On Tech & Vision Podcast

Biosensors: The Future of Diagnostic Medicine

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On Tech and Vision Podcast with Dr. Cal Roberts

This episode is about how biosensor technology is revolutionizing the field of diagnostic and preventive medicine. Biosensors can take many forms – wearable, implantable, and even ingestible. And they can serve many different functions as well, most notably when it comes to detecting the various pressure levels in our bodies. 

Podcast Transcription

Everything looks good, Sir. Passage clear.

Excellent. Prep the exploratory probes to search for any blockages.

Aye-aye, Sir.

What’s going on? Status report!

Bogey rapidly approaching, Sir, Sir, it’s a cluster of white blood cells. They’re right on top of us. 

Battle stations.  Prep the immunosuppressant missiles. If you don’t get to that blood clot, the patient is done for.

Roberts: The clip you just heard is inspired by a movie called The Fantastic Voyage. It’s about a scientist who shrinks a submarine and uses it to explore the human body and destroy a blood clot. Sound unbelievable? Think again.

I’m Doctor Cal Roberts and this is On Tech and Vision. Today’s big idea is the intriguing world of tiny biosensors. The biosensors we’ll be talking about today are incredibly small devices that can be implanted into the body, but they have a huge job. They can measure and then transmit all sorts of information.

One of those measurements is pressure: blood pressure, cranial pressure, and for people with glaucoma, eye pressure. It’s truly the next wave of medical technology and it’s happening now.

To learn more, I spoke to several guests for this episode. One is Doug Adams, a visionary entrepreneur who founded a biosensor company called Qura. The company’s current focus is developing a biosensor to detect hypertension, but Doug’s inspiration for developing biosensors goes back further than that. To help patients with glaucoma. So, talk to us about biosensors. How did you get into that area?

Adams: When I was young in my career, I worked for a company called Humphrey Instruments and they had a visual field machine, which I think everybody is familiar with and I was waiting to see an ophthalmologist and there was a woman in the waiting room. And she told me that she was going blind from glaucoma. And she told me her neighbor told her it was normal to go blind from glaucoma. And I never forgot that experience, and I thought to myself, what could I do that could maybe change the trajectory for potentially hundreds of thousands, if not millions of patients?

So, the first thought that I had about sensors was in 2010. Because I read some technical journals about work being done at a number of universities, and I thought you know, I should call these university researchers and see what they’re up to. And I met the professor from Purdue who was trying to do sensors in ophthalmology, but he didn’t know anything about the eye and he and I formed a partnership along with another person that was from Jackson Labs and the three of us became co-founders in what is now Qura – Q-U-R-A. Qura is a medical device company and we are focused on biosensors in a wide variety of areas, not just the eye. So what’s interesting Cal, is what works in the eye, works in the heart, works in the brain, works in the bladder – anywhere where pressure needs to or can be measured.

Roberts: So, what is a sensor? What does it do?

Adams: So, the sensors we use are designed to measure pressure and temperature. We use a capacitor sensor. There’s a couple of different types. So, this theme of miniaturization was really the background in terms of – Can we do this? And if we can, what are all the elements that we need to invent, modify, change or other, to really develop a system that would be able to record pressure in tiny spaces? And that was the idea. 

And so, to get started, we decided we would do what I call a design input requirements. That’s a simple document that says what do we have to deliver and what do we need this to do as a product? And then will it meet A,B,C,D & E outcomes? And then can that now in that stage go through the clinical trials for validation, and then could that be a product?

Roberts: The technology we’re talking about here is still in the research and development phase. But the innovation process is always in motion and Doug has ideas about where to go next.

Adams: The number one item on the list of requirements was autonomous operation. So what does that mean? It means that the device, once implanted, works without any input on the part of the patient. So, we had an assumption that if we used the methodology to power the implant by having the patient hold something up to their eye and that would provide power, yes, you could take a measurement of pressure, but everything would be determined on, would the patient participate? Would they be compliant? So to me, this issue of taking the patient out of the chain, if you would, was one of the most important requirements, so autonomous operation became top.

