Tag Archives: Harvard University

Tough colour and the flower beetle

The flower beetle Torynorrhina flammea. [downloaded from https://www.nanowerk.com/nanotechnology-news2/newsid=58269.php]

That is one gorgeous beetle and a June 17, 2021 news item on Nanowerk reveals that it features in a structural colour story (i.e, how structures rather than pigments create colour),

The unique mechanical and optical properties found in the exoskeleton of a humble Asian beetle has the potential to offer a fascinating new insight into how to develop new, effective bio-inspired technologies.

Pioneering new research by a team of international scientists, including Professor Pete Vukusic from the University of Exeter, has revealed a distinctive, and previously unknown property within the carapace of the flower beetle – a member of the scarab beetle family.

The study showed that the beetle has small micropillars within the carapace – or the upper section of the exoskeleton – that give the insect both strength and flexibility to withstand damage very effectively.

Crucially, these micropillars are incorporated into highly regular layering in the exoskeleton that concurrently give the beetle an intensely bright metallic colour appearance.

A June 18, 2021 University of Exeter press release (also on EurekAlert but published June 17, 2021), delves further into the researchers’ new insights,

For this new study, the scientists used sophisticated modelling techniques to determine which of the two functions – very high mechanical strength or conspicuously bright colour – were more important to the survival of the beetle.

They found that although these micropillars do create a highly enhanced toughness of the beetle shell, they were most beneficial for optimising the scattering of coloured light that generates its conspicuous appearance.

The research is published this week in the leading journal, Proceedings of the National Academy of Sciences, PNAS.

Professor Vukusic, one of three leads of the research along with Professor Li at Virginia Tech and Professor Kolle at MIT [Massachusetts Institute of Technology], said: “The astonishing insights generated by this research have only been possible through close collaborative work between Virginia Tech, MIT, Harvard and Exeter, in labs that trailblaze the fields of materials, mechanics and optics. Our follow-up venture to make use of these bio-inspired principles will be an even more exciting journey.”.

The seeds of the pioneering research were sown more than 16 years ago as part of a short project created by Professor Vukusic in the Exeter undergraduate Physics labs. Those early tests and measurements, made by enthusiastic undergraduate students, revealed the possibility of intriguing multifunctionality.

The original students examined the form and structure of beetles’ carapce to try to understand the simple origin of their colour. They noticed for the first time, however, the presence of strength-inducing micropillars.

Professor Vukusic ultimately carried these initial findings to collaborators Professor Ling Li at Virginia Tech and Professor Mathias Kolle at Harvard and then MIT who specialise in the materials sciences and applied optics. Using much more sophisticated measurement and modelling techniques, the combined research team were also to confirm the unique role played by the micropillars in enhancing the beetles’ strength and toughness without compromising its intense metallic colour.

The results from the study could also help inspire a new generation of bio-inspired materials, as well as the more traditional evolutionary research.

By understanding which of the functions provides the greater benefit to these beetles, scientists can develop new techniques to replicate and reproduce the exoskeleton structure, while ensuring that it has brilliant colour appearance with highly effective strength and toughness.

Professor Vukusic added: “Such natural systems as these never fail to impress with the way in which they perform, be it optical, mechanical or in another area of function. The way in which their optical or mechanical properties appear highly tolerant of all manner of imperfections too, continues to offer lessons to us about scientific and technological avenues we absolutely should explore. There is exciting science ahead of us on this journey.”

Here’s a link to and a citation for the paper,

Microstructural design for mechanical–optical multifunctionality in the exoskeleton of the flower beetle Torynorrhina flammea by Zian Jia, Matheus C. Fernandes, Zhifei Deng, Ting Yang, Qiuting Zhang, Alfie Lethbridge, Jie Yin, Jae-Hwang Lee, Lin Han, James C. Weaver, Katia Bertoldi, Joanna Aizenberg, Mathias Kolle, Pete Vukusic, and Ling Li. PNAS June 22, 2021 118 (25) e2101017118; DOI: https://doi.org/10.1073/pnas.2101017118

This paper is behind a paywall.

Follow up to the Charles M. Lieber affair and US government efforts to prosecute nanotech scientists

Rebecca Trager in a March 5, 2021 news article for Chemistry World highlights support for Charles M. Lieber (Harvard professor and chair of the chemistry department) from his colleagues (Note: Links have been removed),

More than a year after the chair of Harvard University’s chemistry department was arrested for allegedly hiding his receipt of millions of dollars in research funding from China from his university and the US government, dozens of prominent researchers – including many Nobel Prize winners – are coming to Charles Lieber’s defence. They are calling the US Department of Justice (DOJ) case against him ‘unjust’ and urging the agency to drop it.

Following his January 2020 arrest, Lieber was placed on ‘indefinite’ paid administrative leave. The nanoscience pioneer was indicted in June [2020] on charges of making false statements to federal authorities regarding his participation in China’s Thousand Talents plan – the country’s programme to attract, recruit and cultivate high-level scientific talent from abroad. Lieber faces up to five years in prison and a fine of $250,000 (£179,000) if convicted.

