Tag Archives: Massachusetts Institute of Technology (MIT)

Detect lung cancer early by inhaling a nanosensor

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The technology described in a January 5, 2024 news item on Nanowerk has not been tried in human clinical trials but early pre-clinical trial testing offers promise,

Using a new technology developed at MIT, diagnosing lung cancer could become as easy as inhaling nanoparticle sensors and then taking a urine test that reveals whether a tumor is present.

Key Takeaways

*This non-invasive approach may serve as an alternative or supplement to traditional CT scans, particularly beneficial in areas with limited access to advanced medical equipment.

*The technology focuses on detecting cancer-linked proteins in the lungs, with results obtainable through a simple paper test strip.

*Designed for early-stage lung cancer detection, the method has shown promise in animal models and may soon advance to human clinical trials.

*This innovation holds potential for significantly improving lung cancer screening and early detection, especially in low-resource settings.

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A January 5, 2024 Massachusetts Institute of Technology (MIT) news release (also on EurkeAlert), which originated the news item, goes on to provide some technical details,

The new diagnostic is based on nanosensors that can be delivered by an inhaler or a nebulizer. If the sensors encounter cancer-linked proteins in the lungs, they produce a signal that accumulates in the urine, where it can be detected with a simple paper test strip.

This approach could potentially replace or supplement the current gold standard for diagnosing lung cancer, low-dose computed tomography (CT). It could have an especially significant impact in low- and middle-income countries that don’t have widespread availability of CT scanners, the researchers say.

“Around the world, cancer is going to become more and more prevalent in low- and middle-income countries. The epidemiology of lung cancer globally is that it’s driven by pollution and smoking, so we know that those are settings where accessibility to this kind of technology could have a big impact,” says Sangeeta Bhatia, the John and Dorothy Wilson Professor of Health Sciences and Technology and of Electrical Engineering and Computer Science at MIT, and a member of MIT’s Koch Institute for Integrative Cancer Research and the Institute for Medical Engineering and Science.

Bhatia is the senior author of the paper, which appears today [January 5, 2024] in Science Advances. Qian Zhong, an MIT research scientist, and Edward Tan, a former MIT postdoc, are the lead authors of the study.

Inhalable particles

To help diagnose lung cancer as early as possible, the U.S. Preventive Services Task Force recommends that heavy smokers over the age of 50 undergo annual CT scans. However, not everyone in this target group receives these scans, and the high false-positive rate of the scans can lead to unnecessary, invasive tests.

Bhatia has spent the last decade developing nanosensors for use in diagnosing cancer and other diseases, and in this study, she and her colleagues explored the possibility of using them as a more accessible alternative to CT screening for lung cancer.

These sensors consist of polymer nanoparticles coated with a reporter, such as a DNA barcode, that is cleaved from the particle when the sensor encounters enzymes called proteases, which are often overactive in tumors. Those reporters eventually accumulate in the urine and are excreted from the body.

Previous versions of the sensors, which targeted other cancer sites such as the liver and ovaries, were designed to be given intravenously. For lung cancer diagnosis, the researchers wanted to create a version that could be inhaled, which could make it easier to deploy in lower resource settings.

“When we developed this technology, our goal was to provide a method that can detect cancer with high specificity and sensitivity, and also lower the threshold for accessibility, so that hopefully we can improve the resource disparity and inequity in early detection of lung cancer,” Zhong says.

To achieve that, the researchers created two formulations of their particles: a solution that can be aerosolized and delivered with a nebulizer, and a dry powder that can be delivered using an inhaler.

Once the particles reach the lungs, they are absorbed into the tissue, where they encounter any proteases that may be present. Human cells can express hundreds of different proteases, and some of them are overactive in tumors, where they help cancer cells to escape their original locations by cutting through proteins of the extracellular matrix. These cancerous proteases cleave DNA barcodes from the sensors, allowing the barcodes to circulate in the bloodstream until they are excreted in the urine.

In the earlier versions of this technology, the researchers used mass spectrometry to analyze the urine sample and detect DNA barcodes. However, mass spectrometry requires equipment that might not be available in low-resource areas, so for this version, the researchers created a lateral flow assay, which allows the barcodes to be detected using a paper test strip.

The researchers designed the strip to detect up to four different DNA barcodes, each of which indicates the presence of a different protease. No pre-treatment or processing of the urine sample is required, and the results can be read about 20 minutes after the sample is obtained.

“We were really pushing this assay to be point-of-care available in a low-resource setting, so the idea was to not do any sample processing, not do any amplification, just to be able to put the sample right on the paper and read it out in 20 minutes,” Bhatia says.

Accurate diagnosis

The researchers tested their diagnostic system in mice that are genetically engineered to develop lung tumors similar to those seen in humans. The sensors were administered 7.5 weeks after the tumors started to form, a time point that would likely correlate with stage 1 or 2 cancer in humans.

In their first set of experiments in the mice, the researchers measured the levels of 20 different sensors designed to detect different proteases. Using a machine learning algorithm to analyze those results, the researchers identified a combination of just four sensors that was predicted to give accurate diagnostic results. They then tested that combination in the mouse model and found that it could accurately detect early-stage lung tumors.

For use in humans, it’s possible that more sensors might be needed to make an accurate diagnosis, but that could be achieved by using multiple paper strips, each of which detects four different DNA barcodes, the researchers say.