The second and third were also important. The ability to transmit data out of the eye and to put energy or power into the eye. None of that existed when we got started, and those are just two examples. I’ll build on some more.

So, you have the sensor and calibration. They go together as a pair because you can’t have one without the other, because if they don’t calibrate, then how do you know what pressure is and where you measure. The bio coding became a really big component in this because the device needs to last for 10 plus years in the eye and so biocompatibility becomes extremely important. And Qura developed and invented a new bio coating that should actually last 15 plus years in the eye with little or no inflammation.

We developed an ASIC which is simply an integrated circuit. We had to develop an antenna, a battery hardware, software, firmware that goes inside the implant and then more importantly, we developed what’s called a transceiver. 

So, generally today state-of-the-art from sensors that I’ve seen, getting energy into the eye to take a measurement and getting that back basically, is a function of three to six inches, so the little device that a patient would hold up to the eye needs to be within a couple of inches in order to take that measurement. Our requirement was nine feet, and that had never been done before, and so I was frankly fairly excited when the engineers told me we could do 9 inches, maybe 12.  And I would tell you that where we are today, Cal, we could do 100 yards. And that has never been done before.

Roberts So at one point in time, what you showed me was a sensor in size compared to a grain of rice, how big is the sensor today?

Adams: The very first prototype that our engineers put in front of me was the size of a microwave oven. And when I saw that and they did the demo that showed me in a bell chamber, they could actually get the correct pressure at this curve, no matter where on the curve, it was able to do it. The problem was it was pretty darned large. And my friends, frankly, Cal, made fun of me saying I can’t believe you invested your money in this and to me, at the end of the day when I was flying home, you couldn’t wipe the smile off my face.

I knew if we could do this at that size, it was a matter of time, talent and money to get to that size of a grain of rice, so we are slightly bigger than that now. I would tell you if you let me forecast out a decade from here, this will be sub 1mm and will be delivered in the eye in whatever location you choose through a needle and it will last there for a decade. And so I believe that’s the trajectory.

But, if you look at what happened to sensors, and how they got smaller, same things happening with the ASIC, the antenna, the battery, all these things are working in conjunction. The difficult thing is there were seven areas that required massive innovation to get to this stage of development, and we’re still not done.

Roberts: Creating such an innovative device takes inspiration, dedication and also practical thinking. I spoke to David Hendren, Qura’s chief business officer, to tell me more about the companies development process and why they are developing internal sensors as opposed to external ones.

So more and more of us are having the experience of an Apple Watch and what you can measure, but it’s measuring it externally. Is that the way that we should be measuring? Is that good enough to measure it externally with an Apple Watch? In theory, you have your watch on for many hours a day. You could get a lot of data in the course of the day or there are bracelets that you can wear 24 hours a day and get continuous data that way. I guess what I’m trying to figure out here is when should we be gathering data externally and when should we be gathering data internally?

Hendren: Great question. Good enough is a relative term. So for some an external monitor is going to be useful. That said, the sensing device in those wearables is not going to work for the patient cohort that we are talking about. The people with chronic disease, the people with very difficult to manage blood pressure. Where you need to give yourself every advantage and where you need to eliminate the compliance step in the case of blood pressure, one of the big issues is compliance. 

If a patient needs to have a compliance step, the results suffer and that can be anything from do you have to push a button? Charge something in any number of steps? So, our approach is to make it automatic, seamless. Set it. Forget it. You get the data you need and in our case it’s not only the data goes to the patient and we can all learn a lot from the example of another semi-implantable – the continuous glucose monitors, the Libre and the Dexcoms that we all hear a lot about, where it drives a lot of patient action.

But the separate important thing is that you are automatically getting data to the care group that is taking care of these patients where they were able to see what’s happening, they’re able to see not just a snapshot once in a while, as you’d have from an external pressure cuff, but getting continuous data longitudinally.

