scholarly journals High-throughput screening of large volumes of whole blood using structured illumination and fluorescent on-chip imaging

Lab on a Chip ◽  
2012 ◽  
Vol 12 (23) ◽  
pp. 4968 ◽  
Author(s):  
Serap Altay Arpali ◽  
Caglar Arpali ◽  
Ahmet F. Coskun ◽  
Hsin-Hao Chiang ◽  
Aydogan Ozcan
Keyword(s):  
High Throughput ◽  
Whole Blood ◽  
High Throughput Screening ◽  
Structured Illumination ◽  
On Chip

High-throughput screening of blood samples based on structured illumination on-chip imaging

CLEO: 2013 ◽  
2013 ◽  
Author(s):  
Serap Altay Arpali ◽  
Caglar Arpali ◽  
Ahmet F. Coskun ◽  
Hsin-Hao Chiang ◽  
Aydogan Ozcan
Keyword(s):  
High Throughput ◽  
High Throughput Screening ◽  
Structured Illumination ◽  
Blood Samples ◽  
On Chip

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 High-throughput screening of biomolecules using cell-free gene expression systems

2018 ◽  
Vol 3 (1) ◽  
Author(s):  
Luis E Contreras-Llano ◽  
Cheemeng Tan
Keyword(s):  
High Throughput ◽  
High Throughput Screening ◽  
Screening Method ◽  
Screening Methods ◽  
Free Gene ◽  
On Chip ◽  
Translation Systems ◽  
Selection Of

Abstract The incorporation of cell-free transcription and translation systems into high-throughput screening applications enables the in situ and on-demand expression of peptides and proteins. Coupled with modern microfluidic technology, the cell-free methods allow the screening, directed evolution and selection of desired biomolecules in minimal volumes within a short timescale. Cell-free high-throughput screening applications are classified broadly into in vitro display and on-chip technologies. In this review, we outline the development of cell-free high-throughput screening methods. We further discuss operating principles and representative applications of each screening method. The cell-free high-throughput screening methods may be advanced by the future development of new cell-free systems, miniaturization approaches, and automation technologies.

scholarly journals High-throughput and clogging-free microfluidic filtration platform for on-chip cell separation from undiluted whole blood

2016 ◽  
Vol 10 (1) ◽  
pp. 014118 ◽  
Author(s):  
Yinuo Cheng ◽  
Xiongying Ye ◽  
Zengshuai Ma ◽  
Shuai Xie ◽  
Wenhui Wang
Keyword(s):  
High Throughput ◽  
Whole Blood ◽  
Cell Separation ◽  
On Chip

scholarly journals High-Throughput Screening of Encapsulated Islets Using Wide-Field Lens-Free On-Chip Imaging

ACS Photonics ◽  
2018 ◽  
Vol 5 (6) ◽  
pp. 2081-2086 ◽  
Author(s):  
Yibo Zhang ◽  
Michael Alexander ◽  
Sam Yang ◽  
Yinxu Bian ◽  
Elliot Botvinick ◽  
...  
Keyword(s):  
High Throughput ◽  
High Throughput Screening ◽  
Wide Field ◽  
On Chip

scholarly journals Microfluidic Technologies for High Throughput Screening Through Sorting and On-Chip Culture of C. elegans

Molecules ◽  
2019 ◽  
Vol 24 (23) ◽  
pp. 4292 ◽  
Author(s):  
Daniel Midkiff ◽  
Adriana San-Miguel
Keyword(s):  
High Throughput ◽  
High Throughput Screening ◽  
Model Organism ◽  
Large Data ◽  
Large Data Sets ◽  
Data Sets ◽  
C Elegans ◽  
Drug Candidates ◽  
On Chip ◽  
And Behavior