The researchers now plan to analyze human biopsy samples to see if the sensor panels they are using would also work to detect human cancers. In the longer term, they hope to perform clinical trials in human patients. A company called Sunbird Bio has already run phase 1 trials on a similar sensor developed by Bhatia’s lab, for use in diagnosing liver cancer and a form of hepatitis known as nonalcoholic steatohepatitis (NASH).

In parts of the world where there is limited access to CT scanning, this technology could offer a dramatic improvement in lung cancer screening, especially since the results can be obtained during a single visit.

“The idea would be you come in and then you get an answer about whether you need a follow-up test or not, and we could get patients who have early lesions into the system so that they could get curative surgery or lifesaving medicines,” Bhatia says.

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

Inhalable point-of-care urinary diagnostic platform by Qian Zhong, Edward K. W. Tan, Carmen Martin-Alonso, Tiziana Parisi, Liangliang Hao, Jesse D. Kirkpatrick, Tarek Fadel, Heather E. Fleming, Tyler Jacks, and Sangeeta N. Bhatia. Science Advances 5 Jan 2024 Vol 10, Issue 1 DOI: 10.1126/sciadv.adj9591

This paper is open access.

Sunbird Bio (the company mentioned in the news release) can be found here.

Brainlike transistor and human intelligence

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This brainlike transistor (not a memristor) is important because it functions at room temperature as opposed to others, which require cryogenic temperatures.

A December 20, 2023 Northwestern University news release (received via email; also on EurekAlert) fills in the details,

  • Researchers develop transistor that simultaneously processes and stores information like the human brain
  • Transistor goes beyond categorization tasks to perform associative learning
  • Transistor identified similar patterns, even when given imperfect input
  • Previous similar devices could only operate at cryogenic temperatures; new transistor operates at room temperature, making it more practical

EVANSTON, Ill. — Taking inspiration from the human brain, researchers have developed a new synaptic transistor capable of higher-level thinking.

Designed by researchers at Northwestern University, Boston College and the Massachusetts Institute of Technology (MIT), the device simultaneously processes and stores information just like the human brain. In new experiments, the researchers demonstrated that the transistor goes beyond simple machine-learning tasks to categorize data and is capable of performing associative learning.

Although previous studies have leveraged similar strategies to develop brain-like computing devices, those transistors cannot function outside cryogenic temperatures. The new device, by contrast, is stable at room temperatures. It also operates at fast speeds, consumes very little energy and retains stored information even when power is removed, making it ideal for real-world applications.

The study was published today (Dec. 20 [2023]) in the journal Nature.

“The brain has a fundamentally different architecture than a digital computer,” said Northwestern’s Mark C. Hersam, who co-led the research. “In a digital computer, data move back and forth between a microprocessor and memory, which consumes a lot of energy and creates a bottleneck when attempting to perform multiple tasks at the same time. On the other hand, in the brain, memory and information processing are co-located and fully integrated, resulting in orders of magnitude higher energy efficiency. Our synaptic transistor similarly achieves concurrent memory and information processing functionality to more faithfully mimic the brain.”

Hersam is the Walter P. Murphy Professor of Materials Science and Engineering at Northwestern’s McCormick School of Engineering. He also is chair of the department of materials science and engineering, director of the Materials Research Science and Engineering Center and member of the International Institute for Nanotechnology. Hersam co-led the research with Qiong Ma of Boston College and Pablo Jarillo-Herrero of MIT.

Recent advances in artificial intelligence (AI) have motivated researchers to develop computers that operate more like the human brain. Conventional, digital computing systems have separate processing and storage units, causing data-intensive tasks to devour large amounts of energy. With smart devices continuously collecting vast quantities of data, researchers are scrambling to uncover new ways to process it all without consuming an increasing amount of power. Currently, the memory resistor, or “memristor,” is the most well-developed technology that can perform combined processing and memory function. But memristors still suffer from energy costly switching.

“For several decades, the paradigm in electronics has been to build everything out of transistors and use the same silicon architecture,” Hersam said. “Significant progress has been made by simply packing more and more transistors into integrated circuits. You cannot deny the success of that strategy, but it comes at the cost of high power consumption, especially in the current era of big data where digital computing is on track to overwhelm the grid. We have to rethink computing hardware, especially for AI and machine-learning tasks.”

To rethink this paradigm, Hersam and his team explored new advances in the physics of moiré patterns, a type of geometrical design that arises when two patterns are layered on top of one another. When two-dimensional materials are stacked, new properties emerge that do not exist in one layer alone. And when those layers are twisted to form a moiré pattern, unprecedented tunability of electronic properties becomes possible.

For the new device, the researchers combined two different types of atomically thin materials: bilayer graphene and hexagonal boron nitride. When stacked and purposefully twisted, the materials formed a moiré pattern. By rotating one layer relative to the other, the researchers could achieve different electronic properties in each graphene layer even though they are separated by only atomic-scale dimensions. With the right choice of twist, researchers harnessed moiré physics for neuromorphic functionality at room temperature.

“With twist as a new design parameter, the number of permutations is vast,” Hersam said. “Graphene and hexagonal boron nitride are very similar structurally but just different enough that you get exceptionally strong moiré effects.”

To test the transistor, Hersam and his team trained it to recognize similar — but not identical — patterns. Just earlier this month, Hersam introduced a new nanoelectronic device capable of analyzing and categorizing data in an energy-efficient manner, but his new synaptic transistor takes machine learning and AI one leap further.

