem of predicting a crystal’s shape.

The method described in Nature Computational Science shows using what they call auxiliary edge energies can bring predictions back in line with the Wulff construction, a geometrical recipe in use for more than a century to determine how crystals arrive at their final equilibrium shapes.

The open-access paper by materials physicist Boris Yakobson, lead author and alumnus Luqing Wang and their colleagues at Rice’s George R. Brown School of Engineering introduces algorithms that employ arbitrary numbers for the right-hand factors in the equations and still deliver the proper unique shape-solution. 

“The issue of shape is compelling, but researchers have been trying and failing for years to compute surface energies for asymmetrical crystals,” Yakobson said. “It turns out we were falling down a rabbit hole, but we knew that if nature can find a solution through a gazillion atomic movements, there should also be a way for us to determine it.”

He said the rise of interest in 2D materials in recent times motivated the new study. “We had a ‘eureka’ moment: After switching our geometrical thinking to algebraic we added closure equations that contain arbitrary parameters,” Yakobson said. “These seem useless, but we passed it all through the computer and observed a well-defined shape coming out,” he said. 

“The hard part was convincing our reviewers that edge energy is truly undefinable, but a solution can still be achieved,” Wang said.

The work could provide a valuable tool to researchers who grow crystals from the bottom up for catalytic, light-emitting, sensing, magnetic and plasmonic applications, especially when their shapes and active edges are of particular importance. 

The researchers pointed out that natural crystals enjoy the luxury of geological time. They arrive at their shapes by “relentlessly performing a trial-and-error experiment” as they seek equilibrium, the minimal energy of all their constituent atoms. 

But computational and theoretical approaches simply can’t deal with billions of atoms at once, so they generally lean on the energies of outward-facing atoms. For many crystals that have equivalent facets or edges, that works just fine.

In 2D materials, essentially all of the atoms are “outward-facing.” When their edges are equivalent by symmetry — in rectangles, for instance — completing a Wulff construction is simple after calculating the edge energies via density functional theory.

But in the absence of symmetry, when all the edges are different, the calculated average energy is meaningless, Yakobson said. 

“Nature has the answer to shape a crystal regardless of what it ‘knows’ or doesn’t about the edge energies,” he said. “So there is an answer. Our challenge was to mimic it with theory.”

The first step toward a solution was to consciously give up on finding the unknowable absolute edge energies and deal instead with their well-defined computable combinations, Yakobson said. Geometrically, this was quite a riddle, and for asymmetric bulk materials was hopelessly complicated. 

“But 2D materials and their planar polygons made solving the problem easier to think about than having to deal with multifaceted polyhedra,” he said.

Finding and establishing average energies was just the first step, followed by “closure equations” that used arbitrary latent material energy for the right-hand side of the equation. Even if the latter numbers were intentionally incorrect, applying all to the textbook Wulff construction resulted in the correct crystal shape.

The group tested its theory on several 2D crystals and compared the results to the crystals’ observed final forms. Their versatile equations successfully predicted the shapes, shown experimentally, of the truncated rectangle formed by 2D tin selenide, a promising thermo- and piezoelectric material, and the asymmetric needles formed by silver nitrite. 

Rice alumni Sharmila Shirodkar and Zhuhua Zhang are co-authors of the paper. The work was primarily supported by the Department of Energy and the Basic Energy Sciences program (DE-SC0012547) and in part by the Army Research Office Electronics Division (W911NF-16-1-0255).

-30-

Read the paper at www.doi.org/10.1038/s43588-022-00347-5.

This news release can be found online at https://news.rice.edu/news/2022/crystal-shape-conundrum-finally-solved.

Follow Rice News and Media Relations via Twitter @RiceUNews.

Related materials:

Yakobson Research Group: http://biygroup.blogs.rice.edu

Department of Materials Science and NanoEngineering: https://msne.rice.edu

George R. Brown School of Engineering: https://engineering.rice.edu

Image for download:

https://news-network.rice.edu/news/files/2022/11/1205_SHAPES-1-WEB.jpg

Rice University scientists have developed a method to predict how crystals take shape from their internal chemistry, even when the crystal lacks symmetry. This representation of a silver nitrate crystal has eight edges, none of which match the others. The Rice team’s algorithm was still able to predict its shape. (Credit: Illustration by Luqing Wang/Rice University)

Located on a 300-acre forested campus in Houston, Rice University is consistently ranked among the nation’s top 20 universities by U.S. News & World Report. Rice has highly respected schools of Architecture, Business, Continuing Studies, Engineering, Humanities, Music, Natural Sciences and Social Sciences and is home to the Baker Institute for Public Policy. With 4,240 undergraduates and 3,972 graduate students, Rice’s undergraduate student-to-faculty ratio is just under 6-to-1. Its residential college system builds close-knit communities and lifelong friendships, just one reason why Rice is ranked No. 1 for lots of race/class interaction and No. 1 for quality of life by the Princeton Review. Rice is also rated as a best value among private universities by Kiplinger’s Personal Finance.

