Big Ideas Lab - Implantables

Episode Date: October 29, 2024

Imagine an artificial retina that restores sight or micro-devices implanted to monitor health in real time. This isn’t science fiction—it’s our new reality.In this episode, we journey into the groundbreaking world of implantable technology. Discover the science driving these innovations, explore the life-changing devices already in use, and glimpse the remarkable advancements still on the horizon. How will these tiny marvels shape our understanding of human potential and redefine what it means to be human?--- Big Ideas Lab is a Mission.org original series. Executive Produced and Written by Lacey Peace. Sound Design, Music Edit and Mix by Daniel Brunelle. Story Editing by Daniel Brunelle. Audio Engineering and Editing by Matthew Powell. Narrated by Matthew Powell. Video Production by Levi Hanusch. Guests featured in this episode (in order of appearance): Alison Yorita, Staff Engineer for Lawrence Livermore’s Implantables Microsystem  GroupMatthew Leonard, Associate Professor at the University of California, San Francisco in the Department of NeurosurgeryRazi Haque, Implantable Microsystems Group Lead at LLNLBrought to you in partnership with Lawrence Livermore National Laboratory.

When we talk about implantables, I consider it as any interface that goes into the body. It was July 2014. Fran Fulton sat on the exam table in anticipation. So whether that's monitoring what's going on in the body, whether that's modulating or stimulating parts of the body. Fran was 66 years old. For a decade, she had been living in a world shrouded in darkness. She had completely lost her vision as the result of a relentless degenerative eye disease

called retinitis pigmentosa. Her grandchildren were four years old and seven years old, but she had never seen them. A week ago, Fran underwent cutting-edge surgery that implanted electrodes on her retina. Today, they are testing if those electrodes worked. All around her, doctors and scientists hurried to prepare for the test. They set in front of her a pair of glasses specially designed to connect to those electrodes. Are you ready, Fran? One of the doctors asked. She nodded.

The doctors helped her set the oversized pair of glasses on her face. And in a moment, Fran's world was illuminated once again. Equipped with the groundbreaking artificial retina system, a pair of camera-fitted glasses connected to electrodes implanted in her eye, Fran experienced what she described as the most breathtaking moment of her life. This is not science fiction. This is reality. It is the dawn of a new era where technology unlocks human potential previously thought impossible. The artificial retina is just one of many examples of implantable technology. But what is the science behind this technology?

What other marvels of implantable technology are on the horizon? And how will they shape what it means to be human? This is the Big Ideas Lab. Your weekly exploration inside Lawrence Livermore National Laboratory. Hear untold stories, meet boundary-pushing pioneers, and get unparalleled access inside the gates. From national security challenges to computing revolutions, discover the innovations that are shaping tomorrow, today. So what got me into this field, honestly, was the fact that we don't know too much about the brain, right? There's so little that we understand about something that's between our two ears.

Our tools can be used to delve into that understanding of what's happening in the human brain. That's Allison Ureda, a staff engineer for Lawrence Livermore's Implantables Microsystem Group, where she develops flexible implantable arrays that can detect electrical and chemical signals in the body. While an implantable is any device that goes in the body, it's these brain interface devices that Allison works on that have some of the greatest potential upside. What's fascinating about this technology is that it can be used for so many different applications. We're really supplying the tools to help these neuroscientists and these neurosurgeons understand what's happening in the brain, and then also to help treat some of these afflictions.

ALS or locked-in syndrome, Parkinson's with depression, PTSD. The humbling truth is that there is so much we do not understand about these conditions. As soon as one question is answered about how the brain works, dozens of new questions emerge. What we need is more data so we can achieve greater insight into how the neurons in our brain work together and how that network might vary from person to person. For the team at Lawrence Livermore, neural implants play a vital role in moving our knowledge

and understanding of the brain forward. There's a lot of interesting information that's coming out from some of our collaborators where they're using our tools and other tools or other devices to monitor what happens in the brain. We have collaborators where they're trying to decode speech. This would be really helpful for people who are no longer able to speak, whether that's from something like ALS or locked-in syndrome. Can we take the brainwaves of these people who can't physically speak,

but actually convert it now to speech so that we can give them a voice when they've lost theirs. So that's a really impactful application of this technology that I could see moving forward into the future. You could have something like a speech prosthetic where people, they would just have to think about what they want to say. And then you have something that's said for you that brings them back that quality of life, right? That they've lost. Thinking forward into the future, not only can we use implantables to understand what's going on within the brain, but you can also flip that and say, well, can we use this to actively treat something that's going on as well? For a lot of them, people who have epilepsy, it really limits their ability. Matthew Leonard, an associate professor at the University of California, San Francisco