“If AI is meant to mimic human thought, one of the lowest-level tasks would be to classify data, which is simply sorting into bins,” Hersam said. “Our goal is to advance AI technology in the direction of higher-level thinking. Real-world conditions are often more complicated than current AI algorithms can handle, so we tested our new devices under more complicated conditions to verify their advanced capabilities.”

First the researchers showed the device one pattern: 000 (three zeros in a row). Then, they asked the AI to identify similar patterns, such as 111 or 101. “If we trained it to detect 000 and then gave it 111 and 101, it knows 111 is more similar to 000 than 101,” Hersam explained. “000 and 111 are not exactly the same, but both are three digits in a row. Recognizing that similarity is a higher-level form of cognition known as associative learning.”

In experiments, the new synaptic transistor successfully recognized similar patterns, displaying its associative memory. Even when the researchers threw curveballs — like giving it incomplete patterns — it still successfully demonstrated associative learning.

“Current AI can be easy to confuse, which can cause major problems in certain contexts,” Hersam said. “Imagine if you are using a self-driving vehicle, and the weather conditions deteriorate. The vehicle might not be able to interpret the more complicated sensor data as well as a human driver could. But even when we gave our transistor imperfect input, it could still identify the correct response.”

The study, “Moiré synaptic transistor with room-temperature neuromorphic functionality,” was primarily supported by the National Science Foundation.

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

Moiré synaptic transistor with room-temperature neuromorphic functionality by Xiaodong Yan, Zhiren Zheng, Vinod K. Sangwan, Justin H. Qian, Xueqiao Wang, Stephanie E. Liu, Kenji Watanabe, Takashi Taniguchi, Su-Yang Xu, Pablo Jarillo-Herrero, Qiong Ma & Mark C. Hersam. Nature volume 624, pages 551–556 (2023) DOI: https://doi.org/10.1038/s41586-023-06791-1 Published online: 20 December 2023 Issue Date: 21 December 2023

This paper is behind a paywall.

Health/science journalists/editors: deadline is March 22, 2024 for media boot camp in Boston, Massachusetts

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A February 14, 2023 Broad Institute news release presents an exciting opportunity for health/science journalists and editors,

The Broad Institute of MIT [Massachusetts Institute of Technology] and Harvard is now accepting applications for its 2024 Media Boot Camp.

This annual program connects health/science journalists and editors with faculty from the Broad Institute, Massachusetts Institute of Technology, Harvard University, and Harvard’s teaching hospitals for a two-day event exploring the latest advances in genomics and biomedicine. Journalists will explore possible future storylines, gain fundamental background knowledge, and build relationships with researchers. The program format includes presentations, discussions, and lab tours.

The 2024 Media Boot Camp will take place in person at the Broad Institute in Cambridge, MA on Thursday, May 16 and Friday, May 17 (with an evening welcome reception on Wednesday, May 15).

APPLICATION DEADLINE IS FRIDAY, MARCH 22 (5:00 PM US EASTERN TIME).

2024 Boot Camp topics include:

  • Gene editing
  • New approaches for therapeutic delivery  
  • Cancer biology, drug development
  • Data sciences, machine learning
  • Neurobiology (stem cell models of psychiatric disorders)
  • Antibiotic resistance, microbial biology
  • Medical and population genetics, genomic medicine

Current speakers include: Mimi Bandopadhayay, Clare Bernard,Roby Bhattacharyya, Todd Golub, Laura Kiessling, Eric Lander,David Liu, Ralda Nehme,Heidi Rehm, William Sellers, Feng Zhang, with potentially more to come.

This Media Boot Camp is an educational offering. All presentations are on-background.

Hotel accommodations and meals during the program will be provided by the Broad Institute. Attendees must cover travel costs to and from Boston.

Application Process

By Friday, March 22 [2024] (5:00 PM US Eastern time [2 pm PT]), please send at least one paragraph describing your interest in the program and how you hope it will benefit your reporting, as well as three recent news clips, to David Cameron, Director of External Communications, dcameron@broadinstitute.org

Please contact David at dcameron@broadinstitute.org, or 617-714-7184 with any questions.

I couldn’t find details about eligibility, that said, I wish you good luck with your ‘paragraph and three recent clips’ submission.

When the rocks sing “I got rhythm”

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George Gershwin, along with his brother Ira, wrote jazz standards such as “I got rhythm” in 1930 and, before that, “Fascinating rhythm” in 1924 and both seem à propos in relation to this October 9, 2023 news item on phys.org,

f you could sink through the Earth’s crust, you might hear, with a carefully tuned ear, a cacophany of booms and crackles along the way. The fissures, pores, and defects running through rocks are like strings that resonate when pressed and stressed. And as a team of MIT geologists has found, the rhythm and pace of these sounds can tell you something about the depth and strength of the rocks around you.

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The fissures and pores running through rocks, from the Earth’s crust to the liquid mantle, are like channels and cavities through which sound can resonate. Credit: iStock [downloaded from https://news.mit.edu/2023/boom-crackle-pop-earth-crust-sounds-1009]

An October 9, 2023 Massachusetts Institute of Technology news release (also on EurekAlert) by Jennifer Chu, which originated the news item, (word play alert) delves down into the material, Note: A link has been removed,

“If you were listening to the rocks, they would be singing at higher and higher pitches, the deeper you go,” says MIT geologist Matěj Peč. 

Peč and his colleagues are listening to rocks, to see whether any acoustic patterns, or “fingerprints” emerge when subjected to various pressures. In lab studies, they have now shown that samples of marble, when subjected to low pressures, emit low-pitched “booms,” while at higher pressures, the rocks generate an ‘avalanche’ of higher-pitched crackles. 