What does that mean in terms of how you need to think about administering drugs were taking other measures? And at the end of the day, it’s all about staying ahead. It’s about predicting things that can happen that you want to prevent. The clinical application, and to be clear, we’re not in human beings yet, but we’re anticipating. The device will, in a very simple procedure, be placed next to the radial artery, which is where you would feel for a pulse in a patient’s arm and just slipped in there. Little nick in the skin and a little simple introducer with Novocaine, so it’s not a surgical procedure per se. It looks like a little capsule and it’s placed in adjacent to an artery. Not near other things where either the function of the sensor can be affected or the the function of the human can be affected so it doesn’t interfere or get interfered with by a joint, by tendons or anything like that.

It transmits to a tiny external device, a little external device that does two things. One takes the data out. And separately, wirelessly recharges the little batteries in the implanted sensor. And then that external device sends the data up to the cloud, where it then is both processed and within a matter of seconds, distributed out to where it needs to go, including to the patient to whoever is designated in the care team.

Roberts: So, you get all this data, whether it’s blood pressure, eye pressure, glucose levels, you name it. But then what do you do with all that data? To learn more I spoke to Max Ostermeier, the co-founder and general manager of Implandata Ophthalmic Products. You may remember Max from his appearance in an episode in season 2. For this episode, Max joined me again to discuss the possibilities of biosensor technology and his company’s EYEMATE system.

Ostermeier: EYEMATE is a system to improve the care of glaucoma patients. And as you know, glaucoma is a chronic eye disease where increased pressure inside the eyes causing damage to the optic nerve which over time leads to loss of eye sight in glaucoma patients. So, we are measuring the absolute pressure inside the eye with this kind of technology.

It originates from the automotive industry, tire pressure sensors, where you also have to measure the pressure inside a tire. And so basically we took that technology and advanced it and made it so small that you can also implant these kind of sensors and telemetrically  measure the pressure inside the eye. So, it’s really a tiny implant which right now is placed either in combination with cataract surgery in a kind of a mix similar procedure or in combination with glaucoma surgery.

in the next step we intend to qualify the product also for injection. So, it means that it can be also used independent from cataract or glaucoma surgery. And by that of course we can also address earlier stage patients not in a need yet for eye surgery. We all know that intraocular pressure is highly dynamic. But today you can measure the pressure only in the office which is done in a kind of a snapshot measurement mode. In order to improve the care of glaucoma patients, we have developed an implantable microsensor, a biosensor, which is able to continuously measure intraocular pressure under normal life conditions and from the patient’s home. The data goes straight into web-based database where all the patient data is collected and then shown to the eye doctor.

You can also get an alert. So for example, if a patient’s pressure means his glaucoma is out of control,  the eye doctor will obtain a message, an automated message and knows okay, here, patient B has a problem. I have to take a close look at that patient. And we are also empowering patients by self-monitoring. So, that means that sensor is also connected with the patient’s smartphone. And so, the patient knows exactly what’s going on. So, they do have certainty that therapy working for them, the pressure is under control and if not they can be either more adherent to takes your eye drops or they can go and see the doctor.

Roberts: So this is inside the eye. Does the patient feel it? Can they see it?

Ostermeier: Not at all, not at all. It’s sitting inside the eye, and the sclera. And patients don’t feel any sensation, any pain. You cannot see it from the outside. It’s really very small. And, you know, similar devices, mostly therapeutic devices are already placed now. Cataract surgery, for example, is the most common surgery done in the world, and that’s kind of well understood. So, it’s also now so-called mixed devices, minimally invasive glaucoma stents or tube shunts, which are placed in a similar way. So, there’s a long history of placing devices in respect of the size and location similar to ours, so there is no long term issue with placing sensors or devices like this.

Roberts: So, you made the analogy to the pressure sensor that we have in our tires and I think that’s a great analogy because I think we all have had that experience of of being able to know what the pressure in our tires is by looking at the dashboard of our car. So now, how do you take that technology and make it small enough that it fits in someone eye?

Ostermeier: That was quite a stretch, you know, because these high pressure sensors are rather large and bulky, and you measure really high pressures in bars while within the body we are talking about millibars of pressure. So you have to have a really small sensor. And that really took us overall more than 20 years, but in the last, I would say 10 years these kind of technologies really got small because of that whole smartphone and communication tools.

