Michel Maharbiz & Daniel Cohen, Part 1 of 2

Spectrum

Michel Maharbiz & Daniel Cohen. Michel is an Assoc Prof with EECS-UCB. His research is building micro/nano interfaces to cells and organisms: bio-derived fabrication methods. Daniel received his PhD from UCB and UCSF Dept of Bioengineering in 2013.

Transcript

Speaker 1: Spectrum's next.

Speaker 2: Okay.

Speaker 1: Welcome to spectrum the science and technology show on k a l x Berkeley, a biweekly 30 minute [00:00:30] program bringing you interviews featuring bay area scientists and technologists as well as a calendar of local events and news.

Speaker 3: Hi and good afternoon. My name is Brad Swift. I'm the host of today's show. Today we are presenting part one of two interviews with Michelle and Harb is and Daniel Cohen. Michelle is an associate professor with the Department of Electrical Engineering and computer science at UC Berkeley and the Co director of the Berkeley Sensor and actuator center. [00:01:00] His current research interests include building micro and nano interfaces to cells and organisms and exploring bio derived fabrication methods. Daniel Cohen received his phd from the Joint UC Berkeley and UCLA Department of bioengineering program in 2013 his phd advisor was Michelle Ma harvests. Together they have been working on the fronts project and NSF f Free Grant [00:01:30] F re stands for emerging frontiers and research and innovation fronts is the acronym for flexible, resorbable, organic and nanomaterial therapeutic systems. In part one of our interview, we discuss how they came to the challenge of measuring and understanding the so-called wound field. Here's part one, Michelle [inaudible] and Daniel cone. Welcome to spectrum. Thank you. Thanks. How was it that [00:02:00] electrical fields generated by wounds was discovered? So I think Daniel should take this one cause he's the, he's the group historian on this topic. In fact, he gave us a little dissertation during this thesis talk

Speaker 4: in the day when electricity was sort of still a parlor trick. There was a lot of work being done to try to figure out where it was coming from. There was a lot of mysticism associated with it. And this is in the mid to late 17 hundreds and so Galvani is a name most people have heard. Galvanism was a term [00:02:30] coined for his work and what he found was all the work with frog legs. So he used to dissect frogs and could show that if you had dissimilar metals in contact with different parts of the muscle and the nerves, the legs with twitch and amputate the frog leg. So his conclusion was that electricity had something to do with life and their living things were made alive by having this spark of life. And this was a really super controversial idea because for a long time there had been a philosophical debate raging about vitalism versus mechanism, which is the idea that all living things are special because of some intrinsic vital force versus the idea [00:03:00] that physical principles explain life.

Speaker 4: So the vitalist really liked this idea that electricity is the spark that makes living things special. There's a lot of dispute about this, but eventually Volta who is right after him and who the vault is named after showed that it was really just the movement of ions and things in salt solutions, but it was a little too late and the mystical aspect of this had come along. So the problem then was that this idea prevailed into the early 18 hundreds and so Galvani his nephew Aldini started doing [00:03:30] these experiments in England where he was given permission to take executed criminals and basically play with the corpses and he was able to create a corpus that would go like this. And raise an arm or wink an eye at an audience. And this was the idea of the reanimated corpse. So people were having a lot of fun with this, but it wasn't clear that it wasn't mystical.

Speaker 4: And so this is the long answer to the question, but that's the backdrop where the science starts to come in. So the first thing is Frankenstein gets published out of this, and everybody's getting into the whole vitalism idea [00:04:00] at this point. And Frankenstein was written as a part of a horror story competition. It was almost a joke. But the funny thing is Frankenstein. Well, how would you say Frankenstein? The monster came to life to lightning? Like that's a line. It wasn't a Hollywood fabrication and everyone assumed that. But Mary Shelley never wrote anything about lightning or electricity. She in fact, wrote the technology was too dangerous to describe in texts for the average person. But in her preface, she explains that the whole origin of this idea, and this is where the answer to the question comes from, was that [00:04:30] she had writer's block when she was writing the story and she overheard her husband Percy Shelley and Lord Byron having an argument about work done by Erasmus, Darwin and Erasmus.

