Fabrication and Characterization of 3D Microelectrode Arrays (3D MEAS) with Tri-Modal (Electrical, Optical, and Microfluidic) Interrogation of Electrogenic Cell Constructs

Orico, Julia Freitas; Kundu, Atreyee; Didier, Charles M.; Bosak, Alexander; Moore, Michael J.; Rajaraman, Swaminathan

doi:10.1109/transducers50396.2021.9495378

Cited by 4 publications

(7 citation statements)

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“…250 μm diameter SS needles (Lhasa Ohm, MA) were cut to a height of 2.25 mm, utilizing a custom infrared (IR) laser-scribing approach (Quik Laze 50ST2; Eolite Lasers, OR). Ten needles per device were subsequently inserted from the backside of the device, utilizing a magnetic insertion approach, 48 to define the final height of the needles above the surface of the substrate at ∼500 μm.…”

Section: Methodsmentioning

confidence: 99%

“…After laser ablation, the final microelectrode was determined to be ∼35 μm 2 in size and presented a 1 kHz impedance of 10.2 ± 3.47 kΩ that is closer to other literature-reported MEA values. 28,48,72 The final ∼35 μm 2 -sized 3D microelectrode was subsequently fitted with a modified Randles equivalent circuit to simulate and extract relevant parameters of interest (Figure 8A,D). Typically, a Randles circuit is comprised of the solution resistance (R S ), charge transfer resistance (R CT ), double layer capacitance (C DL ), and Warburg diffusion element (σ).…”

Section: Impedimetric Performance Of Fabricated 3dmentioning

confidence: 99%

“…Approaches utilizing novel substrate/conductor/insulation strategies have formed the basis of the 3D MEA-based neural MPS collaboratively under development between the University of Central Florida, Tulane University, and the University of Wisconsin-Madison. ,,, The collaborative effort approaches the highly custom nature of the desired 3D MEA-enabled human neural nociceptive construct through a unique and novel approach. Herein, we report the microfabrication of a custom polymer and SS-based 3D MEA platform, which incorporated a novel PDA-enhanced adhesion of SiO 2 toward procuring functional electrophysiological recordings from a custom dual-spheroidal neural coculture in excess of 6 months.…”

Section: Introductionmentioning

confidence: 99%

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Fully Integrated 3D Microelectrode Arrays with Polydopamine-Mediated Silicon Dioxide Insulation for Electrophysiological Interrogation of a Novel 3D Human, Neural Microphysiological Construct

Didier

Fox

Pollard

et al. 2023

ACS Appl. Mater. Interfaces

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Advances within in vitro biological system complexity have enabled new possibilities for the "Organs-on-a-Chip" field. Microphysiological systems (MPS) as such incorporate sophisticated biological constructs with custom biological sensors. For microelectromechanical systems (MEMS) sensors, the dielectric layer is critical for device performance, where silicon dioxide (SiO 2 ) represents an excellent candidate due to its biocompatibility and wide utility in MEMS devices. Yet, high temperatures traditionally preclude SiO 2 from incorporation in polymer-based BioMEMS. Electron-beam deposition of SiO 2 may provide a lowtemperature, dielectric serving as a nanoporous MPS growth substrate. Herein, we enable improved adherence of nanoporous SiO 2 to polycarbonate (PC) and 316L stainless steel (SS) via polydopamine (PDA)-mediated chemistry. The resulting stability of the combinatorial PDA−SiO 2 film was interrogated, along with the nature of the intrafilm interactions. A custom polymer−metal three-dimensional (3D) microelectrode array (3D MEA) is then reported utilizing PDA−SiO 2 insulation, for definition of novel dorsal root ganglion (DRG)/nociceptor and dorsal horn (DH) 3D neural constructs in excess of 6 months for the first time. Spontaneous/evoked compound action potentials (CAPs) are successfully reported. Finally, inhibitory drugs treatments showcase pharmacological responsiveness of the reported multipart biological activity. These results represent the initiation of a novel 3D MEA-integrated, 3D neural MPS for the long-term electrophysiological study.

