Design and Operation of Hybrid Microfluidic Iontronic Probes for Regulated Drug Delivery

Abstract

Highly controlled drug delivery devices play an increasingly important role in the development of new neuroengineering tools. Stringent—and sometimes contradicting—demands are placed on such devices, ranging from robustness in freestanding devices, to overall device miniaturization, while maintaining precise spatiotemporal control of delivery with high chemical specificity and high on/off ratio. Here, design principles of a hybrid microfluidic iontronic probe that uses flow for long‐range pressure‐driven transport in combination with an iontronic tip that provides electronically fine‐tuned pressure‐free delivery are explored. Employing a computational model, the effects of decoupling the drug reservoir by exchanging a large passive reservoir with a smaller microfluidic system are reported. The transition at the microfluidic‐iontronic interface is found to require an expanded ion exchange membrane inlet in combination with a constant fluidic flow, to allow a broad range of device operation, including low source concentrations and high delivery currents. Complementary to these findings, the free‐standing hybrid probe monitored in real time by an external sensor is demonstrated. From these computational and experimental results, key design principles for iontronic devices are outlined that seek to use the efficient transport enabled by microfluidics, and further, key observations of hybrid microfluidic iontronic probes are explained.

A unified physiological framework of transitions between seizures, sustained ictal activity and depolarization block at the single neuron level

“…All parameter values were within biophysical ranges (Table 1 ) (Hille, 2001 ; Kandel et al, 1981 ). Recent experimental work, using selective ionic pumps to deliver locally K + , confirmed observations from the model, the elevation of [K + ] modified the spiking profile of a bursting neuron in the hippocampal slice (Arbring Sjöström et al, 2021 ). However, the model has two main limitations.…”

In Vivo Organic Bioelectronics for Neuromodulation

“…In 2021, Arbring Sjöström et al demonstrated a coaxial capillary device (for fluid inlet and outlet) with an “iontronic cap” featuring an AEM ion channel ( Figure 4 d). 74 With the PEDOT-based source electrode (cathode) incorporated onto the surface of the inner capillary, a minimal amount of wiring was needed to drive the device (the anodic counter electrode was a separate piece of PEDOT:PSS), making it simple to mount on a micromanipulator and integrate into a standard electrophysiology setup. Glutamate was delivered (as an anion) into artificial cerebrospinal fluid and used to demonstrate the spatiotemporal precision (via a glutamate biosensor), paving the way for application in brain slice models or as a depth probe.…”

“…(d) Freestanding fluidic capillary-based device with “iontronic cap”. Parts a and d reproduced with permission from refs and , respectively. Copyright 2018 and 2021 John Wiley and Sons.…”

“…The hybrid microfluidic ion pump concept has also been demonstrated by using a free-standing capillary fiber form factor. In 2021, Arbring Sjöström et al demonstrated a coaxial capillary device (for fluid inlet and outlet) with an “iontronic cap” featuring an AEM ion channel (Figure d) . With the PEDOT-based source electrode (cathode) incorporated onto the surface of the inner capillary, a minimal amount of wiring was needed to drive the device (the anodic counter electrode was a separate piece of PEDOT:PSS), making it simple to mount on a micromanipulator and integrate into a standard electrophysiology setup.…”

Streamlining the interface between electronics and neural systems for bidirectional electrochemical communication

“…This is benecial for the stimulation of biological systems with minimal perturbation of the target environment. 133 However, an important operating condition for chemical stimulation with the OEIP is the application of a suitable electrochemical potential to prevent reactive oxygen species (ROS) generation. At low potentials within the ohmic region, the relationship between ionic current and voltage is linear.…”