A 1 March [2021] open letter, drafted and coordinated by Harvard chemist Stuart Schreiber, co-founder of the Broad Institute, and professor emeritus Elias Corey, winner of the 1990 chemistry Nobel prize, says Lieber became the target of a ‘tragically misguided government campaign’. The letter refers to Lieber as ‘one of the great scientist of his generation’ and warns such government actions are discouraging US scientists from collaborating with peers in other countries, particularly China. The open letter also notes that Lieber is fighting to salvage his reputation while suffering from incurable lymphoma.

Ferguson goes on to contrast Lieber’s treatment by Harvard to another embattled colleague’s treatment by his home institution (Note: Links have been removed),

Harvard’s treatment of Lieber stands in contrast to how the Massachusetts Institute of Technology (MIT) handled the more recent case of nanotechnologist Gang Chen, who was arrested in January [2021] for failing to report his ties to the Chinese government. MIT agreed to cover his legal fees, and more than 100 faculty members signed a letter to their university’s president that picked apart the DOJ’s allegations against Chen.

I have more details about the case against Lieber (as it was presented at the time) in a January 28, 2020 posting.

As for Professor Chen, I found this MIT statement dated January 14, 2021 (the date of his arrest) and this January 14, 2021 statement from The United States District Attorney’s Office District of Massachusetts.

Precision targeting of the liver for gene editing

Apparently the magic is in the lipid nanoparticles. A March 1, 2021 news item on Nanowerk announced research into lipid nanoparticles as a means to deliver CRISPR (clustered regularly interspaced short palindromic repeats) to specific organs (Note: A link has been removed),

The genome editing technology CRISPR has emerged as a powerful new tool that can change the way we treat disease. The challenge when altering the genetics of our cells, however, is how to do it safely, effectively, and specifically targeted to the gene, tissue and organ that needs treatment.

Scientists at Tufts University and the Broad Institute of Harvard [University] and MIT [Massachusetts Institute of Technology] have developed unique nanoparticles comprised of lipids — fat molecules — that can package and deliver gene editing machinery specifically to the liver.

In a study published in the Proceedings of the National Academy of Sciences [PNAS] (“Lipid nanoparticle-mediated codelivery of Cas9 mRNA and single-guide RNA achieves liver-specific in vivo genome editing of Angptl3”), they have shown that they can use the lipid nanoparticles (LNPs) to efficiently deliver the CRISPR machinery into the liver of mice, resulting in specific genome editing and the reduction of blood cholesterol levels by as much as 57% — a reduction that can last for at least several months with just one shot.

A March 2, 2021 Tufts University news release (also on EurekAlert but published March 1, 2021), which originated the news item, provides greater insight into and technical detail about the research,

The problem of high cholesterol plagues more than 29 million Americans, according to the Centers for Disease Control and Prevention. The condition is complex and can originate from multiple genes as well as nutritional and lifestyle choices, so it is not easy to treat. The Tufts and Broad researchers, however, have modified one gene that could provide a protective effect against elevated cholesterol if it can be shut down by gene editing.

The gene that the researchers focused on codes for the angiopoietin-like 3 enzyme (Angptl3). That enzyme tamps down the activity of other enzymes – lipases – that help break down cholesterol. If researchers can knock out the Angptl3 gene, they can let the lipases do their work and reduce levels of cholesterol in the blood. It turns out that some lucky people have a natural mutation in their Angptl3 gene, leading to consistently low levels of triglycerides and low-density lipoprotein (LDL) cholesterol, commonly called “bad” cholesterol, in their bloodstream without any known clinical downsides.

“If we can replicate that condition by knocking out the angptl3 gene in others, we have a good chance of having a safe and long term solution to high cholesterol,” said Qiaobing Xu, associate professor of biomedical engineering at Tufts’ School of Engineering and corresponding author of the study. “We just have to make sure we deliver the gene editing package specifically to the liver so as not to create unwanted side effects.”

Xu’s team was able to do precisely that in mouse models. After a single injection of lipid nanoparticles packed with mRNA coding for CRISPR-Cas9 and a single-guide RNA targeting Angptl3, they observed a profound reduction in LDL cholesterol by as much as 57% and triglyceride levels by about 29 %, both of which remained at those lowered levels for at least 100 days. The researchers speculate that the effect may last much longer than that, perhaps limited only by the slow turnover of cells in the liver, which can occur over a period of about a year. The reduction of cholesterol and triglycerides is dose dependent, so their levels could be adjusted by injecting fewer or more LNPs in the single shot, the researchers said.

By comparison, an existing, FDA [US Food and Drug Administration]-approved version of CRISPR mRNA-loaded LNPs could only reduce LDL cholesterol by at most 15.7% and triglycerides by 16.3% when it was tested in mice, according to the researchers.

The trick to making a better LNP was in customizing the components – the molecules that come together to form bubbles around the mRNA. The LNPs are made up of long chain lipids that have a charged or polar head that is attracted to water, a carbon chain tail that points toward the middle of the bubble containing the payload, and a chemical linker between them. Also present are polyethylene glycol, and yes, even some cholesterol – which has a normal role in lipid membranes to make them less leaky – to hold their contents better.

