Tag Archives: Charles M. Lieber

Update on Charles Lieber (former Harvard professor) has been convicted

That was quick. Lieber went on trial Tuesday, December 14, 2021 and he was found guilty of two charges one week later on Tuesday, December 21, 2021. (You can see my December 20, 2021 posting for mention of the trial and a description of the events leading up to it.)

As for the conviction, here’s more from a December 23, 2021 posting by Brian Liu and Raquel Leslie for the Law Fare blog (Note: Links have been removed),

The Justice Department announced on Tuesday [December 21, 2921] that Charles Lieber, former chair of Harvard’s Chemistry and Chemical Biology Department, was convicted by a federal jury in connection with his ties to China’s Thousand Talents Program. Lieber was convicted for failing to report income and making false statements to authorities regarding his affiliation with the Wuhan University of Technology (WUT). The conviction is a significant chapter in the story of the department’s China Initiative, which has recently come under fire by groups who allege that the program has led to racial profiling and amounts to prosecutorial overreach. 

The jury convicted Lieber of knowingly and willfully making a materially false statement to federal authorities regarding his work with China’s Thousand Talents Program. The program, launched in 2008, began with the aim of reversing brain drain by enticing Chinese scientists overseas to return to China. Over time, the program evolved to also recruit foreigners with expertise in key technologies. The program provided Lieber with $50,000 a month to work at WUT, in addition to up to $150,000 in living expenses and more than $1.5 million in grants. Though it is not illegal to participate in Chinese recruitment programs, federal prosecutors alleged that Lieber had failed to report these payments as required of scientists receiving federal funding.

This is why Lieber’s prosecution is such a big deal (from the December 23, 2021 posting),

Lieber was seen by some as a potential Nobel Prize winner [emphasis mine] for his work in nanotechnology. Nanotechnology, the manipulation of materials at a near-atomic level, is a strategically important field with civilian and military application in medicine, green energy, computing and propulsion. In 2012, China’s Academy of Sciences launched a Strategic Pioneering Programme dedicated to nanotechnology research, investing one billion yuan ($152 million) over five years. As a result of the investment, China now ranks first worldwide for the number of patents and articles published on nanotechnology.

Both Liu and Leslie are JD (Juris Doctor) candidates (JD is an advanced law degree) at Yale Law School. Their posting is well worth reading in its entirety as they go on to discuss China and US tensions with regard to science and technology advancements. They also provide links to further commentaries at the end of their posting.

At this point (given limited information and from my admittedly amateur perspective), it looks more like a tax evasion case than anything else.

Charles Lieber, nanoscientist, and the US Dept. of Justice

Charles Lieber, professor at Harvard University and one of the world’s leading researchers in nanotechnology went on trial on Tuesday, December 14, 2021.

Accused of hiding his ties to a People’s Republic of China (PRC)-run recruitment programme, Lieber is probably the highest profile academic and one of the few who was not born in China or has familial origins in China to be charged under the auspices of the US Department of Justice’s ‘China Initiative’.

This US National Public Radio (NPR) December 14, 2021 audio excerpt provides a brief summary of the situation by Ryan Lucas,

A December 14, 2021 article by Jess Aloe, Eileen Guo, and Antonio Regalado for the Massachusetts Institute of Technology (MIT) Technology Review lays out the situation in more detail (Note: A link has been removed),

In January of 2020, agents arrived at Harvard University looking for Charles Lieber, a renowned nanotechnology researcher who chaired the school’s department of chemistry and chemical biology. They were there to arrest him on charges of hiding his financial ties with a university in China. By arresting Lieber steps from Harvard Yard, authorities were sending a loud message to the academic community: failing to disclose such links is a serious crime.

Now Lieber is set to go on trial beginning December 14 [2021] in federal court in Boston. He has pleaded not guilty, and hundreds of academics have signed letters of support. In fact, some critics say it’s the Justice Department’s China Initiative—a far-reaching effort started in 2018 to combat Chinese economic espionage and trade-secret theft—that should be on trial, not Lieber. They are calling the prosecutions fundamentally flawed, a witch hunt that misunderstands the open-book nature of basic science and that is selectively destroying scientific careers over financial misdeeds and paperwork errors without proof of actual espionage or stolen technology.

