Lights and Brains: Injectible LED's Interact with Brain Cells

The quest to put computers in the brain has just come a step closer.  Tiny LED lights have been implanted deep in the brains of rodents.  The LEDs themselves are the size of individual neurons.  They are packaged with other tiny sensors into an ultrathin, flexible device.  The whole device is small enough to be implanted using a needle that positions the device at precise sites deep in the brain. 

Once implanted, the device communicates directly with the brain at the level of cells.  It communicates wirelessly with a module mounted above the rodent’s head, one small enough not to interfere with activity and removable when not in use.  The device itself is completely contained within the brain where it was implanted without any damage to surrounding cells.  Signals sent through the device stimulate genetically modified brain cells, signaling for example for the release of neurotransmitters such as dopamine. 

Photo Credit: MicroLED device next to a human finger.  Image courtesy of University of Illinois-Urbana Champaign and Washington University-St. Louis.

 

"These materials and device structures open up new ways to integrate semiconductor components directly into the brain," said team co-leader John A. Rogers according to a press release from the University of Illinois.  "More generally, the ideas establish a paradigm for delivering sophisticated forms of electronics into the body: ultra-miniaturized devices that are injected into and provide direct interaction with the depths of the tissue."

The device itself is a feat of engineering requiring the effort of an international team based in China, Korea, and at multiple centers across the US.  By miniaturizing the device to the cellular scale and by creating a totally wireless interface, researchers overcame several challenges at once.  For example, larger implantable devices always run the risk of creating scars or lesions in the brain, which may cause serious problems.   "One of the big issues with implanting something into the brain is the potential damage it can cause," team co-leader Michael Bruchas said. "These devices are specifically designed to minimize those problems, and they are much more effective than traditional approaches."

In addition, because this device communicates and receives its power wirelessly, there are no wires or optical fibers passing from the brain to the outside world.  Previous devices were larger and nonflexible. They were implanted only on the surface of brain structures, but this new device is implantable deep within those structures and able to interact with units as small as a single cell.

Along with the LED lights, the device includes temperature and light sensors, microscale heaters, and electrodes that can stimulate and receive brain electrical activity.  Power to the device is provided wirelessly through a radio frequency system. 

It is impossible to predict the future of efforts to connect brains and computers. This work obviously represents a significant advance toward that end.  "These cellular-scale, injectable devices represent frontier technologies with potentially broad implications," Rogers said. Being able to monitor and trigger the brain of living animals at the cellular level is likely to become a profoundly valuable tool for research.  Medical research, too, is also likely to be affected, not just in responding to patients with paralysis but also in research and perhaps even therapy in other diseases involving the brain or other organs, where these devices are also implantable. 

Some, of course, will speculate about even wider implications for this technology.  Will it open the way to control people by controling their brains?  Perhaps.  Will it open the way for our brains to communicate with computers and the internet?  There is little doubt that this step will inspire more work along those lines. 

This article is entitled "Injectable, Cellular-Scale Optoelectronics with Applications for Wireless Optogenetics" and is published in the April 12, 2012 issue of the journal Science, a publication of the American Association for the Advancement of Science. 

A Living, Breathing Lung-on-a-Chip

Human cells can be grown outside the human body. In a petri dish, they may develop in ways that resemble the cells inside the body. But their function and activity are limited. For example, in a dish, lung cells are just lung cells. They don’t breathe.

Using new technology, however, researchers have put lung cells on a chip. The cells on a chip have suddenly become a lung-on-a-chip, active, moving, and breathing.

In a paper published in the in the November 7 issue of Science Translational Medicine, researchers report on their use of recently-developed organ-on-a-chip technology. They describe how they built and used "a biomimetic microdevice that reconstitutes organ-level lung functions to create a human disease model-on-a-chip."

Caption: Wyss Institute's human breathing lung-on-a-chip. Credit: Wyss Institute, Harvard University. Usage Restrictions: None.

Already the device has led to two discoveries directly applicable to the lung disease, edema, which is a major concern for some cancer patients. First, development of the disease is accelerated by the physical movement of the lungs. This is "something that clinicians and scientists never suspected before," according to Donald Ingber, senior author of the study.

Second, researchers identified one drug, currently under development, that might help prevent the problem. For Ingber, this is the main attraction of organ-on-a-chip technology. "This on-chip model of human pulmonary edema can be used to identify new potential therapeutic agents in vitro," Ingber says.

This could accelerate the speed of drug development and testing while reducing the cost. The main advantage is that an organ-on-a-chip gives researchers the opportunity to test a wide array of potential drug compounds. Tests can be run not just on nonhuman animals or on cultured human cells but on functioning or working small-scale models of human organs.

Beyond its value in pharmaceutical research, it is not clear where this research may lead, but it is one more way in which the boundary we once drew between the living and the nonliving is being erased, along with the line between the natural and the artifical.

The work was funded by the National Institutes of Health (NIH) and the Food and Drug Administration (FDA), Defense Advanced Research Projects Agency (DARPA), and the Wyss Institute for Biologically Inspired Engineering at Harvard University. The paper is entitled "A Human Disease Model of Drug Toxicity–Induced Pulmonary Edema in a Lung-on-a-Chip Microdevice" and appears in the November 7, 2012 issue of Science Translational Medicine.

Merging Humans and Robots--More Coffee, Please

With the help of a tiny chip implanted in the brain, human beings who cannot move their own limbs are able to move a robotic arm, in one case taking a drink of coffee on one’s own for the first time in fifteen years.

