SPEAKER_00

Wait, wait. So it's not wired. It's magnetic field.

unknown

Yeah.

SPEAKER_00

The thing you're wearing doesn't actually have to be wired to the thing that's No, no, it's just a wearable. It's like a little patch that you take on the top. So you don't have to worry about all the immunological. No wires. Yeah. So okay. So there is so it really is like a harvesting. Yeah. It's not harvesting from you just have to wear like an armband with a net with a battery. Exactly right. Okay, like over right over the top of it.

SPEAKER_02

Yeah. Okay. Yeah.

SPEAKER_00

This is it. Hi everyone.

unknown

Yeah.

SPEAKER_00

Christian. Yes. He's a professor of electrical engineering at St.

SPEAKER_01

So thanks. Thanks for uh coming by.

SPEAKER_00

Yeah. You're from um you're from Evanston.

SPEAKER_01

So I've had kind of a uh I've been all over. So I grew up in India actually, but I lived in St. Louis for five years, Urbana Champaign for two years, Evanston Rogers Park for three years. So it's St.

SPEAKER_00

Rogers Park. Those aren't the same.

SPEAKER_01

Those are not the same. No, I lived. Well, so I was on Howard. Shut up. Yeah. And uh I was right or just off Howard, just on the Rogers Park side. Okay. Uh I lived there for a couple of years.

SPEAKER_00

Yeah. What you what age were you?

SPEAKER_01

I was in my mid-20s.

SPEAKER_00

That would have been 25 or 26. Okay. So not like grown up, not like you wouldn't know the schools.

SPEAKER_01

No, no, no. This was when I was sort of midway through PhD school. Yeah. Yeah. So your PhD. Uh I started off at uh Urbana Champaign and my PhD advisor moved about two years into my PhD to Northwestern. So midway through I upped and went.

SPEAKER_00

And you know, I rocked you didn't end up downtown to the campus or at the Evanston campus. You were on Howard?

SPEAKER_01

Uh I lived on Howard, but yeah, I would I would bike up to uh the Evanston campus every day. Yeah.

SPEAKER_00

But I mean that's right. That's literally where I grew up.

SPEAKER_01

Oh, really?

SPEAKER_00

So like my cus so I grew up I was born at Grant and Gray, like near it's McCormick, um, but like up near Central Abbott. It's uh um like a mile into Evanston on the north side. Okay, and six we moved to Wilmot, like one block into Wilmot. Okay, because my parents wanted that school system. Yeah, it did. V town's fine, right? Yeah. So I grew up just a couple blocks from Dyke Stadium, which is a little wine field. Yeah. Um and my cousin lived uh at Ashbury. It was so like he lived on the south side of Evanston. Okay, right? Okay, pretty close to I don't know if you would know it as Mount Trashmore then. No, I don't think that was a thing when my when I was there. It was, but it but it's free. So there's this huge hill that's in a big green field. Okay, that kids use as a sledding hill. Okay. Um it's like everything's flat, and then there's this really big hill where it's a garbage dunk that got like soddered over. That's funny. And it's right near where you were. That's interesting. I had like these big athletic feels there, and it's like right in the middle of that.

SPEAKER_01

I think I know the feels you're talking about.

SPEAKER_00

Uh like it's like oakden. What sense? It's like oakden or something like that. It's the is the big, it's like there's Howard and the next big one is like oak something. Right, right.

SPEAKER_01

Right, right. Yeah, yeah, that's interesting. Yeah, that that was uh, I mean, I really enjoyed my out of time in the Midwest. I like a decade, yeah. Yeah, yeah. Yeah, I I I liked it a lot. Uh I didn't necessarily plan to spend a decade in the Midwest, but you know, showed up and sort of quickly took to it. How on earth did you end up at St.

SPEAKER_00

Louis and then in you is was it family like high school? Like when you like how did you because I yeah, I saw Washu and UI. Yeah.

SPEAKER_01

One assumes, right?

SPEAKER_00

Yeah, it's like all like we all kind of, you know, I assumed you were from the area because otherwise you don't know of those schools.

SPEAKER_01

Yeah, so UI.

SPEAKER_00

So okay, so I grew up in an electrical engineer, right? Then U of I would be a thing.

SPEAKER_01

Exactly. So, but Washiu still not really, right? So it was there's actually a funny, weird story about this. I grew up in South India, so in in a city called Chennai, and uh Washu was definitely not on my high school, on my college radar. Uh my sister went to UT Austin, so I knew about you know the big engineering heavy public universities, UT, Illinois, Michigan. These were Berkeley, these were kind of on the radar. Yeah, exactly. And uh well, I my mom fortunately was more plugged in than I was.

SPEAKER_00

But in your family's engineers.

SPEAKER_01

No, I'm the only engineer. My sister's actually an architect. Uh but and my my mom is in, she's worked at she's been in banking for a long time. My dad was an entrepreneur in e-commerce. So no, I I there's practically no engineers in my immediate family. And I have a couple second cousins who did engineering. Yeah, yes. It was a it was a long circuitous journey. I didn't even start off engineering. I started started off Washu. Uh, I don't know if they had this when you were at Washu, but they had something called Interdisciplinary Project in the Humanities IPH. And funny, I did P PNP. PNP, that's right. So that's one of the first year, that's one of the freshman programs.

SPEAKER_00

Like, is it the same? No, is it no?

SPEAKER_01

But there's like this buffet of freshman options you can take. ENP was one, IPH was the other.

SPEAKER_00

It was like brand new when I was there. I discovered it when I was a senior. Ah, okay. Because I I like did psychology and had this whole like insight into like, oh my God, there's like this overlap between psychology and linguistics and evolution. Right. And right, like all these things, right? It was psychology, philosophy, and evolution was there's like this something here. And I was talking to friends about them, they were like, Well, that's the PNP major. Yeah. I was like, oh my God.

SPEAKER_01

So you ended up doing it?

SPEAKER_00

Yeah, after I finished the psych major, I did the PNP majors. Oh, that's cool.

SPEAKER_01

Yeah, I mean, I had a bunch of friends who did PNP, and they I mean, many of them ended up going on to PhDs and things, and they they really loved it, or med school. Yeah, to be a lighting designer for rock bands. Oh did that's even better. Even better. Yeah. Um, but yeah, no, in my case, I did the humanities and I liked it, but you know, and growing up in India, math and physics were pretty heavily emphasized, and I did that. Yeah, uh, and a part of me really liked physics, but uh just the pure physics stuff feel felt you know a little too theoretical for me. Disconnected. Yeah, I like building stuff, right? And so I actually went, ended up going, you know, after my first semester or second semester, I took the physics classes, and I mean, I was I was walking back uh from Olin Library one night, and I saw a light on in one of the labs, and I thought, that's cool. Someone's out there, you know, working little things. Those little things, yeah. We were walking past the bunny rabbit or something. Exactly. It was right by the bunny rabbit. Exactly. Yeah, yeah. And there was a lab right there, and someone was it was the light was on at like 11 p.m. And I was like, that's cool. Someone's there doing real stuff. You're like what I want to do. That's what I want to be doing. 11 p.m. Yeah, exactly. Little did I know that was exactly what I was signing up for.

SPEAKER_00

Right. I want to be in the lab. Right. That's definitely the place to be.