The researchers found that the nature and relative ratio of these components appeared to have profound effects on the delivery of mRNA into the liver, so they tested LNPs with many combinations of heads, tails, linkers and ratios among all components for their ability to target liver cells. Because the in vitro potency of an LNP formulation rarely reflects its in vivo performance, they directly evaluated the delivery specificity and efficacy in mice that have a reporter gene in their cells that lights up red when genome editing occurs. Ultimately, they found a CRISPR mRNA-loaded LNP that lit up just the liver in mice, showing that it could specifically and efficiently deliver gene-editing tools into the liver to do their work.

The LNPs were built upon earlier work at Tufts, where Xu and his team developed LNPs with as much as 90% efficiency in delivering mRNA into cells. A unique feature of those nanoparticles was the presence of disulfide bonds between the long lipid chains. Outside the cells, the LNPs form a stable spherical structure that locks in their contents. When they are inside a cell, the environment within breaks the disulfide bonds to disassemble the nanoparticles. The contents are then quickly and efficiently released into the cell. By preventing loss outside the cell, the LNPs can have a much higher yield in delivering their contents.

“CRISPR is one of the most powerful therapeutic tools for the treatment of diseases with a genetic etiology. We have recently seen the first human clinical trail for CRISPR therapy enabled by LNP delivery to be administered systemically to edit genes inside the human body. Our LNP platform developed here holds great potential for clinical translation,” said Min Qiu, post-doctoral researcher in Xu’s lab at Tufts.  “We envision that with this LNP platform in hand, we could now make CRISPR a practical and safe approach to treat a broad spectrum of liver diseases or disorders,” said Zachary Glass, graduate student in the Xu lab. Qiu and Glass are co-first authors of the study.

Here’s a link to and a citation for the paper,

Lipid nanoparticle-mediated codelivery of Cas9 mRNA and single-guide RNA achieves liver-specific in vivo genome editing of Angptl3 by Min Qiu, Zachary Glass, Jinjin Chen, Mary Haas, Xin Jin, Xuewei Zhao, Xuehui Rui, Zhongfeng Ye, Yamin Li, Feng Zhang, and Qiaobing Xu. PNAS March 9, 2021 118 (10) e2020401118 DOI: https://doi.org/10.1073/pnas.2020401118

This paper appears to be behind a paywall.

Suit up with nanofiber for protection against explosions and high temperatures

Where explosions are concerned you might expect to see some army research and you would be right. A June 29, 2020 news item on ScienceDaily breaks the news,

Since World War I, the vast majority of American combat casualties has come not from gunshot wounds but from explosions. Today, most soldiers wear a heavy, bullet-proof vest to protect their torso but much of their body remains exposed to the indiscriminate aim of explosive fragments and shrapnel.

Designing equipment to protect extremities against the extreme temperatures and deadly projectiles that accompany an explosion has been difficult because of a fundamental property of materials. Materials that are strong enough to protect against ballistic threats can’t protect against extreme temperatures and vice versa. As a result, much of today’s protective equipment is composed of multiple layers of different materials, leading to bulky, heavy gear that, if worn on the arms and legs, would severely limit a soldier’s mobility.

Now, Harvard University researchers, in collaboration with the U.S. Army Combat Capabilities Development Command Soldier Center (CCDC SC) and West Point, have developed a lightweight, multifunctional nanofiber material that can protect wearers from both extreme temperatures and ballistic threats.

A June 29, 2020 Harvard University news release (also on EurekAlert) by Leah Burrows, which originated the news item, expands on the theme,

“When I was in combat in Afghanistan, I saw firsthand how body armor could save lives,” said senior author Kit Parker, the Tarr Family Professor of Bioengineering and Applied Physics at the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS) and a lieutenant colonel in the United States Army Reserve. “I also saw how heavy body armor could limit mobility. As soldiers on the battlefield, the three primary tasks are to move, shoot, and communicate. If you limit one of those, you decrease survivability and you endanger mission success.”

“Our goal was to design a multifunctional material that could protect someone working in an extreme environment, such as an astronaut, firefighter or soldier, from the many different threats they face,” said Grant M. Gonzalez, a postdoctoral fellow at SEAS and first author of the paper.

In order to achieve this practical goal, the researchers needed to explore the tradeoff between mechanical protection and thermal insulation, properties rooted in a material’s molecular structure and orientation.

Materials with strong mechanical protection, such as metals and ceramics, have a highly ordered and aligned molecular structure. This structure allows them to withstand and distribute the energy of a direct blow. Insulating materials, on the other hand, have a much less ordered structure, which prevents the transmission of heat through the material.

Kevlar and Twaron are commercial products used extensively in protective equipment and can provide either ballistic or thermal protection, depending on how they are manufactured. Woven Kevlar, for example, has a highly aligned crystalline structure and is used in protective bulletproof vests. Porous Kevlar aerogels, on the other hand, have been shown to have high thermal insulation.

