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Miniature eel-inspired bio-integrated devices capable of directly stimulating nerve cells for targeted drug therapies and speeding up wound healing

Researchers from the University of Oxford’s Department of Chemistry have made a significant step towards developing miniature powered bio-integrated devices that can interact with and stimulate cells, published today, Aug. 30, in an open-access paper in the journal Nature.

The researchers have developed a miniature power source capable of altering the activity of cultured human nerve cells. Inspired by how electric eels generate electricity, the device uses internal ion gradients to generate energy, rather than electrons.

Important therapeutic applications include delivering targeted drug therapies and speeding up wound healing.

How the technology works

The miniaturized soft-power source is produced by depositing a chain of five nanoliter-sized droplets of a conductive hydrogel (a 3D network of polymer chains containing a large quantity of absorbed water.

Each droplet has a different composition so that a salt concentration gradient is created across the chain. The droplets are separated from their neighbors by lipid bilayers, which provide mechanical support while preventing ions from flowing between the droplets.

The power source is turned on by cooling the structure to 4°C and changing the surrounding medium: this disrupts the lipid bilayers and causes the droplets to form a continuous hydrogel.

This allows the ions to move through the conductive hydrogel, from the high-salt droplets at the two ends to the low-salt droplet in the middle. By connecting the end droplets to electrodes, the energy released from the ion gradients is transformed into electricity, enabling the hydrogel structure to act as a power source for external components.

In the study, the research team demonstrated how living cells could be attached to one end of the device so that their activity could be directly regulated by the ionic current. The team attached the device to droplets containing human neural progenitor cells that had been stained with a fluorescent dye to indicate their activity. When the power source was turned on, time-lapse recording demonstrated waves of intercellular calcium signaling* in the neurons, induced by the local ionic current.

“The miniaturized soft power source represents a breakthrough in bio-integrated devices, Dr. Yujia Zhang (Department of Chemistry, University of Oxford), the lead researcher for the study, said. By harnessing ion gradients, we have developed a miniature, biocompatible system for regulating cells and tissues on the microscale, which opens up a wide range of potential applications in biology and medicine.”

Next-generation wearable devices, bio-hybrid interfaces, implants, synthetic tissues, and microrobots

According to the researchers, the device’s modular design would allow multiple units to be combined to increase the voltage and/or current generated. This could open the door to powering next-generation wearable devices, bio-hybrid interfaces, implants, synthetic tissues, and microrobots.

By combining 20 five-droplet units in series, they were able to illuminate a light-emitting diode, which requires about 2 Volts. They envisage that automating the production of the devices by using a droplet printer, for instance, could produce droplet networks composed of thousands of power units.

“This work addresses the important question of how stimulation produced by soft, biocompatible devices can be coupled with living cells. The potential impact on devices, including bio-hybrid interfaces, implants, and microrobots is substantial,” said Professor Hagan Bayley, University of Oxford.

* Calcium signaling is a key mechanism through which neurons communicate to one another to coordinate biological activities such as neurotransmitter release, neuronal firing, synaptic plasticity, and gene transcription.

Citation: Zhang, Y., Riexinger, J., Yang, X., Mikhailova, E., Jin, Y., Zhou, L., & Bayley, H. (2023). A microscale soft ionic power source modulates neuronal network activity. Nature, 620(7976), 1001-1006. https://doi.org/10.1038/s41586-023-06295-y

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Yes, metal really can heal itself. Seriously. (An update)

In a recent experiment in July at Sandia National Laboratories, a microscopic crack grew in a very small piece of platinum when placed under repetitive stretching. The experiment, designed to study fatigue crack growth, continued as predicted for a while, before something unexpected happened.

The crack apparently stopped growing. Instead, it began to get shorter, effectively “healing” itself, researchers at Sandia National Laboratories claimed. We (Mindplex) took their word for it. We published a story on their finding, mainly because it was reported in the journal Nature.

Dr. Michael Demkowicz, a professor in Texas A&M University’s materials science and engineering department and coauthor of the recent study, explained that nanocrystalline metals make studying self-healing easier because their small grain size allows for more microstructural features that even small cracks can interact with.

Spacefaring technology

He now suggests that self-healing could be possible in conventional metals with larger grain sizes, but future investigations will be needed.

His studies (at Sandia National Laboratories and previously at MIT 10 years ago) found that one such feature, grain boundaries, can affect crack healing depending on the direction of boundary migration relative to the crack. Demkowicz explained that these features are common in many metals and alloys and can be manipulated.

