Professor Igor Efimov and a team at George Washington University in Washington, DC — in collaboration with Professor John Rogers’ laboratory from Northwestern University in Chicago, IL — are pioneering a new class of medical instruments that uses flexible electronics to improve patient outcomes in minimally invasive surgeries.

Tech Briefs: How did you get started on this project?

Dr. Igor Efimov: I’ve done cardiac research for quite some time now. I started my career as an independent investigator at the Cleveland Clinic, which has a long culture of innovating and has had many major breakthroughs. I worked with a number of brilliant cardiologists there and I was truly transformed by that experience.

My work was focused on arrythmia and treatment of heart rhythm disorders. A second important experience was about seven or eight years ago. I was looking for a new platform for implementing medical devices and I came across the work of John Rogers, who was making advances in biologically compatible materials. He had already worked with some biologists, primarily in the field of neuroscience. I invited him to collaborate with me on cardiology, and we have done a great deal of work together since then. First, we created a platform for organ-conformal electronics. Then we went on and created a platform for “smart” electronics — essentially medical devices equipped with their own micro-circuitry, which allows signal processing, amplification, multiplexing, and so on. Our next project was battery-free implantable pacemakers. We are now working to make them body-resorbable so they can be absorbed after they are no longer needed.

Tech Briefs: How is the battery-free device powered?

Dr. Efimov: The pacemaker has an antenna that matches an external antenna. You could have a circuit outside of your body — embedded in your clothing or a wearable patch — which transmits energy and programming into the implanted electronics using inductive power transfer.

In about 2013 we had designed a pacemaker that worked in a mouse. But unfortunately, we used a silver wire electrode that was so stiff it resulted in damage to the heart muscle, so we had a very high mortality with our mice. That gave me the idea of using the soft conformal electronics that John had designed. That was my initial stimulus — I asked him if he could solve my problem, and he did.

Our most recent paper talks about how to create a device for a percutaneous transvenous catheter. It won’t be implanted but will be inserted inside the heart and navigated towards an area of arrythmia. It has five different functions with three types of sensors and actuators that can serve two different functions. This kind of multifunctional, multiphysics allows you to dramatically improve the speed of ablative treatments. Ablation is a state-of-the art technology used for the treatment of heart rhythm disorders. 85% of patients with atrial fibrillation (AF) or ventricular tachycardia cannot be treated with drugs, so they have to live with this disease. That, unfortunately, leads to a dramatic increase in stroke rate and mortality. The US alone has about 5 million AF patients. World-wide, it’s about 15 million, and by 2050 it is projected that there will be 50 million people with atrial fibrillation because of increased life expectancy.

Cardiac ablation is a procedure that can correct atrial fibrillation by destroying the heart tissue that is causing it. Currently, treatment is done by inserting several pieces of hardware. One is used to create electrograms that map the arrhythmia by recording electric signals from the heart. These electrograms can be used for trying to understand the source of the arrhythmia. Another piece of hardware can then be inserted to do the ablation. Ablation means you essentially you burn the tissue, using RF current, which increases the tissue temperature to about 55°C – 60°C [131°F – 140°F]. As a result, you kill the cells responsible for arrhythmia and hopefully kill AF. Because you are doing the procedure asynchronously, one for location and the other for ablation, there are a lot of technical difficulties to do it properly. It requires x-rays, because when you insert electrodes you obviously don’t have direct line-of-sight. The only way you can see hardware inside the heart and navigate properly, is to use X-ray snapshots. This exposes the patient and the physician to a dose of radiation that is not entirely safe. Our technology can reduce the radiation by combining mapping and ablation into one device. You don’t need to displace the device so many times because our device has numerous sensors and actuators that cover a large area of the heart. You can therefore map and ablate without repetitively repositioning the catheter, which will reduce exposure to radiation.

There are a couple of additional modalities that are not typically present in such mapping devices: a matrix of temperature sensors, and another one of force sensors. These two matrices give you readouts in real time. The temperature sensors allow you to monitor temperature as you ablate, which is critical because if you are not in the correct temperature range, the ablation will fail. If you exceed the extinguishing goal by 100°C, it will be dangerous, because you will boil interstitial fluids and blood and this will create problems like bubbles, which can cause infarction and stroke. So, you have to be very precise. The force measurement matrix allows you to establish that you have good physical contact between the ablation matrix and the heart, which is critically important for ablation, because if you don’t have good contact, no matter how much energy you apply to the actuators, they will not deliver the appropriate energy to the heart itself.

