Peter Nguyen

Peter Nguyen: Hey guys. So my name is Peter Nguyen and I’m from the Wyss Institute. And so, if you know us and what we do at the Wyss Institute, you know we’re focused on bio inspired technology. So that’s where I’d like to start, that’s where I want to start for the origin of our journey. Peter Nguyen: With original bio inspiration for any wearable technology, our largest organ the human skin. So the skin is an amazing feat of evolution with depth sensors every second, millisecond of your life, it’s constantly filtering in signals from your environment, pressure, temperature, every hug, every punch, every kiss that you’ve ever had gets filtered through this organ.

00:37 - Peter Nguyen: And it’s also a constant battleground for forces that are trying to invade your body, pathogens, viruses. Furthermore, it’s adaptive, which is quite amazing. It regulates your temperature, it thickens when it senses constant abrasion, it hills your breaches, and it even protects you from light rays by making melanin, right? Peter Nguyen: It’s mind blowing. And I’d like you to consider that clothing is one of the first bio inspired technologies based on what the skin is capable of. Think about it. We were riding around naked for the vast majority of our lifetime, as a species.

01:11 - We learned how to drape ourselves in dead animals and plant tissues. Everybody here is probably wearing either animal tissue or plant tissue right now. Peter Nguyen: So this is an ancient inspired biotechnology, just like our skin. And we design it to wrap around us, for example. We design it to protect us from harm. We design it to regulate our temperature, interface with our environment and of course, to hold our iPods. Sorry. So wearables are a barrier and our interface with the world around us. But when you consider clothing, not much has changed for a very long time. The functionality of our wearables pales in comparison to the human skin. Peter Nguyen: People like Katia, who spoke earlier, are going to try go the opposite route, augmenting our own skin’s capabilities. And so integrating biological systems into the clothing that we wear, our wearables, holds great promise, as we saw in the previous presentation.

02:11 - And we’ve seen, all of these efforts have been very inspirational to us in the Collins lab. Peter Nguyen: And what we want to do is take a step back and consider that integrating living things into wearable technologies has its own peculiar challenges. Just like any other living thing, this has been touched upon in the previous presentation. Take for example, your typical household pet. If you don’t give it water, it dies. If you don’t regulate its temperature, it dies. If you don’t feed it, it dies. If you don’t give it oxygen, it dies. If you don’t remove its waste, it dies.

02:42 - So here are we talking about a pet that we just have for fun. Peter Nguyen: Now what happens when your life depends on a living thing? Here’s a photograph of a coal miner. He’s holding up a canary used in coal mining as a seminal animal. Imagine if one day you forgot to feed the canary and it died or the cage broke and it flew away. Your fellow miners would probably be pretty angry at you for losing their only method of detecting noxious gases.

03:07 - Right? Peter Nguyen: So there are a number of other considerations besides maintenance, which is what I’ve touched on. One is for example, storage. How long can you store things that are made of living materials? We have our clothes for years. Some of us may be days, I don’t know. And also biocontainment. So, that’s one huge issue. FDA, EPA, they don’t want to hear about having genetically engineered materials in a format where it can easily break out and be exposed and run off into the environment. Peter Nguyen: And of course, another one is mutation. Living things love to mutate. If you program them with a genetic program that they don’t like, makes them sick, they’ll find a way around it. They’ll evolve way around it.

03:50 - So what can we do to merge this operational parameter mismatch between synthetic biology and wearable technologies? What can we do to close this gap? Peter Nguyen: Well surprisingly, we actually don’t need living things to operate biological systems. So I’ll say that again. We don’t need living things to operate biological systems. The living part is actually dispensable. So what I’m showing here is something called a cell-free extract, and all it is, is you take a bunch of cells. It can be any cells, it can be bacterial cells, insect cells, rabbit cells, whatever. You crack it open and you take the insides of it out, the extracts.

04:33 - Peter Nguyen: And so here you add it with a programmable DNA and you actually get your protein and this all happens without a living cell. And in the Collins lab, what we found is you can actually take the cell-free extract, freeze dry it, and it’s shelf stable for up to a year and rehydrate it whenever you want. So one year, throw it on the shelf, we basically made synthetic biology into a ramen packet. Peter Nguyen: That’s what we’ve done and we’ve integrated this into paper-based diagnostics, quite inexpensive. And what we wanted to see, we can integrate this into wearable technologies now.

05:10 - And so what we wanted to do, is we want to develop a platform for detecting a variety of environmental signals up top, pathogens, metabolites, toxins and integrate them into a wearable format using traditional fabric technology. Peter Nguyen: Obviously the military is interested in our technology, but we also envisioned this being implemented in other situations. Something that’s on everybody’s mind right now, is those on the front line in clinics and filled hospitals, they have the greatest danger of being exposed. They’re supposed to keep us safe and we need to give them advanced technology for monitoring and detection for their exposure. Peter Nguyen: And so this concept led us to propose our technology.

