Microfluidic arrays of dermal spheroids: a screening platform for active ingredients of skincare products

Chen, Zhengkun; Kheiri, Sina; Gevorkian, Albert; Young, Elton T.; Andre, Valérie; Deisenroth, Ted; Kumacheva, Eugenia

doi:10.1039/d1lc00619c

Cited by 16 publications

(33 citation statements)

References 64 publications

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“…The experimental MF device contained 200 MCTSs in the microwells that were organized in four parallel rows ( Figure 4A ). The microwells were connected to a common channel used to supply cell culture medium and drug treatment [for more details on fabrication, MCTS formation, and cell staining protocols see Supplementary Material and ( Chen et al, 2021 ; Prince et al, 2021 )]. The cell suspension occupied 100% of the microwells in the form of cell-laden droplets; MCTSs formed within 72 h of cell culture.…”

Section: Resultsmentioning

confidence: 99%

Computational Modelling and Big Data Analysis of Flow and Drug Transport in Microfluidic Systems: A Spheroid-on-a-Chip Study

Kheiri

Kumacheva

Young

2021

Front. Bioeng. Biotechnol.

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Microfluidic tumour spheroid-on-a-chip platforms enable control of spheroid size and their microenvironment and offer the capability of high-throughput drug screening, but drug supply to spheroids is a complex process that depends on a combination of mechanical, biochemical, and biophysical factors. To account for these coupled effects, many microfluidic device designs and operating conditions must be considered and optimized in a time- and labour-intensive trial-and-error process. Computational modelling facilitates a systematic exploration of a large design parameter space via in silico simulations, but the majority of in silico models apply only a small set of conditions or parametric levels. Novel approaches to computational modelling are needed to explore large parameter spaces and accelerate the optimization of spheroid-on-a-chip and other organ-on-a-chip designs. Here, we report an efficient computational approach for simulating fluid flow and transport of drugs in a high-throughput arrayed cancer spheroid-on-a-chip platform. Our strategy combines four key factors: i) governing physical equations; ii) parametric sweeping; iii) parallel computing; and iv) extensive dataset analysis, thereby enabling a complete “full-factorial” exploration of the design parameter space in combinatorial fashion. The simulations were conducted in a time-efficient manner without requiring massive computational time. As a case study, we simulated >15,000 microfluidic device designs and flow conditions for a representative multicellular spheroids-on-a-chip arrayed device, thus acquiring a single dataset consisting of ∼10 billion datapoints in ∼95 GBs. To validate our computational model, we performed physical experiments in a representative spheroid-on-a-chip device that showed excellent agreement between experimental and simulated data. This study offers a computational strategy to accelerate the optimization of microfluidic device designs and provide insight on the flow and drug transport in spheroid-on-a-chip and other biomicrofluidic platforms.

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Section: Resultsmentioning

confidence: 99%

Computational Modelling and Big Data Analysis of Flow and Drug Transport in Microfluidic Systems: A Spheroid-on-a-Chip Study

Kheiri

Kumacheva

Young

2021

Front. Bioeng. Biotechnol.

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“…Our group has developed various MF strategies for cell encapsulation, which utilized both hydrodynamic junctions , and hydrodynamic traps. − Emulsification using hydrodynamic junctions enables the generation of cell-laden droplets with a high frequency. Furthermore, several MF droplet generators can be combined to work in parallel.…”

Section: Cell Encapsulation In Dropletsmentioning

confidence: 99%

“…On the other hand, the hydrodynamic trap MF device, despite having a lower (approximately 10 Hz) frequency in droplet generation, provides control over the location on each individual cell-laden droplet in the MF device and hence the ability to monitor cells encapsulated in the droplets during their culture. Therefore, the hydrodynamic trap MF device is beneficial for disease modeling and monitoring the response of cells to the supply of active ingredients such as vitamins and drugs. − …”

