Wireless, battery-free, fully implantable multimodal and multisite pacemakers for applications in small animal models

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Every moment of the day, your heart is dependably beating at a steady pace. Your heart rhythm keeps up with your needs: it goes slower while you rest and faster when you run. However, due to factors ranging from genetics, medical conditions, to environment, your heartbeat may not have a reliable rhythm, and if left untreated, this can cause life-threatening heart attacks. Fortunately, in the 1950s, Earl Bakken was inspired by the metronome to develop the world’s first implantable pacemaker. This battery-powered device is fully implanted into a patient just below the collarbone in order to help maintain a regular heart rhythm by repeatedly delivering tiny electrical pulses to the heart. Pacemakers are primarily used for the treatment of abnormal heart rhythms when your own intrinsic heartbeat is too slow or irregular. Although pacemakers are currently highly effective in treating several abnormal heart rhythms, we still do not truly understand the source of these deviant heartbeat patterns and what prompts them to persist. We need to probe deeper into the cause of how these abnormal heart rhythms, or arrhythmias, develop in order to increase the efficacy of treatment for all types of irregular heart patterns. However, few pacemakers are tiny enough to be fully implanted to recreate conditions in which aberrant heart rhythms arise. We set out to create a miniaturized pacemaker that can deliver both electrical and optical stimuli to develop animal models (3D rendered computed tomography and overlaid magnetic resonant imaging depiction of implanted pacemaker shown below) which allow us to study these irregular heart rhythms with greater detail.

3D rendered computed tomography and overlaid magnetic resonant imaging depiction of implanted pacemaker (pacemaker in blue and heart in red).

While current clinical pacemakers deliver electrical pacing, optical stimulation which, via genetic modification, can address specific cells in the heart can provide a potentially more powerful research tool. Optical pacing is possible with the advent of optogenetics, which allows for controlling the heart rhythm by light. Optogenetics changes the genetic information of cells so that these cells can be stimulated simply by illumination. When a specific color of light shines onto the cells, the resulting effect is comparable to the delivery of an electrical stimulus. Optical pacing of the heart is possible by modifying specific cells in the heart to be sensitive to light so that only those that are genetically modified cells will activate. Optical stimulation greatly expands the methods which are available to scientists in stimulating the heart by inducing spatially specific heart activation patterns in animal models. Optical pacing also eliminates any inflammatory tissue reaction that occurs at the metal electrode-tissue interface that often leads to device failure in long-term applications.

Our device consists of 3 main components: The energy harvesting and control electronics, the electrical and optical stimulation electrode (optrode), and a stretchable interconnect that links both. These components are shown in the image of the device optically stimulating a mouse heart outside the body below. The harvesting electronics transforms an external magnetic field into electric current that is used to run a microprocessor which in turn controls the stimulation. A small platinum electrode and a microscale LED are placed on the optrode and deliver either electrical or optical stimuli, respectively. The tether-free energy harvesting capabilities of the device allow the test subjects to move freely during experiments. Researchers can wirelessly control and instantaneously adjust the device’s stimulation parameters, such as the power, frequency, and intensity of the delivered pacing stimuli. Depending on the stimulation pattern that is programmed into the pacemaker, we can change the activity of the heart in the test subject by administering different stimulation sequences. The device is biocompatible, ultralight, and extremely flexible which enables the device to be fully implanted into tests subjects. Effective encapsulation allows for long-term stimulation with minimal foreign body response, allowing us to manipulate the heart rhythm and frequency over an extended period of time which in turn can reveal new insight in how these abnormalities manifest and can be corrected. The device is also compatible with MRI and CT imaging so that we can visualize the anatomy of the animal model.

Our miniaturized, fully-implantable battery-free pacemaker opens the door to creating a variety of heart pacing abnormalities to uncover why irregular heart rhythms arise. With this device, scientists can uncover the connection between the rhythms observed at the organ scale to what is happening at the cellular, molecular, and genetic level. By finding the mechanisms that underlie irregular heart rhythms, we can develop better treatments and cures targeted at these heart conditions such as arrhythmias and heart failure. The battery-free nature of our pacemaker could be translated into the clinic for patients to improve patient experience by eliminating the battery to minimize the size and weight of pacemaker devices.

Optogenetically modified mouse hearts can be optically paced by illumination from the fully implantable pacemaker.

Text written by Jokubas Ausra and Rose Yin. 

Jokubas Ausra

Graduate Student, The University of Arizona