Inventing a Tiny Pacemaker with John Rogers, PhD

[00:00:02] Erin Spain, MS: The world's smallest pacemaker was recently developed here at Northwestern University. It's no bigger than a grain of rice and is a wireless battery free device engineered to be injected into the body after certain heart surgeries and dissolve after its usefulness is completed. An alternative to the bulky wired temporary pacemakers that are currently being used in patients after certain procedures that require them.This incredible innovation comes from the Lab of Professor John A. Rogers, the Louis A. Simpson, and Kimberly Querry professor of materials science and engineering by a medical engineering and neurological surgery. Professor Rogers also has appointments in Northwestern's McCormick School of Engineering and here at Feinberg School of Medicine.He joins me today to talk about the latest version of this device, which was recently detailed in the journal nature and how his partnership with Feinberg investigators is leading to such innovative solutions to improve human health. Welcome to the show, John. 

[00:01:03] John A. Rogers: Yeah, for having me 

[00:01:04] Erin Spain, MS: I should say, welcome back to this podcast. We've had you on this show a couple of times, once with Dr. Amy Paller to talk about your wireless technology that helps doctors and nurses and parents take better care of babies and neonatal intensive care units. But could you refresh our listeners memories on the focus of your work here at Northwestern and how it intersects with medical research and patient care. 

[00:01:27] John A. Rogers: Yeah, sure. Happy to do that. So, you know, my background is in engineering with a specific emphasis on electronic material science and biomedical engineering. And so we're really interested in developing new technologies that could ultimately have a. Beneficial effect on the way we care for patients. And so we run an institute here at Northwestern the Query Simpson Institute for Bio Electronics. That really helps to support research at the boundaries between engineering, science and, and medical science. And so we have, of course, you know, networks of collaborators here in our school of engineering, but what's even more important is that we have deep engagements across the. Here, not only associated with Feinberg, but the broader, you know, clinical um, you know, apparatus community we have here in Chicago and beyond quite, frankly. So the programs are pretty extensive. We have many different projects that we're pursuing all simultaneously. I think the latest count in terms of numbers of people associated with. So it's postdoctoral fellows, it's medical students, it's MD-PhD students, PhD students, master's students. And we also have a huge cohort of undergraduate students who are involved in our research through mechanisms that enable them to do research for course credit, or we pay them on an hourly basis. So I think we have 80 undergraduate researchers that are embedded in our programs. And so we view that as an important kind of educational kind of, and a training aspect of what we do. But you know, we typically have a number of different IRB approved studies on human patients associated with our device technologies. And, a lot of that has to do with skin interface devices, so minimal risk to patients and so we can get approval to. Do testing in kind of a hospital setting with those devices. But in the context of this current project, we'll talk a little bit more about it's a little bit more invasive. It's an implantable device. And so in those cases, a lot of our research involves uh, animals. Model studies, again, in close collaboration with the clinical community faculty associated with our medical school. but as a precursor to moving toward, ultimate use with humans we really kind of focus on uh, animal model studies. Uh, initially it's kind of kind the way we do things. 

[00:03:50] Erin Spain, MS: Well in, in this case, you collaborated with a team of cardiologists here at Feinberg who want to improve the experience of patients in need of temporary pacemakers. So set the stage for me with this problem. Tell me about temporary pacemakers, the challenges they present, and the problem that this new device may solve. 

