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A Microscale Soft Lithium-Ion Battery for Tissue Stimulation

A recent article in Nature Chemical Engineering presented a microscale, soft, and flexible lithium-ion droplet battery (LiDB), developed using lipid-supported droplets synthesized from a biocompatible silk hydrogel. The LiDB showcased features including triggerable activation, biocompatibility, biodegradability, and high energy capacity.

A Microscale Soft Lithium-Ion Battery for Tissue Stimulation

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Background

Electronic device miniaturization is a rapidly growing field that necessitates the production of tiny batteries. These batteries need to be soft, biocompatible, and biodegradable and offer responsive functionality for minimally invasive biomedical applications. However, a multifunctional, microscale soft battery with these qualities is not yet available.

Although hydrogel-based lithium-ion batteries show promise, they lack the microscale integration of self-assembled hydrogel-based cathode, anode, and separator at submillimeter levels. This makes achieving high-density energy storage while miniaturizing hydrogel-based architectures particularly challenging.

A miniaturized ionic power source using lipid-supported nanoliter hydrogel droplets has been developed. However, it has limitations: it produces less power than conventional Li-ion batteries, depends on oil and temperature-triggered gelation for buffer exchange, and has limited functionality, complicating organ-level stimulation in physiological environments.

Methods

A single LiDB unit encompassed three silk-hydrogel droplets: a cathode droplet containing lithium manganese oxide particles and carbon nanotubes (CNTs), an anode droplet with lithium titanate particles and CNTs, and a central separator droplet with lithium chloride. To make the separator magnetically responsive, 10 % (by volume) of nickel particles were added to the solution.

The cathode, anode, and separator droplets were deposited in a lipid-containing oil using a microinjector. The lipid monolayers formed droplet interface bilayers (DIBs) rapidly upon contact with one another. These were exposed to ultraviolet (UV) light (265 nm) for 60 seconds to photochemically crosslink the silk fibroins, which disrupted the DIBs and created a continuous silk hydrogel structure.

A custom-made measurement system was used to examine the microscale LiDBs. Their electrochemical performance was evaluated using a potentiostat. Additionally, their Fourier-transform infrared spectra (FTIR) were measured.

To enable charged molecule translocation, the LiDB device was transferred into a well containing synthetic cells. Biocompatibility tests were performed on the LiDBs using 3T3 fibroblasts for live/dead imaging. PrestoBlue assays were performed to determine live cell numbers and viability. Human dermal fibroblasts and atrial and ventricular cardiomyocytes were also used to quantify the effects of LiDBs on cell metabolic activity, cytotoxicity, and apoptosis.

Animal experiments were conducted on Langendorff-perfused mouse hearts, which included ex vivo heart preparations and electrocardiogram (ECG) monitoring. The LiDBs were fully charged for 10 minutes at a current of 0.5 μA and immediately applied for heart stimulation to ensure output consistency. A power pack comprising six LiDBs in series was also used for wired stimulation.

Results and Discussion

The fabricated LiDBs generated a direct current discharge (shock) with effective modulation and miniaturized energy output when placed in direct contact with Langendorff-perfused mouse hearts, as shown in ECG results. When gently positioned on the heart surface, the hydrogel adhered directly to the epicardium.

Electrical stimulation and sustained contact with LiDBs had no adverse effects on heart tissue, confirming their biocompatibility. This was further validated through co-culture studies with mouse fibroblasts, human dermal fibroblasts, and human cardiomyocytes. Additionally, cell viability, cytotoxicity, and apoptosis assays performed after 7 days of co-culture indicated the cytocompatibility of LiDBs.

Using LiDB stimulation, optogenetic light pacing successfully generated a regular heart rhythm, accurately reflecting heartbeats. The LiDB's temporary electrical output adjustment was able to restore normal rhythm in unsynchronized cardioversion (defibrillation). By increasing droplet volume within the LiDB, the stimulation contact area expanded, intensifying the shock and temporarily suppressing intrinsic heartbeats.

Advanced cardiac control, such as precise heart pacing, was achieved via wired contact with a LiDB-powered pacemaker circuit, enabling targeted pacing of specific heart regions. These proof-of-concept demonstrations validated the potential clinical utility of LiDBs in performing low-energy defibrillation during cardiac surgery.

Hydrogel compartmentalization enhanced the functionality of LiDBs beyond energy storage. For instance, adding magnetic nickel particles to the central separator droplet enabled magnetic maneuverability without disrupting hydrogel formation or significantly impacting battery output. Thus, the proposed LiDB could be an effective mobile energy courier.

Conclusion

The researchers successfully developed a miniature, soft Li-ion battery (LiDB) using self-assembled nanoliter hydrogel droplets. These LiDBs exhibited UV-triggered activation, a compact 103-fold reduction in unit volume, and higher energy density compared to previous models.

The LiDB demonstrated potential for interfacing with heart tissues to modulate cardiac activity and for translocating charged molecules in synthetic tissues. The biodegradable hydrogel droplet design also enabled expanded functionality, including magnetic maneuverability, suggesting that LiDBs could power microrobots for in vivo applications.

Journal Reference

Zhang, Y., et al. (2024). A microscale soft lithium-ion battery for tissue stimulation. Nature Chemical Engineering. DOI: 10.1038/s44286-024-00136-z, https://www.nature.com/articles/s44286-024-00136-z

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Nidhi Dhull

Written by

Nidhi Dhull

Nidhi Dhull is a freelance scientific writer, editor, and reviewer with a PhD in Physics. Nidhi has an extensive research experience in material sciences. Her research has been mainly focused on biosensing applications of thin films. During her Ph.D., she developed a noninvasive immunosensor for cortisol hormone and a paper-based biosensor for E. coli bacteria. Her works have been published in reputed journals of publishers like Elsevier and Taylor & Francis. She has also made a significant contribution to some pending patents.  

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