in the Department of Neurosurgery, has worked extensively with epilepsy patients. Even if they don't have super frequent seizures, having epilepsy and having seizures at all means for a lot of them, most of them, they can't drive. A lot of them can't live independently. It's always hanging over their heads. They don't know when the next seizure is going to come. And it could be at a time where it's perfectly fine and it's safe and they're surrounded by people who know how to help them. But it could also be at a time that's really dangerous. Epilepsy itself is a very heterogeneous disease that has a lot of different genetic and epigenetic factors that can cause it. Most people with epilepsy can control their seizures by taking a single anti-seizure medicine

or a combination of medicines. But more extreme cases require more extreme interventions. Sometimes these drugs are just not effective or they're effective in terms of reducing the severity of seizures, but maybe not the frequency. And so for a lot of these cases, that's why the sort of more extreme treatment of brain surgery is really necessary and worthwhile for them. To treat epilepsy with surgery, a surgeon must remove the area of the brain that causes seizures. However, every patient is unique, so the parts of the brain affected by epilepsy can vary. Technology, similar to the implantable electrodes developed at Lawrence Livermore, grant doctors greater accuracy when identifying which part of the brain to target for treatment.

This greater accuracy helps to minimize the risks associated with such an invasive surgery. We had one guy who was about 15 years old when he came in for this surgery. He's a musician. He's a really amazingly talented pianist, and he speaks three languages. And, you know, there's some interesting questions about, are there different areas of the brain that are involved if you're bilingual or trilingual? And he actually contacted us beforehand because it was both sort of a concern that he had to make sure that the outcome of the surgery wouldn't affect the things that he enjoys doing. He wanted to be sure that anything that might happen during the brain surgery wouldn't impact his ability to play piano.

The young man came into UCSF early so Matt and his team could monitor his brain activity before surgery. While the UCSF team did not use Lawrence Livermore-provided electrodes in this particular case, they did use devices very similar to the ones Allison described earlier. He was in the hospital with these electrodes for about a week. And the reason for the duration is really just tied to how long it takes for them to record the types of seizures that the individual patient has. So the idea is that they put these electrodes in, they go to a hospital room and they stay there and they're tethered to the wall. They have wires literally coming out of their heads. So they can't really go anywhere.

They're there really until two things happen. One is that they have a couple of seizures that are typical for them because they want to know where the seizures are coming from. The higher the density of the electrodes, the more precisely they can tell exactly where a seizure is coming from and the more precise the surgery can actually be. The other thing that's important is to be able to map out the regions of the brain that are really critical for functions that are necessary, like speech, language, movement, perception, all of these other things. And so one of the ways that that's typically done is by stimulating the brain and asking the patient to do something like produce a sentence. That whole process for both of those goals usually takes anywhere from five days to sometimes up to two or three weeks. The UCSF team created a personalized task list for the young man based on his skills. We worked with him to develop some tasks that he could do while he was in the hospital with these electrodes implanted. Things like having him learn some pieces on the piano that he could come in and play while he had the electrodes implanted in his brain.

He also helped us develop a task that involved translating between the three languages that he knew. And so we could sort of, in this very individualized way, map out the parts of his brain that were involved in these very unique skills and abilities that he had. After a week of having the electrodes in, it was time for the young man to undergo the surgery. After his surgery, after he had gone home from the hospital and he was recovered and all of that, and he had a very successful outcome from the surgery, he came back actually during one of his summer breaks in high school. He came back to the lab and he wanted to look at his own data. He wanted to analyze his own brain data. Matt's story demonstrates not only how far this type of technology has come,

but why continued investment and design improvements are needed. Real-life experiences like these help inform implantable designers and researchers on what areas they can focus on to not only make the designs more effective, but ultimately make the patient experience less burdensome. It was really rewarding to work with him. First of all, he's just such a bright kid, and I think it was very hard for him, you know, not only having epilepsy, but knowing that he had such potential and that this disease was really making it hard for him to see that through. This young man's story is just one example

of how implantable technology is advancing our understanding of the brain and its functions. But the journey doesn't stop there. Researchers at Lawrence Livermore National Laboratory and UCSF are pushing the boundaries even further. In a groundbreaking 2021 study, thin-film electrodes developed at Lawrence Livermore were