“Our idea was to use this Kevlar polymer to combine the woven, ordered structure of fibers with the porosity of aerogels to make long, continuous fibers with porous spacing in between,” said Gonzalez. “In this system, the long fibers could resist a mechanical impact while the pores would limit heat diffusion.”

The research team used immersion Rotary Jet-Spinning (iRJS), a technique developed by Parker’s Disease Biophysics Group, to manufacture the fibers. In this technique, a liquid polymer solution is loaded into a reservoir and pushed out through a tiny opening by centrifugal force as the device spins. When the polymer solution shoots out of the reservoir, it first passes through an area of open air, where the polymers elongate and the chains align. Then the solution hits a liquid bath that removes the solvent and precipitates the polymers to form solid fibers. Since the bath is also spinning — like water in a salad spinner — the nanofibers follow the stream of the vortex and wrap around a rotating collector at the base of the device.

By tuning the viscosity of the liquid polymer solution, the researchers were able to spin long, aligned nanofibers into porous sheets — providing enough order to protect against projectiles but enough disorder to protect against heat. In about 10 minutes, the team could spin sheets about 10 by 30 centimeters in size.

To test the sheets, the Harvard team turned to their collaborators to perform ballistic tests. Researchers at CCDC SC in Natick, Massachusetts simulated shrapnel impact by shooting large, BB-like projectiles at the sample. The team performed tests by sandwiching the nanofiber sheets between sheets of woven Twaron. They observed little difference in protection between a stack of all woven Twaron sheets and a combined stack of woven Twaron and spun nanofibers.

“The capabilities of the CCDC SC allow us to quantify the successes of our fibers from the perspective of protective equipment for warfighters, specifically,” said Gonzalez.

“Academic collaborations, especially those with distinguished local universities such as Harvard, provide CCDC SC the opportunity to leverage cutting-edge expertise and facilities to augment our own R&D capabilities,” said Kathleen Swana, a researcher at CCDC SC and one of the paper’s authors. “CCDC SC, in return, provides valuable scientific and soldier-centric expertise and testing capabilities to help drive the research forward.”

In testing for thermal protection, the researchers found that the nanofibers provided 20 times the heat insulation capability of commercial Twaron and Kevlar.

“While there are improvements that could be made, we have pushed the boundaries of what’s possible and started moving the field towards this kind of multifunctional material,” said Gonzalez.

“We’ve shown that you can develop highly protective textiles for people that work in harm’s way,” said Parker. “Our challenge now is to evolve the scientific advances to innovative products for my brothers and sisters in arms.”

Harvard’s Office of Technology Development has filed a patent application for the technology and is actively seeking commercialization opportunities.

Here’s a link to and a citation for the paper,

para-Aramid Fiber Sheets for Simultaneous Mechanical and Thermal Protection in Extreme Environments by Grant M. Gonzalez, Janet Ward, John Song, Kathleen Swana, Stephen A. Fossey, Jesse L. Palmer, Felita W. Zhang, Veronica M. Lucian, Luca Cera, John F. Zimmerman, F. John Burpo, Kevin Kit Parker. Matter DOI: https://doi.org/10.1016/j.matt.2020.06.001 Published:June 29, 2020

This paper is behind a paywall.

While this is the first time I’ve featured clothing/armour that’s protective against explosions I have on at least two occasions featured bulletproof clothing in a Canadian context. A November 4, 2013 posting had a story about a Toronto-based tailoring establishment, Garrison Bespoke, that was going to publicly test a bulletproof business suit. Should you be interested, it is possible to order the suit here. There’s also a February 11, 2020 posting announcing research into “Comfortable, bulletproof clothing for Canada’s Department of National Defence.”

US Food and Drug Administration (FDA) gives first authorization for CRISPR (clustered regularly interspersed short palindromic repeats) use in COVID-19 crisis

Clustered regularly interspersed short palindromic repeats (CRISPR) gene editing has been largely confined to laboratory use or tested in agricultural trials. I believe that is true worldwide excepting the CRISPR twin scandal. (There are numerous postings about the CRISPR twins here including a Nov. 28, 2018 post, a May 17, 2019 post, and a June 20, 2019 post. Update: It was reported (3rd. para.) in December 2019 that He had been sentenced to three years jail time.)

Connie Lin in a May 7, 2020 article for Fast Company reports on this surprising decision by the US Food and Drug Administration (FDA), Note: A link has been removed),

The U.S. Food and Drug Administration has granted Emergency Use Authorization to a COVID-19 test that uses controversial gene-editing technology CRISPR.

This marks the first time CRISPR has been authorized by the FDA, although only for the purpose of detecting the coronavirus, and not for its far more contentious applications. The new test kit, developed by Cambridge, Massachusetts-based Sherlock Biosciences, will be deployed in laboratories certified to carry out high-complexity procedures and is “rapid,” returning results in about an hour as opposed to those that rely on the standard polymerase chain reaction method, which typically requires six hours.

The announcement was made in the FDA’s Coronavirus (COVID-19) Update: May 7, 2020 Daily Roundup (4th item in the bulleted list), Or, you can read the May 6, 2020 letter (PDF) sent to John Vozella of Sherlock Biosciences by the FDA.