---

JOURNAL

Nature Computational Science

DOI

10.1038/s43588-022-00347-5 

METHOD OF RESEARCH

Computational simulation/modeling

SUBJECT OF RESEARCH

Not applicable

ARTICLE TITLE

Defining shapes of two-dimensional crystals with undefinable edge energies

COVID-19 has had positive effect on astronomy research, but negative effect on new and female researchers

Peer-Reviewed Publication

KAVLI INSTITUTE FOR THE PHYSICS AND MATHEMATICS OF THE UNIVERSE

 

IMAGE: (FROM LEFT) UC BERKELEY POSTDOCTORAL FELLOW VANESSA BOHM (CREDIT:TRAVIS CLOSE) AND KAVLI IPMU PROJECT ASSOCIATE PROFESSOR JIA LIU (CREDIT: KAVLI IPMU). view more 

CREDIT: (FROM LEFT) UC BERKELEY POSTDOCTORAL FELLOW VANESSA BOHM (CREDIT:TRAVIS CLOSE) AND KAVLI IPMU PROJECT ASSOCIATE PROFESSOR JIA LIU (CREDIT: KAVLI IPMU).

The COVID-19 pandemic has had both positive and negative impacts on astronomy research, where overall the number of research papers being produced increased, but the number of new or junior researchers entering the field has dropped. The researchers who carried out the study also found that no single country's female astronomers were able to be more productive than their male colleagues on average, suggests a new study in Nature Astronomy.

In 2021, Project Associate Professor Jia Liu joined the Kavli Institute for the Physics and Mathematics of the Universe (Kavli IPMU) in Tokyo and settled into a new country and job in amidst a global pandemic. 

”As a new mother and an early career scientist, my life has been heavily affected by the pandemic –– lost childcare, dropped productivity, disconnection from my colleagues, and a tough job market. While rebuilding my research and life routines, I couldn’t stop wondering: how are others in my field affected by the pandemic? Am I alone," said Liu.

Collaborating with University of California, Berkeley, Postdoctoral Fellow Vanessa Böhm, the researchers decided to find out themselves after not finding the answers in the limited studies available at the time.

The computational cosmologists used their data mining skills to download more than 1.2 million records of astronomical publications since 1950. They wanted to analyze publication patterns by gender and country, but such information is confidential. So, the researchers assigned a gender probability to each author based on their given name and assigned a country based on the paper author's affiliation or affiliations listed in their paper.

The results were surprising, said Liu.

Overall output in astronomy, measured by the annual paper count, had increased. 

"While one may assume that COVID has mostly negative impacts on the world, this positive phenomenon may not be hard to understand: COVID-induced changes such as increased flexibility in work arrangement, reduced commutes and business trips, as well as improved virtual technologies, among others, are potentially favorable for conducting scientific research," said Liu.

However, when the researchers looked into whether the positive outcome was result of more researchers entering the field, or an increase in individual productivity, they found the latter was mainly responsible for the trend.

"When we counted the average number of papers each researcher produced, we saw boosted individual productivity seen across most countries. Meanwhile, a decreasing number of incoming new researchers is seen in most of the countries we studied. This result indicates larger barriers for new researchers to enter the field, or for junior researchers to complete their very first project during COVID," said Liu.

Finally, the researchers found the productivity of female astronomers was worst affected. Fourteen out of 25 countries studied saw a smaller fraction of papers written by women, and fewer women researchers entering the astronomy field. During COVID-19 so far, no female researchers were able to be more productive than their male colleagues, even in countries including the Netherlands, Australia, and Switzerland, where female researchers had been as productive as male colleagues before the pandemic.

The researchers say their data only studies trends over a limited period of time as the pandemic still continues. While they were able to study quantitative outputs during the pandemic, the quality of these papers is yet to be studied. 

Details of this study were published in Nature Astronomy on 28 November.

