On-chip on-demand delivery of K+ for <i>in vitro</i> bioelectronics

Dechiraju, Harika; Selberg, John; Jia, Manping; Pansodtee, Pattawong; Li, Houpu; Hsieh, Hao‐Chieh; Hernández, Cristián E.; Asefifeyzabadi, Narges; Nguyen, Tiffany; Baniya, Prabhat; Marquez, Giovanny; Rasmussen-Ivey, Cody; Bradley, Carrie; Teodorescu, Mircea; Gomez, Marcella; Levin, Michael; Rolandi, Marco

doi:10.1063/5.0129134

Cited by 12 publications

(14 citation statements)

References 31 publications

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“…Across 15 mice, the bioelectronic bandage consistently delivered the desired dose with some variability (Figure 3J, left). This variability in delivered dose can be easily amended with current control using closed-loop control algorithms, as we have previously demonstrated with other ion pumps [18]. This variability allowed us to qualitatively correlate the dose of Flx + and wound healing as measured by the percentage of re-epithelization (Figure 3J, right).…”

Section: Resultsmentioning

confidence: 75%

Programmable delivery of fluoxetine via wearable bioelectronics for wound healing in vivo

Li,

Yang,

Asefifeyzabadi

et al. 2023

Preprint

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The ability to deliver drugs with precise dosages at specific time points can significantly improve disease treatment while reducing side effects. Drug encapsulation for gradual delivery has opened up the doors for superior treatment regimen. To expand on this ability, programming bioelectronic devices to deliver small molecules enables ad-hoc personalized therapeutic profiles that are more complex than simple gradual release. Here, we introduce a wearable bioelectronic bandage with an integrated electrophoretic ion pump that affords on-demand drug delivery with precise dose control. Delivery of fluoxetine to wounds in mice resulted in a 27.2% decrease in the macrophage ratio (M1/M2) and a 39.9% increase in re-epithelialization, indicating a shorter inflammatory phase and faster overall healing. Programmable drug delivery using wearable bioelectronics in wounds introduces a broadly applicable strategy for the long-term delivery of a prescribed treatment regimen with minimal external intervention.

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Section: Resultsmentioning

confidence: 75%

Programmable delivery of fluoxetine via wearable bioelectronics for wound healing in vivo

Li,

Yang,

Asefifeyzabadi

et al. 2023

Preprint

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“…Ion pumps are bioelectronic devices that can perform precise electrophoretic delivery of ions and molecules from a region of high concentration in the device, known as the reservoir, to the region of interest, known as the target [ 9 , 20 ]. Over the years, ion pumps have been used to modulate pH in a local environment [ 21 ], treat neurological disorders [ 22 , 23 ], induce macrophage recruitment [ 24 ] and even to deliver biochemicals in plants [ 25 ]. In this work, we use the ion pump to deliver Fluoxetine, a biochemical which is a selective serotonin reuptake inhibitor known to have immunomodulatory effects [ 19 ].…”

Section: Methodsmentioning

confidence: 99%

“…Jumper cables are used to connect this PCB to a Raspberry Pi-based external voltage controller which can connect to the WiFi [ 35 ]. The device is seated in a six-well plate with a buffer solution acting as the target for delivery [ 24 ]. The external voltage controller applies the control commands it receives from the sliding mode controller to the ion pump.…”

Section: Methodsmentioning

confidence: 99%

Delivering biochemicals with precision using bioelectronic devices enhanced with feedback control

Marquez,

Dechiraju,

Baniya

et al. 2024

PLoS ONE

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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.

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“…Here, we use the term "efficiency" to refer to achieving a higher level of ionic current with a voltage as opposed to the ion-selective transport efficiency often used to characterize IEMs. [17,22]…”

Section: Introductionmentioning

confidence: 99%

The Importance of Electrode Material in Bioelectronic Electrophoretic Ion Pumps

Nguyen

Asefifeyzabadi

et al. 2023

Adv Materials Technologies

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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.

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On-chip on-demand delivery of K+ for in vitro bioelectronics

Cited by 12 publications

References 31 publications

Programmable delivery of fluoxetine via wearable bioelectronics for wound healing in vivo

Programmable delivery of fluoxetine via wearable bioelectronics for wound healing in vivo

Delivering biochemicals with precision using bioelectronic devices enhanced with feedback control

The Importance of Electrode Material in Bioelectronic Electrophoretic Ion Pumps

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