Speaker 4: Darwin was a big natural philosopher or scientist at the time who was a big vitalist. So he's really into the idea of the spark of life and also this idea of spontaneous generation that where does life come from when you have a compost heap, fruit flies appear. There was an idea that be composing garbage produced life, and that was part of spontaneous generation. And he did a lot of experiments where he'd seal things like wet flour into a bell jar [00:05:00] and to show that organisms came out in a sealed environment and they just didn't know about microorganisms and things like that. So he did a famous experiment where he dehydrated some species called Vermicelli all. Sorry, I made the mistake. I'm about to talk about 40 cello, which is a little organism. And when he added water again, they came back to life. Now, Lord Byron and Percy Shelley didn't understand any of this, and the conversation that Mary Shelley eavesdropped on was one where they said that Erasmus Darwin had taken Vermicelli Pasta, put it inside the Bell Jar, sealed [00:05:30] it, and through some magic of his own allowed it to twitch.

Speaker 4: So he had essentially given life to pasta. Now Mary Shelley wrote that she didn't believe any of this was actually really what happened. But this idea of animating the inanimate gave her the idea for Frankenstein. Then she writes the one line that links it to electricity, which is, and if any technology would have done this, it would probably have been galvanism, which is this idea of applying electricity to something. And so that's where this whole idea of life and electricity came from. By that point, the scientists had finally [00:06:00] caught up with all the mysticism and started to do more serious experiments, and that's when Carlo met Tucci in 18 and 30 something found that when you cut yourself, there's some sort of electrical signal at the injury source. And that was his main contribution that was called the wound current or the wound field and then after him was the guy who really formalized the whole thing, which was do Bob Raymond, who was a German electrophysiologist who found that if you have any sort of injury, he could actually measure a current flowing at the side of the injury.

Speaker 4: He could show that that changed over time. He cut his own thumb and [00:06:30] measured the current flow and they didn't have an explanation for why it happened, but they knew that it had something to do with the electric chemistry there. This was the birth of electrophysiology and then he went off and did all these things with action potentials in neurons, which is why almost no one's heard about this injury side and the fact that electricity's everywhere in the body normally and it's not mystical, it's electrochemical. We're much more familiar with the neural stuff and this other stuff on the wound side sort of languished until maybe the late 19 hundreds because it was rare. It was weird. It wasn't clearly important [00:07:00] and a lot of the players involved were so caught up in all sorts of other things that we tend to forget about this. So that was the whole long winded history of where the wound field came from. But it's a good story. It is a good story. Yeah.

Speaker 5: [inaudible] you are listening to spectrum KALX Berkeley. Our guests are Michael ml harvest and and Daniel Colon. They're both bioengineers in the next segment they talk about the genesis of the fronts [00:07:30] project.

Speaker 6: Michelle, when you approached the NSF yeah. For a grant for this idea, how long had you been thinking about it? The smart bandage idea, how far down stream were you with the idea? We had been toying with the idea for quite some time and there's a bit of background to this as well. So my group amongst other things builds flexible electrode systems. [00:08:00] You can call them for neuroscience in your engineering, and most of those systems are intended to record electrical signals across many different points across many electrodes usually honor in the brain. And so we had this basic technology lying around. This is sort of a competence that the group has had for quite awhile. The other thing that was beginning to intrigue us, and I have to credit Daniel for sort of beginning of the discussions and kind of pushing this along in the early years, so Daniel and I have like a tube man club of sitting around thinking of crazy things and [00:08:30] one of the things that Daniel had been interested in was the idea of resorbing or having so some of the materials disappear as they do their job in the body and this is a notion that's become very popular recently actually over the last couple of years in into community in the engineering community in general.

Speaker 6: Which brings us to another question I had, which is the difference between resorption

Speaker 4: and absorption. Absorption might imply that you're taking the components up and they're becoming part of the body. Resorption is really just a very strange [00:09:00] semantic term. That means something like the body's breaking it down or it's breaking down in some form and it's not really the same as that material winding up elsewhere in your tissues. It may just get excreted or it may go somewhere else. So really we use it when we don't really know what's going on. Yeah, we had been looking at this general area and then I think the last piece of the puzzle, I think in our minds looking at the extant literature, the idea that we could take meaningful electrical data from a wound began to really interest us. And so the [00:09:30] two parts of this really are one, can you use portable, resorbable systems? Something like a bandage, you know, something that that isn't going to require you to walk around with a handcart.

