Highly durable crack sensor integrated with silicone rubber cantilever for measuring cardiac contractility

Kim, Dong–Su; Choi, Yong Whan; Jeong, Yun-Jin; Park, Jong Sung; Oyunbaatar, Nomin-Erdene; Kim, Eung-Sam; Choi, Mansoo; Lee, Dong-Weon

doi:10.1038/s41467-019-14019-y

Cited by 84 publications

(96 citation statements)

References 39 publications

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“…Furthermore, the present system has the advantage of showing a wider dynamic range in the measurement of the forces of cell sheets. Even though the forces of cell sheets have been measured by cantilever-and fibrin gel sheet-based systems thus far [18][19][20] , the reported systems could not measure a small force under 0.1 mN due to bulk scale detection. On the other hand, the detection limit of the present study is approximately 0.0077 mN, which corresponds to the displacement of a particle displacement distance of 1.6 μm in a microchannel.…”

Section: Discussionmentioning

confidence: 99%

“…To apply biomimetic human heart tissue-like structures, such as the aforementioned human iPSC-derived cardiac microtissues, to drug discovery and cardiac toxicity tests, it is indispensable to develop a bioassay system to convert the small pulsations of cardiac microtissues into indicators of tissue function with higher sensitivity and versatility compared to those of previously reported systems based on cantilever or force measurement devices [18][19][20] . Organ-on-a-chip is an emerging concept to recapitulate organ function using polymeric organosilicon compounds such as polydimethylsiloxane (PDMS) by utilizing Micro Electro Mechanical Systems (MEMS) technology, which would be applied for the establishment of the bioassay system [21][22][23] .…”

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confidence: 99%

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Establishment of a heart-on-a-chip microdevice based on human iPS cells for the evaluation of human heart tissue function

Abulaiti

Yalikun

Murata

et al. 2020

Sci Rep

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Human iPS cell (iPSC)-derived cardiomyocytes (CMs) hold promise for drug discovery for heart diseases and cardiac toxicity tests. To utilize human iPSC-derived CMs, the establishment of three-dimensional (3D) heart tissues from iPSC-derived CMs and other heart cells, and a sensitive bioassay system to depict physiological heart function are anticipated. We have developed a heart-on-a-chip microdevice (HMD) as a novel system consisting of dynamic culture-based 3D cardiac microtissues derived from human iPSCs and microelectromechanical system (MEMS)-based microfluidic chips. The HMDs could visualize the kinetics of cardiac microtissue pulsations by monitoring particle displacement, which enabled us to quantify the physiological parameters, including fluidic output, pressure, and force. The HMDs demonstrated a strong correlation between particle displacement and the frequency of external electrical stimulation. The transition patterns were validated by a previously reported versatile video-based system to evaluate contractile function. The patterns are also consistent with oscillations of intracellular calcium ion concentration of CMs, which is a fundamental biological component of CM contraction. The HMDs showed a pharmacological response to isoproterenol, a β-adrenoceptor agonist, that resulted in a strong correlation between beating rate and particle displacement. Thus, we have validated the basic performance of HMDs as a resource for human iPSC-based pharmacological investigations.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Establishment of a heart-on-a-chip microdevice based on human iPS cells for the evaluation of human heart tissue function

Abulaiti

Yalikun

Murata

et al. 2020

Sci Rep

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“…Adapted with permission. [147] Copyright 2020, Springer Nature. cantilever, [142] whose displacement caused by the contractile force of cardiomyocytes significantly enhanced after electromechanical stimulation.…”

Section: Cantilever and Elastic Thin Filmmentioning

confidence: 99%

“…Recently, to improve the sensitivity and durability of the cantilever device, they proposed a silicone rubber cantilever device integrated with a highly sensitive PDMS‐encapsulated crack sensor (Figure 6D). [ 147 ] This crack sensor‐integrated cantilever can measure the cardiac contractility continuously without changing its gauge factor for up to 26 days, which can be applied to drug‐toxicity testing.…”

Section: Contractile Force 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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“…In addition to conventional electrophysiological methods, many researches have become interested in measuring the change in contractile force of cardiomyocytes. In order to measure mechanical response in the form of contraction force, micro-posts and cantilevers have been used, such that these devices would measure the amount of deflection occurring because of the cardiomyocytes and contraction force can be calculated based on this deflection [5][6][7][8]. Flexible polydimethylsiloxane (PDMS) micro-posts have been fabricated with 2 of 14 microgrooves to measure the contraction force of cardiomyocytes [5].…”

Section: Introductionmentioning

confidence: 99%

Polymer-Based Functional Cantilevers Integrated with Interdigitated Electrode Arrays—A Novel Platform for Cardiac Sensing

2020

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Heart related ailments are some of the most common causes for death in the world, and some of the causes are cardiac toxicity due to drugs. Several platforms have been developed in this regard over the years that can measure electrical or mechanical behavior of cardiomyocytes. In this study, we have demonstrated a biomedical device that can simultaneously measure electrophysiology and contraction force of cardiomyocytes. This dual-function device is composed of a photosensitive polymer-based cantilever, with a pair of metal-based interdigitated electrodes on its surface, such that the cantilever can measure the contraction force of cardiomyocytes and the electrodes can measure the impedance between cells and substrate. The cantilever is patterned with microgrooves so that the cardiomyocytes can align to the cantilever in order to make a higher cantilever deflection in response to contraction force. Preliminary experimental results have identified the potential for use in the drug-induced cardiac toxicity tests, and further optimization is desirable to extend the technique to various bio-sensor areas.

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Highly durable crack sensor integrated with silicone rubber cantilever for measuring cardiac contractility

Cited by 84 publications

References 39 publications

Establishment of a heart-on-a-chip microdevice based on human iPS cells for the evaluation of human heart tissue function

Establishment of a heart-on-a-chip microdevice based on human iPS cells for the evaluation of human heart tissue function

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

Polymer-Based Functional Cantilevers Integrated with Interdigitated Electrode Arrays—A Novel Platform for Cardiac Sensing

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