Peč says these acoustic patterns in rocks can help scientists estimate the types of cracks, fissures, and other defects that the Earth’s crust experiences with depth, which they can then use to identify unstable regions below the surface, where there is potential for earthquakes or eruptions. The team’s results, published in the Proceedings of the National Academy of Sciences, could also help inform surveyors’ efforts to drill for renewable, geothermal energy. 

“If we want to tap these very hot geothermal sources, we will have to learn how to drill into rocks that are in this mixed-mode condition, where they are not purely brittle, but also flow a bit,” says Peč, who is an assistant professor in MIT’s Department of Earth, Atmospheric and Planetary Sciences (EAPS). “But overall, this is fundamental science that can help us understand where the lithosphere is strongest.” 

Peč’s collaborators at MIT are lead author and research scientist Hoagy O. Ghaffari, technical associate Ulrich Mok, graduate student Hilary Chang, and professor emeritus of geophysics Brian Evans. Tushar Mittal, co-author and former EAPS postdoc, is now an assistant professor at Penn State University.

Fracture and flow

The Earth’s crust is often compared to the skin of an apple. At its thickest, the crust can be 70 kilometers deep — a tiny fraction of the globe’s total, 12,700-kilometer diameter. And yet, the rocks that make up the planet’s thin peel vary greatly in their strength and stability. Geologists infer that rocks near the surface are brittle and fracture easily, compared to rocks at greater depths, where immense pressures, and heat from the core, can make rocks flow. 

The fact that rocks are brittle at the surface and more ductile at depth implies there must be an in-between — a phase in which rocks transition from one to the other, and may have properties of both, able to fracture like granite, and flow like honey. This “brittle-to-ductile transition” is not well understood, though geologists believe it may be where rocks are at their strongest within the crust. 

“This transition state of partly flowing, partly fracturing, is really important, because that’s where we think the peak of the lithosphere’s strength is and where the largest earthquakes nucleate,” Peč says. “But we don’t have a good handle on this type of mixed-mode behavior.”

He and his colleagues are studying how the strength and stability of rocks — whether brittle, ductile, or somewhere in between — varies, based on a rock’s microscopic defects. The size, density, and distribution of defects such as microscopic cracks, fissures, and pores can shape how brittle or ductile a rock can be. 

But measuring the microscopic defects in rocks, under conditions that simulate the Earth’s various pressures and depths, is no trivial task. There is, for instance, no visual-imaging technique that allows scientists to see inside rocks to map their microscopic imperfections. So the team turned to ultrasound, and the idea that, any sound wave traveling through a rock should bounce, vibrate, and reflect off any microscopic cracks and crevices, in specific ways that should reveal something about the pattern of those defects. 

All these defects will also generate their own sounds when they move under stress and therefore both actively sounding through the rock as well as listening to it should give them a great deal of information. They found that the idea should work with ultrasound waves, at megahertz frequencies.

“This kind of ultrasound method is analogous to what seismologists do in nature, but at much higher frequencies,” Peč explains. “This helps us to understand the physics that occur at microscopic scales, during the deformation of these rocks.” 

A rock in a hard place

In their experiments, the team tested cylinders of Carrara marble. 

“It’s the same material as what Michaelangelo’s David is made from,” Peč notes. “It’s a very well-characterized material, and we know exactly what it should be doing.”

The team placed each marble cylinder in a a vice-like apparatus made from pistons of aluminum, zirconium, and steel, which together can generate extreme stresses. They placed the vice in a pressurized chamber, then subjected each cylinder to pressures similar to what rocks experience throughout the Earth’s crust.  

As they slowly crushed each rock, the team sent pulses of ultrasound through the top of the sample, and recorded the acoustic pattern that exited through the bottom. When the sensors were not pulsing, they were listening to any naturally occurring acoustic emissions.

They found that at the lower end of the pressure range, where rocks are brittle, the marble indeed formed sudden fractures in response, and the sound waves resembled large, low-frequency booms. At the highest pressures, where rocks are more ductile, the acoustic waves resembled a higher-pitched crackling. The team believes this crackling was produced by microscopic defects called dislocations that then spread and flow like an avalanche. 

“For the first time, we have recorded the ‘noises’ that rocks make when they are deformed across this brittle-to-ductile transition, and we link these noises to the individual microscopic defects that cause them,” Peč says. “We found that these defects massively change their size and propagation velocity as they cross this transition. It’s more complicated than people had thought.”

The team’s characterizations of rocks and their defects at various pressures can help scientists estimate how the Earth’s crust will behave at various depths, such as how rocks might fracture in an earthquake, or flow in an eruption.    

“When rocks are partly fracturing and partly flowing, how does that feed back into the earthquake cycle? And how does that affect the movement of magma through a network of rocks?” Peč says. “Those are larger scale questions that can be tackled with research like this.”

This research was supported, in part, by the National Science Foundation.

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

Microscopic defect dynamics during a brittle-to-ductile transition by Hoagy O’Ghaffari, Matěj Peč, Tushar Mittal, Ulrich Mok, Hilary Chang, and Brian Evans. Proceedings of the National Academy of Sciences 120 (42) e2305667120 DOI: https://doi.org/10.1073/pnas.2305667120 October 9, 2023

This paper is behind a paywall.