A group of engineers from Northwestern and the George Washington University recently developed a new balloon-shaped catheter that will improve treatment for cardiac arrhythmia. They have already created a company called NuSera Biosystems that will help commercialize the instrument. (Image Credit: Northwestern University and the George Washington University)

The way ablation is done now, is with a single one-point catheter, literally a wire that you insert inside the heart, which you poke around spot by spot. In our case, we’ll have 100s of sensors covering a large area of the heart. This very critical contact can only be established using force measurement. You cannot, unfortunately, see the heart with an x-ray because it’s a soft tissue and the contact with the heart muscle is very small. So, you can see the catheter with an x-ray but not the heart itself.

Our device also enables us to do an alternative type of ablation. Currently it’s done primarily by RF, which is called thermal ablation because RF current increases the temperature. Alternatively, we can use cryoablation, a widely used, although less common, procedure where you freeze the heart.

Another method emerging now, is called irreversible electroporation, where instead of burning the tissue, you zap it with a high current that punches holes in cell membranes and thus kills the cells. It’s done in microseconds, while thermal methods like RF require a few minutes to kind of cook the tissue so it can kill it. Irreversible electroporation is now emerging as a non-thermal technology, although It hasn’t yet been fully developed for cardiac applications. However, our device has the ability to do it.

To sum up: our device can do ablation in multiple locations — you don’t need to move a catheter around. You can ablate the whole area as you need to, based on the arrhythmia map derived from the same device. This is unique — it hasn’t been done before, having mapping and ablation in the same device. Plus, thermal and force sensing to ensure safety.

Tech Briefs: One question: For electroporation, does the current go through the cell?

Dr. Efimov: Yes, when you apply a sufficient amount of energy by stimulating tissue or cells, you disrupt the membrane because the current flows through lipid membranes, which are typically nonconductive. They consist of fat, essentially, which is not electrically conductive, but if you apply sufficient energy you will porate the membrane and will kill the cell.

Reversible electroporation is another application, which uses slightly less energy. It’s used for the delivery of macromolecules. For gene therapy, to cite one example, you also have to porate cells, make holes in them, but mild holes. And those holes will repair themselves subsequently. This allows you to put macromolecules inside the cell, such as pieces of RNA or proteins or some other large molecules. These cannot penetrate through the membrane of an intact cell, but they can go through the pores created by the electroporating current. We are planning for our device to be used for that as well. So, if someone needs gene therapy in some area of the heart, we can deliver the electroporating current and provide appropriate therapy.

Tech Briefs: How do you get the RF power into the device and how do you get enough RF power for heating?

Dr. Efimov: Good question. It shows why this device will not be able to be really implantable. Our device is a catheter connected with a cable to the outside electronics and is instrumented on a balloon-like structure. You make an incision, you open up a vein, usually in the groin area, and you go through the vein into the heart, but it’s connected by a cable to the outside electronics. When it’s in the heart you deploy it, you unsheathe it, and it takes shape. Or you can insert saline inside the balloon, and it takes the appropriate shape. Although it comes into contact with tissue, it is hard-wired. That’s how you deliver sufficient energy. Right now, I don’t know of a source of energy big enough to deliver something like that wirelessly or from a battery.

Tech Briefs: And is the same true for electroporation?

Dr. Efimov: Yes, electroporation in particular actually requires even higher energy. For this procedure, however, you don’t need anything implantable. Hundreds of thousands of patients a year in the United States alone, are ablated for an indication of arrythmia. As I said, drugs usually don’t work, so the only way you can do something about it, is to ablate. For ablation, you insert the electrode, the patient lies on a table and is lightly sedated. You insert the cable, you do the procedure, you remove the hardware, and then the patient goes home.

But we are working on another procedure as well. In fact, I have developed an implantable device for treatment of atrial or ventricular fibrillation with lower energy therapy, but we don’t ablate with this device. We apply a sequence of pulses at low energy to terminate the arrhythmia. However, implantable devices have much tighter requirements because you’re going to leave them in the body of a patient for a long time.

