Graphene Microelectrode Arrays for Electrical and Optical Measurements of Human Stem Cell-Derived Cardiomyocytes

Rastogi, Sahil Kumar; Bliley, Jacqueline M.; Shiwarski, Daniel J.; Raghavan, Guruprasad; Feinberg, Adam W.; Cohen‐Karni, Tzahi

doi:10.1007/s12195-018-0525-z

Cited by 45 publications

(53 citation statements)

References 47 publications

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“…As proof-of-principle and to demonstrate the robustness of our technique, we demonstrated that MEAs with silk-passivated interconnects could record signals both from cultured cells (HL-1) as well as primary tissues (brain, heart). Significantly, in the case of HL-1 cells we recorded signals with signal-to-noise >78, which compares favorably other devices recently used to study cardiac monolayers, including graphene MEAs with SU8 passivation 7 .…”

Section: Discussionmentioning

confidence: 61%

“…Examples of bioelectronic devices include multi-electrode arrays (MEAs) and field-effect transistors (FETs) which have been interfaced with neuron or cardiac cells for multiplexed, realtime readouts of electrophysiological activity 4 , while other classes of devices have achieved ondemand drug delivery, localized stimulation, power generation and chemical sensing capabilities 5,6 . Advances in nanoscience have played a key role in each of these areas by enabling cellular-scale, noninvasive devices such as transparent graphene MEAs 7 and freestanding nanowire arrays 8,9 that could access the cytosol for intracellular measurements.…”

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confidence: 99%

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Photo–cross-linkable, insulating silk fibroin for bioelectronics with enhanced cell affinity

Cairns

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

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Bioelectronic scaffolds that support devices while promoting tissue integration could enable tissue hybrids with augmented electronic capabilities. Here, we demonstrate a photo–cross-linkable silk fibroin (PSF) derivative and investigate its structural, electrical, and chemical properties. Lithographically defined PSF films offered tunable thickness and <1-µm spatial resolution and could be released from a relief layer yielding freestanding scaffolds with centimeter-scale uniformity. These constructs were electrically insulating; multielectrode arrays with PSF-passivated interconnects provided stable electrophysiological readouts from HL-1 cardiac model cells, brain slices, and hearts. Compared to SU8, a ubiquitous biomaterial, PSF exhibited superior affinity toward neurons which we attribute to its favorable surface charge and enhanced attachment of poly-d-lysine adhesion factors. This finding is of significant importance in bioelectronics, where tight junctions between devices and cell membranes are necessary for electronic communication. Collectively, our findings are generalizable to a variety of geometries, devices, and tissues, establishing PSF as a promising bioelectronic platform.

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Section: Discussionmentioning

confidence: 61%

mentioning

confidence: 99%

Photo–cross-linkable, insulating silk fibroin for bioelectronics with enhanced cell affinity

Cairns

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

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“…Moreover, transparent and biocompatible indium tin oxide (ITO) and graphene‐based MEAs were fabricated to achieve the simultaneous optical and electrical recordings. [ 42–44 ] Interestingly, conductive hydrogel micropillars were applied to MEAs fabrication, showing improved signal amplitude and SNR. [ 45 ] Recently, an electrical shell‐like recording device that wrapped around the cell in 3D was reported to improve the cell–electrode coupling.…”

Section: Electrophysiology Detectionmentioning

confidence: 99%

Advances in Multidimensional Cardiac Biosensing Technologies: From Electrophysiology to Mechanical Motion and Contractile Force

Wei

Zhuang

et al. 2020

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Cardiovascular disease (CVD) is the number one killer in the world. According to the World Health Organization (WHO) estimation, about 17.9 million people died from CVD each year, accounting for 31% of all deaths worldwide. [1] Among these deaths, about 7.4 million died from coronary heart disease, while 6.7 million from a stroke. According to China cardiovascular disease report in 2018, [2] around 290 million people suffer from CVD, including 13 million strokes, 11 million coronary heart disease, 5 million pulmonary heart disease, 4.5 million heart failure, 2.5 million rheumatic heart disease, 2 million congenital heart disease, and 270 million hypertension. Cardiovascular disease was also the leading cause of all death in rural and urban areas, with 45.01% in rural areas and 42.61% in urban areas. According to heart disease and stroke statistics from the American Heart Association (AHA) in 2018, [3] around 92.1 million American adults have a certain form of cardiovascular disease or suffer from stroke sequelae. CVD killed 836546 Americans in 2015. Coronary heart disease was the leading cause (43.8%) of death in CVD, followed by stroke (16.8%), heart failure (9.0%), hypertension (9.4%), arterial disease (3.1%) and other cardiovascular diseases (17.9%). According to the European cardiovascular disease statistics in 2017, [4] around 3.9 million people died from CVD each year, which accounts for 45% of all deaths in Europe. Ischemic heart disease (IHD) and stroke are the main forms of CVD in Europe. Among all deaths in Europe each year, IHD is the leading single cause of mortality, responsible for 19% and 20% among men and women, while stroke is the second most common single cause of death, accounting for 9% in men and 13% in women. Therefore, the prevention and treatment of CVD have aroused extensive public concern worldwide. Moreover, cardiac toxicity induced by drugs has been the main cause of the withdrawal from the market and drugs attrition during the last decades. [5,6] On the one hand, drug-induced cardiotoxicity will also threaten people's health, even life. For example, acute arrhythmia can lead to sudden death, while Cardiovascular disease is currently a leading killer to human, while druginduced cardiotoxicity remains the main cause of the withdrawal and attrition of drugs. Taking clinical correlation and throughput into account, cardiomyocyte is perfect as in vitro cardiac model for heart disease modeling, drug discovery, and cardiotoxicity assessment by accurately measuring the physiological multiparameters of cardiomyocytes. Remarkably, cardiomyocytes present both electrophysiological and biomechanical characteristics due to the unique excitation-contraction coupling, which plays a significant role in studying the cardiomyocytes. This review mainly focuses on the recent advances of biosensing technologies for the 2D and 3D cardiac models with three special properties: electrophysiology, mechanical motion, and contractile force. These high-performance multidimensional cardiac models are popular and ef...

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“…To characterize the impedance of the electrodes before and after PEDOT:PSS electrodeposition, electrochemical impedance spectroscopy (EIS) was performed in a threeelectrode electrochemical cell using a potentiostat (Gamry R600+, Gamry Instruments). 17…”

Section: Electrochemical Characterization Of Microelectrodesmentioning

confidence: 99%

Bioelectrical Interfaces with Cortical Spheroids in Three-Dimensions

Kalmykov

Reddy²,

Bedoyan³

et al. 2020

Preprint

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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 Ca2+ 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 Ca2+ imaging. Our entire system, including the 3D-SR-BA integrated with neural spheroid culture, enables simultaneous electrophysiology recording and functional Ca2+ 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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Graphene Microelectrode Arrays for Electrical and Optical Measurements of Human Stem Cell-Derived Cardiomyocytes

Abstract: Associate Editor William E. Bentley oversaw the review of this article.

Cited by 45 publications

References 47 publications

Photo–cross-linkable, insulating silk fibroin for bioelectronics with enhanced cell affinity

Photo–cross-linkable, insulating silk fibroin for bioelectronics with enhanced cell affinity

Advances in Multidimensional Cardiac Biosensing Technologies: From Electrophysiology to Mechanical Motion and Contractile Force

Bioelectrical Interfaces with Cortical Spheroids in Three-Dimensions

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