Silk micro or nanoparticles for tracking seeds

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I hadn’t heard of counterfeit seeds before but this March 22, 2023 news item on phys.org describes the problem and announces an approach to prevention,

Average crop yields in Africa are consistently far below expected, and one significant reason is the prevalence of counterfeit seeds whose germination rates are far lower than those of the genuine ones. The World Bank estimates that as much as half of all seeds sold in some African countries are fake, which could help to account for crop production that is far below potential.

There have been many attempts to prevent this counterfeiting through tracking labels, but none have proved effective; among other issues, such labels have been vulnerable to hacking because of the deterministic nature of their encoding systems. But now, a team of MIT [Massachusetts Institute of Technology] researchers has come up with a kind of tiny, biodegradable tag that can be applied directly to the seeds themselves, and that provides a unique randomly created code that cannot be duplicated.

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I found this picture helped me to understand how ‘tracking’ these seeds could be useful,

As a way to reduce seed counterfeiting, MIT researchers developed a silk-based tag that, when applied to seeds, provides a unique code that cannot be duplicated. Credits: Credit: Photograph courtesy of the researchers. Edited by Jose-Luis Olivares, MIT

A March 22, 2023 Massachusetts Institute of Technology (MIT) news release by David Chandler (also on EurekAlert), which originated the news item, describes the work in more detail (Note: I’m glad to see David Chandler is getting bylines again even if it’s on the EurekAlert version only),

The new system, which uses minuscule dots of silk-based material, each containing a unique combination of different chemical signatures, is described today in the journal Science Advances in a paper by MIT’s dean of engineering Anantha Chandrakasan, professor of civil and environmental engineering Benedetto Marelli, postdoc Hui Sun, and graduate student Saurav Maji.

The problem of counterfeiting is an enormous one globally, the researchers point out, affecting everything from drugs to luxury goods, and many different systems have been developed to try to combat this. But there has been less attention to the problem in the area of agriculture, even though the consequences can be severe. In sub-Saharan Africa, for example, the World Bank estimates that counterfeit seeds are a significant factor in crop yields that average less than one-fifth of the potential for maize, and less than one-third for rice. 

Marelli explains that a key to the new system is creating a randomly-produced physical object whose exact composition is virtually impossible to duplicate. The labels they create “leverage randomness and uncertainty in the process of application, to generate unique signature features that can be read, and that cannot be replicated,” he says.

What they’re dealing with, Sun adds, “is the very old job of trying, basically, not to get your stuff stolen. And you can try as much as you can, but eventually somebody is always smart enough to figure out how to do it, so nothing is really unbreakable. But the idea is, it’s almost impossible, if not impossible, to replicate it, or it takes so much effort that it’s not worth it anymore.”

The idea of an “unclonable” code was originally developed as a way of protecting the authenticity of computer chips, explains Chandrakasan, who is the Vannevar Bush Professor of Electrical Engineering and Computer Science. “In integrated circuits, individual transistors have slightly different properties coined device variations,” he explains, “and you could then use that variability and combine that variability with higher-level circuits to create a unique ID for the device. And once you have that, then you can use that unique ID as a part of a security protocol. Something like transistor variability is hard to replicate from device to device, so that’s what gives it its uniqueness, versus storing a particular fixed ID.” The concept is based on what are known as physically unclonable functions, or PUFs.

The team decided to try to apply that PUF principle to the problem of fake seeds, and the use of silk proteins was a natural choice because the material is not only harmless to the environment but also classified by the Food and Drug Administration in the “generally recognized as safe” category, so it requires no special approval for use on food products.

“You could coat it on top of seeds,” Maji says, “and if you synthesize silk in a certain way, it will also have natural random variations. So that’s the idea, that every seed or every bag could have a unique signature.”

Developing effective secure system solutions have long been one of Chandrakasan’s specialties, while Marelli has spent many years developing systems for applying silk coatings to a variety of fruits, vegetables, and seeds, so their collaboration was a natural for developing such a silk-based coding system towards enhanced security. 

“The challenge was what type of form factor to give to silk,” Sun says, “so that it can be fabricated very easily.” They developed a simple drop-casting approach that produces tags that are less than one-tenth of an inch in diameter. The second challenge was to develop “a way where we can read the uniqueness, in also a very high throughput and easy way.”

For the unique silk-based codes, Marelli says, “eventually we found a way to add a color to these microparticles [emphasis mine] so that they assemble in random structures.” The resulting unique patterns can be read out not only by a spectrograph or a portable microscope, but even by an ordinary cellphone camera with a macro lens. This image can be processed locally to generate the PUF code and then sent to the cloud and compared with a secure database to ensure the authenticity of the product. “It’s random so that people cannot easily replicate it,” says Sun. “People cannot predict it without measuring it.”

And the number of possible permutations that could result from the way they mix four basic types of colored silk nanoparticles [emphasis mine] is astronomical. “We were able to show that with a minimal amount of silk, we were able to generate 128 random bits of security,” Maji says. “So this gives rise to 2 to the power 128 possible combinations, which is extremely difficult to crack given the computational capabilities of the state-of-the-art computing systems.”

Marelli says that “for us, it’s a good test bed in order to think out-of-the-box, and how we can have a path that somehow is more democratic.” In this case, that means “something that you can literally read with your phone, and you can fabricate by simply drop casting a solution, without using any advanced manufacturing technique, without going in a clean room.”

Some additional work will be needed to make this a practical commercial product, Chandrakasan says. “There will have to be a development for at-scale reading” via smartphones. “So. that’s clearly a future opportunity.” But the principle now shows a clear path to the day when “a farmer could at least, maybe not every seed, but could maybe take some random seeds in a particular batch and verify them,” he says.