As well, there’s the May 7, 2020 Sherlock BioSciences news release (the most informative of the lot),

Sherlock Biosciences, an Engineering Biology company dedicated to making diagnostic testing better, faster and more affordable, today announced the company has received Emergency Use Authorization (EUA) from the U.S. Food and Drug Administration (FDA) for its Sherlock™ CRISPR SARS-CoV-2 kit for the detection of the virus that causes COVID-19, providing results in approximately one hour.

“While it has only been a little over a year since the launch of Sherlock Biosciences, today we have made history with the very first FDA-authorized use of CRISPR technology, which will be used to rapidly identify the virus that causes COVID-19,” said Rahul Dhanda, co-founder, president and CEO of Sherlock Biosciences. “We are committed to providing this initial wave of testing kits to physicians, laboratory experts and researchers worldwide to enable them to assist frontline workers leading the charge against this pandemic.”

The Sherlock™ CRISPR SARS-CoV-2 test kit is designed for use in laboratories certified under the Clinical Laboratory Improvement Amendments of 1988 (CLIA), 42 U.S.C. §263a, to perform high complexity tests. Based on the SHERLOCK method, which stands for Specific High-sensitivity Enzymatic Reporter unLOCKing, the kit works by programming a CRISPR molecule to detect the presence of a specific genetic signature – in this case, the genetic signature for SARS-CoV-2 – in a nasal swab, nasopharyngeal swab, oropharyngeal swab or bronchoalveolar lavage (BAL) specimen. When the signature is found, the CRISPR enzyme is activated and releases a detectable signal. In addition to SHERLOCK, the company is also developing its INSPECTR™ platform to create an instrument-free, handheld test – similar to that of an at-home pregnancy test – that utilizes Sherlock Biosciences’ Synthetic Biology platform to provide rapid detection of a genetic match of the SARS-CoV-2 virus.

“When our lab collaborated with Dr. Feng Zhang’s team to develop SHERLOCK, we believed that this CRISPR-based diagnostic method would have a significant impact on global health,” said James J. Collins, co-founder and board member of Sherlock Biosciences and Termeer Professor of Medical Engineering and Science for MIT’s Institute for Medical Engineering and Science (IMES) and Department of Biological Engineering. “During what is a major healthcare crisis across the globe, we are heartened that the first FDA-authorized use of CRISPR will aid in the fight against this global COVID-19 pandemic.”

Access to rapid diagnostics is critical for combating this pandemic and is a primary focus for Sherlock Biosciences co-founder and board member, David R. Walt, Ph.D., who co-leads the Mass [Massachusetts] General Brigham Center for COVID Innovation.

“SHERLOCK enables rapid identification of a single alteration in a DNA or RNA sequence in a single molecule,” said Dr. Walt. “That precision, coupled with its capability to be deployed to multiplex over 100 targets or as a simple point-of-care system, will make it a critical addition to the arsenal of rapid diagnostics already being used to detect COVID-19.”

This development is particularly interesting since there was a major intellectual property dispute over CRISPR between the Broad Institute (a Harvard University and Massachusetts Institute of Technology [MIT] joint initiative), and the University of California at Berkeley (UC Berkeley). The Broad Institute mostly won in the first round of the patent fight, as I noted in a March 15, 2017 post but, as far as I’m aware, UC Berkeley is still disputing that decision.

In the period before receiving authorization, it appears that Sherlock Biosciences was doing a little public relations and ‘consciousness raising’ work. Here’s a sample from a May 5, 2020 article by Sharon Begley for STAT (Note: Links have been removed),

The revolutionary genetic technique better known for its potential to cure thousands of inherited diseases could also solve the challenge of Covid-19 diagnostic testing, scientists announced on Tuesday. A team headed by biologist Feng Zhang of the McGovern Institute at MIT and the Broad Institute has repurposed the genome-editing tool CRISPR into a test able to quickly detect as few as 100 coronavirus particles in a swab or saliva sample.

Crucially, the technique, dubbed a “one pot” protocol, works in a single test tube and does not require the many specialty chemicals, or reagents, whose shortage has hampered the rollout of widespread Covid-19 testing in the U.S. It takes about an hour to get results, requires minimal handling, and in preliminary studies has been highly accurate, Zhang told STAT. He and his colleagues, led by the McGovern’s Jonathan Gootenberg and Omar Abudayyeh, released the protocol on their STOPCovid.science website.

Because the test has not been approved by the Food and Drug Administration, it is only for research purposes for now. But minutes before speaking to STAT on Monday, Zhang and his colleagues were on a conference call with FDA officials about what they needed to do to receive an “emergency use authorization” that would allow clinical use of the test. The FDA has used EUAs to fast-track Covid-19 diagnostics as well as experimental therapies, including remdesivir, after less extensive testing than usually required.

For an EUA, the agency will require the scientists to validate the test, which they call STOPCovid, on dozens to hundreds of samples. Although “it is still early in the process,” Zhang said, he and his colleagues are confident enough in its accuracy that they are conferring with potential commercial partners who could turn the test into a cartridge-like device, similar to a pregnancy test, enabling Covid-19 testing at doctor offices and other point-of-care sites.