And so the technology movement in the last 10 years really helped us a lot to get this technology really small. But that is always derived from technologies which are already used in other industries. Because for medical product you cannot develop something all by yourself from scratch, you can really derive things which are used already in other technologies and so the current sensor technology, similar sensors are also used in a smart phone, for example. Of course they are not wireless, so our unique point here is we have a wireless sensor means that it’s really powered telemetrically.

Roberts: So, we’ve talked a lot in recent episodes about AI, artificial intelligence and program learning, and we understand that the key to it is just having lots and lots and lots of data and the data is important and so that what AI does is look at huge amounts of data and looks for patterns and looks for correlations and therefore is able to predict on the basis of the data.  And so, one of the outcomes of what you’re doing is just providing so much more data. Then the average person who goes to see the doctor, maybe as frequently as once every three months gets four points of data in a year. Here, you’re getting multiple points of data per day. Why do you think that all that extra data is going to help?

Ostermeier: I think that’s very important point, and I think that the need to include all this data and also data beyond being acquired by a bio center in a kind of an AI assisted system. We know glaucoma is a complex and multifactorial disease. Today, it’s very imaging intensive. But most of the imaging devices like visual feild, like OCT, are imperfect, and again, there is no single test to pinpoint glaucoma or its progression today.

In addition to that, you know also see inter rater variability is extremely high. So there is no really objective database today to truly understand what’s going on with a patient and how a patient responds to a certain therapy. So, by having instead of only random, isolated and often biased measurements taken in the office, now you have real life information. Instead of only having four data points, we are now delivering thousands and at some patients, even 10 thousands of data points and of course eye doctors can be easily confused by that amount of data. So, it means what AI needs to do for us is really to analyze and collect and really process all this data so that the eye doctor really has comprehensible, actionable  information, and I think AI will have an important role.

At the end, any biosensor, it’s an enabling device. So, the real value is the data provided by it. But the data has to be processed in a way that doctors as well as patients understand what’s happening and what they have to do. I think that’s certainly key.

Roberts: The role that AI can play in diagnostic medicine is fascinating. I asked Doug Adams to tell me more about it.

Adams: Think of the data collectively, what it means to say someone who’s got 5,000 glaucoma patients in the practice. if I could show you that in your practice out of the 5,000, let’s say 4,000 are completely controlled with no anomalies, no alerts. So, they are doing exactly what you want them to do. But there’s 1,000 left and they have a variety of different issues or adverse events or things that they are experiencing. If I could show you, by patient, those that need more treatment and care versus those that don’t, can we improve the patient experience for that patient with glaucoma? And I believe the answer is overtime will be a resounding yes.

Roberts: There’s also the issue as to what therapy is most efficacious and what therapy is most efficacious for a particular patient. So, a patient gets diagnosed say with glaucoma. And the question is what are we going to do? Are we going to give the patient eye drops or are we going to give this patient some device? Are we going to do surgery on this patient? How do you know, and hopefully from all the data that we collect from thousands or hundreds of thousands of patients, it will give us predictive analytics so that when a patient presents, we can say, Okay Miss Jones, on the basis of what we see the data shows that this would be the most efficacious therapy for you.

Adams: That, to me, is the heart of what we’re trying to offer.

Roberts: So now I’m going to change course here and ask you to think bigger. So far we’ve talked about biosensors that measure pressure. And you also said the biosensors can measure temperature. What else can biosensors do? And how would you go about building a biosensor for some other purpose other than pressure?

Adams: Frankly, I thought about this a lot, so I had a physical a month ago. And along with the physical, they draw blood. And they send their blood off to a lab. I have a feeling in the next decade that goes away. Why do you have to send a vial of blood to the lab? Because if I had a sensor, not even in an artery, but on top of an artery. I could do a complete analysis of everything in that blood that you’re doing from the lab. So, I look at things maybe a little differently. What can go away? What can be changed or improved and the things we’ve been doing for decades, how do we obsolete those and improve the quality of the patient experience?

