Signals through salt: Building machines that use the language of biology
Since life began on Earth, biology has spoken the language of ions. Often called electrolytes, salt-derived ions—such as calcium, potassium, and magnesium—are used in the human body to send signals that regulate processes like nerve signaling and the beating of the heart. Scientists are only just beginning to catch up and develop devices that use ions, rather than electrons, to carry information with charge. In 2007, researchers demonstrated an ion-ejection device built from polymers that controlled the ion signaling of neurons in a petri dish. From there, the nascent field of bioiontronics—communication with living matter through ions and molecules for the detection and modulation of biological activities—has expanded.
The prospect of seamlessly exchanging ionic signals with biological systems makes bioiontronic devices appealing for medical applications. You might envision, for example, using ion pumps and iontronic diodes to modulate brain activities through the one-way release of ions and neurotransmitters. Conversely, ionic signals transmitted from biological environments into bioiontronic devices could enable the detection of biological activities. Iontronic devices for targeted drug delivery are in preclinical stages of development, and certain recording devices, such as DNA sequencers, are already commercially available.
Unlike iontronic devices, conventional metal-based electrodes, such as those used to monitor brain activity or heartbeats, are commonly used for the stimulation and measurement of electrophysiological activities—action potentials from individual cells and local field potentials from groups of cells. Changes in electric fields are the composite result of assorted ion movements. Conventional electrodes, therefore, cannot be used to identify a specific ion species or read out the molecular information behind a given cellular activity. In that regard, bioiontronics offers more precise selection of ionic and molecular species and provides novel capabilities for the detection of disease markers, such as electrolyte imbalances, certain neurotransmitters, and protein biomarkers.
Recent advances in mechanisms, materials, device prototypes, and system designs have shown the potential of iontronic devices at biological interfaces. Below, we explore one category of devices: droplet-based devices, termed dropletronics.
Dropletronics
For minimally invasive applications in medicine, it is preferable for bioiontronic devices to be miniature, soft, and biocompatible and have the capability for both functionality and responsiveness, such as biodegradability and remote-controlled activation. Dropletronics, which are fabricated from tiny hydrogel droplets, hold potential to meet those requirements.
To form dropletronic devices, such as the one shown in figure 1 , picoliter to microliter hydrogel droplets are deposited in a surfactant-containing oil. The surfactants rapidly self-assemble on the droplets’ surfaces to form a monolayer coating. When two droplets are brought together, a metastable bilayer forms between them. Multiple droplets can be deposited to form linear, 2D, or 3D networks.
Figure 1.
To create dropletronic devices, hydrogel droplets are deposited into a surfactant-containing oil with a micropipette, and the droplets self-assemble through the formation of droplet interface bilayers. Protein nanopores (left) can be inserted into the bilayers to permit ionic and molecular conduction. Alternatively, photoinitiated rupture of the droplet interface bilayers can be used to form a continuous ion-conductive structure (right).
There are three key benefits of the surfactant-supported droplet assembly process. First, each droplet can contain different materials, including nanoparticles and various solutes. The droplets can therefore be used to build heterostructured, tailored devices, such as power sources, transistors, and logic gates like those used in conventional electronics.
Second, the droplet interface bilayers can incorporate nanopores or channels to allow communication between droplets. That ability has been used to investigate ion transport through membrane channels and to develop synthetic tissues. Third, external activation sources, such as temperature, light, or pressure changes, can be used to rupture the droplet interface bilayers and produce a continuous hydrogel structure without compromising the distinctness of each droplet. That hydrogel structure offers biocompatibility, strong mechanical stability, and, after bilayer rupture, high ionic conductivity.
Stand-alone dropletronic devices will require a battery to power them. With a design inspired by the electricity-producing cells in electric eels, teams (led by the authors of this article) at the University of Oxford and EPFL, the Swiss Federal Institute of Technology in Lausanne, produced a power source by depositing a five-droplet chain consisting of a low-salt droplet and two high-salt droplets separated by two charge-selective droplets, as shown in figure 2 . The five droplets create a salt concentration gradient that allows cation movement in one direction and anion movement in the other, thereby producing an output ionic current. The bilayers between the droplets enable the formation of a stable droplet network in which energy is not dissipated until a connection is made between droplets, either through nanopores or triggered rupture of the bilayers.