---

JOURNAL

Nature Astronomy

DOI

10.1038/s41550-022-01830-9 

ARTICLE TITLE

Impact of the COVID-19 pandemic on publishing in astronomy in the initial two years

For female astronomers, the COVID-19 pandemic widened publishing’s gender gap

Productivity increased for all astronomers in first two years of pandemic, but less for women

Peer-Reviewed Publication

UNIVERSITY OF CALIFORNIA - BERKELEY

 

IMAGE: WOMEN COMPRISE ABOUT 20% OF ALL ASTRONOMERS WORLDWIDE, BUT THEIR PRODUCTIVITY, AS MEASURED BY ANNUAL NUMBER OF PUBLICATIONS, HAS LAGGED BEHIND THAT OF THEIR MALE COLLEAGUES. THE COVID-19 PANDEMIC SET THEM BACK EVEN MORE, A NEW STUDY FINDS. view more 

CREDIT: NIEL FREESE, UC BERKELEY

Before the COVID-19 pandemic abruptly shut down labs and sent scientists home to work, female astronomers on average published about nine papers for every 10 published by men — a rate that has remained stagnant for decades.

The pandemic appears to have worsened that gender imbalance.

In a paper appearing today in the journal Nature Astronomy, two cosmologists — Vanessa Böhm of the University of California, Berkeley, and Jia Liu of the Kavli Institute for the Physics and Mathematics of the Universe (Kavli IPMU) in Japan — report their analysis of publication rates in the field of astronomy pre-pandemic and as of February 2022, two years into the pandemic.

They found that, while both men and women on average have published more papers since March 2020, when most universities and research institutions closed their doors to prevent the spread of COVID-19, men published a greater number, widening the gender gap. Worldwide, astronomy publications increased by about 13%.

Part of the increase was from publications by new researchers entering the field, Böhm said, though that was caused primarily by an uptick in new researchers publishing in Asia: Japan, Taiwan and China, primarily. In most other countries, though, fewer new researchers published in the field of astronomy during the pandemic, with women lagging behind men. About 25% of new authors are women, a percentage that also hasn’t budged in the past 10 years.

“A decrease in the number of first-time authors indicates barriers for young researchers to enter the field or complete their first projects,” Böhm noted.

When the two looked only at papers by veteran astronomers, however, publications per researcher still were higher than pre-pandemic trends.

“Once we took this out, we still saw an increase in the number of papers — an increase driven by an increase in individual productivity,” Böhm said. “I think the interesting part was that we saw that this increase in productivity was not equally shared by women. Before the pandemic, there were about two or three countries where women were equally as productive as men, among them the Netherlands, Australia and Switzerland. But even there, we saw that after the pandemic, women were less productive than their male counterparts.”

Of 25 countries studied, 14 saw a smaller fraction of astronomy papers written by women and fewer female researchers entering the astronomy field.

Presumably, both men and women were able to devote more time to writing papers during the pandemic because they were not allowed access to research facilities, such as observatories, to obtain new data. With more time, including relief from in-person administrative duties, the pandemic was ideal for finishing off deferred projects.

"While one may assume that COVID has mostly negative impacts on the world, this positive phenomenon may not be hard to understand: COVID-induced changes, such as increased flexibility in work arrangements, reduced commutes and business trips, as well as improved virtual technologies, among others, are potentially favorable for conducting scientific research," Liu said.

The widened gap between men and women’s productivity echo those of other studies that show women regressed, in terms of workplace equity, during the pandemic. While the current study does not address why, some of these other studies found that women, more than men, were saddled with child care and elder care, allowing less time for writing up research results.

Böhm suspects an additional reason: less mentoring of young female astrophysics researchers who may be dealing with “imposter syndrome,” or the idea that they may not be up to par. Women make up only about 20% of the world’s astronomers.

“There are a lot of confidence barriers for young women in the field that are holding them back,” she said.

Child care issues

Liu was a postdoctoral fellow at the Berkeley Center for Cosmological Physics (BCCP) when the pandemic began and was one of those affected by the sudden loss of child care. With a toddler at home and on the hunt for an academic job, she and her husband had to move away from Berkeley to find affordable child care.

”As a new mother and an early career scientist, my life has been heavily affected by the pandemic –– lost child care, dropped productivity, disconnection from my colleagues and a tough job market,” said Liu, who in 2021 joined the Kavli IPMU in Tokyo as a project associate professor. “While rebuilding my research and life routines, I couldn’t stop wondering, ‘How are others in my field affected by the pandemic? Am I alone?’"