SPEAKER_01

So I switched majors uh into engineering. It was actually mechanical engineering. I did as an undergrad and master's student and did research, fell in love with it. Um why why did I do research?

SPEAKER_00

No, no, what was the project you felt like? Because you see like building stuff. What did you build?

SPEAKER_01

Yeah.

SPEAKER_00

So it was like, this is like I love this.

SPEAKER_01

Yeah. So when I was in high school, I actually my grandfather was a big electronics tinkerer nerd kind of person, right? And Radio Shack guy. Yeah, big time, big time. And so he had his whole sort of room was this cool workstation. He didn't have any formal education in this, he was very much one of those self-taught old school tinkerers. He, you know, in the 60s, he bought himself radio kits and would assemble them and things. And just liked having a soldering iron. Exactly, exactly. And he taught me how to do it. And when I was in high school, I was I played like guitar and I obviously wanted to build my own amplifier. I thought that was a cool analog thing to do. And uh, so I said, uh Sim and I actually built this amp together and he taught me how to solder these things, and and it was just so much fun. I mean, I still have the amp, it's it's like not a good amp. Oh heavy on the distortion, but but it was cool and it and it basically worked. No, no. But it worked to first order, it worked, and I thought it was just like so cool. And he brought you and your grandpa together, yeah. 100%. And we've all we were always very close, but this was like his big thing. He never got to go to engineering school because of his circumstances. But I think you know, when I decided to go that path, it was very much informed by loving to build stuff with him, and it was it was great.

SPEAKER_00

That's really nice. Yeah, like that's lovely.

SPEAKER_01

Yeah, him and I were always super close, and yeah, so that kind of pushed me in that direction. I worked in a lab at Wash U that uh did nothing to do with what I'm doing now. It was a combustion lab because I had this idea back then that I wanted to be doing things with energy, and uh I didn't really know how to plug in. You know, 1920, I didn't really know what much about anything. And I said, okay, the first cool lab that, you know, was willing to give an undergrad a summer job, I took on and um combustion. Combustion, yeah, like fossil fuels. Yeah.

SPEAKER_00

I feel like we've we've pretty much established that technology.

SPEAKER_01

Right. And I think the idea there was been engineering that absolutely, yeah. And I that was kind of, you know, it was, you know, there's people trying to make it less suit less suit emitting and less carbon emitting and things like that. That's the basic idea around some of that stuff. But anyway, I did it and I, you know, I really loved the sort of physics and the chemistry behind it. And, you know, I was building all these crazy contraptions and got to play with big flames, and you know, that's always fun. Um, but I think at some point I was like, well, yeah, maybe, you know, moving, looking ahead, I want to do something that feels like it could drive the future, right? And for me, that was really material science. And I and I remember writing in my personal statement. I thought it was so original. I've since read many personal statements that they all say.

SPEAKER_00

Man, there's nothing. Yeah, but but anyway, I'm sure, I'm sure you definitely get much better at writing that is after you read a ton of them. You're like, oh my God. Absolutely. Yeah.

SPEAKER_01

Yeah. And I remember writing, like, well, you know, historically, all of uh all of our historical epochs have been defined by the material we use Bronze Age, Stone Age, Iron Age, all this. So what is, you know, I materials clearly are going to define our future as well. So I want to do material science. So I applied to the best material science program that was sort of MIT. Uh I actually didn't apply to MIT, but the one closest to me that was kind of on my ray. I applied to uh I don't even remember where I applied, but Illinois was very high on my radar, and it's always been a wonderful material science program.

SPEAKER_00

At this point, you're still in India.

SPEAKER_01

No, I was at Washu at this point. I was sort of deep into Washu.

SPEAKER_00

Sorry, I apologize. So you're now you're applying to grad school.

SPEAKER_01

Grad school, yeah. So I was doing research in this combustion lab, and I went to uh I was at Washu and uh Illinois was there. And and this is one more of those. I mean, if I when I actually talk about this, I'm realizing it all sounds very very lucky, and oh my god, I can't believe it happened that way, but I guess that's just how it is. But I was reading a New Yorker article uh right around the time I was applying to grad school. And the New Yorker article had it was they have this annual science issue. And that year in the science issue, they featured a material scientist at the University of Illinois. And literally saw the light on in the lab. Yeah, right. Same thing again. I'm reading this New Yorker article. Uh it was around December. Uh so school's out, finals are done, and I'm it's also grad school application time. So I'm reading the science uh December issue, and the material scientist's name is John Rogers. And uh I just thought it was the most futuristic sci-fi kind of thing where so so what he was working on was taking uh silicon semiconductors, which are the backbone of all integrated circuits and logic and memory, and we use them all the time. Yeah, yeah. And you know, basically making these very rigid, brittle wafer type things and making them giving them the properties of rubber bands, so making them stretchable and soft and sort of integrating them into the body. Right. So he had done a bunch of work on that, I think, early in his career, but then sort of pivoted to wearables. And now you're inside now. You're all about what you'd like to do. I've done a bunch of wearables, yeah. But but I think what he he did was he he sort of made the connection between stretchable silicon circuits, which he had a big role in inventing, uh, and said that you know, biomedical applications are such a natural application of these things. Yeah. Whether it's wearables or organ-mounted devices or brain-implantable neurodevices, e-coggeries.

SPEAKER_00

So yeah, we use those in neurosurgery all the time. Right. Yeah.

SPEAKER_01

Right. So uh so I'm reading this article. It's it's it was incredible stuff, right? And so I'm reading this article in the New Yorker Science issue, and just like my mind was blown. I just thought, oh my God, this is the coolest thing I've ever heard about. So uh, and one of those fortuitous things that I had already sent in my application to U of I. And I got in a couple of weeks later, and the first email I sent was to him saying after you got in. After I sent him an email right away. No, I I I waited a little bit, I got in, but the moment I got that acceptance, I was like, I just got accepted. Please, please, please, can I work in your group?

SPEAKER_02

Yeah.

SPEAKER_01

And uh, you know, he said, okay.

SPEAKER_00

It's a hard thing to refuse. I mean, he just Yeah, because all you want is grad students to like really want to be in your lab. Like you just want them to want to be there.

SPEAKER_01

I mean, I still feel like I was really lucky though, because uh, you know, a lot of people wanted to be in his lab. So maybe I was just early. I don't in hindsight, I don't know.

SPEAKER_00

What maybe maybe your resume was strong, you know.

SPEAKER_01

I in hindsight, I you know, I I don't know what it was, but he said yes, and that kind of was what and I feel a lot of love there, right?

SPEAKER_00

How do you mean well it kind of like for you it kind of like song psychiatrist? Uh-huh, right? Uh there's a lot of reasons people will like find what they do. It's like this is the place where like what is available to me is anger, and this is the place where I can like have my anger. So they might end up in like a boxer or something, or it's available to me is um dominance, right? So like I'm gonna go for dominance, right? Um, and that that uh spreads into everything somebody does, right? For you, like it's so odd, like this is love, right? I I would be your grandfather, right? Like it's like it's just like it's love. Totally. And so be like you would you would very quickly map that to like working with uh Rogers at UI. Like he it would like it's guaranteed that that relation you would you would like walk into that with all the right things for like wanting to see the good, not wanting to see the bad, right? Like wanting to um you know participate, like being willing to listen, right? Like all like all the right stuff would show up because for you it's like this connection with like an older guy who's gonna be your teacher is like you already have this rubric where that like that's just love, right? Yeah, I mean, I think you know it was that's something that like I don't get it from an email, but like you feel that and it's like yeah, I want that around.

