“Brain-on-a-Chip” Devices Are Changing How We Study the Brain

Brain-on-a-Chip

Researchers at the Lawrence Livermore National Laboratory have devised a new use for “brain-on-a-chip” technology: testing the effects of biological and chemical agents on the brain over time. Their research was published in PLOS in November 2017. This work is part of an ever-growing body of research dedicated to developing “brain-on-a-chip” technology in hopes that one day, it may eliminate the need for animal testing.

The so-called brain-on-a-chip is essentially a wafer of semiconductors to which researchers affix a network of nanowires. When brain cells are introduced onto the chip, they can use the nanowire as scaffolding to build functional neuronal circuits that mimic the interconnectivity of neurons in the brain. Once the lattice is constructed, researchers can not only observe the connectivity as-is but study the impact of disease and trauma.

In January 2017, researchers at Harvard’s John A. Paulson School of Engineering and Applied Sciences (SEAS) first made headlines with such a “brain-on-a-chip” device. This chip allowed them to identify the differences between neurons depending on where in the brain they originate from, as well as how those different neurons connect with one another, specifically providing insight into the neurological basis of schizophrenia. Researchers at the Australian National University later refined the nanowire scaffolding technique, developing the first-ever working neuronal circuits.

The latest in brain-on-a-chip applications from LLNL found that the technology can be used to study the impact of long-term exposure to biological and chemical agents on the brain. The team was primarily interested in the kinds of chemical exposures that might be experienced by those in the military — a demographic of patients that are already of interest to neurological study, on account of the prevalence of post-traumatic stress disorder.

Brain Chemicals

In their study, the researchers at LLNL were focused on using their “brain-on-a-chip” to study how brain cells are affected by exposure to a number of chemical agents, and how those agents change the brain over time. The hope is that through a deeper understanding of the mechanisms at play, antidotes, treatments, or preventative efforts could be developed and deployed to troops to help protect them.

The “brain-on-a-chip” device used by the team at LLNL was designed to have custom-built inserts that give them the ability to model different regions of the brain, swapping them in and out to study their interconnectivity as needed. It also lets the researchers shift easily from the “macro world to the micro world,” since they can place multiple cell types in much smaller areas than has ever been possible before.

Lawrence Livermore National Laboratory research engineer Dave Soscia examines the brain-on-a chip device under a microscope.
Lawrence Livermore National Laboratory research engineer Dave Soscia examines the “brain-on-a chip” device under a microscope. Image Credit: Randy Wong/LLNL

From there, the team was able to monitor the bursts that occur between brain cells when they communicate — called “action potential patterns” — as well as give them an idea of how that communication changed over time, particularly if the brain were exposed to something that could change those patterns, like a chemical agent.

“Obviously at a high dose, we know exposure is going to be detrimental, but think about the warfighter who is exposed to a low level of chemical for a long time,” iCHIP principal investigator Elizabeth Wheeler explained in an LLNL press release. “Using this device in the future, we might be able to predict how that brain is going to be affected. If we understand how it’s affected, then we can develop a countermeasure to protect the warfighter.”

No More Lab Rats?

“While we’re not close to the point where we can fully recapitulate a brain outside of the body, this is an important step in terms of increasing complexity of these devices and moving in the right direction,” said co-lead author and LLNL research engineer Dave Soscia in the team’s press release. “The idea is that eventually, the community gets to a point where people are confident enough in the devices that the effects they see from putting chemicals or pharmaceutical drugs into the platform environment are similar to the results we would see in the human body.”

“You could mimic someone getting a brief exposure on a battlefield and then look at the neurons over six months and see what happens,” Kris Kulp, LLNL biologist, further explained. “Maybe they recover from that initial exposure, but six months from now they still have some kind of detriment. This is the only kind of system that would allow for that kind of experimentation on human cells.”

The next step in development will be for the team to connect with computer scientists, statisticians and others who can help them analyze and fully model the data that this extraordinary device has provided.

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For the First Time, Physicists Accelerated Light Beams in Curved Space in the Lab

Curved Space

Physicists have demonstrated accelerating light beams on flat surfaces, where acceleration has caused the beams to follow curved trajectories. However, a new experiment has pushed the boundaries of what’s possible to demonstrate in a lab. For the first time in an expeirment, physicists have demonstrated an accelerating light beam in curved space. Instead of traveling along a geodesic trajectory (the shortest path on a curved surface) it bends away from this trajectory due to the acceleration.

The study, published in the journal Physical Review X, “opens the doors to a new avenue of study in the field of accelerating beams. Thus far, accelerating beams were studied only in a medium with a flat geometry, such as flat free space or slab waveguides. In the current work, optical beams follow curved trajectories in a curved medium,” according to Anatoly Patsyk, a physicist from the Israeli Institute of Technology.

