Shana Kelley: Biosensors to Track Proteins and Inflammation in Our Blood in Real Time

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Eric Topol 0:00
So just a little bit about my perspective before we get rolling. We've had continuous glucose sensors. Everybody's used to them. A lot of people have tried them. We have wearables where they're on the wrist and the ring. But what you have come up with is a whole new world of sensors. And this is actually pretty extraordinary because of your fusion of biomedical engineering and chemistry expertise, you've come into something of being able to basically real-time continuous monitor sensors any protein in the body. Wow. Okay. So we're back to you. We got everybody on board. We have our audio fixed. Thank goodness. And maybe you can restart with telling us about how this protein sensor works.
Shana Kelley 0:55
Yeah, well, I really appreciate, Eric, the way you summed it up. It's something we're very excited about too. And you're right that this all started with glucose sensing, right? It used to be if you were a diabetic, you had to go to the pharmacy to get your glucose measured. And then you got a handheld, right? And that really transformed diabetes management. Now we have continuous glucose monitors that sit on the arm and can read glucose in real time. But at the core of that is a sensor. right, that reads out the glucose concentration. And what's been very elusive when it comes to kind of all other analytes, especially protein analytes, is how to get that same form factor, you know, how to have an autonomous sensor that can just sit in a fluid in the human body and read out concentrations.
Shana Kelley 1:42
And so that's the problem we've been working away on for several years, many years. And we eventually came up with a sensor that's basically like a molecular motion detector. It sits on the surface of an electrode and it's just kind of it's moving around. We use electric fields to kind of move it in a way that we can monitor. And it turns out that when the sensor binds a protein of interest. That slows it down. And so we can just watch that motion, do that over time, and quantitate concentrations of proteins in the blood or in the interstitial fluid is usually where we're making our measurements.
Eric Topol 2:23
Yeah, so it's like a molecular pendulum where you have these strands of DNA that are specifically want to bind to a protein, but it binds so well that you need a little electricity to shake it off. Is that right?
Shana Kelley 2:39
Yeah, that's exactly right. So I have a puppy at home and we throw balls for him all the time. He's really good. He'll go get exactly the ball that you just threw. He'll bring it back, but then he won't let it go. Same thing. So the sensor catches the protein, but it won't let it go. It's a very strong complex.
Eric Topol 2:56
Yeah, every dog I've had had the same problem. Never let the ball go. And that's kind of like the metaphor is powerful. So you figure out how to do this, which is with no reagents. This is unlike a continuous glucose sensor or a lactate sensor. No reagents, a little tiny bit of electricity. And then you sense the protein level. And then you go ahead and you say, okay, let's try this in a diabetic rat model. And you're looking for specific inflammation proteins like interleukin-6, tumor necrosis factor. And what did you find when you did that?
Shana Kelley 3:37
Yeah, so we chose a diabetes model because, you know, diabetes and inflammation go hand in hand, right? If your glucose is out of range, your inflammation is going to start to spike. So we thought that would be a good model. And, you know, we had rats that we allowed to fast and we could see that as they fasted, their pro-inflammatory cytokines would come down. We had animals that we would inject with insulin and we could see the pro-inflammatory markers come down even faster. Interestingly, when we injected the rats with insulin to kind of see how that would affect things, we actually saw a little spike in inflammation just from the needle prick. Like that's how good the resolution is. So that was very cool to see.
Eric Topol 4:19
I was struck by that especially. Yeah, yeah.
Shana Kelley 4:21
Yeah. And then we also dose the rats with molecules that would make their inflammation spike, and we could absolutely see that.

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