SPEAKER_01

That's that's an yeah, that's an interesting uh take on it. I hadn't thought about it that way, but you know, certainly I I wanted to be there. I was I was hungry as well. I just thought it was exactly where I wanted to be. And um and yeah, I I was I was all in, you know, I was completely committed to this thing. And uh pretty much from day one, I I was I don't know, uh I I really loved grad school the whole time. Uh five years, we worked pretty hard. Yeah, so these days my my work is actually quite a bit different than what I was doing in grad school. Yeah. So these days, uh we're working on stuff that I think will be quite exciting for the future uh of drug delivery and medicine. Um, and the basic idea is this when you think about delivering drugs and medicines, and when you tell most people uh say the word drug, they probably are thinking, or medicine, they probably think about like an Advil or a Tylenol or something, uh something over the counter, because those are small molecules and they're routinely available. And they address a small number of druggable targets in the human genome, maybe like 4% or something. But in the last 20 years, we've gotten all of these incredible new drugs, biologic drugs that are things that will allow us to, you know, address cancer and stuff. MABs, hormones, peptides, proteins, all of these incredible new things, RNAs these days, I mean, right? Um and many of them, maybe maybe a large percentage of them, suffer from delivery challenges. So, for example, if you want to get a drug uh that can address cancer in a particular part of your body, you have to administer it systemically, that is everywhere.

SPEAKER_00

There's a lot of tagging work, there's a lot of use of use of peptide to tag it so it'll go for that's I mean, the the the um the hormonal um breast cancer targets. And it's all like we can, we can if you've got the estrogen receptor, then we can hit it. Exactly. You know, the cancer has that. Right. Tumor has that, then you go right for that target. Right. It's pretty easy to deliver the right.

SPEAKER_01

Exactly. So a lot of really fantastic chemistry has happened to enable many of these things to be targeted, but it's still a challenge. Yeah, so um, and there's also this idea of like dose control and making sure it's within, you know, many of these things you put you dose in too much and it's toxic, you dose in too little and it's ineffective. Yeah. So you want it to be in this window. So the basic idea is you can engineer cells, like live cells, uh, to produce drugs. Yeah. Uh and that's actually not that hard to do. Fairly straightforward gene engineering can do that. Yeah. And so the idea is: can you then take these cells, put them inside little devices, like electronic devices, that can have these little porous structures on the outside to prevent the immune system from attacking them.

SPEAKER_00

But also allow nutrition to come in and metabolic waste to go out.

SPEAKER_01

And the and the drug of interest to go out.

SPEAKER_00

Antibodies are pretty small.

SPEAKER_01

Uh antibodies don't kill them, is what we found. You just gotta block, you just gotta block monocytes. Right. So, and then you know, the if you can put them in this device, and then the one other big problem to solve is they tend to block, you gotta block like a cas-based cascade.

SPEAKER_00

Uh you gotta block like a uh a cell, a cell suicide signal cascade, because that would come from a small signaling molecule. You right.

SPEAKER_01

So uh so there's actually been a bunch of work on figuring out just exactly what hydrogel chemistries and device structures can give you that level of protection. Uh, but the basic idea is if you can get that figured out and importantly provide the cells with oxygen because that's a very big limiting reaction.

SPEAKER_00

Yeah, yeah, yeah. Because the diffusion range is low.

SPEAKER_01

Exactly right. Uh you can actually keep that's what this part of the problem for like, yeah.

SPEAKER_00

Yeah, like and you want to be the basic idea, but that I'm gonna I'm gonna die, like I'm gonna go after the like real science. Yeah, yeah. So this is the thing that like I always miss in podcasts. It's like, but what tell me about the real science?

SPEAKER_01

Yeah, yeah. So so the real science is you can uh take engineered cells, put them inside little devices, uh, and then they just produce the biologic drug that you need in an uh in a sustained and continuous way.

SPEAKER_00

It doesn't need to be a human cell. It could be a back because it's easier to engineer bacterials.

SPEAKER_01

It it doesn't need to be a human cell, but I think from a regulatory standpoint, it's probably better if it is. Okay. But there are actually now some FDA-approved human cell lines that you could use uh as well. So yeah, so they're they actually come their retinal retinal pigment epithelium cell line. Um to do what? So a whole host of things. So I'll tell you the the the historical uh idea of this whole field is actually for type 1 diabetes treatment. Okay. And just give you beta cells. Uh in pancreatic isolutes, which are clusters of beta cells, alpha cells, a bunch of things. Exactly. So if someone has type 1 diabetes, then the thinking is you can just trans that they're based they basically don't have pancreatic islet mass to make insulin and so on. So can you just transplant uh pancreatic isolates from a donor, someone who's donated their cells to medicine, and you have to provide immunosuppression for their whole life so that they don't reject it.

SPEAKER_00

Uh I mean why not just give them insulin?

SPEAKER_01

Uh which they do, which has also happened at this point. But I think it's way simpler. But I the the basic uh reason why you this might be better than insulin is when you have insulin pumps and CGMs, you still have profiles where this is the window where you have to be, yeah, you still have like kind of that.

SPEAKER_00

So even with even with the like skin readers and even with that automatic um dispensing.

SPEAKER_01

Yeah, it's gotten better.

SPEAKER_00

The wearable dispensers.

SPEAKER_01

Yeah, the insulin pumps. It's gotten better. But I think if you take an average of the number, the glucose number, it's still in that range.

SPEAKER_00

Is that because there's something else that the islets are doing that we haven't characterized?

SPEAKER_01

So this would be for artificial insulin pumps. They kind of have excursions inside and outside. But the pancreatic islets have what they're doing is they are uh in these transplant models, they are sitting flush up against the vasculature and they are naturally glucose sensing and naturally insulin producing. So the rate at which they can sense glucose and produce insulin in a glucose-responsive manner is faster than what we can do with our glucose readers because there's no time lag. They just can sense and sort of produce uh in an on-demand way. So they're amazing little closed loop drug-producing machines.

SPEAKER_00

It's just it's just a better time delivery sensing.

SPEAKER_01

They can also do another hormone called glucagon, yeah, uh, which increases blood sugar. So they have people with diabetes not have glucagon? They they don't have pancreatic eyelet mass, so they often don't have glucagon either.

SPEAKER_00

Yeah, that's not that's not something we get taught much in med school. Yeah. Like it's not eyelet mass. It's like the test question answer is it's a beta cell. Yeah, not the islet. It's the beta cell in the eyelet.

SPEAKER_01

In fact, it's interesting you say that because one of the really big challenges with type one treatment with these insulin pumps is a really dangerous low blood sugar episode.

SPEAKER_00

Yeah, we know we know that.

SPEAKER_01

And but the reason is because glucagon would prevent that. It because the glucagon's whole job is to bring that back up. Yeah, yeah. And people don't have that.

SPEAKER_03

Yeah.

SPEAKER_01

Yeah. So in fact, we have a hundred.