Completed by physicists at Israel Institute of Technology, Harvard University, and the Harvard-Smithsonian Center for Astrophysics, the success of the experiment will increase research potential for further lab-based studies of phenomena like gravitational lensing. By performing these expeirments in a lab, scientists will be able to study such phenomena which stem from Einstein’s general theory of relativity in a controlled setting.

General Relativity

The team first caused a laser beam to accelerate by reflecting the beam off a spatial light modulator, which is a device used to modulate amplitude, phase, or polarize light waves. Bouncing the beam off this device imprints a specific wavefront on the beam, creating one that accelerates while keeping its shape. The team then pointed the accelerating laser along the inside of an incandescent light bulb painted in such a way that the light both scattered and was visible to the researchers.

The team observed that when moving along the inside of the bulb, the beam’s trajectory breaks apart from the geodesic line. When they compared this movement to a beam that was not accelerating, they found that when it was not accelerating, the beam would follow the line.

The research could be a starting point for future research into phenomena that fall within Einstein’s general theory of relativity. Patsyk stated that “Einstein’s equations of general relativity determine, among other issues, the evolution of electromagnetic waves in curved space. It turns out that the evolution of electromagnetic waves in curved space according to Einstein’s equations is equivalent to the propagation of electromagnetic waves in a material medium described by the electric and magnetic susceptibilities that are allowed to vary in space.”

Patsyk went on to say that this foundation gives “rise to the emulating effects such as gravitational lensing and Einstein’s rings, gravitational blue shift or red shift, which we have studied in the past, and much more.”

In other words, the techniques innovated through this experiment could help physicists more effectively study phenomena like gravitational lensing. The team is also exploring whether plasmonic beams (those that have plasma oscillations instead of light) could also be accelerated in curved space.

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Newly FDA-Approved Platform Will Rapidly “Manufacture” Stem Cells to Repair Our Bodies

Stem Cells Fast

Up until now, any patient receiving stem cells for a medical treatment has had to wait months for their doctors to create enough cells to make multiple doses. But that could soon change: the FDA recently approved an automated bioreactor, developed by scientists at the Mayo Clinic’s Center for Regenerative Medicine, that can manufacture stem cells by the billions in a matter of days.

Mayo Clinic neurologist Guojun Bu watches a technician utilizing the stem cell platform (Image Credit: Mayo Clinic)
Neurologist Guojun Bu watches a technician utilizing the stem cell platform. Image Credit: Mayo Clinic

Stem cells have the unique capability to transform into any sort of specialized cell needed in the body, making them especially promising for medicine that replaces nonfunctional or dead cells. The Mayo Clinic’s new platform allows for the multiplication of stem cells harvested from bone marrow. Significantly, it can manufacture stem cells from a healthy donor as well as from a patient themselves, which could allow treatments even in cases when the patient’s own cells are not usable.

“The new platform represents a giant leap in regenerative medicine, in which stem cells currently are being investigated as treatments for wide-ranging medical conditions,” Guojun Bu, neurologist and associate director of the Mayo Clinic’s Center for Regenerative Medicine, said in a press release.

Therapy of the Future

The new platform is among the U.S.’s first approved automated methods to manufacture stem cells, which may allow the Mayo Clinic to accelerate its existing studies using stem cells. A recent Mayo clinical study found stem cells could be reduce inflammation in patients who have received lung transplants. Another has explored the possibility of using stem cells to treat arthritis.

But in order to bring these treatments out of trials, they need to be tested rigorously; and for that, doctors need lots and lots of stem cells.

“Although Mayo Clinic has been poised to scale up regenerative clinical trials, to date we did not have the capacity to support them,” said Abba Zubair, Mayo Clinic’s medical director for transfusion medicine and the Human Cell Therapy Laboratory, in the press release. “With this new technology, we now can develop phase II trials enrolling larger numbers of patients to fully test the efficacy of cell-based therapies.”

Mayo Clinic doctors plan to use the stem cell platform to advance therapies in areas like Alzheimer’s, Parkinson’s, and even heart disease.

Indeed, stem cells have shown promise in a remarkable range of medical treatments. Scientists have used them to grow working muscle tissue, restore mobility to paralyzed animals, and even treat a leading cause of blindness. Additionally, as doctors have learned how to extract these shape-shifting cells from new sources, like tooth root pulp, it has averted much of the controversy that comes from extracting them from human embryos.

Add in such new methods for rapidly producing cells, and all of this points towards a promising future for medicine in which a patient’s own cells can be used to safely and effectively heal them from within.