For their part, prosecutors believe they have a tight case. They allege that Lieber was recruited into China’s Thousand Talents Plan—a program aimed at attracting top scientists—and paid handsomely to establish a research laboratory at the Wuhan University of Technology, but hid the affiliation from US grant agencies when asked about it (read a copy of the indictment here). Lieber is facing six felony charges: two counts of making false statements to investigators, two counts of filing a false tax return, and two counts of failing to report a foreign bank account. [emphases mine; Note: None of these charges have been proved in court]

The case against Lieber could be a bellwether for the government, which has several similar cases pending against US professors alleging that they didn’t disclose their China affiliations to granting agencies.

As for the China Initiative (from the MIT Technology Review December 14, 2021 article),

The China Initiative was announced in 2018 by Jeff Sessions, then the Trump administration’s attorney general, as a central component of the administration’s tough stance toward China.

An MIT Technology Review investigation published earlier this month [December 2021] found that the China Initiative is an umbrella for various types of prosecutions somehow connected to China, with targets ranging from a Chinese national who ran a turtle-smuggling ring to state-sponsored hackers believed to be behind some of the biggest data breaches in history. In total, MIT Technology Review identified 77 cases brought under the initiative; of those, a quarter have led to guilty pleas or convictions, but nearly two-thirds remain pending.

The government’s prosecution of researchers like Lieber for allegedly hiding ties to Chinese institutions has been the most controversial, and fastest-growing, aspect of the government’s efforts. In 2020, half of the 31 new cases brought under the China Initiative were cases against scientists or researchers. These cases largely did not accuse the defendants of violating the Economic Espionage Act.

… hundreds of academics across the country, from institutions including Stanford University and Princeton University,signed a letter calling on Attorney General Merrick Garland to end the China Initiative. The initiative, they wrote, has drifted from its original mission of combating Chinese intellectual-property theft and is instead harming American research competitiveness by discouraging scholars from coming to or staying in the US.

Lieber’s case is the second [emphasis mine] China Initiative prosecution of an academic to end up in the courtroom. The only previous person to face trial [emphasis mine] on research integrity charges, University of Tennessee–Knoxville professor Anming Hu, was acquitted of all charges [emphasis mine] by a judge in June [2021] after a deadlocked jury led to a mistrial.

Ken Dilanian wrote an October 19, 2021 article for (US) National Broadcasting Corporation’s (NBC) news online about Hu’s eventual acquittal and about the China Inititative (Note: Dilanian’s timeline for the acquittal differs from the timeline in the MIT Technology Review),

The federal government brought the full measure of its legal might against Anming Hu, a nanotechnology expert at the University of Tennessee.

But the Justice Department’s efforts to convict Hu as part of its program to crack down on illicit technology transfer to China failed — spectacularly. A judge acquitted him last month [September 2021] after a lengthy trial offered little evidence of anything other than a paperwork misunderstanding, according to local newspaper coverage. It was the second trial, after the first ended in a hung jury.

“The China Initiative has turned up very little by way of clear espionage and the transfer of genuinely strategic information to the PRC,” said Robert Daly, a China expert at the Wilson Center, referring to the country by its formal name, the People’s Republic of China. “They are mostly process crimes, disclosure issues. A growing number of voices are calling for an end to the China initiative because it’s seen as discriminatory.”

The China Initiative began under President Donald Trump’s attorney general, Jeff Sessions, in 2018. But concerns about Chinese espionage in the United States — and the transfer of technology to China through business and academic relationships — are bipartisan.

John Demers, who departed in June [2021] as head of the Justice Department’s National Security Division, said in an interview that the problem of technology transfer at universities is real. But he said he also believes conflict of interest and disclosure rules were not rigorously enforced for many years. For that reason, he recommended an amnesty program offering academics with undisclosed foreign ties a chance to come clean and avoid penalties. So far, the Biden administration has not implemented such a program.

