On-chip hydrogel arrays individually encapsulating acoustic formed multicellular aggregates for high throughput drug testing

Lab on a Chip ◽  
2020 ◽  
Vol 20 (12) ◽  
pp. 2228-2236 ◽  
Author(s):  
Xuejia Hu ◽  
Shukun Zhao ◽  
Ziyi Luo ◽  
Yunfeng Zuo ◽  
Fang Wang ◽  
...  
Keyword(s):  
Drug Resistance ◽  
High Throughput ◽  
Solid Tumor ◽  
Drug Testing ◽  
Three Dimensional ◽  
Multicellular Aggregates ◽  
3D Environments ◽  
On Chip ◽  
Insight Into

Multicellular aggregates in three-dimensional (3D) environments provide novel solid tumor models that can provide insight into in vivo drug resistance.

scholarly journals Clarifying intact 3D tissues on a microfluidic chip for high-throughput structural analysis

2016 ◽  
Vol 113 (52) ◽  
pp. 14915-14920 ◽  
Author(s):  
Yih Yang Chen ◽  
Pamuditha N. Silva ◽  
Abdullah Muhammad Syed ◽  
Shrey Sindhwani ◽  
Jonathan V. Rocheleau ◽  
...  
Keyword(s):  
High Throughput ◽  
High Throughput Screening ◽  
Three Dimensional ◽  
Microfluidic System ◽  
High Throughput Drug Screening ◽  
Image Analysis Algorithm ◽  
Screening Assays ◽  
On Chip ◽  
Tissue Models

On-chip imaging of intact three-dimensional tissues within microfluidic devices is fundamentally hindered by intratissue optical scattering, which impedes their use as tissue models for high-throughput screening assays. Here, we engineered a microfluidic system that preserves and converts tissues into optically transparent structures in less than 1 d, which is 20× faster than current passive clearing approaches. Accelerated clearing was achieved because the microfluidic system enhanced the exchange of interstitial fluids by 567-fold, which increased the rate of removal of optically scattering lipid molecules from the cross-linked tissue. Our enhanced clearing process allowed us to fluorescently image and map the segregation and compartmentalization of different cells during the formation of tumor spheroids, and to track the degradation of vasculature over time within extracted murine pancreatic islets in static culture, which may have implications on the efficacy of beta-cell transplantation treatments for type 1 diabetes. We further developed an image analysis algorithm that automates the analysis of the vasculature connectivity, volume, and cellular spatial distribution of the intact tissue. Our technique allows whole tissue analysis in microfluidic systems, and has implications in the development of organ-on-a-chip systems, high-throughput drug screening devices, and in regenerative medicine.

scholarly journals Three-dimensional visualization and analysis of flowing droplets in microchannels using real-time quantitative phase microscopy

Lab on a Chip ◽  
2021 ◽  
Vol 21 (1) ◽  
pp. 75-82
Author(s):  
Yingdong Luo ◽  
Jinwu Yang ◽  
Xinqi Zheng ◽  
Jianjun Wang ◽  
Xin Tu ◽  
...  
Keyword(s):  
Real Time ◽  
High Throughput ◽  
Three Dimensional ◽  
Phase Variation ◽  
Quantitative Phase ◽  
Phase Microscopy ◽  
Quantitative Phase Microscopy ◽  
On Chip

We present real-time quantitative phase microscopy (RT-QPM) that can be used for on-chip three-dimensional visualization of droplets and high-throughput quantitative molecular measurement via real-time extraction of sample-induced phase variation.

Selective Laser Foaming for Three-Dimensional Cell Culture on a Compact Disc

2015 ◽  
Author(s):  
JinGyu Ock ◽  
Wei Li
Keyword(s):  
Porous Structure ◽  
High Throughput ◽  
Drug Testing ◽  
3D Structure ◽  
Three Dimensional ◽  
Compact Disc ◽  
Laser Exposure ◽  
Porous Scaffolds ◽  
3D Scaffold ◽  
Tissue Model

A selective laser foaming process is developed to fabricate three-dimensional (3D) scaffold on a commercially available compact disc (CD) made of polycarbonate (PC). The laser-foamed 3D structure could be utilized to form high throughput perfusion-based tissue model device. In this study, effects of significant parameters and the morphology of porous structure were analyzed. As a result, laser foaming of gas saturated polycarbonate creates inverse cone-shaped wells with 3D porous structure on the surface region and the pores are tens of micrometers in diameter. The size of the well is dependent on the laser power and laser exposure time. The pore size relies on the gas concentration in the PC CD samples. The fabricated micro-scale porous scaffolds will be used to create centrifugal force driven two-chamber tissue model system arrays for high throughput drug testing.

scholarly journals Phenotypic assays in yeast and zebrafish reveal drugs that rescue ATP13A2 deficiency

2019 ◽  
Vol 1 (1) ◽  
Author(s):  
Ursula Heins-Marroquin ◽  
Paul P Jung ◽  
Maria Lorena Cordero-Maldonado ◽  
Alexander D Crawford ◽  
Carole L Linster
Keyword(s):  
Heavy Metal ◽  
High Throughput ◽  
High Throughput Screening ◽  
Drug Testing ◽  
Neuronal Ceroid Lipofuscinosis ◽  
Drug Repurposing ◽  
In Vivo Model ◽  
Inherited Disorders ◽  
Zebrafish Model