Böhm, also a postdoctoral fellow, met Liu at BCCP, and they decided to embark on what they called an “all-girls” research project to look at the history of publishing rates in astronomy by gender and country, which had never been done comprehensively, and the impact of the pandemic on those rates.

Their study looked at data from 1950 until February 2022. The computational cosmologists used their data mining skills to download more than 1.2 million records of astronomical publications. They wanted to analyze publication patterns by gender and country, but such information is confidential. So, the researchers assigned a gender probability to each author based on the individual’s given name and assigned a country based on the author's affiliation or affiliations listed in their paper.

"When we counted the average number of papers each researcher produced, we saw boosted individual productivity across most countries. Meanwhile, a decreasing number of incoming new researchers is seen in most of the countries we studied. This result indicates larger barriers for new researchers to enter the field, or for junior researchers to complete their very first project during COVID," said Liu.

They also looked at researchers who had not published in the field of astronomy for the past two years, and found that the chance is about 87% that they will not never publish in the field again. People dropping out of the field also disproportionately affects women.

That includes Böhm herself. With her postdoctoral felliowship now ending, she has elected to apply her data analysis skills elsewhere. She is joining a start-up that uses machine learning-based predictions to reduce fuel waste in the ocean shipping industry.

“This paper was part of an interest shift that I've had — to go to use the skills that I've learned in the last couple of years on more earthbound topics. I'm a little bit more driven these days by what's actually going to make a change here on Earth,” she said.

---

JOURNAL

Nature Astronomy

DOI

10.1038/s41550-022-01830-9 

METHOD OF RESEARCH

Data/statistical analysis

SUBJECT OF RESEARCH

People

ARTICLE TITLE

Impact of the COVID-19 pandemic on publishing in astronomy in the initial two years

ARTICLE PUBLICATION DATE

28-Nov-2022

IAU CPS Statement on BlueWalker 3

Global astronomy community troubled by unprecedented brightness and use of terrestrial frequencies from space of recently launched BlueWalker 3 satellite

Business Announcement

INTERNATIONAL ASTRONOMICAL UNION

 

IMAGE: TRAILS IN THE NIGHT SKY LEFT BY BLUEWALKER 3 ARE JUXTAPOSED AGAINST THE NICHOLAS U. MAYALL 4-METER TELESCOPE AT KITT PEAK NATIONAL OBSERVATORY IN ARIZONA, A PROGRAM OF NSF'S NOIRLAB. THE BREAKS IN THE TRAIL ARE CAUSED BY BREAKS BETWEEN FOUR TWENTY SECOND EXPOSURES THAT WERE STACKED TO CREATE THIS IMAGE. view more 

CREDIT: KPNO/NOIRLAB/IAU/SKAO/NSF/AURA/R. SPARKS

The International Astronomical Union Center for the Protection of the Dark and Quiet Sky from Satellite Constellation Interference expresses concern about the recently launched prototype BlueWalker 3 satellite’s impact on astronomy. New measurements reveal that this low Earth orbiting satellite is now one of the brightest objects in the night sky, outshining all but the brightest stars. In addition, the satellite’s use of terrestrial radio frequencies poses a new challenge to radio astronomy.

On 10 September 2022 AST SpaceMobile (https://ast-science.com/) launched a prototype satellite called BlueWalker 3 into low Earth orbit. This satellite, which has a 64-square-meter (693-square-foot) antenna system (the largest commercial antenna system ever deployed into low Earth orbit), is the first of what is expected to be more than a hundred similar or even larger satellites.

New measurements by observers worldwide, coordinated by the International Astronomical Union’s CPS (http://cps.iau.org) (IAU Center for the Protection of the Dark and Quiet Sky from Satellite Constellation Interference), show that this satellite has become one of the brightest objects in the night sky — more so than other constellation satellites and at times as bright as some of the most recognizable stars [1].

Besides their visible brightness, these new satellites, which serve as “cell phone towers in space,” will transmit strong radio waves at frequencies currently reserved for terrestrial cell-phone communications. These orbiting transmitters, which are not subject to the same radio quiet zone (https://en.wikipedia.org/wiki/Radio_quiet_zone restrictions) [2] as ground-based cellular networks, have the potential to severely impact radio astronomy research as well as geodesy studies and space-physics experiments.

The IAU and its CPS co-hosts, NSF's NOIRLab (https://noirlab.edu/public/) and the SKA Observatory (https://www.skao.int/en) (SKAO), are concerned about the impact these satellites will have on fundamental research and humanity’s ability to experience the natural night sky.