placed on patients undergoing epilepsy-related surgery to record brain activity in the hippocampus, a region crucial for memory and cognition. These flexible arrays allowed neurosurgeons to observe traveling waves of never-before-seen neural activity, shedding new light on how our brains process information. This technology could be the first step toward revolutionizing our understanding of the hippocampus's role in memory function. The electrodes provided a detailed view of how signals move across the hippocampus, revealing a two-way street of information flow that challenged the prevailing view that this activity

was only a one-way street. This new perspective could have profound implications for treating neurological disorders. For instance, researchers observed that the direction of these traveling waves correlated with specific cognitive processes. This means that in the future, we could potentially tailor treatments based on the direction of wave travel in the brain, offering more personalized and effective therapies. As we continue to unravel the mysteries of the brain, technologies like these open up new avenues for understanding and treating a wide range of conditions, from epilepsy

to PTSD. Implantable technology is already changing what we know about the brain and how we can treat conditions like epilepsy, but we still have a long march ahead to make this technology less invasive and more accessible to a greater number of patients. That's where Ruzzy Huck steps into the picture. My name is Ruzzy Huck, and I'm the Implantable Microsystems Group Lead at Lawrence Livermore National Labs. Ruzzy's job is to push the boundaries of the development of this technology, and it's a role that he takes very seriously. We ask everyone in the lab that works on these projects a very simple conceptual question.

At the end of the day, with that device that comes out, would you implant that in your own grandma? That helps put everything in perspective for us that we take it extremely seriously. Everybody would say, no, I'm going to think twice about what I'm doing. I'm going to be very careful about what I'm doing because I want to help my grandma one day. You know, what if this does end up there? I want to make sure that I'm not putting my grandma at any risk. So we take that as part of every step of the process, all the way from the design stage. We document everything that we do. When it comes to putting new technology on the market, especially implantable health tech, having radical responsibility for what you create and the development process that goes into it is absolutely necessary. We recognize that if a

device is going into the brain, that's pretty invasive. That requires a lot of surgery and time to get those into the brain. You don't want somebody to be going in for brain surgery several times a year just to replace the device. Even as the technology develops in a lab setting, the review and approval process of moving devices

from prototype to real-world testing requires rigorous FDA oversight. And so we're pushing to expand our use case from beyond just during surgery temporarily, something that can be implanted and staying in the brain for, you know, days or weeks. And the idea there being in order to have real human impact, you need to be able to have a device that can stay in the brain for months, if not years. It's really important that we get that approval for that level of longevity to be in the brain,

to have that more human impact versus more looking at the research applications only. And so it's a tough process, right? And rightfully so. The FDA wants to make sure that you always have human safety at the forefront. It's a very fast moving field. There's a lot of interest in creating these implantable devices really for neuroscience applications. And so I'm hoping that interest leads to being able to see more of these devices in human applications for that longer term studies.

And I really think we can get there. My name is Fran Fulton. I live right here in Center City, Philadelphia, and I have retinitis pigmentosa. RP is something that you're born with, and it's a degeneration of your peripheral vision. Today, the lab's implantable research focuses primarily on the brain and neuroscience. But a lot of this innovation was built upon a study from the early 2010s that focused on improving patient vision, the Artificial Retina Project. The eye's like a camera, an old-style camera. There's a lens in the front and then film in the back.

The film is the retina, the thin film. And in that film are vision cells, and those vision cells begin to die off over time. This research was aimed at creating a visual prosthetic device to restore vision for people, like Fran Fulton, with certain types of vision loss. The artificial retina project was a very big investment from Department of Energy and a lot of other areas to try to build a visual prosthesis. And that required a lot of know-how that had to be acquired, working with outside companies to translate some of this technology. And it eventually did result in a company that took that technology to the FDA and got FDA clearance and implanted that as a product in humans for the purpose of visual prosthesis.

So that's kind of the foundation of what we do today in that we use that same infrastructure, that tooling, that was an equipment that was kind of put in place at that time. And we've switched gears a little bit and focused on right now, neural implants. The artificial retina technology helped restore sight to numerous blind patients. It opened a lot of doors for researchers to expand on what else could be accomplished through implantables. The development of this technology also opened up opportunities for collaborations with other organizations. I'm really fortunate to be where I am at UCSF and in the broader community within the Bay Area as

well, which includes Lawrence Livermore Lab. Matthew Leonard of UCSF and in the broader community within the Bay Area as well, which includes Lawrence Livermore Lab. Matthew Leonard of UCSF has worked extensively with the lab on these neural implants and seen how exactly these devices have evolved over the years. What's happened over the last decade or so is that the number of electrodes that are put on one of these arrays has gone up and the size of the electrodes has gone down and some of the materials have changed. For the most part, they're things that have been around for a long time because they've been proven to be clinically viable and safe. What LNL has really started to push the frontiers on here is changing the materials that are used in the development of these arrays kind of overcomes some of the barriers to how many electrodes you can put on how small or how large of a surface.

