Peristaltic on-chip pump for tunable media circulation and whole blood perfusion in PDMS-free organ-on-chip and Organ-Disc systems

Schneider, Stefan; Bubeck, Marvin; Rogal, Julia; Weener, Huub J.; Rojas, Cristhian; Weiß, Martin; Heymann, Michaël; Meer, Andries D. van der; Loskill, Peter

doi:10.1039/d1lc00494h

Cited by 25 publications

(13 citation statements)

References 67 publications

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“…Peristaltic pumps displace fluid by mechanically actuating a flexible channel structure. There are a number of advantages to the use of peristaltic pumps over more commonly used gravity driven systems including tunable flow rates, unidirectional fluid flow and the ability to work with low fluid volumes (Schneider et al, 2021). Studies have been undertaken to assess pump-free, tilt based medium recirculation however such systems lack precise flow modification and large fluid volumes are required (Lohasz et al, 2018, Sasserath et al, 2020).…”

Section: Resultsmentioning

confidence: 99%

Mera: A scalable high throughput automated micro-physiological system

Cliffe¹,

Costello²,

Madden³

et al. 2022

Preprint

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There is an urgent need for scalable Microphysiological Systems (MPSs) that can better predict drug efficacy and toxicity at the preclinical screening stage. Here we present Mera, an automated, modular and scalable system for culturing and assaying microtissues with inbuilt environment control and automated image capture. The paradigm presented involves culturing and maturing common microtissue types in rows (rows of e.g., liver, heart, gastro-intestinal or kidney microtissues) and then reorienting fluid flow to create a recirculating circuit composed of inter-connected columns containing distinct microtissues (e.g. individual fluidic circuits with liver, heart, gastrointestinal and kidney micro-tissues inter-connected) to allow drugging or staining. We present data demonstrating the prototype system using an Acetaminophen/HepG2 liver microtissue toxicity assay with Calcein AM and Ethidium Homodimer viability assays. We demonstrate the functionality of the automated image capture system. The prototype microtissue culture plate wells are laid out in a 3x3 or 4x10 grid with viability and toxicity assays demonstrated in both formats. In this paper we set the groundwork for the Mera system as a viable option for scalable microtissue culture and assay development.

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Section: Resultsmentioning

confidence: 99%

Mera: A scalable high throughput automated micro-physiological system

Cliffe¹,

Costello²,

Madden³

et al. 2022

Preprint

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show abstract

“…In the future, technological refinements could aim at scale-up and sensor integration: To achieve parallelized platforms with increased throughput, a combination with enabling technologies might be worthwhile; for example, the WAT-on-chip design could be transferred to the organon-disc platform. [113,114] To enable in-line monitoring of adipose tissue secretions, on-chip sensors based on different technologies could be integrated. [44,46,115,116] To set up the WAT model, we established protocols and processes that allow to source all the different cell types from one individual donor; more specifically, from tissue samples of subcutaneous adipose tissue with skin that are readily available in most hospitals.…”

Section: Discussionmentioning

confidence: 99%

“…In the future, technological refinements could aim at scale‐up and sensor integration: To achieve parallelized platforms with increased throughput, a combination with enabling technologies might be worthwhile; for example, the WAT‐on‐chip design could be transferred to the organ‐on‐disc platform. [ 113 , 114 ] To enable in‐line monitoring of adipose tissue secretions, on‐chip sensors based on different technologies could be integrated. [ 44 , 46 , 115 , 116 ]…”

Section: Discussionmentioning

confidence: 99%

Autologous Human Immunocompetent White Adipose Tissue‐on‐Chip

et al. 2022

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Obesity and associated diseases, such as diabetes, have reached epidemic proportions globally. In this era of "diabesity", white adipose tissue (WAT) has become a target of high interest for therapeutic strategies. To gain insights into mechanisms of adipose (patho-)physiology, researchers traditionally relied on animal models. Leveraging Organ-on-Chip technology, a microphysiological in vitro model of human WAT is introduced: a tailored microfluidic platform featuring vasculature-like perfusion that integrates 3D tissues comprising all major WAT-associated cellular components (mature adipocytes, organotypic endothelial barriers, stromovascular cells including adipose tissue macrophages) in an autologous manner and recapitulates pivotal WAT functions, such as energy storage and mobilization as well as endocrine and immunomodulatory activities. A precisely controllable bottom-up approach enables the generation of a multitude of replicates per donor circumventing inter-donor variability issues and paving the way for personalized medicine. Moreover, it allows to adjust the model's degree of complexity via a flexible mix-and-match approach. This WAT-on-Chip system constitutes the first human-based, autologous, and immunocompetent in vitro adipose tissue model that recapitulates almost full tissue heterogeneity and can become a powerful tool for human-relevant research in the field of metabolism and its associated diseases as well as for compound testing and personalized-and precision medicine applications.

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“…Traditional actuation systems can be directly integrated to the microfluidic platforms. A peristaltic pump for disc-microfluidic systems was demonstrated where steel balls rolled around the central disc axis via a magnetic actuator and compressed flexible pump channels . Pressurized reservoirs can also be miniaturized and placed in direct contact with the chip to obtain a stand-alone flow control system, well suited to long-term culture such as in organ-on-chip applications …”

Section: Instrumentationmentioning

confidence: 99%