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Section: Methodsmentioning

confidence: 99%

Section: Impedimetric Performance Of Fabricated 3dmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Fully Integrated 3D Microelectrode Arrays with Polydopamine-Mediated Silicon Dioxide Insulation for Electrophysiological Interrogation of a Novel 3D Human, Neural Microphysiological Construct

Didier

Fox

Pollard

et al. 2023

ACS Appl. Mater. Interfaces

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“…[85] Additionally, the combination of microfluidic technology with 3D MEA allows for simultaneous in vitro detection and guided neuronal growth. [86,87] Due to the current absence of widely adopted styles and fabrication processes for 3D MEAs, and the fact that planar electrodes are still the most commonly used for in vitro models, research on planar electrodes remains the primary focus at present.…”

Section: In Vitro Mea For Hipsc-dnsmentioning

confidence: 99%

Using Human‐Induced Pluripotent Stem Cell Derived Neurons on Microelectrode Arrays to Model Neurological Disease: A Review

Lv,

He,

Luo

et al. 2023

Advanced Science

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In situ physiological signals of in vitro neural disease models are essential for studying pathogenesis and drug screening. Currently, an increasing number of in vitro neural disease models are established using human‐induced pluripotent stem cell (hiPSC) derived neurons (hiPSC‐DNs) to overcome interspecific gene expression differences. Microelectrode arrays (MEAs) can be readily interfaced with two‐dimensional (2D), and more recently, three‐dimensional (3D) neural stem cell‐derived in vitro models of the human brain to monitor their physiological activity in real time. Therefore, MEAs are emerging and useful tools to model neurological disorders and disease in vitro using human iPSCs. This is enabling a real‐time window into neuronal signaling at the network scale from patient derived. This paper provides a comprehensive review of MEA's role in analyzing neural disease models established by hiPSC‐DNs. It covers the significance of MEA fabrication, surface structure and modification schemes for hiPSC‐DNs culturing and signal detection. Additionally, this review discusses advances in the development and use of MEA technology to study in vitro neural disease models, including epilepsy, autism spectrum developmental disorder (ASD), and others established using hiPSC‐DNs. The paper also highlights the application of MEAs combined with hiPSC‐DNs in detecting in vitro neurotoxic substances. Finally, the future development and outlook of multifunctional and integrated devices for in vitro medical diagnostics and treatment are discussed.

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“…additionally enable robust neural spheroid growth. Previously, MPS approaches utilizing accessible material/insulation strategies, which retain optical clarity (e.g., PDMS) have been explored [3,10,11]. Herein we explore an electron-beam sublimation of nanoporous silicon dioxide (SiO2) technology onto polycarbonate (PC) substrate and 316L stainless-steel (SS) microelectrode materials [11] using PDA to stabilize adhesion.…”

Section: Introductionmentioning

confidence: 99%

Stable, Electron-Beam Sublimated, Nanostructured Silicon Dioxide on Polycarbonate and Stainless-Steel as a Bioadherent Dielectric Towards Neural Microphysiological Systems

Didier,

Fox,

Baksh

et al. 2022

2022 Solid-State, Actuators, and Microsystems Workshop Technical Digest

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Towards the development of biosensors, novel material combinations often impart challenges in microfabrication and process integration, e.g., depositing traditional materials using established processing techniques on new substrate materials. Silicon dioxide, for example, has been widely used in MicroElectroMechanical Systems (MEMS) fabrication but is rarely used in devices in combination with polymers and steel alloys. Herein, we establish an avenue improving the adherence of such an oxide material to polycarbonate and 316L stainless steel via polydopamine mediated chemistry to construct a stable coating that is indicative of its dual purpose as both a dielectric material for microelectrodes and a cell adhesion promoter. This fabrication method is a significant step towards novel BioMEMS devices and integrated biological systems currently under development.

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Fabrication and Characterization of 3D Microelectrode Arrays (3D MEAS) with Tri-Modal (Electrical, Optical, and Microfluidic) Interrogation of Electrogenic Cell Constructs

Cited by 4 publications

References 4 publications

Fully Integrated 3D Microelectrode Arrays with Polydopamine-Mediated Silicon Dioxide Insulation for Electrophysiological Interrogation of a Novel 3D Human, Neural Microphysiological Construct

Fully Integrated 3D Microelectrode Arrays with Polydopamine-Mediated Silicon Dioxide Insulation for Electrophysiological Interrogation of a Novel 3D Human, Neural Microphysiological Construct

Using Human‐Induced Pluripotent Stem Cell Derived Neurons on Microelectrode Arrays to Model Neurological Disease: A Review

Stable, Electron-Beam Sublimated, Nanostructured Silicon Dioxide on Polycarbonate and Stainless-Steel as a Bioadherent Dielectric Towards Neural Microphysiological Systems

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