And so I’m thinking, you know what? If I put a sensor, a chemical sensor into the blood or on top of an artery, I could get that same data. You know, I I look at what the diabetes offerings are and I think they’ve done a phenomenal job putting these sensors on top of the skin. But what if I can put that under the skin and get the same data that you’re looking for? And make it autonomous for the patient so they don’t have to change sensors every two weeks. I think you’re going to see that. I think over time you’re going to put a sensor in the brain, the heart, the eye and the spine, and you’re going to find correlations of data that you have never seen or thought of before.

Roberts: David Hendren has more to add to that thought.

Hendren: We can see having sensors elsewhere. Our particular sensor can work elsewhere. The particular use case for the initial application of measuring waveform blood pressure. The reason it’s going to land on the radial artery. Is because it’s a very simple place to place the technology, but there are use cases where you might for measuring some form of blood pressure, you can put it in different places for measuring different things. So for example, adjacent to a vascular graft.

Roberts: So, there’s a pressure inside your brain and some people have high pressure in their brain and it causes all kinds of problems. Could you put a sensor in someone’s brain and measure their cranial pressure?

Hendren: You are anticipating a bunch of the different applications for the technology beautifully, and in fact, yes there are applications for measuring intracranial pressure. There are applications, for example in bladder pressure. There is a long list of other applications that relate to cardiovascular medicine, where it’s not just about measuring waveform blood pressure on the radial artery, measuring cardiac output, a variety of use cases.

Roberts: Max Ostermeier agrees with this possibility and thinks it can go even further.

Ostermeier: I’m also aware about a company which is developing  a robot pill. So means this pill is as well by the patient and then it can be steered around the stomach and the next steps it will also have a so-called pill surgeon, means that it’s a pill is also able to collect biopsy within the stomach or also remove polyps.

Roberts: I remember this movie years ago, science fiction, where these people were in the submarine and the submarine got shrunk down into a little capsule and then you would swallow it and it would go through your body looking around and things. Oh my gosh, Max science fiction is turning into reality!

Ostermeier: Yeah, yeah, absolutely. Absolutely. There are products going to the digestive tract and going to the stomach and you swallow them and then it takes around 24 hours for these devices to go through the body and at the end of the day, meanwhile, you can also gather real life data from from inside the body.

Now meanwhile, the first generation just went through the body and then at the end you have to really read the data out, but meanwhile can also telemetrically gather pictures from inside all kind of information. I think that’s really science fiction becoming reality.

I think in 50 years it might be only a very small patch attached to the skin which will provide all kind of data, intraocular pressure, physiological data, any data. Because I think in 50 years I think the technology and especially that AI will be so advanced you know, that you don’t have to even go into specific parts of the body to collect data. I think it will be just a kind of an attachable sensor to the skin, providing all kind of data. Or maybe it’s also something like you have very small sensors, Nano sensors going through the body and you can steer them wherever you want and I think this will be the future. If they are still around smartphones – you know with smartphones you’re already now collecting so much data I think also these kind of communication tools will be really crucial. I would see the future a  closed loop therapeutic system where even doctors would not have a major role anymore. I think that’s what I would foresee in the very long future.

Roberts: What Max and our esteemed guests have shared might sound like the plot of a science fiction movie, however, which truly makes a remarkable is that it is grounded in scientific reality. This cutting edge technology is actively being developed today. Thanks to the dedication of individuals such as Max Ostermeier, Doug Adams, David Hendren and countless others, it has the potential to transform the landscape of diagnostic medicine.

While we may not yet be voyaging through blood vessels and miniature submarines, the advancements we learned about today promise a future where we’ll be safer, healthier and more informed for disease treatment and prevention. 

Did this episode spark ideas for you? Let us know at podcasts@lighthouseguild.org and if you liked this episode, please subscribe, rate and review us on Apple Podcasts or wherever you get your podcasts.

I’m Doctor Cal Roberts. On Tech and Vision is produced by Lighthouse Guild. For more information visit www.lighthouseguild.org on tech and vision with Doctor Cal Roberts produced at Lighthouse Guild by my colleagues Jane Schmidt and Anne Marie O’hearn. My thanks to Podfly for their production support. 

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