A microfluidic gradient device for drug screening with human iPSC-derived motoneurons

Mo, Sung Joon; Lee, Ju Hyun; Kye, Hyeon Gi; Lee, Jong Min; Kim, Eun Joong; Geum, Dongho; Sun, Woong; Chung, Bong Geun

doi:10.1039/c9an02384d

Cited by 20 publications

(15 citation statements)

References 33 publications

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“…Cultivation of cells while integrating biomechanical stimulation allows to refine the description of distribution processes. It is worth noticing that some organ-on-a-chip devices on purpose exclude appreciable shear stress with the idea to reduce potential interference of physical stimulation with cell physiology, albeit maintaining chemical/medium exchange [191][192][193]. Microfluidics and 3D structures can be combined to explore the formation of physical and chemical gradients [110,194,195], as well as to study the modulation of barrier systems like the Blood Brain Barrier [90,123,196,197].…”

Section: Distributionmentioning

confidence: 99%

Integrating Biophysics in Toxicology

Favero

Kraegeloh

2020

Cells

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Integration of biophysical stimulation in test systems is established in diverse branches of biomedical sciences including toxicology. This is largely motivated by the need to create novel experimental setups capable of reproducing more closely in vivo physiological conditions. Indeed, we face the need to increase predictive power and experimental output, albeit reducing the use of animals in toxicity testing. In vivo, mechanical stimulation is essential for cellular homeostasis. In vitro, diverse strategies can be used to model this crucial component. The compliance of the extracellular matrix can be tuned by modifying the stiffness or through the deformation of substrates hosting the cells via static or dynamic strain. Moreover, cells can be cultivated under shear stress deriving from the movement of the extracellular fluids. In turn, introduction of physical cues in the cell culture environment modulates differentiation, functional properties, and metabolic competence, thus influencing cellular capability to cope with toxic insults. This review summarizes the state of the art of integration of biophysical stimuli in model systems for toxicity testing, discusses future challenges, and provides perspectives for the further advancement of in vitro cytotoxicity studies.

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Section: Distributionmentioning

confidence: 99%

Integrating Biophysics in Toxicology

Favero

Kraegeloh

2020

Cells

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“…In the mentioned work, the percentage of cellular death in response to five toxins (digitonin, saponin, CoCl 2 , NiCl 2 and acrolein) was obtained when using Live/ Death staining thanks to an adequate cell positioning. Similar idea was used by Mo et al, who combined a micropillar array for uniform cell positioning with a precisely controlled, low flow-rate gradient to reduce the shear stress to human induced pluripotent stem cells (HiPSC) derived neurospheres, and obtain reliable responses against riluzole drug (Mo et al, 2020).…”

Section: Sotf-lithographymentioning

confidence: 99%

“…When a multiserpentine based gradient generator is combined with a highdensity single-cell array, it results in a microsystem for simultaneous cytotoxicity assessment of numerous concentrations of KCN in this case, with single-cell resolution (Hosokawa et al, 2011). However, the flow-rates commonly used in serpentine gradient generators can be harmful for some cell types such as neurons, so in a recent work, an asymmetric microfluidic device was reported for the formation of drug gradients, which requires lower flows to generate gradients, as mentioned in the section above (Mo et al, 2020).…”

Section: Gradient Based Microsystemsmentioning

confidence: 99%

Advances in Microtechnology for Improved Cytotoxicity Assessment

2020

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In vitro cytotoxicity testing is essential in the pharmaceutical and environmental industry to study the effects of potential harmful compounds for human health. Classical assays present several disadvantages: they are commonly based on live-death labelling, are highly time consuming and/or require skilled personnel to be performed. The current trend is to reduce the number of required cells and the time during the analysis, while increasing the screening capability and the accuracy and sensitivity of the assays, aiming single cell resolution. Microfabrication and surface engineering are enabling novel approaches for cytotoxicity assessment, offering high sensitivity and the possibility of automation in order to minimize user intervention. This review aims to overview the different microtechnology approaches available in this field, focusing on the novel developments for high-throughput, dynamic and real time screening of cytotoxic compounds.

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“…With the development of MEMS technology, these limitations can be overcome partially by using microfluidic technology 5–9,39 to reduce measurement costs, and increase the reliability and flexibility. 10–12 Traditional HCS techniques use perforated plates for drug screening, with volumes ranging from tens to hundreds of μL. Theoretically, a single well in the plate contains enough medium and drug solution for a microfluidic chip.…”

Section: Introductionmentioning

confidence: 99%