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Precision medicine endeavors to personalize treatments, considering individual variations in patient responses based on factors like genetic mutations, age, and diet. Integrating this approach dynamically, bioelectronics equipped with real-time sensing and intelligent actuation present a promising avenue. Devices such as ion pumps hold potential for precise therapeutic drug delivery, a pivotal aspect of effective precision medicine. However, implementing bioelectronic devices in precision medicine encounters formidable challenges. Variability in device performance due to fabrication inconsistencies and operational limitations, including voltage saturation, presents significant hurdles. To address this, closed-loop control with adaptive capabilities and explicit handling of saturation becomes imperative. Our research introduces an enhanced sliding mode controller capable of managing saturation, adept at satisfactory control actions amidst model uncertainties. To evaluate the controller's effectiveness, we conducted in silico experiments using an extended mathematical model of the proton pump. Subsequently, we compared the performance of our developed controller with classical Proportional Integral Derivative (PID) and machine learning (ML)–based controllers. Furthermore, in vitro experiments assessed the controller's efficacy using various reference signals for controlled Fluoxetine delivery. These experiments showcased consistent performance across diverse input signals, maintaining the current value near the reference with a relative error of less than 7% in all trials. Our findings underscore the potential of the developed controller to address challenges in bioelectronic device implementation, offering reliable precision in drug delivery strategies within the realm of precision medicine. [ABSTRACT FROM AUTHOR]

Bioelectronic ion pumps deliver ions and biomolecules from a source to a target biological system with high spatiotemporal control for bioengineering and regenerative medicine applications. A voltage between a working electrode and a reference/counter electrode delivers the charged ions and biomolecules from a source to the desired target. The source and the target are separated by an ion exchange membrane so that only the charged molecules of interest are delivered. Future wearable and implantable applications require high efficiency of delivery to minimize power consumption. The majority of recent efforts on improving ion pump efficiency have focused on optimizing the ion exchange membrane. However, the contribution of the working electrode material to the ion pump efficiency has been mostly overlooked. This work identifies how changing the working electrode material greatly affects the efficiency of delivery in ion pumps. With an electrical circuit model analysis, voltammetry studies on silver, platinum, and palladium hydride working electrodes, and implementation of the Butler–Volmer equation, results show that the material‐dependent equilibrium potential at the working electrode surface has a large impact on ion pump efficiency. With this knowledge, a simple predictive model to optimize the working electrode material for delivering each specific ion or molecule of interest is designed. [ABSTRACT FROM AUTHOR]

Bioelectronic devices that interface electronics with biological systems can actuate and control biological processes. The potassium ion plays a vital role in cell membrane physiology, maintaining the cell membrane potential (Vmem) and generating action potentials. In this work, we present two bioelectronic ion pumps that use an electronic signal to modulate the potassium ion concentration in solution. The first ion pump is designed to integrate directly with six-well cell culture plates for optimal ease of integration with in vitro cell culture, and the second on-chip ion pump provides high spatial resolution. These pumps offer increased ease of integration with in vitro systems and demonstrate K+ concentration distribution with high spatial resolution. We systematically investigate the ion pump's performance using electrical characterization and computational modeling, and we explore closed-loop control of K+ concentration using fluorescent dyes as indicators. As a proof-of-concept, we study the effects of modulating K+ concentration on Vmem of THP-1 macrophages. [ABSTRACT FROM AUTHOR]

A potentiostat is an essential piece of analytical equipment for studying electrochemical devices and reactions. As the design of electrochemical devices evolve, applications for systems with multiple working electrodes have become more common. These applications drive a need for low-cost multi-channel potentiostat systems. We have developed a portable, low-cost and scalable system with a modular design that can support 8 to 64 channels at a cost as low as $8 per channel. This design can replace the functionality of commercial potentiostats which cost upwards of $10k for certain applications. Each channel in the multi-channel potentiostat has an independent adjustable voltage source with a built-in ammeter and switch, making the device flexible for various configurations. The multi-channel potentiostat is designed for low current applications (nA range), but its purpose can change by varying its shunt resistor value. The system can either function as a standalone device or remotely controlled. We demonstrate the functionality of this system for the control of a 24-channel bioelectronic ion pump for open- and closed- loop control of pH. [ABSTRACT FROM AUTHOR]

Hybrid biotic abiotic devices can be used to interface electronics with biological systems for novel therapies or to increase device functionality beyond silicon. Many strategies exist to merge the electronic and biological worlds, one dominated by electrons and holes as charge carriers, the other by ions. In the biological world, lipid bilayers and ion channels are essential to compartmentalize the cell machinery and regulate ionic fluxes across the cell membrane. Here, we demonstrate a bioelectronic device in which a lipid bilayer supported on H+-conducting Pd/PdHx contacts contains carbon nanotubes porin (CNTP) channels. This bioelectronic device uses CNTPs to control of H+ flow across the lipid bilayer with a voltage applied to the Pd/PdHx contacts. Potential applications of these devices include local pH sensing and control. [ABSTRACT FROM AUTHOR]

The top working electrode (WE) interfaces with the source solution, while the bottom reference/counter electrode (RE/CE) interfaces with the target solution. Bioelectronics, electrode materials, ion delivery, ion pumps, ions and biomolecules Keywords: bioelectronics; electrode materials; ion delivery; ion pumps; ions and biomolecules EN bioelectronics electrode materials ion delivery ion pumps ions and biomolecules 1 1 1 07/14/23 20230710 NES 230710 B Bioelectronic Ion Pumps b An example of an ion pump for delivering therapeutic ions and biomolecules is demonstrated in article 2201996, by Marco Rolandi and co-workers. [Extracted from the article]

Bioelectronic devices that modulate pH can affect critical biological processes including enzymatic activity, oxidative phosphorylation, and neuronal excitability. A major challenge in controlling pH is the high buffering capacity of many biological media. To overcome this challenge, devices need to be able to store and deliver a large number of protons on demand. Here, a bioelectronic modulator that controls pH using palladium nanoparticles contacts with high surface area as a proton storage medium is developed. Reversible electronically triggered acidosis (low pH) and alkalosis (high pH) in physiologically relevant buffer conditions are achieved. As a proof of principle, this new platform is used to control the degradation and fluorescence of acid sensitive polymeric microparticles loaded with a pH sensitive fluorescent dye. A bioelectronic modulator controls pH using palladium nanoparticle contacts as a proton storage medium. This powerful tool achieves reversible electronically triggered acidosis and alkalosis in physiologically relevant buffer conditions. [ABSTRACT FROM AUTHOR]

In article number 1800935, Marco Rolandi and co‐workers present a bioelectronic proton pump based on palladium hydride that changes pH in physiological conditions. [ABSTRACT FROM AUTHOR]

Bioelectronic devices that modulate pH can affect critical biological processes including enzymatic activity, oxidative phosphorylation, and neuronal excitability. A major challenge in controlling pH is the high buffering capacity of many biological media. To overcome this challenge, devices need to be able to store and deliver a large number of protons on demand. Here, a bioelectronic modulator that controls pH using palladium nanoparticles contacts with high surface area as a proton storage medium is developed. Reversible electronically triggered acidosis (low pH) and alkalosis (high pH) in physiologically relevant buffer conditions are achieved. As a proof of principle, this new platform is used to control the degradation and fluorescence of acid sensitive polymeric microparticles loaded with a pH sensitive fluorescent dye. [ABSTRACT FROM AUTHOR]