“Astronomers build radio telescopes as far away as possible from human activity, looking for places on the planet where there is limited or no cell phone coverage. Frequencies allocated to cell phones are already challenging to observe even in radio quiet zones we have created for our facilities. New satellites such as BlueWalker 3 have the potential to worsen this situation and compromise our ability to do science if not properly mitigated,” said SKAO Director-General Philip Diamond. “This is a key reason why the SKAO is deeply involved in the IAU CPS and promoting the equitable and sustainable use of space.”

The night sky is a unique laboratory that allows scientists to conduct experiments that cannot be done in terrestrial laboratories. Astronomical observations have provided insights into fundamental physics and other research at the boundaries of our knowledge and changed humanity’s view of our place in the cosmos. The pristine night sky is also an important part of humanity’s shared cultural heritage and should be protected for society at large and for future generations.

“BlueWalker 3 is a big shift in the constellation satellite issue and should give us all reason to pause,” said Piero Benvenuti, Director of the IAU CPS.

The IAU and CPS partners recognize that the new satellite constellations have an important role in improving worldwide communications. However, their interference with astronomical observations could severely hamper progress in our understanding of the cosmos. Their deployment should therefore be conducted with due consideration of their side effects and with efforts made to minimize their impact on astronomy.

To better understand the effects of these new satellites, the IAU CPS invites further observations of BlueWalker 3. Visual and telescopic (https://trailblazer.dirac.dev/) observations of BlueWalker 3 can be submitted online (https://forms.gle/aEyrADs5CAR7WFUw8) to SatHub, a worldwide public observing initiative of the IAU CPS.

The IAU recently wrote a letter (https://www.iau.org/news/announcements/detail/ann22039/) on behalf of the global astronomy community to the U.S. Federal Communications Commission (FCC - https://www.fcc.gov/) urging them to seriously consider the potential impacts of satellite constellations on astronomy, the appearance of the night sky, and the environment. Earlier this month, the FCC announced its intention to create an office dedicated to space, to better deal with this rapidly emerging issue, an action that the IAU CPS applauds.

Conversations between the IAU CPS and AST SpaceMobile are being planned. The IAU CPS fosters dialogue and cooperation between satellite operators and scientists. Recent discussions with some operators have led to mitigation measures but much more work is needed.

Notes

[1] The measurements show that BlueWalker 3 is around apparent visual magnitude 1 at its brightest — almost as bright as Antares or Spica (the 15th and 16th brightest stars in the night sky). Apparent magnitude in astronomy is a measure of the brightness of a star or other astronomical object as observed from Earth. The scale is reverse logarithmic: the brighter an object is, the lower its magnitude number. The brightest astronomical objects have negative apparent magnitudes: for example, Venus at −4.2 or Sirius at −1.46. The faintest stars visible with the naked eye on the darkest night have apparent magnitudes of about +6.5.

[2] There are several areas around the globe that have special protections for radio astronomy that prescribe how fixed radio transmitters can be used so they do not interfere with astronomical observations. The United States National Radio Quiet Zone (https://info.nrao.edu/do/spectrum-management/national-radio-quiet-zone-nrqz-1) is a 13,000 square mile (34,000 square kilometer) region in which broadcast antennas must operate at reduced power and use highly directional antennas.

More information

The IAU is the international astronomical organization that brings together more than 12 000 active professional astronomers from more than 100 countries worldwide. Its mission is to promote and safeguard astronomy in all its aspects, including research, communication, education and development, through international cooperation. The IAU also serves as the internationally recognised authority for assigning designations to celestial bodies and the surface features on them. Founded in 1919, the IAU is the world's largest professional body for astronomers.

Links

* CPS website - https://cps.iau.org/

Contacts

Siegfried Eggl
Co-Lead, Sathub, University of Illinois
Email: eggl@illinois.edu

Mike Peel
Co-Lead, Sathub, Instituto de Astrofísica de Canarias
Email: mpeel@iac.es

Piero Benvenuti
Director of the IAU Centre for the Protection of the Dark and Quiet Sky from Satellite Constellation Interference
Email: piero.benvenuti@cps.iau.org

Constance E. Walker
NSF’s NOIRLab
Co-Director of the IAU Center for the Protection of Dark and Quiet Sky from Satellite Constellation Interference
Email: connie.walker@noirlab.edu

Federico Di Vruno
Co-Director of the IAU Centre for the Protection of the Dark and Quiet Sky from Satellite
Constellation Interference, SKAO
Email: federico.divruno@cps.iau.org

