Tiny, minimally invasive, dissolvable: New membrane pacemaker controls heartbeat with light
Leslie Mertz
A new cardiac pacemaker is in development. It is a small, lightweight patch that is delivered through a catheter to the heart, where it regulates the heartbeat via tiny pulses of light, and then dissolves away when it is no longer needed.
The device has already been tested on a live pig, and performed surprisingly well, said developer Bozhi Tian (Figure 1), Ph.D., professor of chemistry at the University of Chicago (UChicago). “I personally never thought it would work the first time, but even with a light intensity that was not that strong, our device achieved very efficient cardiac pacing.”
Figure 1. Bozhi Tian, Ph.D., professor of chemistry at the University of Chicago, led a research group in the development of a membranous cardiac pacemaker that regulates the heartbeat via tiny pulses of light. (Photo courtesy of Bozhi Tian.)
The new pacemaker has numerous qualities that set it apart from conventional pacemakers, Tian said. “The weight of our device is a few orders of magnitude less than a traditional cardiac pacemaker, and it is only 20–30 micrometers in thickness, so it is thinner even than a piece of paper.”
Not your average pacemaker
In comparing it to conventional pacemakers that have one or two electrodes and offer stimulation to set locations on the heart, he noted, “our pacemaker has no limitations on the number of electrodes that can offer the heart stimulation, and we can use light to control the pacing, as well as alter the stimulation location for what we call random-access pacing. This is important because over time, the patient’s symptoms may change and the optimal stimulation location may need to be changed as well.”
“The pacemaker is a membranous semiconducting silicon patch, that can be sized to fit the patient’s circumstance, according to Tian’s graduate student Pengju Li (Figure 2), who is the lead author on the Nature paper describing the work [1]. For instance, if a person is going through open-heart surgery, we only need a patch of about 1 cm × 2 cm to initiate the heart-beating function and maintain it at a normal frequency for a week or two until the heart takes over,” he described, noting that this how they mainly envision the patch to be used.
Figure 2. Pengju Li, a postdoctoral candidate in the University of Chicago Pritzker School of Molecular Engineering and researcher in the lab of Dr. Tian, presents the pacemaker project at the MIT Technology Review Innovators Under 35 Asia Pacific award ceremony. Li was recognized as one of the Innovators for his contributions to the pacemaker technologies. (Photo courtesy of the Pujiang Innovation Forum 2024.)
“If we were to use the device for a patient with ventricular dyssynchrony (left and right ventricles beating out of sync), however, we may need a larger patch to cover both ventricles and perform multi-site resynchronization pacing, and may need it to function for a longer duration,” Li said. “Fortunately, our device is very scalable, and we can use microfabrication to make a membrane up to 20 cm × 20 cm.”
Design process
The design and development of their device stemmed from work on photostimulation of neurons that Tian and his group had begun in 2014–2015. At that time, their focus was on using a nanowire-like material to interface with single neurons, and then shining a light on the material to elicit neural activity [2].
In 2017, Tian welcomed a new group member, postdoc Menahem Rotenberg, who had experience in cardiac tissue engineering and began investigating photostimulation of the heart. Rotenberg started exploring improved materials for the task, and by employing a variety of techniques, he and another graduate student, Aleksander Prominski, were able to create a nanoporous layer on a non-porous silicon wafer. “That nanoporous layer was the key,” Tian said. “It allowed us to generate a highly efficient material that could stimulate neural and heart tissues with relatively low light intensity” [3].
In 2022, the group published results of experiments illustrating that the technology’s could initiate and regulate cardiac pacing in rat hearts in vitro and ex vivo [4].
“At that point,” Tian recalled, “we realized that while we made some good progress, we needed to show the pacemaker’s capability in an animal heart model that was very similar to that of a human, and that meant a pig model.” This presented a number of challenges, not the least of which was the considerably greater size of a pig versus a rat, and Tian suspected they would have no choice but to either use a very high-intensity light or develop a much more efficient material.
