Design of organ-on-a-chip to improve cell capture efficiency

Yang, Qingzhen; Ju, Dapeng; Liu, Yan; Lv, Xuemeng; Xiao, Zhanfeng; Bin, Gao; Song, Fenhong; Feng, Xiuli

doi:10.1016/j.ijmecsci.2021.106705

Cited by 18 publications

(10 citation statements)

References 46 publications

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“…Seeding cells on the micro uidic chip is a key step in organ-on-a-chip (25). The simplest way is to use a pipette to drip cell suspension into microstructures for cell culture, but it is time-consuming and ine cient, impeding high-throughput cell seeding (24)(25).…”

Section: Discussionmentioning

confidence: 99%

Liver-On-A-Chip Model: an Alternative to Animal Models-Development Challenges and Future Perspectives

Gulla

Leber

Butkutė³

et al. 2023

Preprint

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Purpose: To create a fast, affordable, reproducible a liver-on-a chip platform as an alternative to animal models of liver diseases. Methods: The platform was fabricated out of fused silica by using femtosecond laser microprocessing. A channel with integrated filters of micropillars was produced by Selective Laser Etching (SLE) technique. Nano gratings were inscribed inside the glass by using focused femtosecond laser radiation. Subsequently, liver cells were etched in 35% Potassium Hydroxide (KOH) at 90 ° C or Hydrofluoric acid. The contact between both plates was achieved by intense light radiation with an integrated filter. There were 700 fs duration pulses used for SLE and 200 fs for laser welding. The light was focused with a 20 x 0.45 NA objective for SLE and a 0.5 NA aspherical lens for laser welding. The human liver HCC cell line HepG2(GS) was employed for biocompatibility testing. Results: The platform consists of one channel divided into three sub channels by micropillars: the central channel for cells and two side channels for cell medium. All channels have inlet and outlet reservoirs with the depth up to 200 μm, and width of central and side channels up to 200 and 400 μm, respectively. Additionally, the final size of micropillars was 55 x 36 μm with a gap of 14 μm in between. Conclusion: Based on our previously published work, this study provides a step-by-step design and validates the concept of testing human liver cancer cells. In addition, it provides developmental advancements and drawbacks of liver-on-a-chip designs.

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Section: Discussionmentioning

confidence: 99%

Liver-On-A-Chip Model: an Alternative to Animal Models-Development Challenges and Future Perspectives

Gulla

Leber

Butkutė³

et al. 2023

Preprint

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“…Compared to techniques in which the cells are cultivated statically on a polymer membrane, such as Transwell ® inserts, seeding the cells in a sealed microfluidic chip requires more sophisticated procedures [ 13 , 14 , 15 , 16 ]. During such procedures, a high fraction of cells is lost in the peripheral setup, and due to the typical parabolic flow velocity profile, an inhomogeneous distribution of cells occurs.…”

Section: Introductionmentioning

confidence: 99%

Tissue Barrier-on-Chip: A Technology for Reproducible Practice in Drug Testing

et al. 2022

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One key application of organ-on-chip systems is the examination of drug transport and absorption through native cell barriers such the blood–brain barrier. To overcome previous hurdles related to the transferability of existing static cell cultivation protocols and polydimethylsiloxane (PDMS) as the construction material, a chip platform with key innovations for practical use in drug-permeation testing is presented. First, the design allows for the transfer of barrier-forming tissue into the microfluidic system after cells have been seeded on porous polymer or Si3N4 membranes. From this, we can follow highly reproducible models and cultivation protocols established for static drug testing, from coating the membrane to seeding the cells and cell analysis. Second, the perfusion system is a microscopable glass chip with two fluid compartments with transparent embedded electrodes separated by the membrane. The reversible closure in a clamping adapter requires only a very thin PDMS sealing with negligible liquid contact, thereby eliminating well-known disadvantages of PDMS, such as its limited usability in the quantitative measurements of hydrophobic drug molecule concentrations. Equipped with tissue transfer capabilities, perfusion chamber inertness and air bubble trapping, and supplemented with automated fluid control, the presented system is a promising platform for studying established in vitro models of tissue barriers under reproducible microfluidic perfusion conditions.

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“…The advantages of hydrodynamic processing are the ease to implement the inertial focusing of enhanced cell separation and sorting with narrowed sheathed flows. As a disadvantage, the hydrodynamic single cell platform may produce stress on cell samples, and is reported to alter molecular mechanisms, and inhomogeneity issues [ 13 , 14 , 15 , 16 ]. The geometric design of hydrodynamic single cell trapping belongs to the category of “wet fluid-structure interaction (FSI)”; a standard approach is the topology optimization through gradient-based methods [ 17 , 18 ].…”

Section: Introductionmentioning

confidence: 99%

Single Red Blood Cell Hydrodynamic Traps via the Generative Design

et al. 2022

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This paper describes a generative design methodology for a micro hydrodynamic single-RBC (red blood cell) trap for applications in microfluidics-based single-cell analysis. One key challenge in single-cell microfluidic traps is to achieve desired through-slit flowrates to trap cells under implicit constraints. In this work, the cell-trapping design with validation from experimental data has been developed by the generative design methodology with an evolutionary algorithm. L-shaped trapping slits have been generated iteratively for the optimal geometries to trap living-cells suspended in flow channels. Without using the generative design, the slits have low flow velocities incapable of trapping single cells. After a search with 30,000 solutions, the optimized geometry was found to increase the through-slit velocities by 49%. Fabricated and experimentally tested prototypes have achieved 4 out of 4 trapping efficiency of RBCs. This evolutionary algorithm and trapping design can be applied to cells of various sizes.

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Design of organ-on-a-chip to improve cell capture efficiency

Cited by 18 publications

References 46 publications

Liver-On-A-Chip Model: an Alternative to Animal Models-Development Challenges and Future Perspectives

Liver-On-A-Chip Model: an Alternative to Animal Models-Development Challenges and Future Perspectives

Tissue Barrier-on-Chip: A Technology for Reproducible Practice in Drug Testing

Single Red Blood Cell Hydrodynamic Traps via the Generative Design

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