When I first featured the Lieber case in a January 28, 2020 posting I was more focused on the financial elements,

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.

This is messy not least because Lieber and the members of his Harvard lab have done some extraordinary work as per my November 15, 2019 (Human-machine interfaces and ultra-small nanoprobes) posting about injectable electronics.

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.

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.

Long-term brain mapping with injectable electronics

Charles Lieber and his team at Harvard University announced a success with their work on injectable electronics last year (see my June 11, 2015 posting for more) and now they are reporting on their work with more extensive animal studies according to an Aug. 29, 2016 news item on psypost.org,

Scientists in recent years have made great strides in the quest to understand the brain by using implanted probes to explore how specific neural circuits work.

Though effective, those probes also come with their share of problems as a result of rigidity. The inflammation they produce induces chronic recording instability and means probes must be relocated every few days, leaving some of the central questions of neuroscience – like how the neural circuits are reorganized during development, learning and aging- beyond scientists’ reach.

But now, it seems, things are about to change.

Led by Charles Lieber, The Mark Hyman Jr. Professor of Chemistry and chair of the Department of Chemistry and Chemical Biology, a team of researchers that included graduate student Tian-Ming Fu, postdoctoral fellow Guosong Hong, graduate student Tao Zhou and others, has demonstrated that syringe-injectable mesh electronics can stably record neural activity in mice for eight months or more, with none of the inflammation

An Aug. 29, 2016 Harvard University press release, which originated the news item, provides more detail,

“With the ability to follow the same individual neurons in a circuit chronically…there’s a whole suite of things this opens up,” Lieber said. “The eight months we demonstrate in this paper is not a limit, but what this does show is that mesh electronics could be used…to investigate neuro-degenerative diseases like Alzheimer’s, or processes that occur over long time, like aging or learning.”

Lieber and colleagues also demonstrated that the syringe-injectable mesh electronics could be used to deliver electrical stimulation to the brain over three months or more.

“Ultimately, our aim is to create these with the goal of finding clinical applications,” Lieber said. “What we found is that, because of the lack of immune response (to the mesh electronics), which basically insulates neurons, we can deliver stimulation in a much more subtle way, using lower voltages that don’t damage tissue.”

The possibilities, however, don’t end there.

The seamless integration of the electronics and biology, Lieber said, could open the door to an entirely new class of brain-machine interfaces and vast improvements in prosthetics, among other fields.

“Today, brain-machine interfaces are based on traditional implanted probes, and there has been some impressive work that’s been done in that field,” Lieber said. “But all the interfaces rely on the same technique to decode neural signals.”

Because traditional rigid implanted probes are invariably unstable, he explained, researchers and clinicians rely on decoding what they call the “population average” – essentially taking a host of neural signals and applying complex computational tools to determine what they mean.

Using tissue-like mesh electronics, by comparison, researchers may be able to read signals from specific neurons over time, potentially allowing for the development of improved brain-machine interfaces for prosthetics.

“We think this is going to be very powerful, because we can identify circuits and both record and stimulate in a way that just hasn’t been possible before,” Lieber said. “So what I like to say is: I think therefore it happens.”

Lieber even held out the possibility that the syringe-injectable mesh electronics could one day be used to treat catastrophic injuries to the brain and spinal cord.

“I don’t think that’s science-fiction,” he said. “Other people may say that will be possible through, for example, regenerative medicine, but we are pursuing this from a different angle.

“My feeling is that this is about a seamless integration between the biological and the electronic systems, so they’re not distinct entities,” he continued. “If we can make the electronics look like the neural network, they will work together…and that’s where you want to be if you want to exploit the strengths of both.”

In the 2015 posting, Lieber was discussing cyborgs, here he broaches the concept without using the word, “… seamless integration between the biological and the electronic systems, so they’re not distinct entities.”