Lars Lindberg Christensen
IAU Director of Communications
Tel: +1 520 461 0433
Cell: +49 173 38 72 621
Email: lars.christensen@noirlab.edu

LIKE CHIPPED TOAST

Novel method automates the growth of brain tissue organoids on a chip

The new system can increase reproducibility in cerebral organoid research and shows promise for lowering levels of cellular stress

Peer-Reviewed Publication

UNIVERSITY OF CALIFORNIA - SANTA CRUZ

 

IMAGE: TWELVE INDIVIDUAL 12-DAY-OLD CEREBRAL CORTEX CULTURES AT DAY 1 OF AUTOMATED FEEDING. view more 

CREDIT: SPENCER SEILER

A team of engineers at UC Santa Cruz has developed a new method for remote automation of the growth of cerebral organoids – miniature, three-dimensional models of brain tissue grown from stem cells. Cerebral organoids allow researchers to study and engineer key functions of the human brain with a level of accuracy not possible with other models. This has implications for understanding brain development and the effects of pharmaceutical drugs for treating cancer or other diseases.

In a new study published in the journal Nature Scientific Reports, researchers from the UCSC Braingeneers group detail their automated, internet-connected microfluidics system, called “Autoculture.” The system precisely delivers feeding liquid to individual cerebral organoids in order to optimize their growth without the need for human interference with the tissue culture.

Cerebral organoids require a high level of expertise and consistency to maintain the precise conditions for cell growth over weeks or months. Using an automated system, as demonstrated in this study, can eliminate disturbance to cell culture growth caused by human interference or error, provide more robust results, and allow more scientists access to opportunities to conduct research with human brain models. 

Autoculture also addresses variation that arises in organoid growth due to “batch effect” issues, where organoids grown at different times or at different labs under similar conditions may vary just because of the complexity of their growth. Using this uniform, automated system can reduce variation and allow researchers to better compare and validate their results. 

“One of the big challenges is that these cultures are not very reproducible, and in part it's not surprising because these are months-long experiments. You have to change media every couple of days and try to treat these cultures uniformly, which is extremely challenging,” said Sofie Salama, an acting professor of molecular, cellular and developmental biology at UCSC and an author on the study. 

Unique design

Autoculture uses a microfluidic chip designed by the researchers, spearheaded by Associate Professor of Electrical and Computer Engineering Mircea Teodorescu and Biomolecular Engineering Ph.D. student Spencer Seiler. Their novel chips, created from a unique bi-layer mold, have tiny wells and channels for delivering minute amounts of liquid to the organoid, which allow the scientists to have a high level of control over nutrient concentrations and byproducts. Overall, the system uses mostly off-the-shelf, low-cost components, making it accessible and modular. 

“A novel and important feature of this machine is that on one hand, it streamlines the process and makes sure that everything is very consistent,” Teodorescu said. “On the other hand, it's very modular because the system is controlled by the computer, so there are different parts of the chip that are interchangeable and have their own advantages – it's very much a modern agent.”

Because the system delivers a non-stop flow of liquid to the organoids, it more closely resembles the real conditions of the brain, which is constantly fed nutrients through the blood.  

Unlike other methods for organoid growth which grow the cultures together in one dish, the Autoculture system contains a culture plate with 24 individual wells, so each well can be its own experiment in which cultures can be grown independently and fed liquids at varying, programmable concentrations and times. An in-incubator imaging system lets the researchers constantly remotely monitor organoid growth and morphology.  

“The prize of the system is that every organoid has its own, personal micro-environment for which fluid flows in and out of,” Seiler said. “Now we’ve separated them – this would be too laborious to do by hand, but it's fine for a machine.” 

Additionally, a unique feature of the system is that feeding media for each individual culture can be pulled out for analysis at any point during an experiment. This allows researchers to non-invasively measure data such as pH and glucose levels which can be important for monitoring cell growth.  

The microfluidics system is connected to the internet to allow scientists to remotely operate and retrieve real-time data from the system at any point, without disrupting the culture. Another paper from the Braingeneers group, published in the journal Internet of Things, shows how the Autoculture system is one example of the power of extending the internet-of-things to enable remote-controlled experiments – a need which the pandemic made more urgent.

When measuring their cerebral organoids, the researchers found that the stem cells grown using the Autoculture system not only differentiated into various cell types normally, but actually looked healthier than those grown using standard methods. RNA sequencing found lower levels of glycolytic and endoplasmic reticulum stress, showing a first promising set of data for addressing cellular stress identified in a Nature paper by collaborating researchers at UCSF, evidence that the group plans to expand on in ongoing research.