[00:04:09] John A. Rogers: Yeah, sure. I can say a few words about that, but, maybe a little bit of a historical context. To begin with, as I mentioned, my core expertise, technical expertise is in electronic material science and we got interested in the notion of. Electronic circuits built with materials that could dissolve naturally and in a safe manner when exposed to biofluids. And we were thinking about that in the context of, temporary implantable biomedical devices that would operate conceptually similar to the way a Resorbable suture operates in the sense that they provide some kind of function. Over a relevant time period aligned with a natural biological process such as wound healing in the context of a suture, but ultimately disappear after that function is no longer valuable or necessary to eliminate, you know, foreign body reaction risk and device load on the body. So over the years we've really been able to . Put together a complete set of materials that provide all the kind of electronic functionality that you'd be familiar with in consumer electronic gadgetry, but with this unique defining characteristic that all of the materials dissolve slowly and in a controlled manner  When exposed to water biofluids by, extension to biocompatible end products. So, you know, we've been working on this technology for a long time and the clinical use cases that we're exploring now, this temporary pacemaker being a good example of that, have been brought to us by the clinical community. So it's much more of a clinical pull than it is a technology push, and that's kind of where we like to operate because we don't wanna. Develop new technologies and then try to fish around and kind of wedge you know, an application maybe contrived around that technology. But we really wanna kind of be responsive to what the uh, clinical community is struggling with in terms of challenges around patient care. So that's how we got started and it turned out to be a fantastic collaboration involving my group on the engineering side, but also Igor Moff, who's in biomedical engineering and expert in cardiac science, paired with surgeons who do these kinds of procedures and have used in the past conventional temporary pacemakers. And they saw value in this uh, kind of, kind of new approach. And so it was a great collaborative effort, you know, supported in part by our institute, again, at that interdisciplinary boundary between engineering, science and medical science. 

[00:06:34] Erin Spain, MS: And for folks who may not know why a temporary pacemaker would be used, do you mind diving into that? I know you're not a cardiac surgeon, but diving into that a little bit about, you know, why they're being used right now, especially in a lot of cases, small children, and why this is a risk to patients in some ways. 

[00:06:51] John A. Rogers: Yeah, I can say a few words about it, but as you pointed out, and as I'll emphasize again as a caveat, I'm not a doctor. I am just responding to what doctors are telling me is needed for patient care. And to be honest, I had no idea there was such a thing as a temporary pacemaker when we started this project. It was news to me, you know? It turns out and again, this is what I'm told, is that in many cases if a patient comes in and they have to have a cardiac procedure, a surgical procedure very invasive obviously, and you know, as a patient recovers from that surgery, there's various uh, risk factors associated with um, you know, declining health during recovery. And so what. What they will do commonly, especially in pediatric patients, is at the end of the surgery they will insert into the body a pacing lead either on the inner walls of the heart or on the surface of the heart. That pacing leads basically electrodes in contact with the cardiac tissue will then pass through the skin after the surgical site is sutured and the chest is closed, passed through the skin and then connect to an external electrical power supply that can be activated to uh, yield voltage pulses. That can pace, pace the heart in the event that the heart rate drops below a certain threshold level that would represent a serious risk for the patient, and that can happen during the recovery period. And so they want that temporary pacemaker in, in place in the event that they need to pace the heart back up to a healthy level. So what they have to do is two things. One is they have to control that power supply to deliver the stimulus pulses at the proper rate, if that's needed. And so the other thing they need to do then is they need to monitor the heart rate so they can determine when they need to activate that pacemaker and how long they need to activate it before it's no longer needed.So they have a wired system for measuring. Electrocardiograms. So measuring the heart rate using the standard, you know, paste on electrodes with the wires and the external boxes of data acquisition electronics. And then they have the other wire associated with the temporary pacemaker connected to that power supply. So it really turns out to be pretty com cumbersome for the patient. They're wired up in, in two, three different uh, ways in that, in that manner. But, but that's the standard of care there was a perceived need then by the surgeons for an alternative to doing that monitoring and also doing that pacing. Uh, and the key point here is that the pacing is not needed forever. It's not like a permanent pacemaker, but it's only needed for, you know, a couple of weeks during that critical risk period following the surgery. After that, it's no longer needed. So what happens? Well, you can just, you know, take away the electrodes from measuring the ECG. That's not a big problem, but pulling out that temporary pacemaker requires, you know, removal of that pacing lead, which was in contact with the heart and sort of pulls it out through that transcutaneous, you know, access point. And in most cases, that's not a problem. You pull it out and you know, that's, you know, not ideal. And it. Create some pain and discomfort, obviously, for the patient. But, you can kind of do that in some cases. However that pacing lead will become encapsulated in scar tissue over that couple week period. And that was just a natural, you know, foreign body response. You know, that that will be engaged by, by, the that, of that pacing lead. And even that's not a problem because it's just scar tissue. You rip it. The problem is that sometimes that scar tissue is. Adhering not only to the pacing lead, but also to the adjacent healthy cardiac tissue. And when the scar tissue tears, in some cases, that can lead to tearing of the healthy cardiac tissue. And if that happens, that can initiate internal bleeding. And that can be a big problem. And uh, it can in certain cases lead to uh, patient death. And so that is the critical risk factor layered on top of just the cumbersome nature of all of the wired systems that I think served as a motivating consideration for these surgeons to reach out to us and kind of initiate uh, collaborative work in this space. 

