Fabrication of MEA‐based nanocavity sensor arrays for extracellular recording of action potentials

Czeschik, Anna; Offenhäusser, Andreas; Wolfrum, Bernhard

doi:10.1002/pssa.201330365

Cited by 17 publications

(15 citation statements)

References 33 publications

(37 reference statements)

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“…Integration of sensors in various scaffold materials has been successfully demonstrated in several studies. [10,11,[25][26][27] However, fabricating scaffolds with integrated sensors for tissue engineering is usually a time-consuming, complex process, requiring multiple steps. Alternatively, electrospun poly(vinylidene fluoride) (PVDF)based piezoelectric fiber sheets are flexible, low cost, lightweight, and biocompatible, and can serve both as scaffolds and sensors.…”

Section: Introductionmentioning

confidence: 99%

Electrospun Fibrous PVDF‐TrFe Scaffolds for Cardiac Tissue Engineering, Differentiation, and Maturation

Adadi

Yadid

Gal

et al. 2020

Adv Materials Technologies

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Cardiac tissue engineering aims to create cardiac tissue constructs that recapitulate the structure and function of the native heart. This approach has been widely used for creating myocardial implants for regenerative medicine, and more recently, for developing in vitro cardiotoxicity screening assays. However, once the engineered myocardial tissues are implanted or subjected to pharmacological stimuli, their performance should be monitored. Currently, there is no biomaterial that promotes functional tissues assembly while providing real‐time information about their function, in situ. In this study, the piezoelectric phenomenon is sought to be exploited, to measure the contractions generated by engineered cardiac tissues. A poly‐(vinylidene fluoride) (PVDF)‐based electrospun fiber scaffold is developed, and it is hypothesized that the contractions of cardiomyocytes in the scaffold will induce mechanical deformations, which will result in measurable electric voltage. The PVDF scaffolds are characterized and optimized for supporting formation of aligned, functional, cardiac tissues. The scaffolds' function is then validated as sensors for tissue contraction and it is demonstrated that they can sense contractions of tissues constructed from as few as 5 × 105 cardiomyocytes. Furthermore, it is demonstrated that human induced pluripotent stem cells can be directly seeded and differentiated to cardiomyocytes, and then mature over the course of 40 days on the PVDF fiber scaffolds.

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Section: Introductionmentioning

confidence: 99%

Electrospun Fibrous PVDF‐TrFe Scaffolds for Cardiac Tissue Engineering, Differentiation, and Maturation

Adadi

Yadid

Gal

et al. 2020

Adv Materials Technologies

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“…Nanocavity arrays have been presented as a method to efficiently combine the need for a large electrode area with a high spatial resolution. [38][39][40] This sensor type consists of a welldefined cavity between electrode and passivation layer and a small opening aperture that connects the cavity to the cell. Consequently, similar to the planar patch clamp method, 41,42 a low sensor impedance is combined with a high spatial resolution at the single-cell level.…”

Section: Introductionmentioning

confidence: 99%

“…Previously, we have presented planar nanocavity sensors based on sacrificial layer etching, which exhibited low electrical impedance combined with good recording capabilities of action potentials. 38,40 In this study, we introduce a new cavity device with a nanostructured electrode interface. We investigate electrical impedance and cell-sensor coupling for stimulation applications.…”

Section: Introductionmentioning

confidence: 99%

Nanostructured cavity devices for extracellular stimulation of HL-1 cells

et al. 2015

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Microelectrode arrays (MEAs) are state-of-the-art devices for extracellular recording and stimulation on biological tissue. Furthermore, they are a relevant tool for the development of biomedical applications like retina, cochlear and motor prostheses, cardiac pacemakers and drug screening. Hence, research on functional cell-sensor interfaces, as well as the development of new surface structures and modifications for improved electrode characteristics, is a vivid and well established field. However, combining single-cell resolution with sufficient signal coupling remains challenging due to poor cell-electrode sealing. Furthermore, electrodes with diameters below 20 µm often suffer from a high electrical impedance affecting the noise during voltage recordings. In this study, we report on a nanocavity sensor array for voltage-controlled stimulation and extracellular action potential recordings on cellular networks. Nanocavity devices combine the advantages of low-impedance electrodes with small cell-chip interfaces, preserving a high spatial resolution for recording and stimulation. A reservoir between opening aperture and electrode is provided, allowing the cell to access the structure for a tight cell-sensor sealing. We present the well-controlled fabrication process and the effect of cavity formation and electrode patterning on the sensor's impedance. Further, we demonstrate reliable voltage-controlled stimulation using nanostructured cavity devices by capturing the pacemaker of an HL-1 cell network.