Section: Cell Encapsulation In Dropletsmentioning

confidence: 99%

“…Over the past decade, our group has developed microgels derived from alginate, agarose, ,, chitosan, and nanocellulose. − Recently, we developed a biomimetic filamentous hydrogel from aldehyde-functionalized cellulose nanocrystals (a-CNCs) chemically cross-linked with gelatin (later in the text, this gel is referred to as EKGel). − The a-CNCs were responsible for the fibrillar hydrogel structure and enabled control of the hydrogel stiffness, and gelatin provided cell-adhesion ligands. The EKGel offers the biocompatibility and the capability to control the chemical and physical hydrogel properties.…”

Section: Transformation Of Droplets To Microgelsmentioning

confidence: 99%

“…Microgels generated by droplet MFs were used for drug delivery and the delivery of vascular endothelial growth factor to ischemic muscle sites . Recently, we developed MF spheroid-on-a-chip platforms for the generation of multicellular spheroids and organoids, which were utilized for coculturing cells, screening active ingredients, and modeling drug delivery to multicellular spheroids. − …”

Section: Introductionmentioning

confidence: 99%

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Trends in Droplet Microfluidics: From Droplet Generation to Biomedical Applications

et al. 2022

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Over the past decade, droplet microfluidics has attracted growing interest in biology, medicine, and engineering. In this feature article, we review the advances in droplet microfluidics, primarily focusing on the research conducted by our group. Starting from the introduction to the mechanisms of microfluidic droplet formation and the strategies for cell encapsulation in droplets, we then focus on droplet transformation into microgels. Furthermore, we review three biomedical applications of droplet microfluidics, that is, 3D cell culture, single-cell analysis, and in vitro organ and disease modeling. We conclude with our perspective on future directions in the development of droplet microfluidics for biomedical applications.

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Integrating spheroid‐on‐a‐chip with tubeless rocker platform: A high‐throughput biological screening platform

Kheiri

Chen

Yakavets

et al. 2023

Biotechnology Journal

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Spheroid‐on‐a‐chip platforms are emerging as promising in vitro models that enable screening of the efficacy of biologically active ingredients. Generally, the supply of liquids to spheroids occurs in the steady flow mode with the use of syringe pumps; however, the utilization of tubing and connections, especially for multiplexing and high‐throughput screening applications, makes spheroid‐on‐a‐chip platforms labor‐ and cost‐intensive. Gravity‐induced flow using rocker platforms overcomes these challenges. Here, a robust gravity‐driven technique was developed to culture arrays of cancer cell spheroids and dermal fibroblast spheroids in a high‐throughput manner using a rocker platform. The efficiency of the developed rocker‐based platform was benchmarked to syringe pumps for generating multicellular spheroids and their use for screening biologically active ingredients. Cell viability, internal spheroid structure as well as the effect of vitamin C on spheroids' protein synthesis was studied. The rocker‐based platform not only offers comparable or enhanced performance in terms of cell viability, spheroids formation, and protein production by dermal fibroblast spheroids but also, from a practical perspective, offers a smaller footprint, requires a lower cost, and offers an easier method for handling. These results support the application of rocker‐based microfluidic spheroid‐on‐a‐chip platforms for in vitro screening in a high‐throughput manner with industrial scaling‐up opportunities.

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Microfluidic arrays of dermal spheroids: a screening platform for active ingredients of skincare products

Abstract: Organotypic micrometre-size 3D aggregates of skin cells (multicellular spheroids) have emerged as a promising in vitro model that can be utilized as an alternative of animal models to test active...

Cited by 16 publications

References 64 publications

Computational Modelling and Big Data Analysis of Flow and Drug Transport in Microfluidic Systems: A Spheroid-on-a-Chip Study

Computational Modelling and Big Data Analysis of Flow and Drug Transport in Microfluidic Systems: A Spheroid-on-a-Chip Study

Trends in Droplet Microfluidics: From Droplet Generation to Biomedical Applications

Integrating spheroid‐on‐a‐chip with tubeless rocker platform: A high‐throughput biological screening platform

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