But one condition common to both the 2013 theory and the recent experiment: both were conducted in vacuum environments, devoid of foreign matter, explain the researchers. Such outside matter could interfere with crack surfaces’ ability to bond, or cold-weld, back together.

Even with this limitation, applications could still be possible for spacefaring technology or internal cracks that are not exposed to outside air.

Citation: Barr, C. M., Duong, T., Bufford, D. C., Milne, Z., Molkeri, A., Heckman, N. M., Adams, D. P., Srivastava, A., Hattar, K., Demkowicz, M. J., & Boyce, B. L. (2023). Autonomous healing of fatigue cracks via cold welding. Nature, 1-5. https://doi.org/10.1038/s41586-023-06223-0

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Ultra-thin battery charged by saline solution could power smart augmented-reality contact lenses

Imagine lenses that flash data on our corneas, keep an eye on our health, or flag diseases like glaucoma or diabetes

A new flexible battery as thin as a human eye’s cornea could power future smart-contact lenses, which in the future will be capable of displaying visible information on a eye’s cornea. It could be used to access augmented-reality devices, such as the Apple Vision Pro, for example.

Developed by researchers at Nanyang Technological University (NTU) in Singapore, the battery can be recharged simply by immersing it in saline solution. (Existing rechargeable batteries rely on wires or induction coils that contain metal so they are uncomfortable and present risks to the human eye.)

How they work

The new battery, made of biocompatible materials, does not contain wires or toxic heavy metals, such as those in lithium-ion batteries or wireless charging systems.

It has a glucose-based coating that reacts with the sodium and chloride ions in the saline solution surrounding it (water contained in the battery serves as the “wire” or “circuitry” for electricity to be generated).

Powered by tears

“This research began with a simple question: could contact lens batteries be recharged with our tears?” said Associate Professor Lee Seok Woo, from NTU’s School of Electrical and Electronic Engineering (EEE), who led the study. “Previous techniques for lens batteries were not perfect as one side of the battery electrode was charged and the other was not. The battery could be powered by human tears because they contain sodium and potassium ions, at a low concentration.

Testing the current battery with a simulated tear solution, the researchers showed that the battery’s life would be extended one additional hour for every 12-hour wearing cycle it is used. The battery can even be charged conventionally by an external power supply.

Takes just glucose and water to generate electricity

“Our approach can charge both electrodes of a battery through a unique combination of enzymatic reaction and self-reduction reaction. It also relies on just glucose and water to generate electricity, both of which are safe to humans and would be less harmful to the environment when disposed, compared to conventional batteries. The battery, which is about 0.5 millimetrers-thin, generates electrical power by reacting with the constant tears that create a thin film over our eyeballs.”

The NTU team will be conducting further research to improve the amount of electrical current their battery can discharge. They will also be working with several contact lenses companies to implement their technology.

Citation: Yun, J., Li, Z., Miao, X., Li, X., Lee, J. Y., Zhao, W., & Lee, S. W. (2023). Jeonghun Yun et al.  A tear-based battery charged by biofuel for smart contact lenses, Nano Energy, Jun 2023. DOI 1016/j.nanoen.2023.108344 (open-access)

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Meta has created an AI model, ‘SeamlessM4T,’ that can translate and transcribe close to 100 languages across text and speech

The model is “the first all-in-one multilingual multimodal AI translation and transcription model,” Meta claims.

“It can perform speech-to-text, speech-to-speech, text-to-speech, and text-to-text translations for up to 100 languages, depending on the task … without having to first convert to text behind the scenes, among other. We’re developing AI to eliminate language barriers in the physical world and in the metaverse.”

“In keeping with our approach to open science, we’re publicly releasing SeamlessM4T under a research license to allow researchers and developers to build on this work. We’re also releasing the metadata of SeamlessAlign, the biggest open multimodal translation dataset to date, totaling 270,000 hours of mined speech and text alignments.”

Competition

“Beyond the wealth of commercial services and open source models already available from Amazon, Microsoft, OpenAI and a number of startups, Google is creating what it calls the Universal Speech Model, a part of the tech giant’s larger effort to build a model that can understand the world’s 1,000 most-spoken languages,” says TechCrunch.

“Tech Mozilla meanwhile spearheaded Common Voice, one of the largest multi-language collections of voices for training automatic speech recognition algorithms. But SeamlessM4T is among the more ambitious efforts to date to combine translation and transcription capabilities into a single model.