Stepping up the game
That is when Li, a Ph.D. candidate in the UChicago Pritzker School of Molecular Engineering, joined Tian’s group. “Some magic happened,” Tian said. “Pengju optimized the pacemaker membrane to make it so efficient that we do not need to use very high light intensity. In fact, all we need is light intensity similar to 1 Sun, which is the light intensity at a similar level to that we experience outside at noon on a sunny day.” Tian described the new patch as comprising two layers of a P-type silicon material that works much like solar cells to create an electrical charge when exposed to light, and an optimized porous design that produces electricity very efficiently, and stimulates target cells very precisely and locally.
Not only that, Li devised a minimally invasive way to deliver the pacemaker membrane. It involves precisely folding the membrane to fit inside a narrow tube. The tube slides through a thin catheter that leads to the heart through a tiny incision. When the tube reaches the heart surface, a spring helps to deploy the membrane—rather like opening an umbrella—and the membrane seats itself on the heart surface (Figure 3). The catheter and tube then retract, leaving the membrane on the heart. A fine optic fiber, also delivered via the catheter, is also left in place as the light source.
Figure 3. The pacemaker is a photostimulation device with an optimized porous design that produces electricity very efficiently and stimulates target cells very precisely and locally. To deliver it for use, only a small incision is necessary. The device is folded to fit inside a narrow tube, slid through a thin catheter to the heart surface, and deployed rather like opening an umbrella to seat itself on the heart surface. The catheter and tube then retract, leaving the device on the heart. A fine optic fiber, also delivered via the catheter, is also left in place as the light source. (Photo courtesy of the Tian Lab.)
Once the researchers were ready to try it out, Li found surgical collaborators who worked with him to implant and test it in a live pig. “I still remember that day,” Tian said. “It was our first pig experiment, and it worked!”
Next stage
The device is not designed to compete with traditional cardiac pacemakers that are used mostly for chronic disease, Tian said. Rather, at its current stage, it is designed be used as a temporary pacemaker to essentially train the heart to begin beating normally on its own. “Our pacemaker is designed to only last for a few weeks, perhaps up to a few months, and then naturally degrade and dissolve without the need for subsequent surgery to remove it,” he explained.
Li is now busy developing a next-generation pacemaker, which enables a reduction in the required light intensity by three orders of magnitude, Tian said. “That is already a big improvement, and he is also working on adding tissue-regeneration functionality.” Tian declined to go into details, but noted, “I will say that we are very excited about this next-generation cardiac pacemaker, and hope to submit that work for publication early next year.”
In September 2024, the MIT Technology Review recognized Li’s work on the pacemaker, naming him one of the youngest Innovators Under 35 Asia Pacific [5]. Li is not stopping there. He is currently optimizing the pacemaker, while seeking to land a faculty appointment at a top research institution. “Pengju is an extremely creative researcher with a lot of experience in electrical and mechanical engineering,” Tian said. “He is the real hero behind the particular work described in the Nature paper, and I think this work will be a stepping stone toward his career aspiration.”
References
- P. Li et al., “Monolithic silicon for high spatiotemporal translational photostimulation,” Nature, vol. 626, no. 8001, pp. 990–998, Feb. 2024.
- R. Parameswaran et al., “Photoelectrochemical modulation of neuronal activity with free-standing coaxial silicon nanowires,” Nature Nanotechnol., vol. 13, no. 3, pp. 260–266, Mar. 2018.
- R. Parameswaran et al., “Optical stimulation of cardiac cells with a polymer-supported silicon nanowire matrix,” Proc. Nat. Acad. Sci. USA, vol. 116, no. 2, pp. 413–421, Jan. 2019.
- A. Prominski et al., “Porosity-based heterojunctions enable leadless optoelectronic modulation of tissues,” Nature Mater., vol. 21, no. 6, pp. 647–655, Jun. 2022.
- Univ. Chicago. (Sep. 10, 2024). PhD Candidate Pengju Li Takes Top International Innovation Award. Accessed: Sep. 13, 2024. [Online]. Available: https://pme.uchicago.edu/news/phd-candidate-pengju-li-takes-top-international-innovation-award