This research provides an important platform for the ongoing work within the UCSC Live Cell Genomics Center. It is aligned with the center’s mission to apply lessons from the computer revolution to life sciences and is part of a larger drive toward automation of wet labs to make experiments more robust and reproducible.

---

JOURNAL

Scientific Reports

DOI

10.1038/s41598-022-20096-9 

ARTICLE TITLE

Modular automated microfluidic cell culture platform reduces glycolytic stress in cerebral cortex organoids

VAGINA ON A CHIP

A breakthrough in bacterial vaginosis treatment for women’s health

Human Organ Chip allows researchers to study effects of microbiome on vaginal health

Peer-Reviewed Publication

WYSS INSTITUTE FOR BIOLOGICALLY INSPIRED ENGINEERING AT HARVARD

The human microbiome has been a hot topic over the last decade, with research pointing to disrupted bacterial communities as culprits for a host of maladies including irritable bowel syndrome, eczema, and autoimmune diseases. Most studies have focused on the microbiome within the human gut, but there is growing recognition that another oft-ignored bacterial community deserves equal attention - that found in the vagina.

Vaginal microbiome disruptions cause bacterial vaginosis (BV), which afflicts nearly 30% of reproductive-aged women around the globe and costs an estimated $4.8 billion to treat annually. BV doubles the risk of many sexually transmitted infections including HIV and increases the risk of pre-term birth in pregnant women, which is the second-leading cause of death in newborns. BV is currently treated with antibiotics, but it often recurs and can lead to more severe complications including pelvic inflammatory disease and even infertility.

Just as probiotics are now being prescribed to treat gut issues, living biotherapeutics are being explored for the treatment of BV. However, it is difficult to conduct preclinical trials because the human vaginal microbiome is dramatically different from that of common animal models. Studies have found that Lactobacilli bacteria comprise more than 70% of the healthy human vaginal microbiome, but less than 1% of the vaginal microbiome in other mammals.

Researchers at the Wyss Institute at Harvard University have created a solution to that problem in the form of a new Organ Chip that replicates the human vaginal tissue microenvironment including its microbiome in vitro. Composed of human vaginal epithelium and underlying connective tissue cells, the Vagina Chip replicates many of the physiological features of the vagina and can be inoculated with different strains of bacteria to study their effects on the organ’s health. The chip is described in a new paper published in Microbiome.

Modeling the vaginal microbiome

The Vagina Chip was developed with funding from the Bill and Melinda Gates Foundation, which aimed to create a biotherapeutic treatment for BV and move it into human clinical trials to decrease infections of the reproductive tract, prenatal complications, and infant death rates. particularly in low-resource nations.

“A major stumbling block for that effort was that there were no good preclinical models that could be used to study which therapies can actually treat BV in human tissues. Our team’s project was to create a human Vagina Chip to aid in the development and testing of new therapies for BV,” said co-author Aakanksha Gulati, Ph.D., a Postdoctoral Researcher at the Wyss Institute

Using the microfluidic Organ Chip platform developed at the Wyss Institute and subsequently licensed to Emulate, the team seeded the top channel of a polymer chip with human vaginal epithelial cells. They then added human uterine fibroblast cells to the opposite side of the permeable membrane separating the top and bottom channels. This 3D arrangement replicated the structure of the human vaginal wall.

After five days, the Vagina Chip had developed multiple distinct layers of differentiated cells that matched those found in human vaginal tissue. When the scientists introduced the female sex hormone estradiol (a form of estrogen) into the Vagina Chip, the chips’ gene expression patterns changed in response, indicating that it was sensitive to hormones - another critical feature for replicating human reproductive organs in vitro.

Armed with a living model of the human vagina, the team then moved to study the vaginal microbiome. Recent research has shown that healthy human vaginal microbiomes typically contain multiple strains of Lactobacillus bacteria, so they worked with Dr. Jacques Ravel, Ph.D. and his team at University of Maryland School of Medicine, who had created three different consortia each containing several strains of L. crispatus. When they introduced these consortia into the Vagina Chip, all three successfully colonized the chips after three days. The consortia also began producing lactic acid, which helps to maintain the vagina’s low pH and inhibits the growth of other microbes.