In developing it, Meta says that it scraped publicly available text (on the order of ‘tens of billions’ of sentences) and speech (4 million hours) from the web.”

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Machine-learning system based on light could yield more powerful, efficient large language models

An MIT-led team has developed a system based on light that could lead to machine-learning programs several orders of magnitude more powerful than the one behind ChatGPT, and that uses several orders of magnitude less energy than state-of-the-art supercomputers, according to Elizabeth A. Thomson at MIT’s Materials Research Laboratory.

The team reports a greater than 100-fold improvement in energy efficiency and a 25-fold improvement in compute density (a measure of the power of a system) over the state-of-the-art supercomputers behind the machine-learning models of today. 

Computations based on light

In the July 17 issue of Nature Photonics, the researchers report the first experimental demonstration of the new system, which performs its computations based on the movement of light, rather than electrons, using hundreds of micron-scale lasers.

In the paper, the team also cites “substantially several more orders of magnitude for future improvement.” As a result, cell phones and other small devices could become capable of running programs that can currently only be computed at large data centers.

In addition, the components of the system can be created using fabrication processes already in use today, so “we expect that it could be scaled for commercial use in a few years,” says Zaijun Chen, first author, an assistant professor at the University of Southern California. “For example, the laser arrays involved are widely used in cell-phone face ID and data communication.”

Citation: Chen, Z., Sludds, A., Davis, R., Christen, I., Bernstein, L., Ateshian, L., Heuser, T., Heermeier, N., Lott, J. A., Reitzenstein, S., Hamerly, R., & Englund, D. (2023). Deep learning with coherent VCSEL neural networks. Nature Photonics, 17(8), 723-730. https://doi.org/10.1038/s41566-023-01233-w

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Mice on a time-restricted feeding schedule had better memory and less accumulation of amyloid proteins in the brain compared to controls

Circadian modulation by time-restricted feeding rescues brain pathology and improves memory in mouse models of Alzheimer’s disease

One of the hallmarks of Alzheimer’s disease is disruption to the body’s circadian rhythm (the daily internal biological clock that regulates many of our physiological processes). Nearly 80% of people with Alzheimer’s experience these issues, including difficulty sleeping and worsening cognitive function at night.

Surprisingly, there are no existing treatments for Alzheimer’s that target this aspect of the disease.

Improvements

Now, in a new study, published August 21, 2023 in the journal Cell Metabolism, researchers at the University of California San Diego School of Medicine used time-restricted feeding of mice within a six-hour window each day (for humans, this would translate to about 14 hours each day).

The mice showed improvements in memory and reduced accumulation of amyloid proteins in the brain, compared to control mice, who were provided food at all hours.

Mice fed on the time-restricted schedule had better memory, were less hyperactive at night, followed a more regular sleep schedule and experienced fewer disruptions during sleep.

The test mice also performed better on cognitive assessments than control mice, demonstrating that the time-restricted feeding schedule was able to help mitigate the behavioral symptoms of Alzheimer’s disease.

The researchers also observed improvements in the mice on a molecular level. In mice fed on a restricted schedule, the researchers found that multiple genes associated with Alzheimer’s and neuroinflammation were expressed differently.

They also found that the feeding schedule helped reduce the amount of amyloid protein that accumulated in the brain. Amyloid deposits are one of the most well-known features of Alzheimer’s disease.

Circadian disruptions: cause of neurodegeneration?

“For many years, we assumed that the circadian disruptions seen in people with Alzheimer’s are a result of neurodegeneration, but we’re now learning it may be the other way around — circadian disruption may be one of the main drivers of Alzheimer’s pathology,” said senior study author Paula Desplats, PhD, professor in the Department of Neurosciences at UC San Diego School of Medicine.

“This makes circadian disruptions a promising target for new Alzheimer’s treatments, and our findings provide the proof-of-concept for an easy and accessible way to correct these disruptions.”

Biggest health challenge

Alzheimer’s disease affects more than 6 million Americans, and it is considered by many to be the biggest forthcoming health challenge in the United States.

People with Alzheimer’s experience a variety of disruptions to their circadian rhythms, including changes to their sleep/wake cycle, increased cognitive impairment and confusion in the evenings, and difficulty falling and staying asleep.