“It could potentially even be used at home or at workplaces,” Zhang said. “It’s inexpensive, does not require a lab, and can return results within an hour using a paper strip, not unlike a pregnancy test. This helps address the urgent need for widespread, accurate, inexpensive, and accessible Covid-19 testing.” Public health experts say the availability of such a test is one of the keys to safely reopening society, which will require widespread testing, and then tracing and possibly isolating the contacts of those who test positive.

If you have time, do read Begley’s in full.

Harvard professor and leader in nanoscale electronics charged with making false statements about Chinese funding

I may be mistaken but the implication seems to be that Charles M. Lieber’s lies (he was charged today, January 28, 2020 ) are the ‘tip of the iceberg’ of a very large problem. Ellen Barry’s January 28, 2020 article for the New York Times outlines at least part of what the US government is doing to discover and ultimately discourage the theft of biomedical research from US laboratories.

Dr. Lieber, a leader in the field of nanoscale electronics, was one of three Boston-area scientists accused on Tuesday [January 28, 2020] of working on behalf of China. His case involves work with the Thousand Talents Program, a state-run program that seeks to draw talent educated in other countries.

American officials are investigating hundreds of cases of suspected theft of intellectual property by visiting scientists, nearly all of them Chinese nationals or of Chinese descent. Some are accused of obtaining patents in China based on work that is funded by the United States government, and others of setting up laboratories in China that secretly duplicated American research.

Dr. Lieber, who was arrested on Tuesday [January 28, 2020], stands out among the accused scientists, because he is neither Chinese nor of Chinese descent. …

Lieber is the Chair of Harvard’s Department of Chemistry and Chemical Biology and much more, according to his Wikipedia entry (Note: Links have been removed),

Charles M. Lieber (born 1959) is an American chemist and pioneer in the field of nanoscience and nanotechnology. In 2011, Lieber was recognized by Thomson Reuters as the leading chemist in the world for the decade 2000-2010 based on the impact of his scientific publications.[1] Lieber has published over 400 papers in peer-reviewed scientific journals and has edited and contributed to many books on nanoscience.[2] He is the principal inventor on over fifty issued US patents and applications, and founded the nanotechnology company Nanosys in 2001 and Vista Therapeutics in 2007.[3] He is known for his contributions to the synthesis, assembly and characterization of nanoscale materials and nanodevices, the application of nanoelectronic devices in biology, and as a mentor to numerous leaders in nanoscience.[4] Thompson Reuters predicted Lieber to be a recipient of the 2008 Nobel Prize in Chemistry [to date, January 28, 2020, Lieber has not received a Nobel prize].

Should you search Charles Lieber or Charles M. Lieber on this blog’s search engine, you will find a number of postings about his and his students’ work dating from 2012 to as recently as November 15, 2019.

Here’s another example from Barry’s January 28, 2020 article for the New York Times which illustrates just how shocking this is (Note: Links have been removed),

In 2017 he was named a University Professor, Harvard’s highest faculty rank, one of only 26 professors to hold that status. The same year, he earned the National Institutes of Health Director’s Pioneer Award for inventing syringe-injectable mesh electronics that can integrate with the brain.

Harvard’s president at the time, Drew G. Faust, called him “an extraordinary scientist whose work has transformed nanoscience and nanotechnology and has led to a remarkable range of valuable applications that improve the quality of people’s lives.”

Here’s a bit more about the Chinese program that Lieber is affiliated with,

Launched in 2008, its [China] Thousand Talents Program is an effort to recruit Chinese and foreign academics and entrepreneurs. According to a report in the China Daily, new recruits receive 1 million yuan, or about $146,000, from the central government, and a pledge of 10 million yuan for their ongoing research from the Chinese Academy of Sciences.

The recruitment flows both ways. Researchers of Chinese descent make up nearly half of the work force in American research laboratories, in part because American-born scientists are drawn to the private sector and less interested in academic careers.

I encourage you to read Barry’s entire article. It is jaw-dropping and, where Lieber is concerned, sad. It’s beginning to look like US universities are corrupt. The Jeffrey Epstein (a wealthy and convicted sexual predator and more) connection to the Massachusetts Institute of Technology, which led to the resignation of a prominent faculty member (Sept. 19, 2019 article by Anna North for Vox.com), and the Fall 2019 cheating scandal (gaining admission to big name educational institutions by paying someone other than the student to take exams, among many other schemes) suggest a reckoning might be in order.

ETA January 28, 2020 at 1645 hours: I found a January 28, 2020 article by Antonio Regalado for the MIT Technology Review which provides a few more details about Lieber’s situation,

Big money: According to the charging document, Lieber, starting in 2011,  agreed to help set up a research lab at the Wuhan University of Technology and “make strategic visionary and creative research proposals” so that China could do cutting-edge science.

He was well paid for it. Lieber earned a salary when he visited China worth up to $50,000 per month, as well as $150,000 a year in expenses in addition to research funds. According to the complaint, he got paid by way of a Chinese bank account but also was known to send emails asking for cash instead.

