Integration of an oxygen sensor into a polydymethylsiloxane hepatic culture device for two-dimensional gradient characterization

Matsumoto, Satomi; Leclerc, Éric; Maekawa, Toshiro; Kinoshita, Haruyuki; Shinohara, Masanao; Komori, Kikuo; Sakai, Yasuyuki; Fujii, Teruo

doi:10.1016/j.snb.2018.05.053

Cited by 16 publications

(21 citation statements)

References 20 publications

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“…In addition, medium and test substances can easily be exchanged during the continuous measurement, which enables numerous consecutive treatments and versatile treatment schemes (see Table 2 (Tab. 2) ; References in Table 2: Ferrick et al, 2008[ 18 ]; Hynes et al, 2009[ 24 ]; Matsumoto et al, 2018[ 30 ]; Moya et al, 2018[ 32 ]; Prill et al, 2016[ 40 ]; Rennert et al, 2015[ 42 ]; Weltin et al, 2017[ 53 ]). In contrast to electrochemical oxygen sensors (used by e.g.…”

Section: Discussionmentioning

confidence: 99%

Continuous, non-invasive monitoring of oxygen consumption in a parallelized microfluidic in vitro system provides novel insight into the response to nutrients and drugs of primary human hepatocytes

Busche

Rabl

Fischer

et al. 2022

EXCLI Journal; 21:Doc144; ISSN 1611-2156

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Oxygen plays a fundamental role in cellular energy metabolism, differentiation and cell biology in general. Consequently, in vitro oxygen sensing can be used to assess cell vitality and detect specific mechanisms of toxicity. In 2D in vitro models currently used, the oxygen supply provided by diffusion is generally too low, especially for cells having a high oxygen demand. In organ-on-chip systems, a more physiologic oxygen supply can be generated by establishing unidirectional perfusion. We established oxygen sensors in an easy-to-use and parallelized organ-on-chip system. We demonstrated the applicability of this system by analyzing the influence of fructose (40 mM, 80 mM), ammonium chloride (100 mM) and Na-diclofenac (50 µM, 150 µM, 450 µM, 1500 µM) on primary human hepatocytes (PHH). Fructose treatment for two hours showed an immediate drop of oxygen consumption (OC) with subsequent increase to nearly initial levels. Treatment with 80 mM glucose, 20 mM lactate or 20 mM glycerol did not result in any changes in OC which demonstrates a specific effect of fructose. Application of ammonium chloride for two hours did not show any immediate effects on OC, but qualitatively changed the cellular response to FCCP treatment. Na-diclofenac treatment for 24 hours led to a decrease of the maximal respiration and reserve capacity. We also demonstrated the stability of our system by repeatedly treating cells with 40 mM fructose, which led to similar cell responses on the same day as well as on subsequent days. In conclusion, our system enables in depth analysis of cellular respiration after substrate treatment in an unidirectional perfused organ-on-chip system.

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Section: Discussionmentioning

confidence: 99%

Continuous, non-invasive monitoring of oxygen consumption in a parallelized microfluidic in vitro system provides novel insight into the response to nutrients and drugs of primary human hepatocytes

Busche

Rabl

Fischer

et al. 2022

EXCLI Journal; 21:Doc144; ISSN 1611-2156

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“…Pressure was set at 0 Pa for the three other outlets. The oxygen consumption rate was set at qO2 = 5x10 -17 mol/s/cell and Michaelis-Menten kinetics were used to describe the reactions within the chambers 11,[37][38][39][40][41] . These simulations are detailed in Supplementary Information.…”

Section: Methodsmentioning

confidence: 99%

A Versatile Microfluidic Tool for the 3D Culture of HepaRG Cells Seeded at Various Stages of Differentiation

Boul

Benzoubir

Messina

et al. 2021

Preprint

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The development of livers-on-a-chip aims to provide pharmaceutical companies with reliable systems to perform drug screening and toxicological studies. To that end, microfluidic systems are engineered to mimic the functions and architecture of this organ. In this context we have designed a device that reproduces series of liver microarchitectures, each permitting the 3D culture of hepatocytes by confining them to a chamber that is separated from the medium conveying channel by very thin slits. We modified the structure to ensure its compatibility with the culture of hepatocytes from different sources. Our device was adapted to the migratory and adhesion properties of HepaRG cells at various stages of differentiation. To prevent hepatoblast-like cells from migrating out of the chambers, the slit height was decreased and the medium flow rate increased. Maintaining already differentiated and less adherent cells within the chambers required desensitisation of the system to pressure variations. Using this device, it was possible to keep the cells alive for more than 14 days, during which they achieved a 3D organisation and acquired or maintained their differentiation into hepatocytes. With its multiple micro-chambers for hepatocyte culture, this microfluidic device architecture offers a promising opportunity to provide new tools for drug screening applications.

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“…The 2D oxygen gradient that forms upon cell culture in an oxygen impermeable system can be used to access the OCR of the cells under perfusion. Matsumoto et al 139 cultured cells in a microfluidic channel under different flow rates. They monitored the oxygen gradient inside the device with an oxygen sensitive film and simple intensity-based measurements using a microscope.…”

Section: Examples and Applications Of Sensors In Organ-on-chip Systemsmentioning

confidence: 99%

In-Line Analysis of Organ-on-Chip Systems with Sensors: Integration, Fabrication, Challenges, and Potential

Fuchs

Johansson

Tjell

et al. 2021

ACS Biomater. Sci. Eng.

121

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Organ-on-chip systems are promising new in vitro research tools in medical, pharmaceutical, and biological research. Their main benefit, compared to standard cell culture platforms, lies in the improved in vivo resemblance of the cell culture environment. A critical aspect of these systems is the ability to monitor both the cell culture conditions and biological responses of the cultured cells, such as proliferation and differentiation rates, release of signaling molecules, and metabolic activity. Today, this is mostly done using microscopy techniques and off-chip analytical techniques and assays. Integrating in situ analysis methods on-chip enables improved time resolution, continuous measurements, and a faster read-out; hence, more information can be obtained from the developed organ and disease models. Integrated electrical, electrochemical, and optical sensors have been developed and used for chemical analysis in lab-on-a-chip systems for many years, and recently some of these sensing principles have started to find use in organ-on-chip systems as well. This perspective review describes the basic sensing principles, sensor fabrication, and sensor integration in organ-on-chip systems. The review also presents the current state of the art of integrated sensors and discusses future potential. We bring a technological perspective, with the aim of introducing in-line sensing and its promise to advance organ-on-chip systems and the challenges that lie in the integration to researchers without expertise in sensor technology.

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Integration of an oxygen sensor into a polydymethylsiloxane hepatic culture device for two-dimensional gradient characterization

Cited by 16 publications

References 20 publications

Continuous, non-invasive monitoring of oxygen consumption in a parallelized microfluidic in vitro system provides novel insight into the response to nutrients and drugs of primary human hepatocytes

Continuous, non-invasive monitoring of oxygen consumption in a parallelized microfluidic in vitro system provides novel insight into the response to nutrients and drugs of primary human hepatocytes

A Versatile Microfluidic Tool for the 3D Culture of HepaRG Cells Seeded at Various Stages of Differentiation

In-Line Analysis of Organ-on-Chip Systems with Sensors: Integration, Fabrication, Challenges, and Potential

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