SPEAKER_00

Why don't you just add glucagon to the to the insulin pump? Why don't you just add glucagon in the pump also?

SPEAKER_01

Excellent question. Actually, have a whole set of projects around glucagon deliveries.

SPEAKER_00

But you don't have to do all the immunosuppression. I mean, that's I mean, yeah, okay, some jumpiness, but immunosuppression, blah, blah.

SPEAKER_01

It's tough, right? So the the reason and people people are certainly trying to put glucagon in pumps, but the basic challenge is it's not a very stable peptide. So it has like a like a stability of maybe 20 minutes. Exactly.

SPEAKER_00

How interesting.

SPEAKER_01

And so that's actually a good reason. And that's one's stable.

SPEAKER_00

The glucagon isn't stable.

SPEAKER_01

People have spent a lot of time making synthetic stable insulin analogs.

SPEAKER_00

Yeah.

SPEAKER_01

And glucagon is, I guess, a tougher target. There's formation of these fibrils. And uh so people haven't people have started figuring it out. Yeah. Uh I would say there's been a lot of movement in that field in the in the recent past. But yeah, so to first order, we have insulin pumps and you can use these, yeah, but we don't really have glucagon pumps that are ready to go just yet. Yeah. And so one of the biggest outcomes, and there's clinical trials that are uh that are studying dual hormone, insulin and glucagon and so on.

SPEAKER_00

But yeah, maybe a diabetic u acidosis, like the whole thing, right? Like, yeah, yeah, it's disaster.

SPEAKER_01

It's a disaster. So uh so I think there are there are efforts here, but that's that's the basic reason. So the cells can make take this peptide that's not very stable and produce it in an on-demand manner. You're not doing that part of it.

SPEAKER_00

You're doing the build the you're doing the build the container for it.

SPEAKER_01

We kind of do the whole thing. So we uh so pancreatic eyelets are in some sense a primary cell line, so we don't have to engineer them. We just get them and put them in a device and put them in from you can so for example, from or just like IPC. Often rats. Okay. You've we've done uh stem cell work as well, yeah. So you can actually so if you want to take a mouse, for example, you can harvest eyelets from a rat, right? And uh transplant them into a diabetic mouse, and we've shown that we can actually control their diabetes for months this way. Yeah. And and what's exciting about it is a rat and a mouse are different species. A human stem cell and a mouse, that's a very different species. And because we're immunoprotecting them uh in these little devices and oxygenating them, the cells actually stay alive and produce glucose and control these this blood sugar.

SPEAKER_00

And that doesn't block the sensing capacity. You'd think that would also limit the sensing capacity.

SPEAKER_01

It is so I what does block the sensing capacity a little bit is there's a fibrotic tissue formation around this.

SPEAKER_00

So there can be a little bit of a tissue like assist to like while it so there is it, so there is an immune response. Oh, certainly. And you can protect the cell itself from being from being a macrophage, but you can't, but it's still gonna create, it's still gonna bother word, it's escaping me. Um fibrosis, that's a capsule. Yeah, but anyway, yeah, it's just like it's still gonna start. Yeah, it's gonna create a capsule.

SPEAKER_01

Yeah. So that has a little bit of a time that creates a little bit of a time line.

SPEAKER_00

But the cells can you put something in your shield that can you put fibrinogen in your shield? Or uh what's uh fibrinogen? Fibrate, yeah. Fibrate, yeah. Put that in the shield so like elude just very, very seeming to be.

SPEAKER_01

Oh, people have tried all kinds of things. Do it. They've done uh they've tried that, they've tried dexamethasone as a local immunomodulator. They've tried, I mean stero is everything. Uh a whole right. And and you know, to varying degrees of success, but this is certainly not a solved problem. Okay, let's say, especially because we want to do this minimally invasively in subcutaneous sites, so you can put it in and take it out easily. And you know, we're off we don't actually have to get to the bank, it doesn't have to be in the bank to no, it could be systemic for this for this application. Put it in the shoulder. I mean, you know, insulin pumps, for example, right now are just subcutaneous. Right. So cells could be anywhere that you could just put them in your shoulder. Yeah, so we we sometimes talk about like a little bioelectronic artificial pancreas that's sitting under your skin. You put it in, take it out, and so on. Um, but we're up against billions of years of at least. So that if you want to get like wasted on Friday night, you can take it out. Yeah, well, so so the if the cells die, maybe you could take them out and replace them.

SPEAKER_00

Well, by wait, but okay, what's missing in all this is electrical engineering.

SPEAKER_01

Yeah.

SPEAKER_00

Like, where's that?

SPEAKER_01

Yeah. That's what you do. Right, right. So so here's it turns out what uh why EE is probably one of the most best angles with which to attack this problem, which is these devices are uh to make oxygen to uh well, to first order to make oxygen, it's an electrochemical process. The way we're doing it is we're splitting water vapor inside the body and we're holding on to the produced oxygen. So H2O becomes H2NO2, the H2 just kind of Wait, wait, wait, wait, wait, wait.

SPEAKER_00

So, so you're not so you're saying to keep the cells alive, you're not you you you're not trying to obtain oxygen from the bloodstream. You're you're creating the oxygen in in the sh inside the shield. Correct.

SPEAKER_01

Okay. The single biggest impediment to keeping these cells alive for long periods of time is hypoxia. Yeah. Because the bloodstream does doesn't innervate and penetrate these devices because then you don't immune protect them anymore. Yeah. So they get hypoxic and they die. And that's been a huge bottleneck. It's pretty well established at this point. So, you know, this oxygen problem was sitting there.

SPEAKER_00

And so you so you've created a like a hydrolysis electrodes inside. Electrolysis electrode, yeah. And electrolysis, it's hydrolysis. Yeah, yeah. Yeah.

SPEAKER_01

So the the and the and the approach. Yeah, with uh with a couple of small twists, uh, you know, when you think about electrolysis in your high school chemistry set, you think about two electrodes in a bath of solution, and you could say, well, the body's kind of a bath of solution with chlorine and and sodium, so it should work. It does work, but you actually end up generating a lot of chlorine, which is very bad uh because of that. And instead of oxygen, you can have a competing chlorine reaction, and that can be a disaster. So, you know, when we thought about this, uh, we were like, who can we look at who's thought about this problem differently? And in this case, it turned out the fuel cell industry had, because their job is to take tons and tons of seawater and turn it into tons and tons of hydrogen for energy purposes. And they sort of have to these things survive in these briny environments and it's corrosive and all this. So they've come up with these materials called proton exchange membranes that are just like instead of like the traditional electrolysis where you dip it into a bath of salt, a solution, it's a it's a literally a thin polymer sheet. And that thin polymer sheet is a proton transporter, and you can use that to split water vapor directly inside the body.

SPEAKER_00

Okay, tell me how that works.

unknown

Yeah.

SPEAKER_00

Petine transporter like like uh in a mitochondrial membrane.