Harvard eventually wised up to the existence of a Wuhan lab using its name and logo, but when administrators confronted Lieber, he lied and said he didn’t know about a formal joint program, according to the government complaint.

I imagine the money paid by the Chinese government is in addition to Lieber’s Harvard salary (no doubt a substantial one especially since he’s chair of his department and one of a select number of Harvard’s University Professors) and in addition to any other deals he might have on the side.

Human-machine interfaces and ultra-small nanoprobes

We’re back on the cyborg trail or what I sometimes refer to as machine/flesh. A July 3, 2019 news item on ScienceDaily describes the latest attempts to join machine with flesh,

Machine enhanced humans — or cyborgs as they are known in science fiction — could be one step closer to becoming a reality, thanks to new research Lieber Group at Harvard University, as well as scientists from University of Surrey and Yonsei University.

Researchers have conquered the monumental task of manufacturing scalable nanoprobe arrays small enough to record the inner workings of human cardiac cells and primary neurons.

The ability to read electrical activities from cells is the foundation of many biomedical procedures, such as brain activity mapping and neural prosthetics. Developing new tools for intracellular electrophysiology (the electric current running within cells) that push the limits of what is physically possible (spatiotemporal resolution) while reducing invasiveness could provide a deeper understanding of electrogenic cells and their networks in tissues, as well as new directions for human-machine interfaces.

The Lieber Group at Harvard University provided this image illustrating the work,

U-shaped nanowires can record electrical chatter inside a brain or heart cell without causing any damage. The devices are 100 times smaller than their biggest competitors, which kill a cell after recording. Courtesy: University of Surrey

A July 3, 2019 University of Surrey press release (also on EurekAlert), which originated the news item, provides more details about this UK/US/China collaboration,

In a paper published by Nature Nanotechnology, scientists from Surrey’s Advanced Technology Institute (ATI) and Harvard University detail how they produced an array of the ultra-small U-shaped nanowire field-effect transistor probes for intracellular recording. This incredibly small structure was used to record, with great clarity, the inner activity of primary neurons and other electrogenic cells, and the device has the capacity for multi-channel recordings.

Dr Yunlong Zhao from the ATI at the University of Surrey said: “If our medical professionals are to continue to understand our physical condition better and help us live longer, it is important that we continue to push the boundaries of modern science in order to give them the best possible tools to do their jobs. For this to be possible, an intersection between humans and machines is inevitable.

“Our ultra-small, flexible, nanowire probes could be a very powerful tool as they can measure intracellular signals with amplitudes comparable with those measured with patch clamp techniques; with the advantage of the device being scalable, it causes less discomfort and no fatal damage to the cell (cytosol dilation). Through this work, we found clear evidence for how both size and curvature affect device internalisation and intracellular recording signal.”

Professor Charles Lieber from the Department of Chemistry and Chemical Biology at Harvard University said: “This work represents a major step towards tackling the general problem of integrating ‘synthesised’ nanoscale building blocks into chip and wafer scale arrays, and thereby allowing us to address the long-standing challenge of scalable intracellular recording.

“The beauty of science to many, ourselves included, is having such challenges to drive hypotheses and future work. In the longer term, we see these probe developments adding to our capabilities that ultimately drive advanced high-resolution brain-machine interfaces and perhaps eventually bringing cyborgs to reality.”

Professor Ravi Silva, Director of the ATI at the University of Surrey, said: “This incredibly exciting and ambitious piece of work illustrates the value of academic collaboration. Along with the possibility of upgrading the tools we use to monitor cells, this work has laid the foundations for machine and human interfaces that could improve lives across the world.”

Dr Yunlong Zhao and his team are currently working on novel energy storage devices, electrochemical probing, bioelectronic devices, sensors and 3D soft electronic systems. Undergraduate, graduate and postdoc students with backgrounds in energy storage, electrochemistry, nanofabrication, bioelectronics, tissue engineering are very welcome to contact Dr Zhao to explore the opportunities further.

Here’s a link to and a citation for the paper,

Scalable ultrasmall three-dimensional nanowire transistor probes for intracellular recording by Yunlong Zhao, Siheng Sean You, Anqi Zhang, Jae-Hyun Lee, Jinlin Huang & Charles M. Lieber. Nature Nanotechnology (2019) DOI: https://doi.org/10.1038/s41565-019-0478-y Published 01 July 2019

The link I’ve provided leads to a paywall. However, I found a freely accessible version of the paper (this may not be the final published version) here.

Cyborg organoids?

Every time I think I’ve become inured to the idea of a fuzzy boundary between life and nonlife something new crosses my path such as integrating nanoelectronics with cells for cyborg organoids. An August 9, 2019 news item on ScienceDaily makes the announcement,

What happens in the early days of organ development? How do a small group of cells organize to become a heart, a brain, or a kidney? This critical period of development has long remained the black box of developmental biology, in part because no sensor was small or flexible enough to observe this process without damaging the cells.

Now, researchers from the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS) have grown simplified organs known as organoids with fully integrated sensors. These so-called cyborg organoids offer a rare glimpse into the early stages of organ development.