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“…Wolfrum et al overcame this dilemma by creating micropores that interface the cells to larger electrodes. 10,11 A third approach involves decreasing the membrane impedance at the cell-electrode junction. In practice, this involves transiently rapturing the cell membrane by applying a zap voltage to a nanostructured electrode, thus allowing the electrodes to enter the cell and perform pseudo-intracellular recording until the raptured membrane reorganizes.…”

mentioning

confidence: 99%

“…For example, Czeschik et al used nanocavity electrodes and reported recordings of up to $3 mV from cardiomyocytes. 11 The signal amplitude would be expected to be further amplified by incorporating the resistive sheet covering method.…”

mentioning

confidence: 99%

An electrically resistive sheet of glial cells for amplifying signals of neuronal extracellular recordings

Matsumura

Yamamoto

Niwano

et al. 2016

Applied Physics Letters

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Electrical signals of neuronal cells can be recorded non-invasively and with a high degree of temporal resolution using multielectrode arrays (MEAs). However, signals that are recorded with these devices are small, usually 0.01%-0.1% of intracellular recordings. Here, we show that the amplitude of neuronal signals recorded with MEA devices can be amplified by covering neuronal networks with an electrically resistive sheet. The resistive sheet used in this study is a monolayer of glial cells, supportive cells in the brain. The glial cells were grown on a collagen-gel film that is permeable to oxygen and other nutrients. The impedance of the glial sheet was measured by electrochemical impedance spectroscopy, and equivalent circuit simulations were performed to theoretically investigate the effect of covering the neurons with such a resistive sheet. Finally, the effect of the resistive glial sheet was confirmed experimentally, showing a 6-fold increase in neuronal signals. This technique feasibly amplifies signals of MEA recordings. V C 2016 AIP Publishing LLC. Microelectrode array (MEA) technology is widely used to record trains of action potentials from cultured neurons, cardiomyocytes, or brain slice preparations. [1][2][3][4] The major advantage of this method lies in its high temporal resolution (>10 kHz) and non-invasiveness. MEA recordings have been used both in fundamental studies, e.g., to analyse activity patterns of cultured neuronal networks, 5,6 and in pharmacological research, for screening lead compounds in vitro. 7,8 However, small signals that can be detected through extracellularly positioned microelectrodes inhibit MEAs from being used in further applications such as studies of subthreshold activity. The amplitude of extracellularly recorded signals is usually in the order of ten to a hundred microvolts, which is 3-4 orders of magnitude lower than the intracellular change of membrane potential in an action potential ($100 mV).Various attempts have been made to overcome this issue. One approach involves increasing the seal resistance between the cell and the electrode. This can be achieved by using nanostructured electrodes instead of planar electrodes that become engulfed by overlying cells. 1,9 A second approach is to decrease the electrode impedance. To record activity from single cells, the use of a smaller electrode is preferable, but this comes at the cost of increased electrode impedance, which decreases the signal. Wolfrum et al. overcame this dilemma by creating micropores that interface the cells to larger electrodes. 10,11 A third approach involves decreasing the membrane impedance at the cell-electrode junction. In practice, this involves transiently rapturing the cell membrane by applying a zap voltage to a nanostructured electrode, thus allowing the electrodes to enter the cell and perform pseudo-intracellular recording until the raptured membrane reorganizes. 1,12,13 In this letter, we propose an alternative approach to increase the neuron-electrode seal for amplifying signals in ex...

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Fabrication of MEA‐based nanocavity sensor arrays for extracellular recording of action potentials

Cited by 17 publications

References 33 publications

Electrospun Fibrous PVDF‐TrFe Scaffolds for Cardiac Tissue Engineering, Differentiation, and Maturation

Electrospun Fibrous PVDF‐TrFe Scaffolds for Cardiac Tissue Engineering, Differentiation, and Maturation

Nanostructured cavity devices for extracellular stimulation of HL-1 cells

An electrically resistive sheet of glial cells for amplifying signals of neuronal extracellular recordings

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