The nematode Caenorhabditis elegans is a powerful model organism that has been widely used to study molecular biology, cell development, neurobiology, and aging. Despite their use for the past several decades, the conventional techniques for growth, imaging, and behavioral analysis of C. elegans can be cumbersome, and acquiring large data sets in a high-throughput manner can be challenging. Developments in microfluidic “lab-on-a-chip” technologies have improved studies of C. elegans by increasing experimental control and throughput. Microfluidic features such as on-chip control layers, immobilization channels, and chamber arrays have been incorporated to develop increasingly complex platforms that make experimental techniques more powerful. Genetic and chemical screens are performed on C. elegans to determine gene function and phenotypic outcomes of perturbations, to test the effect that chemicals have on health and behavior, and to find drug candidates. In this review, we will discuss microfluidic technologies that have been used to increase the throughput of genetic and chemical screens in C. elegans. We will discuss screens for neurobiology, aging, development, behavior, and many other biological processes. We will also discuss robotic technologies that assist in microfluidic screens, as well as alternate platforms that perform functions similar to microfluidics.

scholarly journals High-Throughput Screening Assay for Sphingosine Kinase Inhibitors in Whole Blood Using RapidFire® Mass Spectrometry

2011 ◽  
Vol 16 (2) ◽  
pp. 272-277 ◽  
Author(s):  
Maureen K. Highkin ◽  
Matthew P. Yates ◽  
Olga V. Nemirovskiy ◽  
William A. Lamarr ◽  
Grace E. Munie ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
High Throughput ◽  
Whole Blood ◽  
High Throughput Screening ◽  
Kinase Inhibitors ◽  
Screening Assay ◽  
High Throughput Screening Assay ◽  
Mass Spectrometry Technology ◽  
Sphingosine 1 Phosphate ◽  
Mass Spectrometry System

To facilitate discovery of compounds modulating sphingosine-1-phosphate (S1P) signaling, the authors used high-throughput mass spectrometry technology to measure S1P formation in human whole blood. Since blood contains endogenous sphingosine (SPH) and S1P, mass spectrometry was chosen to detect the conversion of an exogenously added 17-carbon-long variant of sphingosine, C17SPH, into C17S1P. The authors developed procedures to achieve homogeneous mixing of whole blood in 384-well plates and for a method requiring minimal manipulations to extract S1P from blood in 96- and 384-well plates prior to analyses using the RapidFire® mass spectrometry system.

scholarly journals Vectorchip: Microfluidic platform for highly parallel bite by bite profiling of mosquito-borne pathogen transmission

2020 ◽  
Author(s):  
Shailabh Kumar ◽  
Felix J. H. Hol ◽  
Sujit Pujhari ◽  
Clayton Ellington ◽  
Haripriya Vaidehi Narayanan ◽  
...  
Keyword(s):  
High Throughput ◽  
High Throughput Screening ◽  
Mosquito Species ◽  
Simultaneous Detection ◽  
Pathogen Transmission ◽  
Membrane Thickness ◽  
Human Pathogens ◽  
Microfluidic Platform ◽  
Mechanical Filter ◽  
On Chip

AbstractMosquito bites transmit a number of human pathogens resulting in potentially fatal diseases including malaria, dengue, chikungunya, West Nile encephalitis, and Zika. Although female mosquitoes transmit pathogens via salivary droplets deposited during blood feeding on a host, very little is known about the genomic content of these nanoliter scale droplets, including the transmission dynamics of live pathogens. Here we introduce Vectorchip, a low-cost, scalable microfluidic platform for molecular interrogation of individual mosquito bites in a high-throughput fashion. An ultra-thin PDMS membrane coupled to a microfluidic chip acts as a biting interface, through which freely-behaving mosquitoes deposit saliva droplets by biting into isolated arrayed micro-wells enabling molecular interrogation of individual bites. By modulating membrane thickness, the device enables on-chip comparison of biting capacity and provides a mechanical filter allowing selection of a specific mosquito species. Utilizing Vectorchip, we show on-chip simultaneous detection of mosquito DNA as well as viral RNA from Zika infected Aedes aegypti mosquitoes – demonstrating multiplexed high-throughput screening of vectors and pathogens. Focus-forming assays performed on-chip quantify number of infectious viral particles transmitted during mosquito bites, enabling assessment of active virus transmission. The platform presents a promising approach for single-bite-resolution laboratory and field characterization of vector pathogen communities, to reveal the intricate dynamics of pathogen transmission, and could serve as powerful early warning artificial “sentinel” for mosquito-borne diseases.

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.

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