A microfluidic perspective on conventional in vitro transcranial direct current stimulation methods

Han, Lu; Shaner, Sebastian; Otte, Elisabeth; Asplund, Maria; Vlachos, Andreas

doi:10.1016/j.jneumeth.2022.109761

Cited by 6 publications

(17 citation statements)

References 123 publications

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“…Some studies have shown that a dcEF intensity as low as 0.75 mV mm −1 could trigger long-term potentiation (LTP) like effects 31 and 4.7 mV mm −1 is within this neural activation range. 16,46 According to our recent technical review, 32 it is highly possible that the actual EF intensities used in these studies were higher than 4.7 mV mm −1 , due to a systematic underestimation of dcEF intensity in these studies using conventional calibration approaches. [24][25][26]68 Voroslakos and colleagues have also raised the opinion that the intensity needed for exerting active tDCS effects should be higher than regularly reported literature values.…”

Section: Discussionmentioning

confidence: 97%

“…Meanwhile, the prevalent system of stimulating acute slices with parallel electrodes in elaborate electrophysiological setups is not satisfying regarding its limitations in delivering precise dcEF around brain tissue or obtaining results over a relatively long time course. 32 To address these issues, we developed an inexpensive and high-throughput solution using microfluidic techniques to achieve precise control of uniform EFs in space and time. We displayed various application scenarios using organotypic tissue cultures by extending experiment durations and accommodating cutting-edge probing techniques.…”

Section: Discussionmentioning

confidence: 99%

“…S1). 32 Meanwhile, this control is fundamental to studying dose-dependent and EF orientation-related neural mechanisms. Therefore, we leveraged the microchannel design used in cell electrotaxis experiments 39,40 to create a microfluidic chamber with ge- (i) Live-cell imaging and dcEF of slices within the microfluidic chamber.…”

Section: Microfluidic Chamber Generates Spatiotemporally Uniform Dire...mentioning

confidence: 99%

“…The stimulation electrode material is another factor to consider for delivering constant DC with minimal electrochemically-generated species, which are side reactions to the DC. 32,42 Here, non-metal supercapacitive electrodes (laser-induced graphene coated with the conducting hydrogel PEDOT:PSS) were used. 43 Slow cyclic voltammetry (CV) was used to assess the capacitance of the electrode (Supplemental Note S1 and Fig.…”

Section: Microfluidic Chamber Generates Spatiotemporally Uniform Dire...mentioning

confidence: 99%

“…Our recent review scrutinized these sophisticated setups and revealed their inability to precisely control the electric field (EF) and the risk of negative DC stimulation by-products. 32 The short lifetime of acute slices prevents researchers from studying the effects of repetitive EF stimulation (e.g., several sessions per day) or revisiting the neural tissue hours or days after EF stimulation. Some studies have attempted 4 to address this by placing parallel electrodes inside six-well plates to stimulate tissue or cells inside the incubator, 33,34 while a lack of precise EF control and inevitable electrochemical faradaic reactions still remained.…”

Section: Introductionmentioning

confidence: 99%

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On-chip brain slice stimulation: precise control of electric fields and tissue orientation

Shaner

Han

Lenz

et al. 2023

Preprint

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Non-invasive brain stimulation modalities, including transcranial direct current stimulation (tDCS), are widely used in neuroscience and clinical practice to modulate brain function and treat neuropsychiatric diseases. DC stimulation ofex vivobrain tissue slices has been a method used to understand mechanisms imparted by tDCS. However, delivering spatiotemporally uniform direct current electric fields (dcEFs) that have precisely engineered magnitudes and are also exempt from toxic electrochemical by-products are both significant limitations in conventional experimental setups. As a consequence, bioelectronic dose-response interrelations, the role of EF orientation, and the biomechanisms of prolonged or repeated stimulation over several days all remain not well understood. Here we developed a platform with fluidic, electrochemical, and magnetically-induced spatial control. Fluidically, the chamber geometrically confines precise dcEF delivery to the enclosed brain slice and allows for tissue recovery in order to monitor post-stimulation effects. Electrochemically, conducting hydrogel electrodes mitigate stimulation-induced faradaic reactions typical of commonly-used metal electrodes. Magnetically, we applied ferromagnetic substrates beneath the tissue and used an external permanent magnet to enablein siturotational control in relation to the dcEF. By combining the microfluidic chamber with live-cell calcium imaging and electrophysiological recordings, we showcased the potential to study the acute and lasting effects of dcEFs with the potential of providing multi-session stimulation. This on-chip bioelectronic platform presents a modernized yet simple solution to electrically stimulate explanted tissue by offering more environmental control to users, which unlocks new opportunities to conduct thorough brain stimulation mechanistic investigations.Graphical abstract

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Section: Microfluidic Chamber Generates Spatiotemporally Uniform Dire...mentioning

confidence: 99%

Section: Microfluidic Chamber Generates Spatiotemporally Uniform Dire...mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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On-chip brain slice stimulation: precise control of electric fields and tissue orientation

Shaner

Han

Lenz

et al. 2023

Preprint

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Bioelectronic Direct Current Stimulation at the Transition Between Reversible and Irreversible Charge Transfer

Matter,

Abdullaeva,

Shaner

et al. 2024

Advanced Science

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Many biological processes rely on endogenous electric fields (EFs), including tissue regeneration, cell development, wound healing, and cancer metastasis. Mimicking these biological EFs by applying external direct current stimulation (DCS) is therefore the key to many new therapeutic strategies. During DCS, the charge transfer from electrode to tissue relies on a combination of reversible and irreversible electrochemical processes, which may generate toxic or bio‐altering substances, including metal ions and reactive oxygen species (ROS). Poly(3,4‐ethylenedioxythiophene) (PEDOT) based electrodes are emerging as suitable candidates for DCS to improve biocompatibility compared to metals. This work addresses whether PEDOT electrodes can be tailored to favor reversible biocompatible charge transfer. To this end, different PEDOT formulations and their respective back electrodes are studied using cyclic voltammetry, chronopotentiometry, and direct measurements of H2O2 and O2. This combination of electrochemical methods sheds light on the time dynamics of reversible and irreversible charge transfer and the relationship between capacitance and ROS generation. The results presented here show that although all electrode materials investigated generate ROS, the onset of ROS can be delayed by increasing the electrode's capacitance via PEDOT coating, which has implications for future bioelectronic devices that allow longer reversibly driven pulse durations during DCS.

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How conductivity boundaries influence the electric field induced by transcranial magnetic stimulation in in vitro experiments

Sundaram,

Dong,

Makaroff

et al. 2024

Brain Stimulation

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A microfluidic perspective on conventional in vitro transcranial direct current stimulation methods

Cited by 6 publications

References 123 publications

On-chip brain slice stimulation: precise control of electric fields and tissue orientation

On-chip brain slice stimulation: precise control of electric fields and tissue orientation

Bioelectronic Direct Current Stimulation at the Transition Between Reversible and Irreversible Charge Transfer

How conductivity boundaries influence the electric field induced by transcranial magnetic stimulation in in vitro experiments

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