Speaker 4: Can you use systems like this to measure electrical signals that are relevant to wounds? And then the other question is if you can do that, and if you have, you know, you learn about this, and by the way, we're not the first people to try to do this. There are a number of people that have been measuring electrical signals in the wounds as Daniel set for quite some time. If you can do this, is there a value to [00:10:00] trying to control or modulate that electrical information or those fields or those currents in the wound? Is there a therapeutic value? Perhaps there are scientific value. Is there something you can learn about the way the body works or tissue works? Both of those are open questions and you know we can delve into each of those, but those are really kind of how we think about them separately a little bit.

Speaker 4: The flip side is that when we do a lot of this kind of design for medical things, you will want to know what's already happening and how the body handles its own injuries. And this field doesn't just arise passively. So they had no way of knowing [00:10:30] this when it was first discovered. But when you get this electric field, there is a navigational effect for incoming cells to the injury. So it actually helps guide things in like a lighthouse to the wound site. And so a lot of my phd work was showing how you can steer ourselves with a controlled electric field so you can really hurt them like sheep based on how the electric field goes. And that means that that was a source of this bio inspired part of it, which is we're not adding something that's not already there. We're taking something that's already there and we're modulating it to maybe improve.

Speaker 4: [00:11:00] So evolutionary tools or things that the body has, it just happened to work well enough for us to survive as a species. It doesn't mean it's optimized and this field tends to go away very quickly. Nobody really knows whether extending the duration of the field would improve the healing or if we could shape it. Maybe you can control how scar tissue forms and things like that. So there's this idea of looking at how the body already heals itself and then figuring out where you might start to control it. And electricity is one of the areas that's really been under utilized in medical technology for the sort of thing. Yeah. I think for those of your audience [00:11:30] that are sort of tech junkies, if you will, the resurgence of this type of thing. Occurrent Lee I think arises because we've gotten very good at building very low power, very small electronics, and there's been a whole slew of new polymers and sort of new flexible substrates that are also conductive or can hold conductors. And so those two things together rekindled interest and trying to build gadgets that sit

Speaker 6: on the skin. Or in the NSF case, we're not only doing the skin, but we're trying to develop a tool longterm [00:12:00] for surgeons to do something inside the body. So it'd be nice to be able to leave something that will help you heal, but then it'll be resorts so you don't have to reopen. Right.

Speaker 5: Spectrum is a public affairs show on k a l x Berkeley. Our guests are Michelle. My heart is in Daniel Cohen of UC Berkeley. They want to build a smart bandage for wounds. In the next segment, they talk about the focus of their research.

Speaker 6: [00:12:30] So in your approach to the NSF, was there some sort of focus, there's a technological focus and an application focus? The technological focus for the NSF was to point out that there was a lot of fundamental engineering science that had to be done to produce the type of systems that could do this. You know, we're looking at resorbable batteries are real parts wise, how you would build these systems, what polymers you'd use, what the rates of resorption. There's a lot of just fundamental stuff going on. If you posit that there'll be value to [00:13:00] these kinds of things. That's one focus as the other focus. I would say application wise we're looking at two things. The most ambitious is that you could develop systems that a surgeon could use for internal wounds. So the dream is a surgeon is, for example, let's say you have to resect the part of your intestine.

Speaker 6: You then have to fuse the two parts that are left behind. There are methods for doing this and there's still research going on into what we know. The clinical methodology for this. It would be very useful if you could leave behind something that [00:13:30] could tell you, if nothing else, the state of how that is healing but would then go away because you're certainly not going to go back and open somebody's abdomen to take out a little piece of sensor that was doing something to intestine. Right? That'd be a not a good idea, and so that idea, that dream that you could leave behind, very small, very thin things that could take data if nothing else. Take data is really what was one of the applications. The other one is surface wounds. There are lots of surface wounds caused by illness. For example, advanced diabetes produces a [00:14:00] lot of problems in the extremities and wounds that are chronic that don't heal very well.