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

Stable long-term chronic brain mapping at the single-neuron level by Tian-Ming Fu, Guosong Hong, Tao Zhou, Thomas G Schuhmann, Robert D Viveros, & Charles M Lieber. Nature Methods (2016) doi:10.1038/nmeth.3969 Published online 29 August 2016

This paper is behind a paywall.

‘Bionic’ cardiac patch with nanoelectric scaffolds and living cells

A June 27, 2016 news item on Nanowerk announced that Harvard University researchers may have taken us a step closer to bionic cardiac patches for human hearts (Note: A link has been removed),

Scientists and doctors in recent decades have made vast leaps in the treatment of cardiac problems – particularly with the development in recent years of so-called “cardiac patches,” swaths of engineered heart tissue that can replace heart muscle damaged during a heart attack.

Thanks to the work of Charles Lieber and others, the next leap may be in sight.

The Mark Hyman, Jr. Professor of Chemistry and Chair of the Department of Chemistry and Chemical Biology, Lieber, postdoctoral fellow Xiaochuan Dai and other co-authors of a study that describes the construction of nanoscale electronic scaffolds that can be seeded with cardiac cells to produce a “bionic” cardiac patch. The study is described in a June 27 [2016] paper published in Nature Nanotechnology (“Three-dimensional mapping and regulation of action potential propagation in nanoelectronics-innervated tissues”).

A June 27, 2016 Harvard University press release on EurekAlert, which originated the news item, provides more information,

“I think one of the biggest impacts would ultimately be in the area that involves replaced of damaged cardiac tissue with pre-formed tissue patches,” Lieber said. “Rather than simply implanting an engineered patch built on a passive scaffold, our works suggests it will be possible to surgically implant an innervated patch that would now be able to monitor and subtly adjust its performance.”

Once implanted, Lieber said, the bionic patch could act similarly to a pacemaker – delivering electrical shocks to correct arrhythmia, but the possibilities don’t end there.

“In this study, we’ve shown we can change the frequency and direction of signal propagation,” he continued. “We believe it could be very important for controlling arrhythmia and other cardiac conditions.”

Unlike traditional pacemakers, Lieber said, the bionic patch – because its electronic components are integrated throughout the tissue – can detect arrhythmia far sooner, and operate at far lower voltages.

“Even before a person started to go into large-scale arrhythmia that frequently causes irreversible damage or other heart problems, this could detect the early-stage instabilities and intervene sooner,” he said. “It can also continuously monitor the feedback from the tissue and actively respond.”

“And a normal pacemaker, because it’s on the surface, has to use relatively high voltages,” Lieber added.

The patch might also find use, Lieber said, as a tool to monitor the responses under cardiac drugs, or to help pharmaceutical companies to screen the effectiveness of drugs under development.

Likewise, the bionic cardiac patch can also be a unique platform, he further mentioned, to study the tissue behavior evolving during some developmental processes, such as aging, ischemia or differentiation of stem cells into mature cardiac cells.

Although the bionic cardiac patch has not yet been implanted in animals, “we are interested in identifying collaborators already investigating cardiac patch implantation to treat myocardial infarction in a rodent model,” he said. “I don’t think it would be difficult to build this into a simpler, easily implantable system.”

In the long term, Lieber believes, the development of nanoscale tissue scaffolds represents a new paradigm for integrating biology with electronics in a virtually seamless way.

Using the injectable electronics technology he pioneered last year, Lieber even suggested that similar cardiac patches might one day simply be delivered by injection.

“It may actually be that, in the future, this won’t be done with a surgical patch,” he said. “We could simply do a co-injection of cells with the mesh, and it assembles itself inside the body, so it’s less invasive.”

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

Three-dimensional mapping and regulation of action potential propagation in nanoelectronics-innervated tissues by Xiaochuan Dai, Wei Zhou, Teng Gao, Jia Liu & Charles M. Lieber. Nature Nanotechnology (2016)  doi:10.1038/nnano.2016.96 Published online 27 June 2016

This paper is behind a paywall.

