scholarly journals High-throughput organ-on-chip platform with integrated programmable fluid flow and real-time sensing for complex tissue models in drug development workflows

Lab on a Chip ◽  
2021 ◽  
Vol 21 (8) ◽  
pp. 1454-1474
Author(s):  
H. Azizgolshani ◽  
J. R. Coppeta ◽  
E. M. Vedula ◽  
E. E. Marr ◽  
B. P. Cain ◽  
...  
Keyword(s):  
Fluid Flow ◽  
Drug Development ◽  
Real Time ◽  
High Throughput ◽  
Microfluidic Devices ◽  
On Chip ◽  
Tissue Models

96 microfluidic devices with independent electrical readouts are coupled with 192 micropumps to make a high-throughput organ-on-chip platform.

Vision-Based Real-Time Microflow-Rate Control System for Cell Analysis

2016 ◽  
Vol 28 (6) ◽  
pp. 854-861 ◽  
Author(s):  
Tadayoshi Aoyama ◽  
◽  
Amalka De Zoysa ◽  
Qingyi Gu ◽  
Takeshi Takaki ◽  
...  
Keyword(s):  
Fluid Flow ◽  
Control System ◽  
Real Time ◽  
Flow Rate ◽  
Rate Control ◽  
Microfluidic Devices ◽  
Cell Analysis ◽  
Time Flow ◽  
On Chip ◽  
Flow Rate Control

[abstFig src='/00280006/09.jpg' width='300' text='Snapshots of particle sorting experiment using our system' ] On-chip cell analysis is an important issue for microtechnology research, and microfluidic devices are frequently used in on-chip cell analysis systems. One approach to controlling the fluid flow in microfluidic devices for cell analysis is to use a suitable pumps. However, it is difficult to control the actual flow-rate in a microfluidic device because of the difficulty in placing flow-rate sensors in the device. In this study, we developed a real-time flow-rate control system that uses syringe pumps and high-speed vision to measure the actual fluid flow in microfluidic devices. The developed flow-rate control system was verified through experiments on microparticle velocity control and microparticle sorting.

scholarly journals O23: CHARACTERISING PATIENT-DERIVED COLORECTAL CANCER TISSUE-ORIGINATED ORGANOIDAL SPHEROIDS FOR HIGH-THROUGHPUT MICROFLUIDIC APPLICATIONS

2021 ◽  
Vol 108 (Supplement_1) ◽  
Author(s):  
MI Khot ◽  
M Levenstein ◽  
R Coppo ◽  
J Kondo ◽  
M Inoue ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Fluid Flow ◽  
High Throughput ◽  
Microfluidic Devices ◽  
In Vitro Models ◽  
Fluorescent Imaging ◽  
Cancer Tissue ◽  
Cell Models

Abstract Introduction Three-dimensional (3D) cell models have gained reputation as better representations of in vivo cancers as compared to monolayered cultures. Recently, patient tumour tissue-derived organoids have advanced the scope of complex in vitro models, by allowing patient-specific tumour cultures to be generated for developing new medicines and patient-tailored treatments. Integrating 3D cell and organoid culturing into microfluidics, can streamline traditional protocols and allow complex and precise high-throughput experiments to be performed with ease. Method Patient-derived colorectal cancer tissue-originated organoidal spheroids (CTOS) cultures were acquired from Kyoto University, Japan. CTOS were cultured in Matrigel and stem-cell media. CTOS were treated with 5-fluorouracil and cytotoxicity evaluated via fluorescent imaging and ATP assay. CTOS were embedded, sectioned and subjected to H&E staining and immunofluorescence for ABCG2 and Ki67 proteins. HT29 colorectal cancer spheroids were produced on microfluidic devices using cell suspensions and subjected to 5-fluorouracil treatment via fluid flow. Cytotoxicity was evaluated through fluorescent imaging and LDH assay. Result 5-fluorouracil dose-dependent reduction in cell viability was observed in CTOS cultures (p<0.01). Colorectal CTOS cultures retained the histology, tissue architecture and protein expression of the colonic epithelial structure. Uniform 3D HT29 spheroids were generated in the microfluidic devices. 5-fluorouracil treatment of spheroids and cytotoxic analysis was achieved conveniently through fluid flow. Conclusion Patient-derived CTOS are better complex models of in vivo cancers than 3D cell models and can improve the clinical translation of novel treatments. Microfluidics can streamline high-throughput screening and reduce the practical difficulties of conventional organoid and 3D cell culturing. Take-home message Organoids are the most advanced in vitro models of clinical cancers. Microfluidics can streamline and improve traditional laboratory experiments.