Speaker 6: There's just a lot of ongoing interest in surface wounds and not just the technologies for understanding how they may be healing, but in things that maybe could help heal those surface wounds. Those are our full side view welders. I think of them as there are specific things we want to show we can do with our partners at UCLA, but there's also an entire wealth of engineering science that has to be done to build the fundamental. So the NSF was okay with that broad [00:14:30] a portfolio of research. Well, so that's sort of what their mandate is to go broad like that. Cause that seems like you're, you're doing stuff.

Speaker 4: I think their main concern here is that they specifically discourage healthcare applications as NIH can fund those. But the difference is that what engineers have found for a long time now is that we don't actually know how to engineer biology. So any technology brings quantification

Speaker 6: and an engineering mindset to solving this, like tissue engineering, growing organs. We don't have a lot of engineering for that. But if we start [00:15:00] to monitor everything we can, that chemical signals mechanical, electrical, we build up a set of stimulus and response type rules. We understand how to perturb these systems. So in the same way that you might build a bridge according to a manual of how you build a bridge and how you look at the loads in it and the ways of building a bridge, we might someday build organs. So if that's the pitch, that's much more fundamental science and that's really where it has a medical application. But we can't do it without science and engineering principles that just don't exist right now. There's two points I should mention. First of all, the key is this work [00:15:30] is really looking at the fundamentals of the engineering and the science.

Speaker 6: We certainly have our foot into clinical side because I think it informs some of this, right? So that what you're doing is relevant so that someday you could go down that path so you're not in isolation because if you're not assuming that you're headed in this great direction. Exactly. And then you find clinical guys saying less clinically. Right. So the other were very good. And the second thing is that, um, we're funded under a slightly broader grant mechanism than usual. So we have a, what's called an NSF. Every, I think this is emerging frontiers and research and innovation I think [00:16:00] is what it is and these are sort of headline or marquee type thing. So we're very lucky that we were awarded one of these and so I think the NSF has really looking for this broad, far reaching hard-hitting effort. I think there's a good point to mention that this project is really a big collaboration between a number of us and I'd like to mention who they are because some of the material work has done by very talented people in the department on a rds and the Vec Subramanian are two professors in the ECS department and they're very well known for flexible printed systems and [00:16:30] the materials that go into them and we work also with Shovel Roy at UCF and Mike Harrison and Mike is a sort of brilliant pediatric surgeon and shovel.

Speaker 6: Roy's well known for the technologies he builds at the interface with clinical need. It's really the fact that all these people come together that we're building all of these tools.

Speaker 7: [inaudible]

Speaker 3: spectrum is a science and technology show on KALX Berkeley. We are talking with Michelle Mull Harvest Daniel Cohen. [00:17:00] They are researching the electrical field that is generated by wounds in mammals. Their hope is to collect meaningful data from sensors embedded in bandages placed on wounds.

Speaker 6: If you approached interpreting and analyzing the electrical field data that you're getting out of the wounds in an animal right now we're being very cautious. We started a first few experiments with rodents over the last six months. What we've [00:17:30] built is a, is a series of systems. You can think of them as insulators with lots of little electrodes all over them. An array of of little electrodes. They're on order of a centimeter or less in terms of you can think of a postage stamp, maybe a bit smaller. We have different varieties of them. Some are stiff, some are very flexible. You can think of it as contact lenses or transparency paper, that kind of thing. And these arrays are connected to electrical sensing equipment. There's a miniaturize a little board that runs everything [00:18:00] and sends data to a block and all this data is collected and what we're currently looking at as a variety of different signals on both open wounds.

Speaker 6: So if I, for example, cut the skin and on pressure wounds, pressure wounds or something that people that don't see clinics very often or hospitals aren't familiar with but in fact are huge, huge problem in hospitals right now. Then we lay these arrays over the tissue and we measure a variety of different things. One thing we measure what's known as electrical impedance between different [00:18:30] points on the array and you can think of electrical impedance as how much resistance to an electric current that tissue might produce. It's not a steady current, it's a time bearing current, so we sort of wiggle the current on and off, on and off negative, positive, negative, a sinusoidal and how quickly that current responds and how much of it there is. That allows us to calculate the impedance and there's a lot you can tell from that. You can tell whether things are very wet and conductive.