Beyond helping to maintain an acidic environment, the presence of the L. crispatus bacteria also affected the Vagina Chip’s innate immune responses. Chips with bacterial consortia produced lower levels of several inflammation-causing cytokine molecules than chips without the bacteria, which is consistent with the current theory that these “good” microbes help keep inflammation in check in healthy human vaginas.

Bad bacterial tenants, on a chip

Having created a healthy Vagina Chip with optimal bacterial residents, the team then conducted a new experiment in which they inoculated chips with different species of bacteria that are associated with BV: Gardnerella vaginalis, Prevotella bivia, and Atopobium vaginae. A consortium of those three “bad” microbes caused the chips’ pH to increase, damaging the vaginal epithelial cells and significantly increasing the production of multiple proinflammatory cytokines - all responses that were similar to what has been observed in human patients with BV.

“It was very striking that the different microbial species produced such opposite effects on the human vaginal cells, and we were able to observe and measure those effects quite easily using our Vagina Chip,” said co-author Abidemi Junaid, Ph.D., a Research Scientist at the Wyss Institute. “The success of these studies demonstrate that this model can be used to test different combinations of microbes to help identify the best probiotic treatments for BV and other conditions.”

The team is now using the Vagina Chip to test new and existing treatments for BV to identify effective therapies that can be advanced into clinical trials. They are also working on integrating immune cells into the chip to study how the vaginal microbiome might drive systemic immune system responses.

“There is growing recognition that taking care of women’s health is critical for the health of all humans, but the creation of tools to study human female physiology is lagging,” said senior author Don Ingber, M.D., Ph.D., who is the Wyss Institute’s Founding Director. “We’re hopeful that this new preclinical model will drive the development of new treatments for BV as well as new insight into female reproductive health.” Ingber is also the Judah Folkman Professor of Vascular Biology at Harvard Medical School and Boston Children’s Hospital and the Hansjörg Wyss Professor of Bioinspired Engineering at the Harvard John A. Paulson School of Engineering and Applied Sciences.

Additional authors of the paper include Tania To, Nina LoGrande, Zohreh Izadifar, Sanjay Timilsina, Viktor Horvath, and Girija Goyal from the Wyss Institute; former Wyss Institute members Erin Doherty, Arlene Sutherland, Jennifer Grant, Roberto Plebani, Rachelle Prantil-Baun, and first author Gautam Mahajan; Michael France and Jacques Ravel from the University of Maryland School of Medicine; Indriati Hood-Pishchany and Seth Rakoff-Nahoum from Boston Children’s Hospital and Harvard Medical School; and Douglas Kwon from Massachusetts General Hospital.

This work was supported by the Bill and Melinda Gates Foundation and the Wyss Institute for Biologically Inspired Engineering at Harvard University.

JOURNAL

Microbiome

DOI

10.1186/s40168-022-01400-1 

METHOD OF RESEARCH

Experimental study

SUBJECT OF RESEARCH

Lab-produced tissue samples

ARTICLE TITLE

Vaginal microbiome-host interactions modeled in a human vagina-on-a-chip

New programming tool turns sketches, handwriting into code

Reports and Proceedings

CORNELL UNIVERSITY

ITHACA, N.Y. – Cornell University researchers have created an interface that allows users to handwrite and sketch within computer code – a challenge to conventional coding, which typically relies on typing.

The pen-based interface, called Notate, lets users of computational, digital notebooks open drawing canvases and handwrite diagrams within lines of traditional, digitized computer code.

Powered by a deep learning model, the interface bridges handwritten and textual programming contexts: notation in the handwritten diagram can reference textual code and vice versa. For instance, Notate recognizes handwritten programming symbols, like “n”, and then links them up to their typewritten equivalents.

“A system like this would be great for data science, specifically with sketching plots and charts that then inter-operate with textual code,” said Ian Arawjo, lead author of the paper and doctoral student in the field of information science. “Our work shows that the current infrastructure of programming is actually holding us back. People are ready for this type of feature, but developers of interfaces for typing code need to take note of this and support images and graphical interfaces inside code.”

Arawjo also said the work demonstrates a new path forward by introducing artificial intelligence-powered, pen-based coding at a time when drawing tablets are becoming more widely used.

“Tools like Notate are important because they open us up to new ways to think about what programming is, and how different tools and representational practices can change that perspective,” said Tapan Parikh, associate professor of information science and paper co-author.

The tool was described in “Notational Programming for Notebook Environments: A Case Study with Quantum Circuits”.

For additional information, see this Cornell Chronicle story.

Cornell University has dedicated television and audio studios available for media interviews.

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DOI

10.1145/3526113.3545619