A device, implantable in the brain, activated by remote control…no, this isn’t Mission: Impossible XII or another remake of The Manchurian Candidate. It’s a unique medication delivery system that, although being used only on rodents, could potentially change pain management. First we'll hear from Jae-Woong Jeong, PhD, an engineer and the developer of the device; cofirst author of the study; a former postdoctoral researcher at the University of Illinois and now assistant professor of electrical, computer, and energy engineering at the University of Colorado, Boulder; and then Michael R. Bruchas, PhD, coprincipal investigator and associate professor of anesthesiology and neurobiology at Washington University in St. Louis. (Read a Daily Dose about the device.)
DR. JAE-WOONG JEONG:
Q: What is your engineering background?
JWJ: I got my PhD in Electrical Engineering and did postdoctoral research in Materials Science and Engineering. I am interested in developing innovative soft biomedical devices and tools based on this multidisciplinary knowledge and techniques. I want to define myself as a bioengineer.
Q: When you were a kid, did you hope to be doing things like this when you “grew up”?
JWJ: When I was a kid, I wanted to be someone who develops human-like robots. As I grew up, my interest shifted from robot to human. I wanted to apply science and engineering to benefit human health.
Q: What lead you to realize the need for this device?
JWJ: Conventional neural devices are tethered, therefore limiting animals’ free movement. Motivation to enable animals’ natural behavior–to study function of the brain–led me to think about the wireless neural device that can be implanted in the brain.
Q: How long have you been working on it?
JWJ: I have been making collaborative efforts with Bruchas lab at Washington University for almost 2 years.
Q: What’s it like for a scientist to see the fruits of his work? This device could do amazing things! What would be the icing on your cake, so to speak?
JWJ: It’s a thrill. Once I achieve the goal of a research, I get higher desire to solve more challenging problems. For the next generation devices, I want to add a refillable drug cartridge concept to enable long-term neuroscience research and clinical treatment. Also, I want to miniaturize the device even further.
Q: Can you imagine a future where these implants are commonplace?
JWJ: This technology could be applied to treat brain disorders like Parkinson’s disease, epilepsy, and many others. Also, it could be used to treat a brain tumor while minimizing side effects of chemotherapy by delivering a drug only to a targeted brain region.
Q: How are the implants actually made?
JWJ: We used soft lithography technique to fabricate ultrathin, soft microfluidic channels that deliver drugs. The cellular-scale micro-LEDs are fabricated on a wafer using the standard semiconductor fabrication process and are integrated with the microfluidic channels. This way, we could achieve soft, multifunctional neural probes that can be injected into the brain tissue and that can function for a long time without causing inflammation and neural damage.
Q: Was the trial and error period depressing? Were you ever tempted to give up?
JWJ: Manufacturing of hair-thin neural probes was very challenging. Indeed I went through numerous trials and error to develop the fabrication process that works. Sometimes I felt frustrated after failure, but never thought about giving up. I believed it would work eventually.
Q: When you’re not “engineering,” how do you like to spend your time?
JWJ: I love to spend time with my kid when I am not “engineering.” We go hiking, go on a picnic, or play for exercise together.
DR. MICHAEL R. BRUCHAS:
Q: Can you please explain, simply, what is optogenetics?
MB: Optogenetics is the ability to use light to control specific cell types. This takes advantage of light sensitive proteins that naturally occur in nature (in bacteria or algae), and engineering genetic approaches to express them into tissue such as brain. Then using fiber optic approaches, one can take control of specific neuronal populations and selectively control their activity.
Q: I read that the human-hair-width implant could carry drugs directly to the brain. This seems like it has amazing potential for pain relief.
MB: This might have some potential for pain relief in future versions of the device; for example, if we can implant this into peripheral tissue, or we can utilize these current implants in areas of the brain associated with descending modulation of pain. The periacquaductal gray, raphe magnus, etc.
Q: How often would the implants need refilling?
MB: The current prototype doesn’t have the ability to refill, but instead has 4 chambers. However we are developing fillable implants, that could be refilled.
Q: Do the implants stay in forever?
MB: The implants are permanent at this point, but in the future reusable versions would be developed. They don’t move and they stay intact.
Q: What are the implants made of?
MB: The devices are composed of a variety of materials, including silicon and plastic-like substances, all of which are biocompatible for optimal integration with the tissue.
Q: You have studied this process in mice. Is the next step a larger animal? When might humans benefit from the implant?
MB: We did test this in mice, to be able to combine genetic approaches with pharmacology. We also used rats in one study, and the rats seemed to also tolerate the devices well. We do hope that we can move into primates or other larger mammals in future iterations.
Q: Are there any side effects?
MB: The animals tolerate the implants over several weeks and their behavior appears normal, so it appears that they integrate well with the animals, with little observed side effects or complications.
Q: What diseases and pain syndromes would most benefit from this discovery?
MB: There are numerous applications for the technology…including but not limited to pain, epilepsy, chronic depression, and addiction. Furthermore, targeted wireless drug delivery combined with light could bring about new drugs that are photosensitive and allow for unprecedented restriction to specific subregions of brain tissue.
Q: How long is the process of putting in the device and activating the medication(s)?
MB: For implanting and performing these studies it took between 2 to 3 weeks of total time. The device responds to a simple remote, much like in your TV, so it is very fast in triggering drug release once the implant has been successfully implanted.
Q: In a perfect world, how would you like to see this technology best utilized?
MB: I think the goal is to use this in 2 ways. 1) For neuroscience research to better dissect how the brain functions in normal and disease states. We are interested in how the brain encodes information through receptors and circuits, and this device will help with that process. We are working to distribute the technology to the rest of the neuroscience community. 2) Combining this technology with new developments in chemistry, particularly photochemistry, will allow for drugs to be sensitive to light and activated in very discrete space and time. This will hopefully reduce side effects and allow for better therapeutics.
Q: What is a dream project you hope to work on?
MB: Following up on this research, we are pursuing devices that are more flexible and can accommodate other tissue types such as spinal cord. We also hope to be able to integrate this technology with the photopharmacology I described above, to allow for activation of drugs in very discrete regions and time lines.