SPEAKER_01

No, it's it's it's quite a bit simple. It's not like a proton pump, like a transmembrane or some prote uh protein or something. It's actually just a sheet. And because of the chemistry of that that polymer backbone, uh, it is very preferential to the transport of H. So what that means. Give me the details, so it's how does the sheet do that? Yeah, the the chemistry is it's basically um you can to first order think about it like a modified version of Teflon. It's a parflorinated don't know enough about Teflon. Yeah, it's and and a lot of this stuff is pretty deep in the weeds of like, you know, polymer fuel cell chemistry. But the basic idea is when the that backbone gets hydrated, there's basically conductive channels in its backbone that allow protons to go through, and that's been sort of experimentally validated and things. But what that means is when you put this thing in the presence of water, any water, liquid water, vapor water, it doesn't matter, and you apply that same water splitting voltage across it. So imagine you have a sheet of like this polymer, you have some catalysts loaded on either side, and you apply some voltage through metal electrodes on either side of it. So imagine this like really thin sandwich in the presence of water, then the on one side, the anode, the water comes in, yeah, it gets split into oxygen and H plus, and the H plus gets sucked in through the very thin membrane. That's the other important thing about it. It's thin, so it doesn't have to go very far. Yeah. Um, it comes out on the other side, recombines with uh with electrons, and makes H2 on the other side. So you basically have this very thin polymer sheet that can, in the presence of uh to prevent the chlorine, the chlorination reaction.

SPEAKER_00

So then the next thing that's what you've like the oxygen you're gonna make either way. It's you don't want to have the free radicals.

SPEAKER_01

So the next the the uh it turned out that the most uh uh one of the most important things was how to prevent the chlorine. So this is good because it prevents the need for big sloshing liquids handling and all this. You can do it in vapor.

SPEAKER_00

Right. So you don't have to worry about it. Right. Um and although you do, because mitochondria are like profoundly self-destructive.

SPEAKER_01

Well, in this case, it's just a thin sheet, right? And it's just water vapor. So but but it turns out that people have done a lot of work on understanding better catalysts to make to suppress chlorine and and promote oxygen. And uh I I don't know that much catalytic chemistry. So I would just figured that was a very daunting problem. So the idea, I guess, was well, you know, silicones like rubber silicones are well known to be very good at very permeable to water, oxygen and hydrogen, but they are not permeable to chlorine and sodium and any other dissolved salt species. So what if we just encapsulate it? I got this is but I'm sorry. Oh sure.

SPEAKER_00

My my uh my my phone is I got I didn't think to turn off my I could turn that off. And I also, now that I'm doing it, I realize like I have an alarm set for 115, but I'm gonna turn it off. And we can just try to put it. Do you have like do you have the time?

SPEAKER_02

I have my watch, yeah. Yeah, okay.

SPEAKER_00

Um back in here. Wait, okay, so wait, go back to okay, so go back to where we just were.

SPEAKER_01

Yeah, so so think of silicone silicone member uh rubbers. That that do what specifically like they're well known for so yeah, so selective isn't the word I would use though, that's exactly what they are. So they are well known to be very permeable to uh water, oxygen, and hydrogen.

SPEAKER_03

Okay.

SPEAKER_01

Okay. They are not permeable to dissolved salt species. So if you had salt solution and uh you put you basically you try to filter something out with the silicone, the water's like an NACL, just something like simple salt water, which is basically what our body is. We're just big bags of salt water.

SPEAKER_00

Why is silicone impermeable to chlorine, but not impermeable to the other.

SPEAKER_01

It's a really interesting physical chemistry question, and it comes down to the chain again of the polymer where uh silicones, like a common one is something called PDMS. It's a it's a common silicone, uh, has a fairly large free volume in its backbone, and little water and oxygen things like essentially can undergo a process of uh evaporation where they evaporate from the water, dissolve into the silicone because there's a high solubility to these species because of the free volume, and then they can evaporate out the other side. But the sodium and the chlorine can't really do that. I do not. It's probably because of their charge state, I would guess.

SPEAKER_00

Yeah, but oxy, like but that's what that was my first right, or size. Yeah. But sodium's not a very large, like hydrogen's small, sodium's not that much bigger.

SPEAKER_01

Yeah, but it's certainly not. But here's what's happening, right? In this system, you're not actually getting charged species diffusing through the silicone. So here's what's happening. You have this the water itself. It's the water, exactly. So the water is coming through.

SPEAKER_00

And water, it's okay.

SPEAKER_01

It's coming through.

SPEAKER_00

It's not that it's permeable to hydrogen and oxygen and water. It's that it's permeable to water.

SPEAKER_01

It's permeable to water, it's permeable to these molecular species, not a charged ionic species necessarily, right? So it's coming in as water, it's hitting the reaction surface, it's getting split into hydrogen and oxygen. So you use the silicone to pull in the water.

SPEAKER_00

Uh and you've got a different you've got now this electrolysis membrane. That that's that's coming from you know salt water chemistry. Right. Right. Okay.

SPEAKER_01

And then the and then the hydrogen recombines and makes H2, and then that diffuses out the other side from the silicone, and the oxygen diffuses in and keeps the cells happy.

SPEAKER_00

Why does the hydrogen not diffuse why does the hydrogen diffuse out the other way?

SPEAKER_01

Because we we've designed the device so that the hydrogen is kind of the back end and it just kind of like is uh open, exhausted to the body. And the oxygen is perfusing the cells, the transplanted cells. Yeah, so this is a sort of a whole bunch of You realize you're like You're engineering combustion. No, it's not quite combustion, it's almost more like photosynthesis, I would say, where you're trying to nice. Yeah, you know, but I mean it sounds like you're trying to engineer an engine.

SPEAKER_00

Like it's exactly the thing you first got into it, it said, but I wouldn't want to do it.

SPEAKER_01

That's interesting. I didn't think about it like that. Exactly. The only difference is in combustion, oxygen is a reactant, uh, right? For uh That's exactly what I mean. You can't get it into the react to be a reactant. That well, here it's a product from our process that's now a reactant for the cells to stay alive, I suppose. Yeah, yeah.

SPEAKER_00

So But that's part of the like, you know.

SPEAKER_01

Yeah. But anyway, I mean look, oxygen is the one of the foundations of life, uh, as we know it.

SPEAKER_00

Why do you see it like photosynthesis?

SPEAKER_01

Um because uh in photosynthesis, what you're trying to do is take uh water and let me think about this. I've actually come up with this analogy before, but now I'm blanking on why. Let me let me tell you what.

SPEAKER_00

No, yeah, look, go to the pictures. Go to the pictures, right? Like I immediately support fernin to manganese and we're like, right?

SPEAKER_01

No, I'm just thinking about it at like a system level where you are taking in water vapor, you're taking in water, and you're creating oxygen and hydrogen. It's just like super simple electrolysis. But um, if I remember my plants, and I don't think that I do very well, uh I think the basic idea of what photosynthesis is, it's taking in uh energy from the sun, solar energy, it's taking in water vapor and carbon dioxide and carbon dioxide, and it's basically making like a food source. Makes glucose. It makes glucose. Yeah, yeah. And here we're taking in energy in the form of a voltage, like an applied electrical voltage, and we're taking water vapor and we're creating oxygen.

SPEAKER_00

How on earth do you create a voltage? It's something that small that's to be maintained over time. So like soaked a battery in there? Like, what do you can't? It's got to be something that like reacts and generates a voltage to the surroundings. Otherwise, you'd have to recharge it.

SPEAKER_01

So we're electrical engineers. Uh, and so what we developed electrical engineers. Right. That's fantastic. We got there. So we got there. So we're actually uh we built wireless power harvesting systems. So exactly right, power harvesting.