[00:11:20] Erin Spain, MS: Now, you've been working on this with your team for more than four years. There's been many different versions of this, but this latest is the size of a grain of rice. So, so, so tiny. Tell me how important it was for you to continue modifying this and making it as tiny as possible. That's important here. 

[00:11:39] John A. Rogers: Yeah. So as you point out I think we started working collaboratively in this space maybe three, four years ago. Our first engineering design involved wireless operation via wireless power transfer. So mechanisms. Are very similar to those that use for contact payments. So it's kind of an electromagnetic coupling between an external kind of coil, essentially an antenna and a receiver coil that's integrated with the implanted temporary pacemaker, the bioresorbable pacemaker. So that works pretty well. You know, it ends up being a device that's kind of. Thin like paper and it's flexible. And it adheres to the outside surface of the heart, has a couple of pacing leads that interface with the cardiac tissue to deliver the pacing stimulus. And then those leads connect to that receiver coil that wirelessly couples to the external coil. So you eliminate the wires that I was mentioning before, which is great. Eliminate any kind of risk associated with surgical extraction because you don't need to extract it, it just melts away. Over time. And so that's great. I guess once we get started, a lot of times as engineers we get started on a project like this and then we begin to develop all kinds of ideas to improve an initial design. And so that's kind of what happened here but we figured, you know, maybe there's some ideas to make it much smaller and in fact make it so miniaturized that you could envision. The use of multiple pacemakers at different locations across the surface of the heart. So you could stimulate in a time coordinated fashion that would lead to a more natural beat cycle. And that was something that was identified to us by our collaborator. Igor Mof is very much an expert in the engineering kind of aspects of how the heart works, and so we're thinking like multiple site time coordinated stimulation might kind of enhance the way that you. That you could pace the heart. We also thought, you know, these little wireless, you know, resorbable pacemakers, maybe if you made them small enough, you could put them on various kinds of existing cardiac devices like tAVR valves and other things like that. So, we perceive there could be a lot of additional opportunities for making the device in sort of a millimeter scale geometry. And then from a practical standpoint, it would just reduce the burden on the patient. You just miniaturize the device. I think you minimize associated risk factors and things like that. We haven't seen problems as you can imagine, so there's a lot of reasons why I. Miniaturization was of interest to us and began to think about that. And the limiting factor with the original design is we need an antenna large enough to receive sufficient power from that external power source to, to drive the, cardiac rhythm. And that was just defined by physics. We're not gonna make that any smaller. There's not really any way to do that. So then we begin to think, well, maybe there's a different way we could power the device. And I had a really great postdoc who did her PhD studies in battery technology. So she was very familiar with all kinds of different battery chemistries, and she suggested that maybe we could integrate a battery right into the, device, thereby eliminating the need to wirelessly deliver power because the power would be on board, so may make a very tiny battery essentially, and integrate it directly with the pacemaker. And that seemed pretty interesting. And we kind of ran the numbers and we figured, okay, if we use these two types of metals, we could make a primary battery where the circuit is closed by the surrounding bio fluids. And we could do that and we could see, okay, we generate enough power that way. But then the question is, how are you gonna control it? How are you gonna? Turn it on and off remotely. You don't have physical access to it. With the wireless power delivery scheme, it was easy to turn it on and off 'cause we could just turn on and off. The external transmission antenna, when it's on the device, is powered. When it's off, it's not. And so we could just modulate that, that power to the transmission antenna on and off to set the pacing rate. No problem. But if you have self-power, divisive, this tiny battery, how are you gonna trigger it? And so then that became a challenge. And what we're able to do there is we created a bioresorbable photodetector, essentially a light activated switch.And it can be made very tiny, actually as small as this very tiny battery with the electrodes to interface to. And we selected a photo detector. This photo activated switch to operate at a wavelength range for which transmission through tissue can occur with very little absorption. So it turns out that infrared light, so you think about red light, is a little bit longer wavelength than red light, so it's invisible to the eye, but it will pass right through your body pretty effectively. So we decided, wow, if we had a photo activated switch integrated with this tiny battery in the electrodes, then we could use a skin mounted light source and we could turn that light on and off to switch the pacemaker into an on or an off state. And so that's what we've done. And I have one of these pacemakers here. It's about the size of a grain of rice, maybe a little bit smaller.I don't know where the camera is here. Yeah, it's there. So. 