“Circadian disruptions in Alzheimer’s are the leading cause of nursing home placement,” said Desplats. “Anything we can do to help patients restore their circadian rhythm will make a huge difference in how we manage Alzheimer’s in the clinic and how caregivers help patients manage the disease at home.”

Because the time-restricted feeding schedule was able to substantially change the course of Alzheimer’s in the mice, the researchers are optimistic that the findings could be easily translatable to the clinic, especially since the new treatment approach relies on a lifestyle change rather than a drug.

“Time-restricted feeding is a strategy that people can easily and immediately integrate into their lives,” said Desplats. “If we can reproduce our results in humans, this approach could be a simple way to dramatically improve the lives of people living with Alzheimer’s and those who care for them.”

This study was funded, in part, by the National Institute on Aging (grants AG061831 and 5T32AG066596-02) and the National Insititute of Neurological Disorders and Stroke (grant P30NS047101).

Citation: Whittaker, D. S., Akhmetova, L., Carlin, D., Romero, H., Welsh, D. K., Colwell, C. S., & Desplats, P. (2023). Circadian modulation by time-restricted feeding rescues brain pathology and improves memory in mouse models of Alzheimer’s disease. Cell Metabolism. https://doi.org/10.1016/j.cmet.2023.07.014 (open-access).

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Can’t exercise? A protein from blood platelets may rejuvenate your neurons

University of Queensland researchers have discovered that injecting platelets, the blood cells responsible for blood clotting, secretes a protein that rejuvenates neurons in aged mice in a similar way to physical exercise.

Stimulating neuron production in the brain

This “platelet factor 4” protein could help the very elderly (or someone who has had a brain injury or stroke) improve cognition, said Dr. Odette Leiter, at UQ’s Queensland Brain Institute. The researchers plan to test this response in Alzheimer-diseased mice, before moving towards human trials. If successful, the study could lead to drug interventions.

Citation: Leiter, O., Brici, D., Fletcher, S.J. et al. Platelet-derived exerkine CXCL4/platelet factor 4 rejuvenates hippocampal neurogenesis and restores cognitive function in aged mice. Nat Commun 14, 4375 (2023). https://doi.org/10.1038/s41467-023-39873-9 (open-access)

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Neuroscientists decode Pink Floyd song from brain recordings

May allow for adding musical elements to brain–computer interface (BCI) applications

Neuroscientists at the University of California, Berkeley recorded EEG (electrical) activity from two areas of the brain as patients listened to the Pink Floyd song, “Another Brick in the Wall, Pt. 1.”

They captured the electrical activity of specific brain regions on the surface of the brain related to attributes of the music—tone, rhythm, harmony and words—to see if they could reconstruct what the patient was hearing.

Using AI software, they were able to reconstruct the song from 29 brain recordings a decade later—the first (known) time a song has been reconstructed from intracranial EEG recordings.

The phrase “All in all it was just a brick in the wall” comes through recognizably, with rhythms intact and the words muddy, but decipherable.

“Our findings show the feasibility of applying predictive modeling on short datasets acquired in single patients, paving the way for adding musical elements to brain–computer interface (BCI) applications,” the researchers note.

A head X-ray of one participant in the experiment shows the placement of electrodes over the frontal (top) and temporal (bottom) regions of the brain—these electrodes were placed on the surface of the brain to locate the origin points of epileptic seizures. While waiting for days in their hospital rooms, patients volunteered for other brain studies, including one attempting to pinpoint the brain regions that respond to music. The researchers also confirmed that the right side of the brain is more attuned to music than the left side. (credit: Ludovic Bellier and Robert Knight, UC Berkeley)

The musicality of speech

“For people who have trouble communicating, whether because of stroke or paralysis, such recordings from electrodes on the brain surface could help reproduce the musicality of speech that’s missing from today’s robot-like reconstructions,” the researchers suggest.

As brain recording techniques improve, it may be possible someday to make such recordings without opening the brain, perhaps using sensitive electrodes attached to the scalp. (See “How To Measure Your Brain Activity Using A EEG Sensor Mounted On A VR Headset.“)

“Currently, scalp EEG can measure brain activity to detect an individual letter from a stream of letters, but the approach takes at least 20 seconds to identify a single letter, making communication effortful and difficult,” said Robert Knight, a neurologist and UC Berkeley professor of psychology in the Helen Wills Neuroscience Institute.