SPEAKER_00

A power harvesting system, not not power, not batteries.

SPEAKER_01

You could use a battery, you just need to recharge it, but then you'd use your power harvesting to recharge your battery. But oh yeah, do it, man.

SPEAKER_00

What's the power of? See, now we're getting into photosynthesis, like power harvesting. Right. Oh, let's do it, man.

SPEAKER_01

Yeah, so the way that works is kind of fun. So it's actually the same physics.

SPEAKER_00

I don't know. I think it's all pretty fun.

SPEAKER_01

Uh I I I do too. I do too. Uh so the way uh we do it is the physics is actually very similar, practically identical to your uh RFID credit card payment systems. No idea how that works. So how it works is actually pretty neat. When you tap your card or you tap some your your your ID card and get into a building, yeah, there's no battery inside your card. Right. And yet there's clearly some information transfer happening to the card reader that's saying that you're you and you should then open that door for you, right? And what's happening is as you bring that card closer to the reader, uh, and I'm not saying you should do this, but if you if you ever dissolve the plastic in your card, you'd actually see a little wireless uh receiver. And what that's doing is it's harvesting power and then powering up a tiny chip inside your card that is then encrypting information and sending that information back to the reader about you.

SPEAKER_00

So the reader has some kind of a wireless power generation power transmission. Exactly right. Exactly. Which is what? It's it's uh it's magnetic field, slightly. Exactly right. It's a magnetic field. Yeah, and it's and it's the movement of the card.

SPEAKER_01

It's not even the movement. Actually, what's happening is it's an alternating magnetic field, alternating electrical field at 13.56 megahertz, typically alternating electric fields create magnetic fields, and that magnetic field then couples into your card.

SPEAKER_00

And that well, it was our yeah, but like so the so the hence the move, I was the movement of the card to generate the magnet, to like to generate the m the elect electrical field through the change in the magnetic field, but it's the the thing itself as an oscillator, and that's exactly it's an AC field. Is it yeah? Is it is it is it generating is it generating an electrical field or magnet? It's got to be an electrical field because magnetic. Electrical, changing electrical fields create magnetic fields. Right. The reader is gener is generating is a changing electrical field. It's a changing electrical field, right? Right.

SPEAKER_01

It's it's a voltage source.

SPEAKER_02

And powerful. Yeah.

SPEAKER_01

So uh it's creating it's a voltage source.

SPEAKER_00

That's my favorite thing, is uh how the um red light how the uh the red light sensors work. Oh, like the IR sensors? No, no, no, no, red light sensors, it's sub lights. Oh how do you have to learn? Yeah, yeah. How do they work? My AP physics teacher, uh Mr. Bricks. Um everybody thinks it's pressure. Everybody thinks it's like a plate or something. You drive up and it's a plate. It's not. When you drive up to uh um uh an intersection, you'll see these sort of like squares in the road, right? And all that is is just cuts in the in the pavement, they drop in a wire. And the and the natural uh magnetism, the like magnetic field of the earth and the mag and the magnetic um state of your car is sufficient that when you drive your car over it, the shift in the magnetic field induces a current. Oh, cool. And that gets red in the box. Cool. Yeah. Yeah, that's cool. There you're shifting the base. So that's where, but you're there, you're shifting the magnetic field to induce it, but you have a 3,000 pound magnet. Right, right.

SPEAKER_01

Right. Or or something with plenty of magnetic material in it. Yeah, that's exactly right. That's cool. Yeah, I was aware of those types of sensors. I did not know that's how a traffic light actually used them. That's cool. Like, we're not like pressure plates, it's just like a little loop of water. That's cool. That's really cool. Um, anyway, yeah, so we basically have so that how do you put that on a chip? Yeah, so it's it's quite uh straightforward in some senses. What you do is you take a circuit board, a flexible circuit board.

SPEAKER_00

So now we've got now we've got a silicone pol we've got a silicone polym like polymer that's gonna that's gonna give us oxygen, right? Specifically. And then we've got another layer that's going to that's gonna what's the next one? Now I'm a little on the case. It's a whole stack, yeah. It's like we just like we already talked about like, oh, the next thing is the is the is the thing that pulls the chlorine out.

SPEAKER_01

Uh so so there's okay, so there's the proton exchange membrane, right? Kind of sandwiched in the middle. There's silicone all around it to prevent chlorine from getting to the reaction surface. Right. And then uh underneath that though, uh right on top of the proton exchange membrane is a couple of metal electrodes. So you can actually make electrical connections and apply voltage and things like that. That whole thing is covered up in a silicone polymer. Uh the electrical uh uh electrodes, they are connected to a circuit board. And the circuit board is the thing that produces the or supplies the voltage that you need to split that water vapor.

SPEAKER_00

Yeah, and we need the electricity because we because there's no this is so far, all the diffusions, this is all passive. So now we have to do this active thing of split the get the oxygen.

SPEAKER_01

And that needs energy, and then energy is being produced by a wireless power harvesting circuit. Which is what? So the which is This is what you build. Right, right. Actually, like you built this.

SPEAKER_00

Like this is the work.

SPEAKER_01

Yeah, yeah, yeah. We built the whole thing actually. Uh we didn't invent the materials, but yeah, we sort of integrated the whole stack together. And then remember, there's another layer on top of that, which is the actual live cells. So those are in there too. Yeah. Uh so but the circuit is it's it's uh it's a circuit board, and you've probably seen many circuit boards. You take apart any electronics, and there's a big board with a bunch of components. But this is a flexible circuit board. Okay. And the way you make it back to the back to Roger. Exactly. Yeah. So I had this whole thing with flexible electronics, and you and and the basic idea is you just make a flex circuit board super thin and it ends up being flexible. That's just first order, that's how you do it. Okay.

SPEAKER_00

Okay. It's not meaningfully different materials, or is it also that?

SPEAKER_01

It's slightly different materials, but it's just plastic and metal at the end of the day. Okay. Just different thicknesses. Okay. Right. Uh, and you can uh attach components onto it to do various electrical things. Yeah. Right. Um, but in directly inside that circuit board, what you can do is you can actually cut out metal traces that are in the shape of these coils, these magnetic coils, these planar 2D coils.

SPEAKER_00

Oh man, tell me you're gonna make up uh oh, why is the word escaping me? Um tell me you're gonna end up with a solenoid here.

SPEAKER_01

Uh it's funny you say that.

SPEAKER_00

Yeah, it's it's it's essentially a planar solenoid. But if we're back to like the tr the shifting from electronic to magnetic fields, so solenoids are gotta be the coolest thing we have invented.

SPEAKER_01

They're they're super cool. They're super cool. And you can get a lot of power coupled in through those. Um so it's yeah, it's that really what you what now that's why we're getting in coils? It's c it's a coupled magnetic field. So the physics is is basically very similar to a solenoid.

SPEAKER_00

Okay, so okay, it's a walk me through it because this is faux man is cool.

SPEAKER_01

Yeah, it's it's fun stuff, right? So you so imagine then you have like a little wearable patch that's sitting on your skin. Yeah, yeah. And you're that wearable patch is creating that that alternating voltage, just like your card reader is generating.

SPEAKER_00

How is it creating the voltage?