Dexter Johnson in a June 27, 2016 posting on his Nanoclast blog (on the IEEE [Institute of Electrical and Electronics Engineers] website) provides more technical detail (Note: Links have been removed),

In research described in the journal Nature Nanotechnology, Lieber and his team employed a bottom-up approach that started with the fabrication of doped p-type silicon nanowires. Lieber has been spearheading the use of silicon nanowires as a scaffold for growing nerve, heart, and muscle tissue for years now.

In this latest work, Lieber and his team fabricated the nanowires, applied them onto a polymer surface, and arranged them into a field-effect transistor (FET). The researchers avoided an increase in the device’s impedance as its dimensions were reduced by adopting this FET approach as opposed to simply configuring the device as an electrode. Each FET, along with its source-drain interconnects, created a 4-micrometer-by-20-micrometer-by-350-nanometer pad. Each of these pads was, in effect, a single recording device.

I recommend reading Dexter’s posting in its entirety as Charles Lieber shares additional technical information not found in the news release.

Injectable electronics

Having taught a course on bioelectronics for Simon Fraser University’s (Vancouver, Canada) Continuing Studies Program, this  latest work from Harvard University (US) caught my attention. A Harvard research team has developed a technique which could allow doctors to inject us with electronics, should we need them. From a June 8, 2015 news item on phys.org,

It’s a notion that might be pulled from the pages of science-fiction novel – electronic devices that can be injected directly into the brain, or other body parts, and treat everything from neurodegenerative disorders to paralysis.

It sounds unlikely, until you visit Charles Lieber’s lab.

A team of international researchers, led by Lieber, the Mark Hyman, Jr. Professor of Chemistry, an international team of researchers developed a method for fabricating nano-scale electronic scaffolds that can be injected via syringe. Once connected to electronic devices, the scaffolds can be used to monitor neural activity, stimulate tissues and even promote regenerations of neurons. …

Here’s an image provided by the researchers,

Bright-field image showing the mesh electronics being injected through sub-100 micrometer inner diameter glass needle into aqueous solution. mage courtesy of Lieber Research Group, Harvard University

Bright-field image showing the mesh electronics being injected through sub-100 micrometer inner diameter glass needle into aqueous solution. mage courtesy of Lieber Research Group, Harvard University

A June 8, 2015 Harvard University new release by Peter Reuell (also on EurekAlert), which originated the news item, describes the work in more detail,

“I do feel that this has the potential to be revolutionary,” Lieber said. “This opens up a completely new frontier where we can explore the interface between electronic structures and biology. For the past thirty years, people have made incremental improvements in micro-fabrication techniques that have allowed us to make rigid probes smaller and smaller, but no one has addressed this issue – the electronics/cellular interface – at the level at which biology works.”

The idea of merging the biological with the electronic is not a new one for Lieber.

In an earlier study, scientists in Lieber’s lab demonstrated that the scaffolds could be used to create “cyborg” tissue – when cardiac or nerve cells were grown with embedded scaffolds. [emphasis mine] Researchers were then able to use the devices to record electrical signals generated by the tissues, and to measure changes in those signals as they administered cardio- or neuro-stimulating drugs.

“We were able to demonstrate that we could make this scaffold and culture cells within it, but we didn’t really have an idea how to insert that into pre-existing tissue,” Lieber said. “But if you want to study the brain or develop the tools to explore the brain-machine interface, you need to stick something into the body. When releasing the electronics scaffold completely from the fabrication substrate, we noticed that it was almost invisible and very flexible like a polymer and could literally be sucked into a glass needle or pipette. From there, we simply asked, would it be possible to deliver the mesh electronics by syringe needle injection, a process common to delivery of many species in biology and medicine – you could go to the doctor and you inject this and you’re wired up.'”

Though not the first attempts at implanting electronics into the brain – deep brain stimulation has been used to treat a variety of disorders for decades – the nano-fabricated scaffolds operate on a completely different scale.

“Existing techniques are crude relative to the way the brain is wired,” Lieber explained. “Whether it’s a silicon probe or flexible polymers…they cause inflammation in the tissue that requires periodically changing the position or the stimulation. But with our injectable electronics, it’s as if it’s not there at all. They are one million times more flexible than any state-of-the-art flexible electronics and have subcellular feature sizes. They’re what I call “neuro-philic” – they actually like to interact with neurons..”

