Building Tiny Biocompatible Batteries with Heart-Defibrillating Power

Last month’s report (DOI: 10.1038/s44286-024-00136-z) outlined how the researchers assembled batteries from separate droplets that individually contain cathode, anode, or electrolyte materials to create functional, rechargeable batteries that can power LEDs, drive charged molecule translocation or stimulate cardiac activity.  

Dr. Yujia Zhang, postdoctoral researcher in the laboratory of senior author Hagan Bayley and first author of both papers, explained how these microbatteries can be incorporated into different biomedical applications.  

“Fundamentally what we want to do for these applications is to replace the traditional bulky battery with a more advanced soft battery,” Zhang said. “We want to implant the power source into an animal’s body to achieve certain biological functions.” The concept is reminiscent of biobatteries, which can harness energy using bacterial or enzymatic mechanisms to power various sensors. 

Last year, Zhang and colleagues first developed a similar droplet-based approach inspired by the shock mechanism of the electric eel. In that design, different unit drops were designed such that an ion gradient could be established along a row of them. Then, when that gradient is released, a pulse of electrical current is created that can be captured through chemically active electrodes. They showed that these ionotronic power sources could stimulate neuronal activity in vitro or with ex vivo mouse brain slices.  

However, “we were thinking maybe we need a more powerful mechanism to generate the power,” Zhang said. They turned to traditional battery materials for this next generation, and lithium-ion droplet batteries (LiDBs) were born. 

Hydrogels and Silk 

In both their prior work and for these LiDBs, Zhang and colleagues base their design around hydrogels, soft and flexible structures largely composed of water. Hydrogels require an insoluble component to provide structure, and the group used silk fibroin (a silk protein) in this latest work. To protect individual droplets, they essentially mimic biological cells. An aqueous solution containing the silk fibroin and other battery components is dropped into an oil containing phospholipids. The lipids encapsulate the droplet, forming a single protective layer. When a second droplet is added adjacent to the first, another monolayer surrounds, but the droplets merge and form a full lipid bilayer between them, preventing their contents from intermingling. 

To create functional microbatteries, the researchers used lithium manganese oxide (LMO) in cathode droplets and lithium titanate in anode droplets. Lithium chloride with some additives served as the electrolyte in all droplets, and carbon nanotubes were added to cathode and anode solutions to improve conductivity. Separator droplets only contained the electrolyte, enabling lithium ions to transit while preventing electrical conductivity.  

A specialized printer ejects the droplets in as little as 0.5-nanoliter volumes, each on the scale of a human hair width. However, the smallest batteries studied used 10-nanoliter volumes (it would take about 50,000 of these droplets to fill a teaspoon). The completed batteries consist of just 3 droplets—cathode, separator, and anode—to form complete structures that are as small as 200 x 600 micrometers, about the size of a hyphen (-) on most computer screens.  

For now, it’s a somewhat manual process of depositing droplets at the proper location, but Zhang says the printers can be automated, and other options such as microfluidics could streamline the process.  

In addition to recognizable battery components, the droplets contain ultraviolet (UV) light-activatable crosslinking reagents. Upon exposure to UV, two important changes occur: the crosslinking of silk fibroin through tyrosine residues causes the material to gel, and at the same time, the membrane bilayers are disrupted, which allows the contents to mix and for lithium ions to relocate. Importantly, this design allows batteries to be synthesized in an inactivated or dormant state with on-demand activation. 

Small Power, Visible Output 

In line with their diminutive dimensions, the maximum energy density reported for these LiDBs was 570 nAh/µl—about 0.3% of what you’ll encounter in your phone or laptop, which makes sense as they are mostly water. Additionally, the researchers were limited to 20% lithium in their droplets, because higher concentrations clogged the nozzles of their printers. Although the energy density is low compared with macroscale lithium ion batteries, the report states that this is at least a ten-fold improvement in energy density, “unprecedented for all-hydrogel lithium-ion batteries,” and a more than 1,000-fold size reduction compared with other hydrogel batteries. 

Each individual LiDB produced an operating voltage of about 0.65 V. Connecting six of these units in series raised the voltage to 3.3 V, which was sufficient to power three small LEDs for “tens of seconds,” Zhang said. The batteries also retained 72% capacity after 50 charge-discharge cycles. 