SPEAKER_01

It has a small battery that you can wear on your skin, like any, like any wearable. Oh, so there is a battery in that. Outside, not not implanted.

SPEAKER_00

So you oh, so you so I thought we were we were harvesting energy.

SPEAKER_01

You're harvesting energy, the implant inside your body is harvesting energy. Okay. That power needs to be harvested from somewhere. And you could uh provide that power through you through some kind of external device that sits outside your skin, you can put on, take off, whatever, right? Just then if then you don't have to harvest like then you just it's a battery.

SPEAKER_00

Then it's a battery. That's the battery. So it's an external battery. Yeah. Oh, I thought we were gonna go into some kind of crazy thing where it's like the motion of the blood around it, where like you know, it's funny. Like I never look back.

SPEAKER_01

You know, it's interesting. People have spent uh have have looked at uh physics like that, piezoelectric, transducers, things like that. I think that's really exciting stuff. So far, the type the amount of power you can collect with those types of approaches is probably not sufficient to power these types of devices. You're still a little bit lower than you need to be.

SPEAKER_00

So the solenoid on the chip is just to use the electricity that's coming in from the battery.

SPEAKER_01

From outside your body. Yeah. Yeah. That's exactly right. Yeah. So that what that's doing then is it's when I say power harvesting, it's harvesting power wire. It's there's no battery on the implantable device. Yeah. The same way your credit card or your ID card is harvesting power from the reader to turn on and do something. Yeah. This implant is harvesting power from that external thing, which is acting like the reader. Yeah. Right. Um, so that's how uh coupling in that power through a magnetic field. And then that power is then being converted from an AC power to a DC power. Wait, wait.

SPEAKER_00

So it's not wired, it's magnetic field. Yeah. The thing you're wearing doesn't actually have to be wired to the thing that's No, no, it's just a wearable. It's like a little patch that you take on. So you don't have to wear that all the immunological immunology. No wires. Yeah. So okay. So there is, so it really is like a harvesting. Yeah. It's a harvesting wire. So it's not harvesting from you just have to wear like an armband with a met with a battery. Exactly right. Okay, like over like right over the top of it.

SPEAKER_01

Yeah. Okay. Yeah. So uh, and and you know, when you're doing these things in mice. And it's generating an AC current. It's generating an AC current.

SPEAKER_00

And that's the shift in the magnetic field that then the solar is going to switch into an electric field. So exactly right.

SPEAKER_01

So it couples in magnetic field, that magnetic field then gets transformed into an electric field. That electric field is then uh essentially a voltage uh that you then can uh use to power your to like separate oxygen distribution. Exactly right.

SPEAKER_00

Yeah, which no longer has chlorine because the s the cell uh the the I keep the Teflon layer. Uh yeah, yeah. I forget I'm proton exchange membrane. Proton exchange membrane is is is keeping out the cell species. Right.

SPEAKER_01

Yeah, that's exactly right. So it's a whole it's a whole integrated.

SPEAKER_00

All of this is just to get oxygen to this to the pilot cells. Correct. Which then have to like also do all kinds of other like you're gonna need sugar and you need to need to transport carbon dioxide back out. Yeah.

SPEAKER_01

Yeah, yeah, correct. So I think you know, we think about this as sort of first order and second order problems. The historical thinking in the field is that oxygen is the first order problem. All this other stuff, that's the limiting reagent.

SPEAKER_03

Yeah.

SPEAKER_01

The everything else, the waste transport, the carbon dioxide, the you name it, right?

SPEAKER_00

Yeah. I mean, there's a million metabolic things that have to go on in there. And even and even you the insulin's got to come back out in the glucose. Those are large, insulin's large bits.

SPEAKER_01

Yeah. So these things are often encapsulated in these little sheet uh slabs of hydrogel. Uh, and hydrogels are a class of materials that are basically mostly water. Uh, they're a little bit of polymer and a lot of water. And it's, you know, it's the simplest way to describe a hydrogel is it's basically jello. It is very chemically similar to jello, right? So it's this big sort of soft, wobbly thing. It's mostly chemically water. And because it's mostly chemically water, it actually has the permeability and the diffusivity uh of water to many of these species. Okay. So stuff can get in and get out pretty easily for the most part. Certainly anything in the body.

unknown

Right.

SPEAKER_00

What can't get this is all getting transported by water.

SPEAKER_01

Right, all molecular things anyway. And then you could say, okay, but what about oxygen? Why do you need to only produce oxygen then? And the reason for that is if you pack a lot of these cells together, then and you don't have any external blood supply, then they just don't have enough oxygen to supply their metabolic demand. Because oxygen just doesn't diffuse that far. It doesn't diffuse that far.

SPEAKER_00

Right. Well, you get like a hundred angstroms or something like that. Like oxygen just doesn't diffuse that far.

SPEAKER_01

I think there's a I've heard this saying if we didn't have blood supply and vasculature, life wouldn't have evolved to be more than like a cubic millimeter.

SPEAKER_00

Yeah. Right? Like it's uh yeah, because you and that's like the whole structure. It's you gotta have very near, very near delivery.

SPEAKER_01

Right. I mean, practically all life on earth anyway has uh uh has some kind of vascular thing in that like any leaf you look at, any tree, any living, any mammal, any whatever, they all have some sort of network of uh supply of oxygen.

SPEAKER_00

All the rest of it's fine.

SPEAKER_01

I wouldn't say it's fine, but it's not a first order effect. Okay. You know, the cells can at least stay alive. And I think all these other things are are challenges, and we're working on interesting 3D architectures in my lab to get past some of these challenges. But to first order, we found that if you can keep them oxygenated, you can keep them alive, and if you keep them alive, you can keep them producing drugs.

SPEAKER_03

Yeah.

SPEAKER_01

And if you can keep them producing drugs for many some diseases where you need a continuous replacement of enzymes. So let's say, you know, there's uh for for HIV, you need to be infusing in anti-HIV antibodies. You can just sort of continuously keep producing those, and you don't need like periodic infusions, for example. Oh, wow. That's one, that's one way. Or if you need uh, I don't know, like a GLP one or something continuously produced, then you could do that. Or if you need something else continuously produced.

SPEAKER_00

God, it's all this Huxley. We're all just gonna have like a box that is part of our makeup and like whatever our structure like needs, we'll get our box and we'll have to make sure we have our magnet over our boss, you know, like over our box. Or or a rechargeable battery for you don't use the box all the package all the time. It'll have it'll have a whole slew of cell types that are doing all kinds of different things.

SPEAKER_01

Yeah, and you know, the next frontier for this is you don't just have to use these cells as drug delivery devices, you can use them as sensors. So, for example, uh, you know, when we think about biosensing, we our our human-made uh sensors, we can measure stuff like glucose reasonably well, small molecules, but there's still a huge need to measure complex circulating biomarkers, so inflammatory markers or some other disease marker. We we don't really have a good way to even even something like insulin, which you know, everyone knows about insulin, but it's actually quite challenging to measure insulin inside the body. Why? Uh, because the best binders we have for insulin only last for a certain period of time inside the body. And then they are not very stable, so they can drift over time and have all kinds of challenges. So we've just about made our first decent sensors, but they're not these chronic long-lived things. But then you contrast that to cells, which routinely sense insulin. That's like a hepatic cell, a liver cell, that's its whole thing. It measures insulin and then produces glucose in response to that. So cells have this sort of multi-billion year advantage in terms of binding and receptor elements. They just have this exquisite machinery of binding and then downstream uh gene circuits that can turn stuff on and off, right? So then it's reasonable to ask well, can we just sort of hack that? Can we use the cells binding and receptor machinery? Well, you're already using cells. Exactly.