Despite their enormous potential, the fabrication of the injectable scaffolds is surprisingly easy.

“That’s the beauty of this – it’s compatible with conventional manufacturing techniques,” Lieber said.

The process is similar to that used to etch microchips, and begins with a dissolvable layer deposited on a substrate. To create the scaffold, researchers lay out a mesh of nanowires sandwiched in layers of organic polymer. The first layer is then dissolved, leaving the flexible mesh, which can be drawn into a syringe needle and administered like any other injection.

After injection, the input/output of the mesh can be connected to standard measurement electronics so that the integrated devices can be addressed and used to stimulate or record neural activity.

“These type of things have never been done before, from both a fundamental neuroscience and medical perspective,” Lieber said. “It’s really exciting – there are a lot of potential applications.”

Going forward, Lieber said, researchers hope to better understand how the brain and other tissues react to the injectable electronics over longer periods.

Lieber’s earlier work on “cyborg tissue” was briefly mentioned here in a Feb. 20, 2014 posting.

Getting back to the most recent work, here’s a link to and a citation for the paper,

Syringe-injectable electronics by Jia Liu, Tian-Ming Fu, Zengguang Cheng, Guosong Hong, Tao Zhou, Lihua Jin, Madhavi Duvvuri, Zhe Jiang, Peter Kruskal, Chong Xie, Zhigang Suo, Ying Fang, & Charles M. Lieber. Nature Nanotechnology (2015) doi:10.1038/nnano.2015.115 Published online 08 June 2015

This paper is behind a paywall but there is a free preview via ReadCube Access.

One final note, the researchers have tested the injectable electronics (or mesh electronics) in vivo (live animals).

Making nanoelectronic devices last longer in the body could lead to ‘cyborg’ tissue

An American Chemical Society (ACS) Feb. 19, 2014 news release (also on EurekAlert), describes some research devoted to extending a nanoelectronic device’s ‘life’ when implanted in the body,

The debut of cyborgs who are part human and part machine may be a long way off, but researchers say they now may be getting closer. In a study published in ACS’ journal Nano Letters, they report development of a coating that makes nanoelectronics much more stable in conditions mimicking those in the human body. [emphases mine] The advance could also aid in the development of very small implanted medical devices for monitoring health and disease.

Charles Lieber and colleagues note that nanoelectronic devices with nanowire components have unique abilities to probe and interface with living cells. They are much smaller than most implanted medical devices used today. For example, a pacemaker that regulates the heart is the size of a U.S. 50-cent coin, but nanoelectronics are so small that several hundred such devices would fit in the period at the end of this sentence. Laboratory versions made of silicon nanowires can detect disease biomarkers and even single virus cells, or record heart cells as they beat. Lieber’s team also has integrated nanoelectronics into living tissues in three dimensions — creating a “cyborg tissue.” One obstacle to the practical, long-term use of these devices is that they typically fall apart within weeks or days when implanted. In the current study, the researchers set out to make them much more stable.

They found that coating silicon nanowires with a metal oxide shell allowed nanowire devices to last for several months. This was in conditions that mimicked the temperature and composition of the inside of the human body. In preliminary studies, one shell material appears to extend the lifespan of nanoelectronics to about two years.

Depending on how you define the term cyborg, it could be said there are already cyborgs amongst us as I noted in an April 20, 2012 posting titled: My mother is a cyborg. Personally I’m fascinated by the news release’s mention of ‘cyborg tissue’ although there’s no further explanation of what the term might mean.

For the curious, here’s a link to and a citation for the paper,

Long Term Stability of Nanowire Nanoelectronics in Physiological Environments by Wei Zhou, Xiaochuan Dai, Tian-Ming Fu, Chong Xie, Jia Liu, and Charles M. Lieber. Nano Lett., Article ASAP DOI: 10.1021/nl500070h Publication Date (Web): January 30, 2014
Copyright © 2014 American Chemical Society

This paper is behind a paywall.