About every two years, computer chips get more powerful while becoming smaller and cheaper. This is possible because the number of transistors on a microchip doubles while the cost of the computer actually falls. This is known as Moore's law, and it is as true for these implants as it is with computer chips. The number of electrodes that can fit on an implant are increasing, meaning more connectivity, while the size of the implant is actually decreasing. But with those gains in power comes complexity in manufacturing. As these devices get smaller and smaller, building them becomes an increasingly delicate process. Fortunately, in addition to designing these devices at Lawrence Livermore National Laboratory, they also build them on site.

Back to Allison. And so the way we make these are actually all using microfabrication technology. That's the same technology that we use to make computer chips. And so the way we make these are actually all using microfabrication technology. That's the same technology that we use to make computer chips. We're just repurposing it for this bioengineering application. Because these devices are going to be used in humans, they have to be perfectly designed and manufactured. So if you've seen those commercials where people were in these bunny suits and they're inside these what are called clean rooms, where there's really clean environments and they're making sure there's no dust particles they're especially designed to handle silicon wafers or glass wafers that are 150 millimeter

in diameter or six inches in diameter and we place those in these tools and then they will deposit gold iridium platinum like different like different metals, precious metals, metals that are safe for use in the body. And then there's equipment that can etch that material or basically remove some of that material selectively. We use a process called photolithography to define kind of patterns. You can think of it very similar to developing film.

You've got certain kind of lighting in the room to prevent kind of premature development of our patterns. So we use that as the method of how we build these things. So we've got photolithography, we've got deposition, and we've got etching. We combine all of these in a variety of steps and we build things up layer by layer, step by step. But the challenges don't start or end

at the creation of the device itself. The process of getting the people and team together to build these devices functions more like the research itself, as a step-by-step process. Step one is define the project, what are we going to build, and the funding source to continue, and how long can we work on this? Step two is defining the team, making sure that we have the ability to address all the challenges. It is a highly interdisciplinary problem. So we've got, you know, for example, electronics, we've got software, we've got packaging, and then we've got our actual devices that go in the brain or wherever they go in the body. We also include our quality

management system where we go talk to surgeons, talk to patients, talk to everyone that could be impacted by something and make sure we're encompassing all those needs and properly addressing the challenge that they face. In the medical industry, there's a lot of steps and it's very complicated, as you know. There's insurance to pay for it. There's physicians who want to treat their patients for a specific disease. And then there's, of course, the patients who have to have an implant or take medication. There's a lot of different players in this, and they all have really important roles. Step three is we build these devices and we make sure that it met our specifications. We review that again, make sure that it did what we said we were going to build.

Then we can go into the biocompatibility studies where we're verifying that the way we built this and the materials we used are safe for use. It's a complicated process that has to take place in just the right order, with just the right people, in just the right conditions. But as Fran can attest, the results are well worth it. Fran's artificial retina was able to capture her surroundings and convert it into simple light and dark signals that the brain can understand as contrast and basic shapes. It may have been crude compared to normal human vision,

but for Fran, being able to make out the outline of her grandchildren was more than she could have wished for. In the decades since Fran's experience in 2014, the teams at Lawrence Livermore have continued to expand the potential of these electrodes. With the promise of personalized real-time monitoring, precise interventions, and advanced treatment alternatives, these innovations herald a new era of potential in enhancing human health and well-being. We have these dreams of being able to help people who are paralyzed or people who can't speak. There's people who suffer from locked-in syndrome who can't talk.

Can we get them to talk one day? There's been amazing progress in that example already. There's commercially available devices out there that people use to treat Parkinson's. Can we build upon those devices and make them so that they have even more of these electrodes on the device and make those treatments more accurate? How do we get this out of the clinical environment, out of the hospital and into the real world? The possible space of scientific questions that we can ask is really kind of endless. I think any kind of behavior that we're interested in is really up for grabs with this type of technology. And this progress isn't showing any signs of slowing. The field of implantables is expected

to continue evolving with advancements in areas such as bioengineering, regenerative medicine, and neural interfaces, each offering new hopes for better treatments and outcomes. As we've heard, there's a world of possibilities waiting to be discovered. Thank you for tuning in to Big Ideas Lab. If you loved what you heard, please let us know by leaving a rating and review. And if you haven't already, don't forget to hit the follow or subscribe button in your podcast app to keep up with our latest episode. Thanks for listening.