An August 8, 2019 Harvard John A. Paulson School of Engineering and Applied Sciences news release (also on EurekAlert but published August 9, 2019) by Leah Burrows, which originated the news item, expands on the theme,

“I was so inspired by the natural organ development process in high school, in which 3D organs start from few cells in 2D structures. I think if we can develop nanoelectronics that are so flexible, stretchable, and soft that they can grow together with developing tissue through their natural development process, the embedded sensors can measure the entire activity of this developmental process,” said Jia Liu, Assistant Professor of Bioengineering at SEAS and senior author of the study. “The end result is a piece of tissue with a nanoscale device completely distributed and integrated across the entire three-dimensional volume of the tissue.”

This type of device emerges from the work that Liu began as a graduate student in the lab of Charles M. Lieber, the Joshua and Beth Friedman University Professor. In Lieber’s lab, Liu once developed flexible, mesh-like nanoelectronics that could be injected in specific regions of tissue.

Building on that design, Liu and his team increased the stretchability of the nanoelectronics by changing the shape of the mesh from straight lines to serpentine structures (similar structures are used in wearable electronics). Then, the team transferred the mesh nanoelectronics onto a 2D sheet of stem cells, where the cells covered and interwove with the nanoelectronics via cell-cell attraction forces. As the stem cells began to morph into a 3D structure, the nanoelectronics seamlessly reconfigured themselves along with the cells, resulting in fully-grown 3D organoids with embedded sensors.

The stem cells were then differentiated into cardiomyocytes — heart cells — and the researchers were able to monitor and record the electrophysiological activity for 90 days.

“This method allows us to continuously monitor the developmental process and understand how the dynamics of individual cells start to interact and synchronize during the entire developmental process,” said Liu. “It could be used to turn any organoid into cyborg organoids, including brain and pancreas organoids.”

In addition to helping answer fundamental questions about biology, cyborg organoids could be used to test and monitor patient-specific drug treatments and potentially used for transplantations.

Here’s a link to and a citation for the paper

Cyborg Organoids: Implantation of Nanoelectronics via Organogenesis for Tissue-Wide Electrophysiology by Qiang Li, Kewang Nan, Paul Le Floch, Zuwan Lin, Hao Sheng, Thomas S. Blum, Jia Liu. Nano Lett.20191985781-5789 DOI: https://doi.org/10.1021/acs.nanolett.9b02512 Publication Date:July 26, 2019 Copyright © 2019 American Chemical Society

This paper is behind a paywall.

Ouchies no more! Not from bandages, anyway.

An adhesive that US and Chinese scientists have developed shows great promise not just for bandages but wearable robotics too. From a December 14, 2018 news item on Nanowerk,

Researchers from the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS) and Xi’an Jiaotong University in China have developed a new type of adhesive that can strongly adhere wet materials — such as hydrogel and living tissue — and be easily detached with a specific frequency of light.

The adhesives could be used to attach and painlessly detach wound dressings, transdermal drug delivery devices, and wearable robotics.

A December 18, 2018 SEAS news release by Leah Burrows (also on EurekAlert but published Dec. 14, 2018), which originated the news item, delves further,

“Strong adhesion usually requires covalent bonds, physical interactions, or a combination of both,” said Yang Gao, first author of the paper and researcher at Xi’an Jiaotong University. “Adhesion through covalent bonds is hard to remove and adhesion through physical interactions usually requires solvents, which can be time-consuming and environmentally harmful. Our method of using light to trigger detachment is non-invasive and painless.”

The adhesive uses an aqueous solution of polymer chains spread between two, non-sticky materials — like jam between two slices of bread. On their own, the two materials adhere poorly together but the polymer chains act as a molecular suture, stitching the two materials together by forming a network with the two preexisting polymer networks. This process is known as topological entanglement.

When exposed to ultra-violet light, the network of stitches dissolves, separating the two materials.

The researchers, led by Zhigang Suo, the Allen E. and Marilyn M. Puckett Professor of Mechanics and Materials at SEAS, tested adhesion and detachment on a range of materials, sticking together hydrogels; hydrogels and organic tissue; elastomers; hydrogels and elastomers; and hydrogels and inorganic solids.

“Our strategy works across a range of materials and may enable broad applications,” said Kangling Wu, co-lead author and researcher at Xi’an Jiaotong University in China.
While the researchers focused on using UV light to trigger detachment, their work suggests the possibility that the stitching polymer could detach with near-infrared light, a feature which could be applied to a range of new medical procedures.

“In nature, wet materials don’t like to adhere together,” said Suo. “We have discovered a general approach to overcome this challenge. Our molecular sutures can strongly adhere wet materials together. Furthermore, the strong adhesion can be made permanent, transient, or detachable on demand, in response to a cue. So, as we see it, nature is full of loopholes, waiting to be stitched.”

Here’s a link to and  a citation for the paper,

Photodetachable Adhesion by Yang Gao, Kangling Wu, Zhigang Suo. https://doi.org/10.1002/adma.201806948 First published: 14 December 2018

This paper is behind a paywall.