The body as an electronic device—adding electronics to biological tissue

What makes this particular combination of electronic s  and living tissue special is t that it was achieved in 3-D rather than 2-D.  From the Boston Children’s Hospital Aug. 26, 2012 news release on EurekAlert,

A multi-institutional research team has developed a method for embedding networks of biocompatible nanoscale wires within engineered tissues. These networks—which mark the first time that electronics and tissue have been truly merged in 3D—allow direct tissue sensing and potentially stimulation, a potential boon for development of engineered tissues that incorporate capabilities for monitoring and stimulation, and of devices for screening new drugs.

The Aug. 27, 2012 news item on Nanowerk provides more detail about integration of the cells and electronics,

Until now, the only cellular platforms that incorporated electronic sensors consisted of flat layers of cells grown on planar metal electrodes or transistors. Those two-dimensional systems do not accurately replicate natural tissue, so the research team set out to design a 3-D scaffold that could monitor electrical activity, allowing them to see how cells inside the structure would respond to specific drugs.

The researchers built their new scaffold out of epoxy, a nontoxic material that can take on a porous, 3-D structure. Silicon nanowires embedded in the scaffold carry electrical signals to and from cells grown within the structure.

“The scaffold is not just a mechanical support for cells, it contains multiple sensors. We seed cells into the scaffold and eventually it becomes a 3-D engineered tissue,” Tian says [Bozhi Tian, a former postdoc at MIT {Massachusetts Institute of Technology} and Children’s Hospital and a lead author of the paper ].

The team chose silicon nanowires for electronic sensors because they are small, stable, can be safely implanted into living tissue and are more electrically sensitive than metal electrodes. The nanowires, which range in diameter from 30 to 80 nanometers (about 1,000 times smaller than a human hair), can detect voltages less than one-thousandth of a watt, which is the level of electricity that might be seen in a cell.

Here’s more about why the researchers want to integrate living tissue and electronics, from the Harvard University Aug. 26, 2012 news release on EurekAlert,

“The current methods we have for monitoring or interacting with living systems are limited,” said Lieber [Charles M. Lieber, the Mark Hyman, Jr. Professor of Chemistry at Harvard and one of the study’s team leaders]. “We can use electrodes to measure activity in cells or tissue, but that damages them. With this technology, for the first time, we can work at the same scale as the unit of biological system without interrupting it. Ultimately, this is about merging tissue with electronics in a way that it becomes difficult to determine where the tissue ends and the electronics begin.”

The research addresses a concern that has long been associated with work on bioengineered tissue – how to create systems capable of sensing chemical or electrical changes in the tissue after it has been grown and implanted. The system might also represent a solution to researchers’ struggles in developing methods to directly stimulate engineered tissues and measure cellular reactions.

“In the body, the autonomic nervous system keeps track of pH, chemistry, oxygen and other factors, and triggers responses as needed,” Kohane [Daniel Kohane, a Harvard Medical School professor in the Department of Anesthesia at Children’s Hospital Boston and a team leader] explained. “We need to be able to mimic the kind of intrinsic feedback loops the body has evolved in order to maintain fine control at the cellular and tissue level.”

Here’s a citation and a link to the paper (which is behind a paywall),

Macroporous nanowire nanoelectronic scaffolds for synthetic tissues by Bozhi Tian, Jia Lin, Tal Dvir, Lihua Jin, Jonathan H. Tsui, Quan  Qing, Zhigang Suo, Robert Langer, Daniel S. Kohane, and Charles M. Lieber in Nature Materials (2012) doi:10.1038/nmat3404 Published onlin26 August 2012.

This is the image MIT included with its Aug 27, 2012 news release (which originated the news item on Nanowerk),

A 3-D reconstructed confocal fluorescence micrograph of a tissue scaffold.
Image: Charles M. Lieber and Daniel S. Kohane.

At this point they’re discussing therapeutic possibilities but I expect that ‘enhancement’ is also being considered although not mentioned for public consumption.