I’ve looked at the paper (very quickly) and haven’t spotted any mention of silk nanoparticles. It’s all silk microparticles.

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

Integrating biopolymer design with physical unclonable functions for anticounterfeiting and product traceability in agriculture by Hui Sun, Saurav Maji, Anantha P. Chandrakasan, and Benedetto Marelli. Science Advances 22 Mar 2023 Vol 9, Issue 12 DOI: 10.1126/sciadv.adf1978

This paper is open access.

Sound waves for wearable patches that deliver drugs painlessly

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While watching this video I started wondering if they were testing their research on students but that’s not the case; these wearable patches were tested on porcine (pig) skin, which is quite similar to human skin, Note: They tested a B vitamin called niacinamide so, it’s highly unlikely the pigs suffered from it,

An April 20, 2023 news item on ScienceDaily announces the research into using ultrasonic waves for drug delivery,

The skin is an appealing route for drug delivery because it allows drugs to go directly to the site where they’re needed, which could be useful for wound healing, pain relief, or other medical and cosmetic applications. However, delivering drugs through the skin is difficult because the tough outer layer of the skin prevents most small molecules from passing through it.

In hopes of making it easier to deliver drugs through the skin, MIT [Massachusetts Institute of Technology] researchers have developed a wearable patch that applies painless ultrasonic waves to the skin, creating tiny channels that drugs can pass through. This approach could lend itself to delivery of treatments for a variety of skin conditions, and could also be adapted to deliver hormones, muscle relaxants, and other drugs, the researchers say.

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An April 20, 2023 Massachusetts Institute of Technology (MIT) news release (also on EurekAlert), which originated the news item, provides technical details about the research, Note: A link has been removed,

“The ease-of-use and high-repeatability offered by this system provides a game-changing alternative to patients and consumers suffering from skin conditions and premature skin aging,” says Canan Dagdeviren, an associate professor in MIT’s Media Lab and the senior author of the study. “Delivering drugs this way could offer less systemic toxicity and is more local, comfortable, and controllable.”

MIT research assistants Chia-Chen Yu and Aastha Shah are the lead authors of the paper, which appears in Advanced Materials, as part of the journal’s “Rising Stars” series, which showcases the outstanding work of researchers in the early stages of their independent careers. Other MIT authors include Research Assistant Colin Marcus and postdoc Md Osman Goni Nayeem. Nikta Amiri, Amit Kumar Bhayadia, and Amin Karami of the University of Buffalo are also authors of the paper.

A boost from sound waves

The researchers began this project as an exploration of alternative ways to deliver drugs. Most drugs are delivered orally or intravenously, but the skin is a route that could offer much more targeted drug delivery for certain applications.

“The main benefit with skin is that you bypass the whole gastrointestinal tract. With oral delivery, you have to deliver a much larger dose in order to account for the loss that you would have in the gastric system,” Shah says. “This is a much more targeted, focused modality of drug delivery.”

Ultrasound exposure has been shown to enhance the skin’s permeability to small-molecule drugs, but most of the existing techniques for performing this kind of drug delivery require bulky equipment. The MIT team wanted to come up with a way to perform this kind of transdermal drug delivery with a lightweight, wearable patch, which could make it easier to use for a variety of applications.

The device that they designed consists of a patch embedded with several disc-shaped piezoelectric transducers, which can convert electric currents into mechanical energy. Each disc is embedded in a polymeric cavity that contains the drug molecules dissolved in a liquid solution. When an electric current is applied to the piezoelectric elements, they generate pressure waves in the fluid, creating bubbles that burst against the skin. These bursting bubbles produce microjets of fluid that can penetrate through the skin’s tough outer layer, the stratum corneum.

“This works open the door to using vibrations to enhance drug delivery. There are several parameters that result in generation of different kinds of waveform patterns. Both mechanical and biological aspects of drug delivery can be improved by this new toolset,” Karami says.

The patch is made of PDMS, a silicone-based polymer that can adhere to the skin without tape. In this study, the researchers tested the device by delivering a B vitamin called niacinamide, an ingredient in many sunscreens and moisturizers.

In tests using pig skin, the researchers showed that when they delivered niacinamide using the ultrasound patch, the amount of drug that penetrated the skin was 26 times greater than the amount that could pass through the skin without ultrasonic assistance.

The researchers also compared the results from their new device to microneedling, a technique sometimes used for transdermal drug delivery, which involves puncturing the skin with miniature needles. The researchers found that their patch was able to deliver the same amount of niacinamide in 30 minutes that could be delivered with microneedles over a six-hour period.

Local delivery

With the current version of the device, drugs can penetrate a few millimeters into the skin, making this approach potentially useful for drugs that act locally within the skin. These could include niacinamide or vitamin C, which is used to treat age spots or other dark spots on the skin, or topical drugs used to heal burns.

With further modifications to increase the penetration depth, this technique could also be used for drugs that need to reach the bloodstream, such as caffeine, fentanyl, or lidocaine. Dagdeviren also envisions that this kind of patch could be useful for delivering hormones such as progesterone. In addition, the researchers are now exploring the possibility of implanting similar devices inside the body to deliver drugs to treat cancer or other diseases.

The researchers are also working on further optimizing the wearable patch, in hopes of testing it soon on human volunteers. They also plan to repeat the lab experiments they did in this study, with larger drug molecules.