"The smile on her face was a remarkable thing to see. For all of us involved, we were encouraged that the research is making the kind of progress that we had all hoped," said the trial's lead investigator, Leigh Hochberg, M.D., Ph.D., in a press release issued by the National Institutes of Health, which provided some of the funding. Hochberg is an associate professor of engineering at Brown University and a critical care neurologist at Massachusetts General Hospital (MGH)/Harvard Medical School.

The field of brain-computer interface research is not new, but this is the first peer-reviewed report of people using brain signals to control a robotic arm, making it perform in three-dimensional space much as their natural arms once did. By imagining they were controlling their paralyzed limb, they were able to move the robotic arm. Brain activity is detected as electrical activity by the BrainGate chip, processed by an external computer, and fed into a robot that translates the signals into movement.

More research is underway, and in fact this clinical trial is recruiting more volunteers.

Caption: The BrainGate array, which is implanted on the motor cortex, comprises nearly 100 electrodes on a chip the size of a baby aspirin. Credit: www.braingate2.org Usage Restrictions: With Credit.

With future advances, researchers hope to be able to improve the quality of movement in prosthetic limbs or to restore in part the function of paralyzed limbs, perhaps by creating an electronic by-pass to normal nerves.

"This is another big jump forward to control the movements of a robotic arm in three-dimensional space. We're getting closer to restoring some level of everyday function to people with limb paralysis," said John Donoghue, Ph.D., who leads the development of BrainGate technology and is the director of the Institute for Brain Science at Brown University.

Beyond therapy, it is possible to imagine other uses as we humans and our machines co-evolve and increasingly converge, probably to do more than drink coffee.

This report is published in the May 17, 2012 issue of Nature.

Stem Cells, Working Brains, and Human Enhancement

Research using human pluripotent stem cells—whether derived from an embryo or induced into a pluripotent state—holds great promise for regenerating parts of the human body by producing new cells to replace diseased or damaged cells. Nowhere is this potential more intriguing than in the human brain.

During the past decade, researchers have learned to turn human pluripotent cells into neurons. They have tested these neurons in cell cultures, where they seem to function like normal neurons. They have implanted these human neurons in mouse brains, where human cells thrive like normal cells. The big question is whether they do the work of brain cells. Long before cells are implanted in human brains, researchers want to know whether the cells will function properly in any working brain, starting with a mouse brain.

Now comes evidence that the implanted cells seem to be fully function, integrated in the basic process of the mouse brain. In the report published in the November 21 issue of PNAS, researchers at the University of Wisconsin report on their use of a new technology, optogenetics, to test the function of the implanted cells. This technology uses light rather than electricity to stimulate implanted neurons. The result, it is claimed, is the best evidence so far that implanted cells are integrated fully into the functioning brain, sending and receiving signals as part of living neural networks.

”We show for the first time that these transplanted cells can both listen and talk to surrounding neurons of the adult brain,” said lead author Jason P. Weick in a press release from the University.

By using optogenetics, this study provides evidence that implanted human neurons derived from pluripotent stem cells can become functionally integrated into systems of a living brain, sending and receiving signals from surrounding or “host” cells and interacting with brain circuitry in a way that is consistent with normal brain rhythms.

According to the paper published in PNAS, the neurons derived from pluripotent cells “can participate in and modulate neural network activity through functional synaptic integration, suggesting they are capable of contributing to neural network information processing…”

What’s more, the researchers discovered that optogenetics may someday have a clinical use far beyond its value as a research tool. The fact that implanted cells can be stimulated using a light signal may someday become part of the way stem cells are used on human patients. According to Su-Chun Zhang, also an author of the report, “You can imagine that if the transplanted cells don't behave as they should, you could use this system to modulate them using light.”

Still more challenges must be met before neurons derived from human pluripotent cells are implanted successfully in the human brain. But this study advances the field in a critically important way and provides strong evidence that implanted cells might one day take on the function of damaged cells in the living human brain.

If human brains can be regenerated even in highly limited ways, the consequences will be profound. The most obvious applications will be to treat patients who have lost some part of brain function due to stroke, brain injury, or disease.

And if that becomes possible, it is not hard to imagine that the same technology will be used to regenerate the brains of those whose only “disease” is aging. Furthermore, it is quite likely that at some point in the future, implanted neurons derived from pluripotent cells will be genetically modified first, perhaps to prevent disease but also perhaps to enhance the performance of the brain into which they become functionally integrated.

It is important to stress that treatment for complex disorders of the brain, such as Alzheimer’s Disease, are still a long way off. But this research is an important step, showing that the basic concept of stem cell treatment may provide one form of treatment. But is that becomes possible, it may also become possible to enhance the cognitive capacity of people without disease.

The milestone reported here is just one more step--of which there must be hundreds or thousands--leading us closer to the day when human brains might be regenerated or renewed. Few will object to the use of such treatments to restore functioning neurons to those with Huntington's disease or early onset Alzheimers. And if early onset Alzheimers, why not late onset? And if late onset dementia, why not age-related cognitive decline? At what point do we cross the line from therapy to enhancement, and does such a line even exist?

So while we stress that these treatments are not available today--and may never be--they will very likely come in time. And when they come, they will open the path for completely new ways to extend the functional lifespan of the human brain.
The report, entitled "Human embryonic stem cell-derived neurons adopt and regulate the activity of an established neural network," appeared in the Nov 21, 2011 issue of PNAS.