Tech Briefs: I saw in your illustration that you have a large number of sensors and actuators on the balloon at the end of the catheter. How do you interconnect them?

Dr. Efimov: You can directly connect with serpentine wires, which allows flexibility, but in that case, you would have a bottleneck. So, we equip each sensor and actuator with its own circuitry. If it’s a sensor, we have a circuit for amplification, filtering, and multiplexing. If it’s an actuator, we do multiplexing. If you’re talking about high throughput systems, multiplexing is required. In the future, I expect we will need from the high hundreds to thousands of sensors and actuators, so that will definitely require multiplexing.

Tech Briefs: What kinds of actuators do you use?

Dr. Efimov: For this application, just electric, whether it’s for RF ablation or for irreversible electroporation. However, previously we wrote about how we could have actuators for light, for example, for optical spectroscopy. An actuator on that kind of device would have an LED and a photodiode. The LED will emit light of a certain wavelength, which will excite fluorescence in molecules inside the heart and the photodiode will collect that fluorescence. That will give us a readout for various cellular processes in the heart, for example, metabolism. So, there are various types of sensors and actuators.

Tech Briefs: Have you tested this on lab animals?

Dr. Efimov: For our previous project, where we developed a miniature battery-free pacemaker, we showed we could implant it in a rat, who could have it for a month or so, and use it as a cardio-stimulator long-term.

Tech Briefs: So, have you also tested this device in rats?

Dr. Efimov: We tested this device in a couple of settings, in explanted human hearts, that are not acceptable for transplantation, which we received from our local organ procurement organization in Washington DC. Ultimately, we plan to test it in humans. But we did do a test in pigs. We cannot test these catheters in small animals because they are designed for the size of the human heart.

Tech Briefs: Do you have some general idea of when this might be commercialized?

Dr. Efimov: I would say safely that three to five years is a good number. For a clinical startup, we need to get venture capital — that’s our next step.

Tech Briefs: What about your previous work on implantable defibrillators?

Dr. Efimov: My goal was to reduce the amount of energy required for defibrillation. Currently, defibrillators, which are implanted in the human chest for ventricular arrhythmias or sudden cardiac death, save lives. But they can go off inappropriately sometimes when the patient is conscious and that is extremely painful. It’s a huge amount of energy delivered to the chest. Because of the shock-induced pain, they cannot be used for patients with atrial fibrillation. Patients with atrial fibrillation are conscious, unlike patients in the state of sudden cardiac death due to ventricular fibrillation, who are already unconscious, and for whom it is a matter of life and death, so for them, it is not about pain.

Our work was about how to change the defibrillation strategy to make it pain-free. That’s what I did for several years. We are now conducting clinical trials with implantable defibrillator technology.

Tech Briefs: It seems to me that your work will make major changes in the treatments for heart ailments.

Dr. Efimov: I think so. What John Rogers has been working on for many years as a material scientist — he took it upon himself to develop a whole manufacturing tradition for electronics, of materials that are biologically compliant: soft, stretchable, compliant, and don’t cause inflammation. All of this work is now coming to fruition in many areas of medicine. I’m particularly interested in cardiology, but there is also work being done in neurology, brain-computer interface, in muscle control for patients with nerve damage, and on and on. So, this is a really good time to be in the field of bioelectronics. I think the next ten to fifteen years will be incredibly fantastic!

For example, I’m part of a community founded by NIH; a program called SPARC, which is focusing on how to control peripheral nerves that control peripheral organs to essentially control different diseases. The sympathetic and parasympathetic nervous systems control all of the organs in the body: heart, lungs, stomach, gut, and so on. You can reduce the burden of many diseases, or even eliminate a disease, if you can control the nerves. We are now working on building an interface that will be able to stimulate sympathetic and parasympathetic nerves and also to record them. This will also be transformational in many areas of medicine.

Tech Briefs: Sounds like science fiction to me.

Dr. Efimov: Ten years ago, it was science fiction. In fact, I am writing another grant right now along with a couple of collaborators for which I proposed using the now-forgotten word “cyborg” in the title, because it is both cybernetic and organic.

An edited version of this interview appeared in the November 2020 issue of Tech Briefs.