Power Conveyor 

Having achieved basic functionality for the LiDBs, the researchers demonstrated several additional capabilities. In one case, they added nickel to the separator droplets, making the entire battery magnetic. With this enhancement, the researchers could magnetically guide the batteries through a small maze and deliver their energy to a capacitor at the other end. They repeated this process for several cycles of charge, deliver, discharge, and return, increasing the stored charge in the capacitor at the end of each run, and demonstrating the potential for these batteries to act as reusable energy couriers.  

With thoughts toward cellular interactions and drug delivery mechanisms, the researchers also created a different kind of droplet to convert electron current to ion flux. By attaching these converting droplets to LiDB cathode and anode, they demonstrated that the current from the batteries could drive directional cation or anion translocation in connected hydrogel droplets or in synthetic aqueous cells. The LiDBs also showed good biocompatibility with various cell types growing in culture, having no significant effects on cell viability.  

Heart Defibrillation and Pacing 

Zhang explained that their batteries don’t actually need to be that powerful, depending on the application. He pointed to the conventional automated external defibrillator (AED) devices used to treat heart attacks as a kind of overkill. “Why do we need tons of volts to defibrillate the heart?” Zhang asked. “It’s because the current needs to go through the skin, the muscle, the bones to reach the heart.” The shocks associated with these AEDs are painful and a contributing factor to depression and post-traumatic stress disorder in many cases. In contrast, if the voltage was applied directly to the heart, much less would be necessary, and perhaps the shock could be delivered in tiny injectable packets of energy, such as these. 

To test this possibility, Zhang and colleagues performed several experiments with ex vivo perfused mouse hearts. The prepared LiDBs can be sucked into a pipette and deposited directly onto a beating, artificially supported heart (you can watch a video of the process). Thanks to the silk fibroin, the batteries adhere easily. By observing the electrical activity through electrocardiogram traces, the researchers demonstrated that while discharged LiDBs did not impact heart rhythm, charged LiDBs produced extra spikes, and the larger the LiDBs (composed of up to 3-microliter droplets), the greater the effect on normal heart rhythm. Next, the researchers pharmaceutically induced tachycardia and ventricular fibrillation before applying LiDBs. In this case, the application of a single LiDB restored normal sinus rhythm, and control experiments indicated this was mediated through approximately 30 µA of current. LiDBs were also used to regulate heart pacing through wired contacts. 

What Can’t Droplets Do? 

Zhang has some big ideas about where these batteries will lead. “We are writing a patent,” he said. “We can inject not just one battery, but let’s say tens of these small batteries, into blood vessels, and translocate or move them to the target organ and then release the energy to, for example, defibrillate the heart or to achieve some other biomedical functions.” This is the shorter-term vision. “We inject it, move it, then release the energy, and eventually it’s biodegradable, so it will disappear within the body,” he said.  

But there’s a much bigger idea. “The battery is just one part of the whole system, if you think of it as a droplet-based computer,” Zhang said. This is where today’s report in Science comes in, as it demonstrates how droplets can be used to build functional ion-based components of processors. They term this field “dropletronics.” Zhang explained that what they can make is “basically a droplet-based circuit, but we use ions instead of electrons. We use droplets to build diodes, transistors, logic gates, etc.” These may find use in complex sensors, in neural and muscular stimulation, and in additional injectable, ingestible, or wearable, biodegradable, function-enhancing devices. Their miniaturization will help to make them minimally invasive and able to reach otherwise inaccessible areas. In one example, Zhang and colleagues produced biocompatible sensors that detected the electrical signals from sheets of beating heart cells. In a press release for the newer publication, coauthor Christopher Toepfer said, “this finding is an exciting step toward the fabrication of more complex biological devices that will sense a variety of abnormalities in an organ and react by delivering drugs intelligently inside the body.” 

Zhang is leaving his postdoctoral position and starting a new lab at École Polytechnique Fédérale de Lausanne, Switzerland, in January. Zhang explained some of his excitement for this ongoing work. “What we are doing in EPFL, we’re trying to develop a bottoms-up approach. We directly use biomaterials to mimic cells and tissues, and we use ions that can directly talk to cells or tissues, and that’s why it’s more efficient in my opinion.” Additionally, Zhang said that “it is possible to further decrease the size or the volume of those droplets, but we need more time, more people… I’m looking forward to working on that with my new lab members.”