“After we characterize the drug penetration profiles for much larger drugs, we would then see which candidates, like hormones or insulin, can be delivered using this technology, to provide a painless alternative for those who are currently bound to self-administer injections on a daily basis,” Shah says.

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

A Conformable Ultrasound Patch for Cavitation-Enhanced Transdermal Cosmeceutical Delivery by Chia-Chen Yu, Aastha Shah, Nikta Amiri, Colin Marcus, Md Osman Goni Nayeem, Amit Kumar Bhayadia, Amin Karami, Canan Dagdeviren. Advanced Materials Volume35, Issue 23 June 8, 2023 2300066 DOI: https://doi.org/10.1002/adma.202300066 First published online: 19 March 2023

This paper is open access.

Gene editing the lungs with nanoparticles

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The nanoparticles in question are lipid nanoparticles designed for delivery to the lungs and they are somewhat similar to the ones in some of the COVID-19 vaccines (mRNA vaccines). From a March 30, 2023 news item on Nanowerk,

Engineers at MIT [Massachusetts Institute of Technology] and the University of Massachusetts Medical School have designed a new type of nanoparticle that can be administered to the lungs, where it can deliver messenger RNA encoding useful proteins.

With further development, these particles could offer an inhalable treatment for cystic fibrosis and other diseases of the lung, the researchers say.

“This is the first demonstration of highly efficient delivery of RNA to the lungs in mice. We are hopeful that it can be used to treat or repair a range of genetic diseases, including cystic fibrosis,” says Daniel Anderson, a professor in MIT’s Department of Chemical Engineering and a member of MIT’s Koch Institute for Integrative Cancer Research and Institute for Medical Engineering and Science (IMES).

In a study of mice, Anderson and his colleagues used the particles to deliver mRNA encoding the machinery needed for CRISPR/Cas9 gene editing. That could open the door to designing therapeutic nanoparticles that can snip out and replace disease-causing genes.

Engineers at MIT and the University of Massachusetts Medical School have designed a new type of nanoparticle that can be administered to the lungs, where it can deliver messenger RNA encoding useful proteins. Credits: Image: iStock, edited by MIT News

A March 30, 2023 MIT news release, also on EurekAlert, which originated the news item, describes the research in more detail,

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Targeting the lungs

Messenger RNA holds great potential as a therapeutic for treating a variety of diseases caused by faulty genes. One obstacle to its deployment thus far has been difficulty in delivering it to the right part of the body, without off-target effects. Injected nanoparticles often accumulate in the liver, so several clinical trials evaluating potential mRNA treatments for diseases of the liver are now underway. RNA-based Covid-19 vaccines, which are injected directly into muscle tissue, have also proven effective. In many of those cases, mRNA is encapsulated in a lipid nanoparticle — a fatty sphere that protects mRNA from being broken down prematurely and helps it enter target cells. 

Several years ago, Anderson’s lab set out to design particles that would be better able to transfect the epithelial cells that make up most of the lining of the lungs. In 2019, his lab created nanoparticles that could deliver mRNA encoding a bioluminescent protein to lung cells. Those particles were made from polymers instead of lipids, which made them easier to aerosolize for inhalation into the lungs. However, more work is needed on those particles to increase their potency and maximize their usefulness. 

In their new study, the researchers set out to develop lipid nanoparticles that could target the lungs. The particles are made up of molecules that contain two parts: a positively charged headgroup and a long lipid tail. The positive charge of the headgroup helps the particles to interact with negatively charged mRNA, and it also help mRNA to escape from the cellular structures that engulf the particles once they enter cells. 

The lipid tail structure, meanwhile, helps the particles to pass through the cell membrane. The researchers came up with 10 different chemical structures for the lipid tails, along with 72 different headgroups. By screening different combinations of these structures in mice, the researchers were able to identify those that were most likely to reach the lungs. 

Efficient delivery

In further tests in mice, the researchers showed that they could use the particles to deliver mRNA encoding CRISPR/Cas9 components designed to cut out a stop signal that was genetically encoded into the animals’ lung cells. When that stop signal is removed, a gene for a fluorescent protein turns on. Measuring this fluorescent signal allows the researchers to determine what percentage of the cells successfully expressed the mRNA.

After one dose of mRNA, about 40 percent of lung epithelial cells were transfected, the researchers found. Two doses brought the level to more than 50 percent, and three doses up to 60 percent. The most important targets for treating lung disease are two types of epithelial cells called club cells and ciliated cells, and each of these was transfected at about 15 percent. 

“This means that the cells we were able to edit are really the cells of interest for lung disease,” Li says. “This lipid can enable us to deliver mRNA to the lung much more efficiently than any other delivery system that has been reported so far.”

The new particles also break down quickly, allowing them to be cleared from the lung within a few days and reducing the risk of inflammation. The particles could also be delivered multiple times to the same patient if repeat doses are needed. This gives them an advantage over another approach to delivering mRNA, which uses a modified version of harmless adenoviruses. Those viruses are very effective at delivering RNA but can’t be given repeatedly because they induce an immune response in the host.

To deliver the particles in this study, the researchers used a method called intratracheal instillation, which is often used as a way to model delivery of medication to the lungs. They are now working on making their nanoparticles more stable, so they could be aerosolized and inhaled using a nebulizer. 

The researchers also plan to test the particles to deliver mRNA that could correct the genetic mutation found in the gene that causes cystic fibrosis, in a mouse model of the disease. They also hope to develop treatments for other lung diseases, such as idiopathic pulmonary fibrosis, as well as mRNA vaccines that could be delivered directly to the lungs.

