A mesh microelectrode array for non-invasive electrophysiology within neural organoids

McDonald, Matthew; D, Sebinger; Brauns, Lisa; Gonzalez-Cano, Laura; Menuchin-Lasowski, Yotam; Psathaki, Olympia-Ekaterini; Stumpf, Angelika; Rauen, Thomas; Schöler, Hans R.; Jones, Peter D.

doi:10.1101/2020.09.02.279125

Cited by 15 publications

(17 citation statements)

References 29 publications

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“…11 Two-dimensional (2D) microelectrode arrays (MEAs) have been used to interface with neuronal organoids but exhibit a limited 2D interface with the organoid. [12][13] Optical techniques, such as functional Ca 2+ imaging, which provide high spatial resolution and throughput, lack the temporal precision of ephys techniques (msec resolution), required to study the temporal dynamics of neural activity. 14 Here, we present a platform consisting of a 3D self-rolled biosensor array (3D-SR-BA) 15 that wraps around the 3D structure of a rat cortical spheroid.…”

Section: Introductionmentioning

confidence: 99%

Bioelectrical interfaces with cortical spheroids in three-dimensions

Kalmykov¹,

Reddy²,

Bedoyan³

et al. 2021

J. Neural Eng.

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Three-dimensional (3D) neuronal spheroid culture serves as a powerful model system for the investigation of neurological disorders and drug discovery. The success of such a model system requires techniques that enable high-resolution functional readout across the entire spheroid.Conventional microelectrode arrays and implantable neural probes cannot monitor the electrophysiology activity across the entire native 3D geometry of the cellular construct. Here, we demonstrate a 3D self-rolled biosensor array (3D-SR-BA) integrated with a 3D cortical spheroid culture for simultaneous in-vitro electrophysiology recording, functional Ca 2+ imaging, and drug effect monitoring. We have also developed a signal processing pipeline to detect neural firings with high spatiotemporal resolution from the electrophysiology recordings based on established spike sorting methods. The 3D-SR-BAs cortical spheroid interface provides a stable, high sensitivity recording of neural action potentials (< 50 µV peak-to-peak amplitude). The 3D-SR-BA is demonstrated as a potential drug screening platform through the investigation of the neural response to the excitatory neurotransmitter glutamate. Upon addition of glutamate, the neuronal firing rates increased notably corresponding well with the functional Ca 2+ imaging. Our entire system, including the 3D-SR-BA integrated with neural spheroid culture, enables simultaneous electrophysiology recording and functional Ca 2+ imaging with high spatiotemporal resolution in conjunction with chemical stimulation. We demonstrate a powerful toolset for future studies of tissue development, disease progression, and drug testing and screening, especially when combined with native spheroid cultures directly extracted from humans.

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Section: Introductionmentioning

confidence: 99%

Bioelectrical interfaces with cortical spheroids in three-dimensions

Kalmykov¹,

Reddy²,

Bedoyan³

et al. 2021

J. Neural Eng.

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show abstract

“…Recent work shows great promise, e.g., a 3D flexible MEAplatform, which was able to form a three-dimensional interface to a brain model including both astrocytes and neurons in a hydrogel matrix (Soscia et al 2020). McDonald et al showed how a flexible mesh-like MEA-array can be used to interface brain organoids (McDonald et al 2021).…”

Section: Advanced Sensors For Studying Neuro-coagulationmentioning

confidence: 99%

Technology-based approaches toward a better understanding of neuro-coagulation in brain homeostasis

et al. 2021

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Blood coagulation factors can enter the brain under pathological conditions that affect the blood–brain interface. Besides their contribution to pathological brain states, such as neural hyperexcitability, neurodegeneration, and scar formation, coagulation factors have been linked to several physiological brain functions. It is for example well established that the coagulation factor thrombin modulates synaptic plasticity; it affects neural excitability and induces epileptic seizures via activation of protease-activated receptors in the brain. However, major limitations of current experimental and clinical approaches have prevented us from obtaining a profound mechanistic understanding of “neuro-coagulation” in health and disease. Here, we present how novel human relevant models, i.e., Organ-on-Chips equipped with advanced sensors, can help overcoming some of the limitations in the field, thus providing a perspective toward a better understanding of neuro-coagulation in brain homeostasis.

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“…Electrical measurement techniques such as 2D microelectrode arrays (MEA) 15,16 and patch-clamp 17,18 have been applied to measure the functional development of brain organoids, but they can only capture the activities from the bottom surface of brain organoids [19][20][21] or assay one cell at a time with cell membrane disruption. The recent development of 3D bioelectronics enables 3D interfaces with brain organoids 1,19,[21][22][23][24][25] . However, they can only contact organoids at the surface by flexible electronics or penetrate organoids invasively by rigid probes, which cannot further accommodate volume and morphological changes of brain organoids during development.…”

Section: Introductionmentioning

confidence: 99%

A method for three-dimensional single-cell chronic electrophysiology from developing brain organoids

et al. 2021

Preprint

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Human induced pluripotent stem cell-derived brain organoids have shown great potential for studies of human brain development and neurological disorders. However, quantifying the evolution and development of electrical functions in brain organoids is currently limited by measurement techniques that cannot provide long-term stable three-dimensional (3D) bioelectrical interfaces with brain organoids during development. Here, we report a cyborg brain organoid platform, in which 2D progenitor or stem cell sheets can fold "tissue-like" stretchable mesh nanoelectronics through organogenesis, distributing stretchable electrode arrays across 3D organoids. The tissue-wide integrated stretchable electrode arrays show no interruption to neuronal differentiation, adapt to the volume and morphological changes during organogenesis, and provide long-term stable electrical contacts with neurons within brain organoids during development. The seamless and non-invasive coupling of electrodes to neurons enables a 6-month continuous recording of the same brain organoids and captures the emergence of single-cell action potentials from early-stage brain organoid development.

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A mesh microelectrode array for non-invasive electrophysiology within neural organoids

Cited by 15 publications

References 29 publications

Bioelectrical interfaces with cortical spheroids in three-dimensions

Bioelectrical interfaces with cortical spheroids in three-dimensions

Technology-based approaches toward a better understanding of neuro-coagulation in brain homeostasis

A method for three-dimensional single-cell chronic electrophysiology from developing brain organoids

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