Speaker 6: You can tell whether the tissue is tight knit, so that doesn't let things through a oily. You can tell whether there [00:19:00] might be changes in from one tissue to another. You can infer things about what tissues are might be underneath. The other thing we measure is actually electric potential when the wounds are immediately after they're made. We try to look at what kind of potentials arise and how they're changing. So right now that's in terms of measurement. That's really what we're looking at it. And another thing I should point out as we do these measurements as a function of frequency across a wide range of frequency spectrum up to hundreds of kilohertz. And that's sort of the rapidity with which we wiggle the signal because different components in the tissue [00:19:30] will respond differently at different legal frequencies. Once we have that complete plot, we can look at the difference between them and by to see whether we can build models that tell us, oh well we've, you see this type of distribution.

Speaker 6: There's a in tech skin for example. So the dream, in this case, you put your bandaid on and your doctor checks his eye, his or her iPhone every 12 to 24 hours and just gets a different little map of how it's working without ever having to remove the dressing. How are you doing in understanding what those signals mean in terms of healing? [00:20:00] But we just had a meeting, they're doing great. They've basically collected a great deal of data on the latest set of wounds they did and now they're in fact proposing models and seeing how the data fits. They're fitting their models to the data to try to use those fits as ways of discriminating different types of tissues. So we're in the middle of it right now. I couldn't tell you much. We're still putting all that story together for publication. So, and are you able to leverage the work that other people are doing? Oh, absolutely. Sure. Well, I mean you always do that. Like I said, nothing is in a vacuum, right? So absolutely. We follow [00:20:30] the literature and, and we build off of what other people have found and try to add our own contributions. That's, that's how it works. Maybe these ideas came from discoveries from the 18 hundreds and then later on in the 1980s onwards, a bunch of really good developmental biologists have really pioneered a lot of this and gone down as, as showing that

Speaker 4: even in an embryo you can detect changes in electrical potential at the surface of the embryo where limbs will form and things like that. So there's a huge amount of stuff out there that gave us the idea for the original thing, but we're barely scratching the surface. [00:21:00] We were technologist, right? We're engineers. So part of one thing and figure it out. Yeah. So the idea of trying to analyze the wound field data, do you have to solve that problem first before you can take on anything else? Like trying to instigate the healing? Yeah. Yeah, I would say so. You would never put this in the body without knowing, knowing that a real lot works. But on the surface it's a different healing mechanism than say a fracture, but it's still the idea that we don't necessarily know what the cause and [00:21:30] effect is yet. So we have to show that getting a field out relates to some state that we can say the wound is in and that we can intelligently put a field back in that actually helps. So we need some metric of success. And without that metric, that number that says the wound is doing better or worse, we're not confident saying that our stimulation is helping. So that's why getting this data first is really important.

Speaker 6: The parameter space is fairly large, right? To number of things you could possibly change. Some of the effects are very subtle. And so just willy nilly going [00:22:00] in there and saying, oh, I applied some fields, you know, likely not gonna be very useful. And then there's another subtlety, which is that there are probably clinical contexts in which this is of limited utility, even if it works. And so that is, uh, something we spend a lot of time thinking about. So let me give you an example. Let's say I told you I can make that little cut on your knees heal 5% faster with a $15 bandaid. I'm pretty sure you're not going to buy a $15 [inaudible] except maybe once for the novelty of it. You know it tickles. But [00:22:30] there are contexts where, and Daniel alluded to this earlier, for example, scar formation is a big deal, right?

Speaker 6: How a scar forms and the trajectory of the wound healing for certain load-bearing wounds of really big deal, right? Think of your abdomen if you had to go in there and hurt those muscles or hernia. And there are many things like this and so if, and I want to be very careful to say if if it was founded, electrical interventions can affect that type of healing in a way that produces a useful outcome, right? Much better scar developments so that your load bearing properties are [00:23:00] maybe not as good as the original, but a lot better than just letting it sit around with a dressing. That'll be a very big deal. But that's a very big space, right?

Speaker 4: And that's why we split it into this in Vivo work on monitoring the surface and wound properties and in vitro work where we have cells and tissues and culture where we can directly stimulate them in culture in a very controlled environment and watch exactly how they respond to different shapes of fields and types of fields and come up with a way of describing how they behave. That doesn't require the Nvivo work. So we have two parallel tracks [00:23:30] right now and hopefully we can put them together.