Citation: Bellier L, Llorens A, Marciano D, Gunduz A, Schalk G, Brunner P, et al. (2023) Music can be reconstructed from human auditory cortex activity using nonlinear decoding models. PLoS Biol 21(8): e3002176. https://doi.org/10.1371/journal.pbio.3002176 (open-access)

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Scientists find way to wipe a cell’s memory to better reprogram it as an embryonic stem cell

In a groundbreaking study published in the journal Nature today (Aug. 16, 2023), Australian scientists say they have developed a new method to reprogram human cells, better mimicking embryonic stem cells, with significant implications for biomedical and therapeutic uses.

Called “transient-naive-treatment (TNT) reprogramming,” the method mimics the reset of a cell’s epigenome that happens in very early embryonic development, and it addresses a long-term problem in regenerative medicine.

“We need stem cells to replace our old cells, which are capable of only a limited number of replications,” explained Dr. Deborah Duong, CTO of Rejuve.AI and an AI researcher for Singularity Net. “However, the amount of stem cells we have decreases as we age. So this could be part of an answer, but there is still a long way to go.”

The research is led by Professor Ryan Lister from the Harry Perkins Institute of Medical Research and The University of Western Australia and Professor Jose M. Polo from Monash University and the University of Adelaide.

Citation: Sam Buckberry et al. Aug. 16, 2023. Transient naive reprogramming corrects hiPS cells functionally and epigenetically. Nature /s41586-023-06424-7 (open-access)

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Source of hidden consciousness in ‘comatose’ brain injury patients found

Imagine you’re in a hospital for a football brain injury. You can hear and understand everything that’s going on, including a doctor’s verbal commands, like “open and close your hand.” But you can’t carry out those commands, despite your awareness. 

Hidden consciousness revealed

Now a study by Columbia University researchers suggests that patients with hidden consciousness … cannot carry out those commands because of injuries in brain circuits that relay instructions from the brain to the muscles,” says study leader Jan Claassen, MD..

Classen is associate professor of neurology at Columbia University Vagelos College of Physicians and Surgeons and chief of critical care and hospitalist neurology at NewYork-Presbyterian/Columbia University Irving Medical Center.  

The findings could help physicians more quickly identify brain-injured patients who might have hidden consciousness, and better predict which patients are likely to recover with rehabilitation. 

Brain circuits disrupted

Hidden consciousness, also known as “cognitive motor dissociation” (CMD), occurs in about 15% to 25% of patients, with brain injuries stemming from head trauma, brain hemorrhage or cardiac arrest.

In previous research, Claassen and colleagues found that subtle brainwaves detectable with EEG are the strongest predictor of hidden consciousness and eventual recovery for unresponsive brain-injured patients.  

Identifying patients with CMD

But the precise pathways in the brain that become disrupted in this condition were unknown. In the new study, the researchers used EEG to examine 107 brain injury patients. The technique can determine when patients are trying, though unable, to respond to a command such as “keep opening and closing your right hand.”  

“Using a technique we developed called bi-clustering analysis, we were able to identify patients with CMD and contrast to those without CMD,” says co-lead author Qi Shen, PhD, associate research scientist in the Claassen lab and an expert in signal processing, machine learning and biostatistics. 

Using EEG (brain-wave detection), the researchers found that all of the CMD patients had intact brain structures that were related to arousal and command comprehension. This supported the notion that these patients were hearing and understanding the commands, but were unable to carry them out.  

“We saw that all of the CMD patients had deficits in brain regions responsible for integrating comprehended motor commands with motor (muscular, etc.) output, preventing CMD patients from acting on verbal commands,” says Claassen. 

MRI identification of CMD

The findings may now allow researchers to better understand which brain injury patients have CMD. That will be useful for clinical trials that support the recovery of consciousness. 

“However, our study shows that it may be possible to screen for hidden consciousness using widely available structural brain imaging, moving the detection of CMD one step closer to general clinical use,” Claassen says. 

“Not every critical care unit may have resources and staff that is trained in using EEG to detect hidden consciousness, so MRI may offer a simple way to identify patients who require further screening and diagnosis.”

Citation: Eva Franzova, Qi Shen, Kevin Doyle, Justine M Chen, Jennifer Egbebike, Athina Vrosgou, Jerina C Carmona, Lauren Grobois, Gregory A Heinonen, Angela Velazquez et al. 14 August 2023. Injury patterns associated with cognitive motor dissociation. Brain, https://doi.org/10.1093/brain/awad197

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