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

Combinatorial design of nanoparticles for pulmonary mRNA delivery and genome editing by Bowen Li, Rajith Singh Manan, Shun-Qing Liang, Akiva Gordon, Allen Jiang, Andrew Varley, Guangping Gao, Robert Langer, Wen Xue & Daniel Anderson. Nature Biotechnology (2023) DOI: https://doi.org/10.1038/s41587-023-01679-x Published 30 March 2023

This paper is behind a paywall.

Combining silicon with metal oxide memristors to create powerful, low-energy intensive chips enabling AI in portable devices

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In this one week, I’m publishing my first stories (see also June 13, 2023 posting “ChatGPT and a neuromorphic [brainlike] synapse“) where artificial intelligence (AI) software is combined with a memristor (hardware component) for brainlike (neuromorphic) computing.

Here’s more about some of the latest research from a March 30, 2023 news item on ScienceDaily,

Everyone is talking about the newest AI and the power of neural networks, forgetting that software is limited by the hardware on which it runs. But it is hardware, says USC [University of Southern California] Professor of Electrical and Computer Engineering Joshua Yang, that has become “the bottleneck.” Now, Yang’s new research with collaborators might change that. They believe that they have developed a new type of chip with the best memory of any chip thus far for edge AI (AI in portable devices).

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A March 29, 2023 University of Southern California (USC) news release (also on EurekAlert), which originated the news item, contextualizes the research and delves further into the topic of neuromorphic hardware,

For approximately the past 30 years, while the size of the neural networks needed for AI and data science applications doubled every 3.5 months, the hardware capability needed to process them doubled only every 3.5 years. According to Yang, hardware presents a more and more severe problem for which few have patience. 

Governments, industry, and academia are trying to address this hardware challenge worldwide. Some continue to work on hardware solutions with silicon chips, while others are experimenting with new types of materials and devices.  Yang’s work falls into the middle—focusing on exploiting and combining the advantages of the new materials and traditional silicon technology that could support heavy AI and data science computation. 

Their new paper in Nature focuses on the understanding of fundamental physics that leads to a drastic increase in memory capacity needed for AI hardware. The team led by Yang, with researchers from USC (including Han Wang’s group), MIT [Massachusetts Institute of Technology], and the University of Massachusetts, developed a protocol for devices to reduce “noise” and demonstrated the practicality of using this protocol in integrated chips. This demonstration was made at TetraMem, a startup company co-founded by Yang and his co-authors  (Miao Hu, Qiangfei Xia, and Glenn Ge), to commercialize AI acceleration technology. According to Yang, this new memory chip has the highest information density per device (11 bits) among all types of known memory technologies thus far. Such small but powerful devices could play a critical role in bringing incredible power to the devices in our pockets. The chips are not just for memory but also for the processor. And millions of them in a small chip, working in parallel to rapidly run your AI tasks, could only require a small battery to power it. 

The chips that Yang and his colleagues are creating combine silicon with metal oxide memristors in order to create powerful but low-energy intensive chips. The technique focuses on using the positions of atoms to represent information rather than the number of electrons (which is the current technique involved in computations on chips). The positions of the atoms offer a compact and stable way to store more information in an analog, instead of digital fashion. Moreover, the information can be processed where it is stored instead of being sent to one of the few dedicated ‘processors,’ eliminating the so-called ‘von Neumann bottleneck’ existing in current computing systems.  In this way, says Yang, computing for AI is “more energy efficient with a higher throughput.”

How it works: 

Yang explains that electrons which are manipulated in traditional chips, are “light.” And this lightness, makes them prone to moving around and being more volatile.  Instead of storing memory through electrons, Yang and collaborators are storing memory in full atoms. Here is why this memory matters. Normally, says Yang, when one turns off a computer, the information memory is gone—but if you need that memory to run a new computation and your computer needs the information all over again, you have lost both time and energy.  This new method, focusing on activating atoms rather than electrons, does not require battery power to maintain stored information. Similar scenarios happen in AI computations, where a stable memory capable of high information density is crucial. Yang imagines this new tech that may enable powerful AI capability in edge devices, such as Google Glasses, which he says previously suffered from a frequent recharging issue.

Further, by converting chips to rely on atoms as opposed to electrons, chips become smaller.  Yang adds that with this new method, there is more computing capacity at a smaller scale. And this method, he says, could offer “many more levels of memory to help increase information density.” 

To put it in context, right now, ChatGPT is running on a cloud. The new innovation, followed by some further development, could put the power of a mini version of ChatGPT in everyone’s personal device. It could make such high-powered tech more affordable and accessible for all sorts of applications. 

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

Thousands of conductance levels in memristors integrated on CMOS by Mingyi Rao, Hao Tang, Jiangbin Wu, Wenhao Song, Max Zhang, Wenbo Yin, Ye Zhuo, Fatemeh Kiani, Benjamin Chen, Xiangqi Jiang, Hefei Liu, Hung-Yu Chen, Rivu Midya, Fan Ye, Hao Jiang, Zhongrui Wang, Mingche Wu, Miao Hu, Han Wang, Qiangfei Xia, Ning Ge, Ju Li & J. Joshua Yang. Nature volume 615, pages 823–829 (2023) DOI: https://doi.org/10.1038/s41586-023-05759-5 Issue Date: 30 March 2023 Published: 29 March 2023

This paper is behind a paywall.