SPEAKER_00

Yeah.

SPEAKER_01

So instead of spitting out some other metabolic thing, it just spits out like a fluorescent protein. So if you measure the fluorescent protein, then you can measure the biomarker. So you repurposing these cells as sensors is something that we're we're you could sense anything that the body can already sense.

SPEAKER_00

Right.

SPEAKER_01

You just like get the gene, put it in a right, right, exactly. So I mean, groups are thinking about this, we're thinking about this. I think it's a really exciting frontier.

SPEAKER_00

You don't even need a fluorescent protein, you don't even need a whole cell. You just need a you just need a set like a cell membrane. Uh and you could and you just need the sensor, you just need the the whatever the external component of the sense of the sensor yeah, right, like of the G-coupled protein is whatever, right, whatever the external component component is. Right. And then on the on the internal side, when you when there's you know the multi two or three pathways that a G-coupled protein receptor can, you just put a wire there.

SPEAKER_01

Yeah, or if you can read. If you can get it that sensitive, yeah, for sure. Yeah, if you can actually get the thing to be stable and not drift because of voltages and things, but yeah, there's different ways to do it. I mean, um, but I think the sort of simplest, hackiest way to do it is just take what the cell does anyway and replace out one pathway for your own little pathway. Yeah. So it has something you can read out.

SPEAKER_00

Could we already do in all kinds of well, like that's a lot of biogenes.

SPEAKER_01

Right, exactly. So you can take cells and use them as sensors, you can use them as drug delivery devices. So that's you know a big part of what we think about.

SPEAKER_00

What are you gonna, what is your first target for proof of concept of the sensei?

SPEAKER_01

So honestly, at this point, if we can show some some, we can just show some basic uh pro-inflammatory cytokine, we'd be happy. There's been other groups that have shown, I think TNF Alpha is one that other groups have shown. I think these are really good targets because right now, I think inflammation is something that we would like to understand much better. Yeah. And uh we part of that is measuring the stuff in real time. And this is a something a lot of groups are interested in. So I would say that's a good starting point. So don't even we don't even understand the the the pathways internally.

SPEAKER_00

Yeah. We for like what the inflammatory like when we learn this med school, it's like they're cytokides, right? Right. And we know we learn some of the pathways that are like well characterized, but it's very sort of like loosey-goosey and like maybe like we sort of think like here's something that we can teach you because we can test you. Right. Right. But you should know that also, like they probably do a thousand other things. Right. We don't really know. Right. The classic example is well, as as far as I understand it, we don't know how Tylenol works. Right. I've heard that, yeah. Which is lovely. Yeah. It's like, are you gonna like we jet we don't know how Tylenol brings fever down? It does work, though. Well, that's the thing. Right. It's like, you know, at some point it's like who cares if you know how it works. Right. It's just like it works. The system's like once if once we can characterize how it works, then there's all kinds of things we can do with understanding the system. But for now, like, yeah. I mean, even something like long COVID, for example, right?

SPEAKER_01

Where there's it's there, man. Oh my goodness. It's I mean, and just just imagine where uh a situation we're actually able to track an inflammatory cascade in vivo in real time. I mean, I think it'll you could track it. You could capture it. We could open it would open many doors, I think. And so a lot of people are very interested in this.

SPEAKER_00

You could make kidney. I mean, you could make you know artificial kidney-like fun functions that just filter them out if they're too high. Yeah. And if your body's doing something that evolutionarily made sense uh, you know, a million years ago. Come up with druggable targets and find medicines for these, yeah, all kinds of things. Don't need that much bile anymore because we've got enough, we're we're eating enough cholesterol now.

SPEAKER_01

Yeah. I mean, even to first order, I think all good medicine comes from first. Well, not all, but lots of good medicine comes from understanding the physiology, right? And I think a good sensor would maybe give us a pathway to get there. So, yeah, we're very interested in building these out. And we've just started many of these efforts, and several groups have been working on this stuff. But what I'm excited about for us is we've now, I think, shown that we can start to keep these uh these transplanted cells alive in the body in a different species, even for for months. And so if we could that's that's challenge number one, if you can keep them alive. Have you done human trials? No, but I mean, like we've done a bunch of mouse and rat trials, for example. So you say different species. Mouse mice and rats. Well, right. Oh, but you don't you don't mean you're still within species for the cells. No, so we've put human cells and mice. Okay. We've put uh we've put rat cells in mice, we've put human stem cells in mice, we've put, yeah, different species.

SPEAKER_00

Yeah, and you keep them keeping a lot and then also have them do something, or just yeah, we produce drugs.

SPEAKER_01

So we've cured a mouse diabetes for months with these things with the little chip under their skin.

SPEAKER_00

Uh, why did it end up running out after a month?

SPEAKER_01

Oh, it didn't run out. We just ended the experiment. We took the device out and the blood sugar went back up.

SPEAKER_00

Wow. Yeah. Wow. Why didn't you have a whole uh second experimental line where you're just gonna keep them alive as long as you could?

SPEAKER_01

Uh to write up the paper and start my job at Stanford.

SPEAKER_00

Yeah, but you can't know, right? You're right. Yeah. This is the problem with this is the problem with long-term. Yeah, yeah. But it is, it is something we're thinking about. That's that's really because if you could prove it never like do the um like will the cell semest? Will the cell do they need to divide? These are these are great questions.

SPEAKER_01

Some of them will divide, eyelids probably don't divide. Um but do they need to? Can they survive for a decade? So, you know, frequently do you have to replace them? There are patients who have gotten the first ever eyelid transplantations 20 plus years ago, uh, who have been on immunosuppression and their eyelids are still alive and they're insulin independent to this day. So, you know, the thinking is that if you keep the cells alive and well engrafted, they could last for a long, long time.

SPEAKER_00

Yeah. Yeah. And the cells aren't divided, those those cells aren't dividing. They don't dividing. They're surviving for 20 years. I'm I didn't think any cells in the body lasted that long.

SPEAKER_01

No, pancreatic islets uh are they they don't divide. So what you have is what you have. Even when you're born. I more or less, yeah.

SPEAKER_00

I thought the longest lasting cells in the body, like I thought the whole tissue, the whole structure of the body was replaced every, you know, like I thought the longest lasting cell we had like was like beta, um, was the beta um immunologic lines.

SPEAKER_01

No, like for example, I don't think we I could be wrong. Don't you're you're you're the you're the PNP graduate.

SPEAKER_00

Come on, that's velocity.

SPEAKER_01

But I don't think we make new neurons in our brain, do we?

SPEAKER_00

No, but I thought they sort of somehow, yeah, but somehow we replaced or somehow like there was some kind of turnover that that were there.

SPEAKER_01

I think I mean again, I could be wrong about this, but I think there are some cells where what you have is what you have.

SPEAKER_00

It must be.

SPEAKER_01

Yeah.

SPEAKER_00

Wow.