[00:17:15] Erin Spain, MS: Itty bitty. 

[00:17:16] John A. Rogers: So on one side of this device, we have a pair of electrodes. Two different types of metals that are bioresorbable and biocompatible have different characteristics. And so when they're joined by a, you know,biofluid, which is ionically conductive it, it forms a battery. And then on the backside of this device is that photo activated switch. And so you can load this up, you know, into a um, into a syringe, and you can just deliver it wherever you want or you can, you know, quite frankly, you can just sprinkle 'em around. And each one can be designed to operate at a different optical wavelength. So I can turn this one on without turning this one on, and then I can time them out and do all kinds of crazy things. I. So that, that's what the implantable device, and then this is the, the wearable device. So it has two component parts. This is the uh, light emitting uh, diode that's providing that near infrared light to activate that photo switch.And then we have two electrodes here that uh, are designed to measure electrocardiograms. So this device goes on on the chest right above the heart, so when the light activates, it transmits right through the skin, through the tissue. Illuminates the uh, cardiac pacemaker, turns it on whenever the light's on, and then these electrodes are measuring the cardiac rhythm through ECG monitoring. So it's measuring the heart rate. And then we have a microprocessor built into this device that detects the heart rate. And if the heart rate drops below a user defined threshold setting, It will activate the LED and therefore pace the heart back up to a healthy rhythm. So it kind of combines some of the work that you were talking about before in terms of neonatal monitoring.That's kind of, this is an adapted version of that with a very advanced version of our previously reported, uh, temporary uh, uh, pacemaker, the bioresorbable device. 

[00:19:16] Erin Spain, MS: I mean, you holding up that tiny little device, it's so little. I'd be worried that I would lose it in the lab. Can you talk about some of the challenges with working with such teeny tiny 

[00:19:27] John A. Rogers: Well, we have a little, little container like that. I dunno if you can see the device there, but it, but it is hard to hold it with with your fingertips. We have, you know, tweezers and different things like that but, but we're uh, experts in fabricating ti tiny things, you know uh, I would say gen, generally speaking, um, we use a lot of the techniques that are are established and developed in the semiconductor industry for forming, you know, integrated circuits and very tiny wires and. Transistors and things like that. And, and, we're adapting a lot of those approaches for building, you know, unusual classes of biomedical devices like, like this. So actually that photo activated switch is a silicon-based technology. We actually produce it on a silicon wafer and then we have ways to sort of shave it off of the wafer and kind of integrate it with the battery. But it's a resorbable type of uh, silicon, you know, photo switch. 

[00:20:22] Erin Spain, MS: Well, and just for people listening who are talking about this resorbable, like this is going into your body and basically dissolving, disappearing, tell me about some of those materials and where they're going once they dissolve, like what happens, like why are they such good matches for this type of technology? 