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.

Investigation of Automated Cell Manipulation in Optical Tweezers-Assisted Microfluidic Chamber Using Simulations

2011 ◽  
Author(s):  
Sagar Chowdhury ◽  
Petr Svec ◽  
Chenlu Wang ◽  
Kevin T. Seale ◽  
John P. Wikswo ◽  
...  
Keyword(s):  
Fluid Flow ◽  
Optical Tweezers ◽  
High Precision ◽  
High Throughput ◽  
Microfluidic Devices ◽  
Cell Manipulation ◽  
Precise Control ◽  
Biological Objects ◽  
Microfluidic Chamber ◽  
Manipulation Process

Microfluidic devices are well suited for the study of biological objects because of their indirect nature of manipulation and high throughput. However, the cell manipulation process solely depends on the fluid flow and hence precise control is difficult to attain inside a microfluidic chamber. Utilizing optical tweezers as a complementary tool provides precise manipulation control. We have presented an automated cell manipulation approach using optical tweezers operating inside a microfluidic chamber. To test and demonstrate the effectiveness of the approach we have developed a physics-based simulator that is completely automated and allows high precision of manipulation.

scholarly journals A high-throughput microfluidic bilayer co-culture platform to study endothelial-pericyte interactions

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Miles T. Rogers ◽  
Ashley L. Gard ◽  
Robert Gaibler ◽  
Thomas J. Mulhern ◽  
Rivka Strelnikov ◽  
...  
Keyword(s):  
High Throughput ◽  
Fluid Shear Stress ◽  
Cell Types ◽  
Fluid Shear ◽  
Multiple Cell ◽  
Cell Type Specific ◽  
On Chip ◽  
Tissue Models ◽  
Macromolecular Permeability

AbstractMicrophysiological organ-on-chip models offer the potential to improve the prediction of drug safety and efficacy through recapitulation of human physiological responses. The importance of including multiple cell types within tissue models has been well documented. However, the study of cell interactions in vitro can be limited by complexity of the tissue model and throughput of current culture systems. Here, we describe the development of a co-culture microvascular model and relevant assays in a high-throughput thermoplastic organ-on-chip platform, PREDICT96. The system consists of 96 arrayed bilayer microfluidic devices containing retinal microvascular endothelial cells and pericytes cultured on opposing sides of a microporous membrane. Compatibility of the PREDICT96 platform with a variety of quantifiable and scalable assays, including macromolecular permeability, image-based screening, Luminex, and qPCR, is demonstrated. In addition, the bilayer design of the devices allows for channel- or cell type-specific readouts, such as cytokine profiles and gene expression. The microvascular model was responsive to perturbations including barrier disruption, inflammatory stimulation, and fluid shear stress, and our results corroborated the improved robustness of co-culture over endothelial mono-cultures. We anticipate the PREDICT96 platform and adapted assays will be suitable for other complex tissues, including applications to disease models and drug discovery.

scholarly journals An Open-Source, Programmable Pneumatic Setup for Operation and Automated Control of Single- and Multi-Layer Microfluidic Devices