Figure 2.
A microscale droplet-based 125 mV power source is shown schematically (left) and in a bright-field image (right). Food dyes are used to distinguish droplets with different compositions.
(Figure adapted from Y. Zhang et al., “A microscale soft ionic power source modulates neuronal network activity ,” Nature 620, 1001, 2023.)
The design provides a soft ionic power source that is more than five orders of magnitude smaller by volume than previous hydrogel power sources. The device has been used as a biocompatible current source to modulate the electrical activities of neural tissues in vitro and in ex vivo mouse brain slices.
Other dropletronic power sources have been developed through the incorporation of various energizing materials, such as lithium-containing particles, used to form tiny lithium-ion batteries, and metabolic molecules, used for enzyme-enabled biobatteries. The inclusion of magnetic particles enables dropletronic devices to move under an external magnetic field in a way that allows them to be used as microrobots, including ones that are microscale mobile power sources. In research settings, those techniques have been used to power the movement of charged drug molecules and the defibrillation and pacing of ex vivo mouse hearts.
By configuring droplet combinations, the teams have developed diodes, transistors, various reconfigurable logic gates, and synthetic synapses with ionic memory effects. The various dropletronic components and their circuitry configurations represent a step forward in the development of integrated iontronic circuits with a wide range of potential applications. Already, researchers have fabricated a dropletronic device that can interface with living heart cells and record the ionic signals produced by their coordinated beating.
Outlook
Several challenges remain for developing dropletronic devices. For example, interfaces between droplets can currently undergo a one-time-only irreversible rupture that serves as an off-to-on switch for the dropletronic power source. A reversible process would be a significant improvement for energy applications and other functionalities. In biological environments, the harnessing of endogenous energy resources, such as glucose or ATP (adenosine triphosphate), might provide a long-term energy solution for dropletronic implants. Further, enhanced robustness under biological conditions demands advances in the selection of materials, device design, system integration, and encapsulation.
Dropletronics are just one example of the variety and potential of bioiontronics. Other bioiontronic device platforms include solid-state nanofluidic chips and macroscopic polymer devices, to name but two. The future of the field lies in the fabrication of complete bioiontronic systems and the integration of those components with living tissues. Potential applications for bioiontronics include quantitative sensing, early disease detection, in situ drug synthesis, spatiotemporal control of drug delivery, and the motility and control of microrobots. Achieving that potential will require interdisciplinary knowledge, from fields including microtechnology, physics, chemical biology, electrochemistry, bioelectronics, and biomedical engineering.
Additional resources
► J. Luo, A. Remy, Y. Zhang, “Iontronic devices from biological nanopores to artificial systems: Emerging applications and future perspectives ,” Chem. Rev. 125, 11840 (2025).
► D. Wei et al., “Flexible iontronics based on 2D nanofluidic material ,” Nat. Commun. 13, 4965 (2022).
► M. Berggren et al., “In vivo organic bioelectronics for neuromodulation ,” Chem. Rev., 122, 4826 (2022).
► Y. Zhang et al., “A microscale soft ionic power source modulates neuronal network activity ,” Nature 620, 1001 (2023).
► J. Isaksson et al., “Electronic control of Ca2+ signalling in neuronal cells using an organic electronic ion pump ,” Nat. Mater. 6, 673 (2007).
More about the authors
Yujia Zhang is an assistant professor of electrical engineering and microengineering at EPFL, the Swiss Federal Institute of Technology in Lausanne. His group focuses on the development of bioiontronics for biointerfaces and hybrid intelligent systems.
Hagan Bayley is a principal scientist at the Ellison Institute of Technology and professor of chemical biology at the University of Oxford. His group focuses on nanopore sensing and sequencing and new approaches to tissue engineering.