[00:20:39] John A. Rogers: Yeah it's, it's a great question. So we think a lot about that. Obviously, you know the materials needed to satisfy certain requirements and electrical performance characteristics. So we can build useful devices uh, but they also rigorously have to be biocompatible, not only the materials themselves, but also the products of their. Dissolution and degradation in the body. Those reaction products also have to be biocompatible. So, there are few components here. Um. One involves metal, um, um, films that define the battery and the electrical interface to the heart. That's kind of one part of the system. And then, as I mentioned, on the backside of the device, we have this silicon-based uh, photo uh, photo, switch. And then the entire structure, both the battery and the photo switch are integrated together with a polymeric. Kind, Kind of material. So we just step you through the different materials that are involved in. So the polymers start with the polymers serving as the substrate and kind of the glue to hold the whole thing together. We use uh, polymers that are already FDA approved uh, for temporary implants, but not electronic implants 'cause nobody's ever done that before. But polymers that uh, are designed for, um. temporary, you know, screws in orthopedic implants or um, passive drug release uh, vehicles, various kinds of platforms. So there's, there's a number of FDA approved, um, um, biodegradable polymers. Uh, And there's some biomaterials that we've used in the past as well. Silk fibroin, it's a good choice. For example, it's a biomaterial itself, so purified from silkworm cocoon. So, that, that there's a, a, wide range of choices for, for the polymeric component. Then you'd ask about, okay, what about the metals that we're using, this galvanic pair that we're using for the battery? We actually have a number of choices there. Uh, as well, we like magnesium and zinc. Uh, So you put those two uh, metals together. You get a battery uh, when, when they're joined by an electrolyte, like, like a biofluid. So then you would ask, well, what's. Magnesium and zinc. Do I have to worry about that? Uh, You have to worry about everything but, do you have to really worry about it or you just have to kind of pay attention to it? It's useful to point out that uh, both magnesium and zinc are recommended parts of a daily diet. They're essential elements. For natural biological processes. Yeah, exactly right. So, it's not crazy materials, you know, this is stuff that, you know, you're ingesting and required to, you know, consume to, to remain uh, remain healthy, quite frankly. Uh, The other thing about magnesium specifically is that it's been extensively explored for, um, bioresorbable stents, which are kind of mechanical structures that hold vessels open. So it's been studied. As an implantable biodegradable material. Not an electronic device but in other contexts. So there's a base of literature around that. The other thing that we do is we do, um, uh, extensive animal model tests where we look at. The um, the, any kind of inflammation or immune response is happening local to the device. And then the other thing that we do is we do ct uh, and MRI imaging at various stages of the dissolution process so we can watch how it's disappearing within the body of the animal. And then the third thing that we do is we look at the concentrations of these various elements uh, In blood samples. Collected at various stages of the degradation process. Uh, And so we can watch just natural excretion processes, eliminate any kind of elevated concentrations of these materials in the body over time. So we haven't seen any, any problem. But these have not been used in humans, so they've been used with human hearts, but explants, so not in human PA patients, but organ donors. So we know that it works at a human scale, but we have not used them in humans. I think that's where we want uh, things to go, obviously but we haven't done that work yet. So then the final component is the uh, photo switch itself. It's made predominantly out of silicon. Uh, There's a little bit of metal in there for the kind of electrode structures that you need, but we like to use magnesium. Same uh, metals that we're using for the battery we use for the electrodes in the photo switch. Silicon, like magnesium and zinc is also a required element for natural body processes. So if you look at a vitamin tablet, it has a lot of silicon in it. It has a lot of magnesium in it. So again, these are materials and elements that are in the body. They need to be in the body and you know, so it's not exotic stuff.Final comment that I would make is the additional advantage of miniaturization is you just minimize the dose of these materials in the body. So we're talking about just very tiny amounts, just like a grain of sand level of material. And you know, compared to the full, you know, way to the body mass of the body's very tiny. In fact, if you look at the mass content of these various elements that I just mentioned in that Millimeter scale temporary pacemaker. It's comparable to or less than what you would see in a one a day multivitamin tablet. So it's not a lot of material. Another great thing about miniaturization, so you don't have to worry about any kind of dose that would be problematic just from a standpoint of total total mass content. 