Speaker 5: [inaudible] be sure to catch part two of this interview with Michelle Maha Urbis and Daniel Cohen on the next spectrum in two weeks. In that interview, Michelle and Daniel talk about the limitations of sensors on or in humans, the ethics of sensing and inputs into living systems and moving research discoveries

Speaker 8: into startup companies. Spectrum shows are [00:24:00] archived on iTunes university. We've created a simple link to get you there. The link is tiny url.com/k a l ex spectrum. We hope you can get out to a few of the science and technology events happening locally over the next two weeks. Renee Rao and Rick Karnofsky present the calendar

Speaker 9: nerd night east space first show of 2014 will be happening January 27th the show features three great Speakers. [00:24:30] First nerd night, San Francisco alum, Bradley boy tech. We'll guide you through how scientists organize and present some of the vast amounts of data available today. Then the Chabot space centers, Benjamin [inaudible] will discuss the most likely places to find life off of planet earth. Of course, finally KQ Eighties Lisa Allah Ferris will tell you what you need to know about Obamacare. The show will be held this Monday, the 27th at the new Parkway Theater in Oakland. Doors open at seven to get tickets for the HR event. [00:25:00] Go to East Bay nerd night, spelled n I t e.com this February 2nd the California Academy of Sciences will host a lecture on the Ice Age Fonda of the bay area. There's a good chance that wherever you happen to be sitting or standing is a spot where Colombian mamis giants laws direwolves, saber tooth cats and other megafauna. Also Rome during the ice age. Learn about the real giants of San Francisco and how you can embark upon [00:25:30] a local journey to see evidence of these extraordinary extinct animals. The lecture will be held@theacademyonfebruarysecondfromninefortyfiveamtotwelvepmticketsareavailableonlineatcalacademy.org

Speaker 8: February's East Bay Science cafe. We'll be on Wednesday the fifth from seven to 9:00 PM at Cafe Val Paris, CEO 1403 Solano in Albany, Dr. Harry Green. We'll discuss his book [00:26:00] tracks and shadows field biology as art green, a herpetologist at Cornell blends personal memoir with natural history. He'll discuss the nuts and bolts of field research and teaching how he sees science aiding and in conservation and appreciation of nature, as well as give many tales about his favorite subject. Snakes. For more information about this free event, visit the cafes page on the website of the Berkeley Natural History Museum at BN [00:26:30] h m. Dot berkeley.edu/about/science cafe dot PHP. A feature of spectrum is to present news stories we find interesting. Rick Karnofsky and Rene Rao present our news in a letter published in January 15th nature. James us or would a locomotor biomechanist at the Royal Veterinary College at the University of London and colleagues explain why Birds Migrate In v-shaped [00:27:00] formations. The team fitted several northern bald ibis is with gps trackers and accelerometers to measure wing movement. They found that the birds positioned themselves in optimum positions that agree with their aerodynamic models. Further the birds flap in phase with one another when in such permissions instead of the antifreeze flapping, they performed when following immediately behind each other. This in phase flapping maximizes lifted the plot [00:27:30] and is surprising as a team noted. The aerodynamic accomplishments were previously not thought possible for birds because of the complex flight dynamics and sensory feedback that would be required to perform such a feat.

Speaker 9: The tenuous place in the human family tree of artifice guest room, it is a 4.4 million year old African primate has recently been solidified. Fossil remains Ardipithecus Ramidus or rd as a species is known first discovered by UC Berkeley [00:28:00] Professor Tim White and his team in Ethiopia in the 1990s and have proven a consternation to classify ever sense rd displays an unusual mixture of human and ape traits. Fossils reveals small human like teeth and upper pelvis adapted to bipedal motion, but a disproportionately small brain and grasping large toes, best suited for climbing trees. Scientists split over whether rd was our distant relative, essentially an ape that retained a few human features from along a common ancestor [00:28:30] or our close cousin, possibly even an ancestor. Recently Tim white among many others coauthored a paper with Arizona State Universities, William Kimball in which they successfully linked the rd to Australopithecus and thereby to humans. The team examine the basis of rd skulls and found surprising similarities to human and Australopithecines skulls indicating that those had already been may have been small. It was far more similar to a hominids than an apes

Speaker 7: in in

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