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Scientists Coax Human Stem Cells Into Becoming Touch Neurons

Sense of Touch

Sensory interneurons, the cells that give us our sense of touch, allow us to experience the world through tactile experiences that can become lost to us in the case of paralysis. This unique sense not only shapes our life experiences but helps keep us safe. It’s what allows us to perceive the potential danger of something like a hot stove or a sharp edge. A new study exploring these cells hopes to find a way to restore sensation to those suffering from paralysis. The study from UCLA, published in the journal Stem Cell Reports, resulted in a remarkable first: researchers successfully coaxed human stem cells to become sensory interneurons.

Led by Samantha Butler, a UCLA associate professor of neurobiology who is also a part of the Broad Stem Cell Research Center, the study built on previous work published by Butler and her colleagues in September. In the previous study, Butler and her team explored how certain proteins contribute to the development of sensory interneurons in chicken embryos. Their latest research took the principles and information gleaned from the previous study and applied them to human stem cells.

The team added proteins, which establish the structure bone with a signaling molecule, to human embryonic stem cells. This mixture created two separate types of sensory interneurons: dI1 sensory interneurons, which help us determine where our body is in relation to what’s around us in our environment and dI3 sensory interneurons, which give us the ability to feel pressure.

Human embryonic stem cell-derived neurons (green) showing nuclei in blue. Each side shows a different mixture to try to create sensory interneurons. Image Credit: UCLA Broad Stem Cell Research Center/Stem Cell Reports
Human embryonic stem cell-derived neurons (green) showing nuclei in blue. Each side shows a different mixture to try to create sensory interneurons. Image Credit: UCLA Broad Stem Cell Research Center/Stem Cell Reports

Restoring Feeling

The team also found that they could create the same sensory interneurons mixture by adding signaling molecules to induced pluripotent stem cells. Induced pluripotent stem cells are created from the patient’s own cells, which are then “reprogrammed. This could give researchers the ability to better explore restorative treatments that work with the patients’ body and reduce or eliminate the potential for rejection.

While this area of research is often focused on helping paralyzed patients walk again, Butler’s team is interested in restoring the broader experience of touch. In a press release from the UCLA Newsroom, she said “The field has for a long time focused on making people walk again. Making people feel again doesn’t have quite the same ring. But to walk, you need to be able to feel and to sense your body in space; the two processes really go hand in glove.”

That said, the team does hope their research could prove helpful in developing restorative therapies for patients with paralysis. As Butler put it, “This is a long path. We haven’t solved how to restore touch but we’ve made a major first step by working out some of these protocols to create sensory interneurons.”

While the research marks a major first, there is still a lot of additional research to be done. Butler and her team hope that additional studies will help them exactify mixtures that would allow them to coax stem cells into a variety of different sensory interneurons.

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A Robotic Implant Could Treat Congenital Disorders in Babies

Robotic Implant

When implanted, a new robot is able to promote tissue growth by pulling and tugging at organs. It may sound alarming, but this new device could revolutionize the way doctors treat esophageal atresia, a congenital defect in which part of the esophagus is missing at birth. With future developments, the robotic implant could also promote growth in other organs.

Developed by scientists at Boston Children’s Hospital, this robot has so far only been tested in pigs, but the researchers hope to one day use this in regular medical practice.

In the study, which was published in the journal Science Robotics, the robot was implanted in live pigs and then slowly and gradually stretched tubular organs like the esophagus while the animals remained active. The pigs showed no discomfort and were even able to continue eating as the robot lengthened the esophagus by around 77 percent.

Additionally, cell multiplication was shown as a result of this technique. “This shows we didn’t simply stretch the esophagus — it lengthened through cell growth,” Pierre Dupont, the study’s senior investigator, said in a press release.

Expanding Applications

The use of this robot would be in place of existing treatment methods which require the patient to be put into a medically-induced coma for four weeks during which the esophagus has to be surgically and manually manipulated.

But it will take some time for the current treatment to become obsolete. There is still much research to be done before this robot is used as a medical tool with humans. Additionally, it has only been studied with the esophagus. However, the team has started to test this robot in a large animal model of short bowel syndrome, a condition in which a piece of the bowel is missing.

Pill Robots: The Future of Non-Invasive Surgery [INFOGRAPHIC]
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If this robot proves effective in more organs, its potential as a medical device will continue to rise. Hopefully, the implant will be shown to be safe for regular use in medical practices, allowing it to replace previous surgical methods that are costly, extremely painful, and — most detrimentally — fraught with risk. If this is the case, then this little robot is well positioned to improve and extend lives.

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