[00:26:09] Erin Spain, MS: No, that's such a great explanation because I do think people wonder. It just sounds so, so, you know, futuristic, what happens when this dissolves into your body. But you make some great points there. Another thing that you mentioned was MRI scans. This device is compatible with MRI scans with traditional pacemakers, you can't do that. They're metal. This kind of solves a problem that way as well. 

[00:26:30] John A. Rogers: glad you brought, brought, that up because it's a question we always get, you know, is it MRI compatible? That's like the first question. You know, any kind of new, new device because uh, you know, that's an important part of patient care.So. It's very tiny that we've seen no um, you know, adverse, like any current heating or any kind of sha significant shadowing or any kind of issueWith, with MRI uh, you know, imaging and 

[00:26:54] Erin Spain, MS: Well, and you mentioned that you were doing some of the studying and on human heart models. On animal models, really promising results so far. And as you said, now people are really wondering when might this go into clinical trials? So, do you have an update for us? What could we expect? 

[00:27:09] John A. Rogers: Well, we'd love to go in that direction. I mean, I think if you're a biomedical engineer and you're working kind of on New device technologies, you know, your goal really needs to be human use ultimately. So we're very translational.So we have a nascent startup with Igor OV and some of our other collaborators. Seed money uh, in, into that into that activity. And so uh, we're, you know, putting the pieces in place to kind of, kind of start moving things in that direction. We're pretty happy with the technology. But there are two factors. One is that it's an implantable device. It's designed to be a life saving device for critically ill patients in the context of a technology that FDA has never looked at before, because there's never been a resorbable electronic implant before. It does not exist. There's no predicate. And so there's, you know, a road that's going that we're gonna have to go down, you know, in order to make it happen, but. We wanna do that because we don't wanna get in the business of publishing hero papers and then kind of moving on to the next thing. And that's not our style. So, so we're, we're kind of figuring out how to put the financing in place and how to begin to uh, assemble a team. But to put a specific timeline on it would be difficult. It's not next year, it's not the year after. It might be five years. Realistically, 

[00:28:32] Erin Spain, MS: Well, John Rogers, thank you so much for being on the podcast today.  

[00:28:35] John A. Rogers: Yeah. Great. Thanks for having me. 

[00:28:39] Erin Spain, MS: Thanks for listening. Please click the bell to receive notifications about our latest episodes and follow us on social media at NU Feinberg Med to stay up to date with our latest research findings. 

Physicians who listen to this podcast may claim continuing medical education credit after listening to an episode of this program.

Target Audience

Academic/Research, Multiple specialties

Learning Objectives

At the conclusion of this activity, participants will be able to:

1. Identify the research interests and initiatives of Feinberg faculty.
2. Discuss new updates in clinical and translational research.

Accreditation Statement

The Northwestern University Feinberg School of Medicine is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.

Credit Designation Statement

The Northwestern University Feinberg School of Medicine designates this Enduring Material for a maximum of 0.50 AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

American Board of Surgery Continuous Certification Program

Successful completion of this CME activity enables the learner to earn credit toward the CME requirement(s) of the American Board of Surgery’s Continuous Certification program. It is the CME activity provider's responsibility to submit learner completion information to ACCME for the purpose of granting ABS credit.

Disclosure Statement

John Rogers, PhD, has disclosed financial relationships as founder of Sibel Health and Epicore Biosystems. Course director, Robert Rosa, MD, has nothing to disclose. Planning committee member, Erin Spain, has nothing to disclose. FSM’s CME Leadership, Review Committee, and Staff have no relevant financial relationships with ineligible companies to disclose.

All the relevant financial relationships for these individuals have been mitigated.

CME Credit Opportunity Coming Soon