05:45 - We were developing this and we won the Johnson&Johnson quickfire challenge award few years ago to develop a lab coat with this technology integrated into it. And so this is what we’ve come up with. Peter Nguyen: So you can see we’re going to integrate freeze dried, cell-free, synthetic biology reactions into clothing. And once it gets rehydrated, it’ll automatically generate an output foray to show what you’ve been exposed to. And the way we’re going to do this, we’re going to design little prototypes. These are modular and eventually there’ll be integrated into clothing.

06:18 - Peter Nguyen: You can see it’s flexible, stretchable, and it basically wicks in anything that you’ve been exposed to. And so time for some hard data, some hard science now. So in the blue here, I’m basically showing, the blue on top is giving you a color metric signal. On the left I’m just adding in DNA or not adding in DNA. You can see when you add in DNA, it turns from yellow to purple. Peter Nguyen: Now on the right, what I’m showing is actual synthetic biology circuit. Now this is actually detecting anhydrotetracycline, a small molecule. So you can detect chemicals using these freeze dried wearable circuits. Furthermore, on the left now, you can also detect viruses. So now this is something called a toehold switch, synthetic biology circuit, and we’re throwing Ebola RNA at it and it can detect this within half an hour.

07:09 - So within half an hour, you will know if you’ve been exposed to Ebola. Peter Nguyen: On the right here, we have another riboswitch. This one is detecting another small molecule, diethylene. You can see within 30 minutes you have yellow to purple change. And so we wanted to expand on this. This is great to have a color metric change on you, but you’re not going to be looking at yourself all the time, right? Peter Nguyen: So we want to take it to the next level.

07:33 - We wanted to develop a prototype that was self reporting and was capable of fluorescent outputs. It’s fundamentally how labs now work to detect influenza and the coronavirus, they use fluorescent outputs. And so the sample will come in from the top, it’ll get drawn into this reaction chamber .and fiber optics integrated into our wearable will actually constantly detect to see if anything is being detected. Peter Nguyen: And so again, we have a diethylene riboswitch. This is just to show that you can detect chemicals. You can see on the very top is where the chemical is and the reaction happens. Whereas on the bottom, we don’t add anything and there’s basically just water and you don’t see any fluorescents. Peter Nguyen: And this is an amazing example here. We threw HIV RNA into another toehold switch and you can see within 10 minutes, you actually have a signal that you can detect showing you that you’ve been exposed to HIV somehow.

08:31 - And also we wanted to develop nerve agent sensor. So this is a nerve agent, the kind that the Russian agents used, supposedly. And so we can actually detect nerve agents, is what the military really wanted us to go for. Peter Nguyen: And we also integrated something that Luis talked about earlier, which is CRISPR-based sensors. And so in these CRISPR-based sensors, the CRISPR cast 12 is the enzyme that actually detects a nucleic acid molecule.

08:59 - And when it does, it actually chews up everything else around it, including these fluorescent tags that we throw in as well. Peter Nguyen: And here what I’m showing is four different genes that are antibiotic resistance genes that are separately being detected by our CRISPR system. And this is again, on a wearable. One thing we love about CRISPR is that you can multiplex it. And so within one patch, we can detect three different genes and they’re completely orthogonal. Meaning, I can detect your exposure and tell you all three of these genes are there or not.

09:33 - And this is at a level that laboratory diagnostics strive to hit. So this is quite sensitive. Peter Nguyen: So this is our final prototype. We’ve integrated other bells and whistles such as wireless automated alerts to your cell phone. It’ll ping you and tell you you have a potential exposure. For example, on your sleeve or anywhere on you. GPS tracking for automated contact tracing. It’ll tell you where you were when you got contaminated and where you have been since. So now you know who you potentially exposed decontamination to. Peter Nguyen: And the cost surprisingly is cheap, from tens to maybe a hundred dollars depending on the density of the sensors. And this is just to keep first responders safe.

10:14 - Consider that I can go to Nordstrom today and buy a cashmere sweater for $3000. It has no other function than depleting my bank account. I mean, that’s pretty amazing. This technology works, it’s scalable and it’s ready for commercialization. Peter Nguyen: So in closing, I hope I’ve convinced you that we’ve achieved something truly remarkable in wearables. A platform where synthetic biology circuits can be integrated and detect your environment at laboratory sensitivities.

10:43 - So it’s shelf stable, programmable, and of course, wearable. All this work was two years in the making and it’ll be published in a couple of months. So keep your eyes open, keep your eyes peeled. Peter Nguyen: And with that I’d like to thank the PI, Jim Collins who really pushed us into this area to explore. And also my partner in crime, Luis. He presented CRISPR materials. He was my partner on this and he is also doing machine learning, so he’s all over the place.

11:09 - Peter Nguyen: And with that, I’d like to thank our sponsors and you guys, the organizers, and you guys for listening to me ramble for 10 minutes. Thank you. .