A flexible 3-dimensional microelectrode array for <i>in vitro</i> brain models

Soscia, David A.; Lam, Doris; Tooker, Angela; Enright, Heather A.; Triplett, Michael; Karande, Piyush; Peters, Sandra K. G.; Sales, Ana Paula; Wheeler, Elizabeth K.; Fischer, Nicholas O.

doi:10.1039/c9lc01148j

Cited by 138 publications

(139 citation statements)

References 57 publications

(71 reference statements)

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“…Notably, the volumetric coverage to which the microelectrodes corresponded was approximately 114 sites⋅mm -3 . The density of the recording sites was ~33 sites⋅mm −3 , which was significantly higher than that of a 3D MEA that was reported recently 23 .…”

Section: Resultscontrasting

confidence: 54%

“…In this work, we cultured for up to 14 days to observe the changes in connectivity among neurons according to maturation because we started observing cell death after 14 days due to the lack of nutrient supply. Because of both the higher cell seeding density than other typical 3D in vitro neural models 13 , 15 , 22 , 23 and continuous proliferation of small portions of non-neuronal cells (e.g., glia), included during the isolation of primary neurons from embryonic brains, we needed to change the culture medium more frequently for sufficient supply of nutrients after 14 days. We note that the 3D culture for up to 14 days was sufficient for synapse formation.…”

Section: Methodsmentioning

confidence: 99%

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3D high-density microelectrode array with optical stimulation and drug delivery for investigating neural circuit dynamics

et al. 2021

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Investigation of neural circuit dynamics is crucial for deciphering the functional connections among regions of the brain and understanding the mechanism of brain dysfunction. Despite the advancements of neural circuit models in vitro, technologies for both precisely monitoring and modulating neural activities within three-dimensional (3D) neural circuit models have yet to be developed. Specifically, no existing 3D microelectrode arrays (MEAs) have integrated capabilities to stimulate surrounding neurons and to monitor the temporal evolution of the formation of a neural network in real time. Herein, we present a 3D high-density multifunctional MEA with optical stimulation and drug delivery for investigating neural circuit dynamics within engineered 3D neural tissues. We demonstrate precise measurements of synaptic latencies in 3D neural networks. We expect our 3D multifunctional MEA to open up opportunities for studies of neural circuits through precise, in vitro investigations of neural circuit dynamics with 3D brain models.

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Section: Resultscontrasting

confidence: 54%

Section: Methodsmentioning

confidence: 99%

3D high-density microelectrode array with optical stimulation and drug delivery for investigating neural circuit dynamics

et al. 2021

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“…The array consists of 256 recording or stimulation channels. The action potential spike and burst activity were recorded for human-induced pluripotent stem cell (hiPSC)-derived neurons and astrocytes entrapped in a collagen-based hydrogel and seeded onto the 3DMEA, over 45 days in vitro [90].…”

Section: In Vitro Recordingmentioning

confidence: 99%

A Single-Neuron: Current Trends and Future Prospects

Gupta

Balasubramaniam

Chang

et al. 2020

Cells

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The brain is an intricate network with complex organizational principles facilitating a concerted communication between single-neurons, distinct neuron populations, and remote brain areas. The communication, technically referred to as connectivity, between single-neurons, is the center of many investigations aimed at elucidating pathophysiology, anatomical differences, and structural and functional features. In comparison with bulk analysis, single-neuron analysis can provide precise information about neurons or even sub-neuron level electrophysiology, anatomical differences, pathophysiology, structural and functional features, in addition to their communications with other neurons, and can promote essential information to understand the brain and its activity. This review highlights various single-neuron models and their behaviors, followed by different analysis methods. Again, to elucidate cellular dynamics in terms of electrophysiology at the single-neuron level, we emphasize in detail the role of single-neuron mapping and electrophysiological recording. We also elaborate on the recent development of single-neuron isolation, manipulation, and therapeutic progress using advanced micro/nanofluidic devices, as well as microinjection, electroporation, microelectrode array, optical transfection, optogenetic techniques. Further, the development in the field of artificial intelligence in relation to single-neurons is highlighted. The review concludes with between limitations and future prospects of single-neuron analyses.

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“…Mathematical models can also be applied to this data in order to allow the exploration of various cellular parameters that cannot be readily measured directly [3]. These advantages have triggered the broad adoption of impedance sensing in a wide variety of applications, with a range of custom instruments having been developed [4][5][6][7]. However, the adoption of these systems has been limited, as the construction of a specialist instrumentation is technically challenging.…”

Section: Introductionmentioning

confidence: 99%

Comparison of Leading Biosensor Technologies to Measure Endothelial Adhesion, Barrier Properties, and Responses to Cytokines in Real-Time

Hucklesby

Anchan

O’Carroll

et al. 2020

The 1st International Electronic Conference on Biosensors

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Electric Cell-substrate Impedance Sensing (ECIS), xCELLigence and cellZscope are commercially available instruments which are able to measure the impedance of cellular monolayers continuously and with high precision. The small currents used allow the label-free, real-time monitoring of the cells in a non-invasive manner. Despite the widespread use of these systems individually, direct comparisons between the systems have not been published. In order to compare the sensitivity of the instruments, the responses of the brain microvascular endothelial cell line hCMVEC to the inflammatory cytokines TNFα and IL1β were measured on all three instruments simultaneously. All three instruments showed transient decreases, followed by prolonged increases in impedance. Although xCELLigence could detect these changes, it was unable to determine which component of the barrier was affected. In contrast, ECIS and cellZscope were both able to attribute responses to particular barrier components, and ECIS had a higher sensitivity than cellZscope. Finally, as cellZscope uses Transwells, it allows access to the basolateral compartment, an important advantage of this technology. Furthermore, although xCELLigence readings are equivalent to ECIS, the reduced frequency range greatly limits interpretation. This work demonstrates that instruments must be carefully selected in order to ensure that they are appropriate for the experimental questions being asked.

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A flexible 3-dimensional microelectrode array for in vitro brain models

Abstract: A flexible 3D microelectrode array (3DMEA) device was developed that non-invasively interrogates electrophysiology of 3D in vitro neuronal cultures.

Cited by 138 publications

References 57 publications

3D high-density microelectrode array with optical stimulation and drug delivery for investigating neural circuit dynamics

3D high-density microelectrode array with optical stimulation and drug delivery for investigating neural circuit dynamics

A Single-Neuron: Current Trends and Future Prospects

Comparison of Leading Biosensor Technologies to Measure Endothelial Adhesion, Barrier Properties, and Responses to Cytokines in Real-Time

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