2017 ◽  
Author(s):  
Kara Brower ◽  
Robert Puccinelli ◽  
Craig J. Markin ◽  
Tyler C. Shimko ◽  
Scott A. Longwell ◽  
...  
Keyword(s):  
Open Source ◽  
High Throughput ◽  
Modular Design ◽  
Microfluidic Devices ◽  
Automated Control ◽  
Fluid Physics ◽  
Biochemical Measurements ◽  
On Chip ◽  
The Cost ◽  
Valve Actuation

AbstractMicrofluidic technologies have been used across diverse disciplines (e.g. high-throughput biological measurement, fluid physics, laboratory fluid manipulation) but widespread adoption has been limited due to the lack of openly disseminated resources that enable non-specialist labs to make and operate their own devices. Here, we report the open-source build of a pneumatic setup capable of operating both single and multilayer (Quake-style) microfluidic devices with programmable scripting automation. This setup can operate both simple and complex devices with 48 device valve control inputs and 18 sample inputs, with modular design for easy expansion, at a fraction of the cost of similar commercial solutions. We present a detailed step-by-step guide to building the pneumatic instrumentation, as well as instructions for custom device operation using our software, Geppetto, through an easy-to-use GUI for live on-chip valve actuation and a scripting system for experiment automation. We show robust valve actuation with near real-time software feedback and demonstrate use of the setup for high-throughput biochemical measurements on-chip. This open-source setup will enable specialists and novices alike to run microfluidic devices easily in their own laboratories. Specifications table

scholarly journals A Multi-Omics Human Liver Organoid Screening Platform for DILI Risk Prediction

2021 ◽  
Author(s):  
Charles J. Zhang ◽  
Matthew J. O’Meara ◽  
Sophia R. Meyer ◽  
Sha Huang ◽  
Meghan M. Capeling ◽  
...  
Keyword(s):  
Drug Development ◽  
Risk Prediction ◽  
High Throughput ◽  
High Throughput Screening ◽  
Human Liver ◽  
Drug Induced ◽  
Predictive Capacity ◽  
On Chip

AbstractBackground and AimsDrug-induced liver injury (DILI) is a prominent failure mode in drug development resulting in clinical trial failures and post-approval withdrawal. Improved in vitro models for DILI risk prediction that can model diverse genetics are needed to improve safety and reduce high attrition rates in drug development. In this study, we evaluated the utility of human liver organoids (HLOs) for high-throughput DILI risk prediction and in an organ-on-chip system. The recent clinical failure of inarigivir soproxil due to DILI underscores the need for improved models.MethodsHLOs were adapted for high-throughput drug screening in dispersed-cell 384-well format and a collection of DILI-associated drugs were screened. HLOs were also adapted to a liver-chip system to investigate enhanced in vivo-like function. Both platforms were benchmarked for their ability to predict DILI using combined biochemical assays, microscopy-based morphological profiling, and transcriptomics.ResultsDispersed HLOs retained DILI predictive capacity of intact HLOs and are amenable to high-throughput screening allowing for measurable IC50 values for cytotoxicity. Distinct morphological differences were observed in cells treated with drugs exerting differing mechanisms of action. HLOs on chips were shown to increase albumin production, CYP450 expression and also release ALT/AST when treated with known DILI drugs. Importantly, HLO liver chips were able to predict hepatotoxicity of tenofovir-inarigivir and showed steatosis and mitochondrial perturbation via phenotypic and transcriptomic analysis.ConclusionsThe high throughput and liver-on-chip system exhibit enhanced in vivo-like function and demonstrate the utility of the platforms in early and late-stage drug development. Tenofovir-inarigivr associated hepatotoxicity was observed and highly correlates with the clinical manifestation of DILI.

Review of Microfluidic Devices for On-Chip Chemical Sensing

2016 ◽  
Vol 136 (6) ◽  
pp. 244-249
Author(s):  
Takahiro Watanabe ◽  
Fumihiro Sassa ◽  
Yoshitaka Yoshizumi ◽  
Hiroaki Suzuki
Keyword(s):  
Chemical Sensing ◽  
Microfluidic Devices ◽  
On Chip
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