Abstract Mutations in ATP13A2 (PARK9) are causally linked to the rare neurodegenerative disorders Kufor-Rakeb syndrome, hereditary spastic paraplegia and neuronal ceroid lipofuscinosis. This suggests that ATP13A2, a lysosomal cation-transporting ATPase, plays a crucial role in neuronal cells. The heterogeneity of the clinical spectrum of ATP13A2-associated disorders is not yet well understood and currently, these diseases remain without effective treatment. Interestingly, ATP13A2 is widely conserved among eukaryotes, and the yeast model for ATP13A2 deficiency was the first to indicate a role in heavy metal homeostasis, which was later confirmed in human cells. In this study, we show that the deletion of YPK9 (the yeast orthologue of ATP13A2) in Saccharomyces cerevisiae leads to growth impairment in the presence of Zn2+, Mn2+, Co2+ and Ni2+, with the strongest phenotype being observed in the presence of zinc. Using the ypk9Δ mutant, we developed a high-throughput growth rescue screen based on the Zn2+ sensitivity phenotype. Screening of two libraries of Food and Drug Administration-approved drugs identified 11 compounds that rescued growth. Subsequently, we generated a zebrafish model for ATP13A2 deficiency and found that both partial and complete loss of atp13a2 function led to increased sensitivity to Mn2+. Based on this phenotype, we confirmed two of the drugs found in the yeast screen to also exert a rescue effect in zebrafish—N-acetylcysteine, a potent antioxidant, and furaltadone, a nitrofuran antibiotic. This study further supports that combining the high-throughput screening capacity of yeast with rapid in vivo drug testing in zebrafish can represent an efficient drug repurposing strategy in the context of rare inherited disorders involving conserved genes. This work also deepens the understanding of the role of ATP13A2 in heavy metal detoxification and provides a new in vivo model for investigating ATP13A2 deficiency.

scholarly journals Quantitative high throughput screening using a primary human three-dimensional organotypic culture predicts in vivo efficacy

2015 ◽  
Vol 6 (1) ◽  
Author(s):  
Hilary A. Kenny ◽  
Madhu Lal-Nag ◽  
Erin A. White ◽  
Min Shen ◽  
Chun-Yi Chiang ◽  
...  
Keyword(s):  
High Throughput ◽  
High Throughput Screening ◽  
Organotypic Culture ◽  
Three Dimensional ◽  
In Vivo Efficacy

scholarly journals Engineered Heterochronic Parabiosis in 3D Microphysiological System for Identification of Muscle Rejuvenating Factors

2020 ◽  
Author(s):  
Yunki Lee ◽  
Jeongmoon J. Choi ◽  
Song Ih Ahn ◽  
Nan Hee Leea ◽  
Woojin M. Han ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Function ◽  
Three Dimensional ◽  
Muscle Stem Cell ◽  
Organ Systems ◽  
Systemic Factors ◽  
Underlying Mechanisms ◽  
On Chip

AbstractExposure of aged mice to a young systemic milieu revealed remarkable rejuvenation effects on aged tissues, including skeletal muscle. Although some candidate factors have been identified, the exact identity and the underlying mechanisms of putative rejuvenating factors remain elusive, mainly due to the complexity of in vivo parabiosis. Here, we present an in vitro muscle parabiosis system that integrates young- and old-muscle stem cell vascular niche on a three-dimensional microfluidic platform designed to recapitulate key features of native muscle stem cell microenvironment. This innovative system enables mechanistic studies of cellular dynamics and molecular interactions within the muscle stem cell niche, especially in response to conditional extrinsic stimuli of local and systemic factors. We demonstrate that vascular endothelial growth factor (VEGF) signaling from endothelial cells and myotubes synergistically contribute to the rejuvenation of the aged muscle stem cell function. Moreover, with the adjustable on-chip system, we can mimic both blood transfusion and parabiosis and detect the time-varying effects of anti-geronic and pro-geronic factors in a single organ or multi-organ systems. Our unique approach presents a complementary in vitro model to supplement in vivo parabiosis for identifying potential anti-geronic factors responsible for revitalizing aging organs.

scholarly journals An automated microfluidic platform integrating functional vascularized organoids-on-chip

2021 ◽  
Author(s):  
Clément Quintard ◽  
Gustav Jonsson ◽  
Camille Laporte ◽  
Caroline Bissardon ◽  
Amandine Pitaval ◽  
...  
Keyword(s):  
Three Dimensional ◽  
Biological Tissues ◽  
Vascular Networks ◽  
Network Systems ◽  
Microvascular Network ◽  
Networks On Chip ◽  
On Chip ◽  
Dimensional Cell

The development of vascular networks on-chip is crucial for the long-term culture of three-dimensional cell aggregates such as organoids, spheroids, tumoroids, and tissue explants. Despite the rapid advancement of microvascular network systems and organoid technology, vascularizing organoids-on-chips remains a challenge in tissue engineering. Moreover, most existing microfluidic devices poorly reflect the complexity of in vivo flows and require complex technical settings to operate. Considering these constraints, we developed an innovative platform to establish and monitor the formation of endothelial networks around model spheroids of mesenchymal and endothelial cells as well as blood vessel organoids generated from pluripotent stem cells, cultured for up to 15 days on-chip. Importantly, these networks were functional, demonstrating intravascular perfusion within the spheroids or vascular organoids connected to neighbouring endothelial beds. This microphysiological system thus represents a viable organ-on-chip model to vascularize biological tissues and should allow to establish perfusion into organoids using advanced microfluidics.

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