Biophysical phenotyping of C. elegans in a microfluidic chip for high-throughput drug screening

2021 ◽  
pp. 261-293
Author(s):  
Samuel Sofela ◽  
Yongxiang Feng ◽  
Navajit S. Baban ◽  
Christopher J. Stubbs ◽  
Yong-Ak Song ◽  
...  
Keyword(s):  
High Throughput ◽  
Drug Screening ◽  
Microfluidic Chip ◽  
C Elegans ◽  
High Throughput Drug Screening

The Developing Status of High-Throughput Drug Screening Microfluidic Chip by FRET on Medicine

2018 ◽  
Vol 914 ◽  
pp. 19-28
Author(s):  
Xin Yu Zhang ◽  
Qiu Hong Huang ◽  
Mei Yang ◽  
Xiao Ling Liao ◽  
Ze Yu Shao ◽  
...  
Keyword(s):  
High Throughput ◽  
Drug Screening ◽  
Microfluidic Chip ◽  
High Throughput Screening ◽  
Functional Integration ◽  
Resonance Energy Transfer ◽  
Resonance Energy ◽  
Cell Detection ◽  
High Throughput Drug Screening ◽  
Efficient Detection

High-throughput drug screening microfluidic chip has good biocompatibility and faveriable functional integration, which is the excellent platform for high-throughput screening. Importantly, FRET (Fluorescence Resonance Energy Transfer) technology is the most efficient detection means at present. In this paper, we introduce the development of drug screening microfluidic chip on cellular level and the application of FRET technology on cell detection. Further, we discusse the possibility of FRET applied in the field of microfluidic biochip.

scholarly journals Detecting and Trapping of a Single C. elegans Worm in a Microfluidic Chip for Automated Microplate Dispensing

2016 ◽  
Vol 22 (4) ◽  
pp. 431-436 ◽  
Author(s):  
Israel T. Desta ◽  
Abdelrazak Al-Sharif ◽  
Nour AlGharibeh ◽  
Nahal Mustafa ◽  
Ajymurat Orozaliev ◽  
...  
Keyword(s):  
Optical Fibers ◽  
High Throughput ◽  
Microfluidic Chip ◽  
Experimental Studies ◽  
Microfluidic System ◽  
C Elegans ◽  
High Throughput Drug Screening ◽  
Pneumatic Valves ◽  
Free Living Nematode ◽  
Control Layer

Microfluidic devices offer new technical possibilities for a precise manipulation of Caenorhabditis elegans due to the comparable length scale. C. elegans is a small, free-living nematode worm that is a popular model system for genetic, genomic, and high-throughput experimental studies of animal development and neurobiology. In this paper, we demonstrate a microfluidic system in polydimethylsiloxane (PDMS) for dispensing of a single C. elegans worm into a 96-well plate. It consists of two PDMS layers, a flow and a control layer. Using five microfluidic pneumatic valves in the control layer, a single worm is trapped upon optical detection with a pair of optical fibers integrated perpendicular to the constriction channel and then dispensed into a microplate well with a dispensing tip attached to a robotic handling system. Due to its simple design and facile fabrication, we expect that our microfluidic chip can be expanded to a multiplexed dispensation system of C. elegans worms for high-throughput drug screening.

High-Throughput Drug Screening of FDA-Approved Cancer Drugs Reveals Novel Therapies for Patients with Chordomas

2019 ◽  
Author(s):  
Philip Tatman ◽  
Anthony Fringuello ◽  
Denise Damek ◽  
Samy Youssef ◽  
Randy Jensn ◽  
...  
Keyword(s):  
High Throughput ◽  
Drug Screening ◽  
Novel Therapies ◽  
Cancer Drugs ◽  
High Throughput Drug Screening

High-Throughput Drug Screening of ECM Deposition Inhibitors for Antifibrotic Drug Discovery

2019 ◽  
Author(s):  
Michael Gerckens ◽  
Hani Alsafadi ◽  
Darcy Wagner ◽  
Katharina Heinzelmann ◽  
Kenji Schorpp ◽  
...  
Keyword(s):  
Drug Discovery ◽  
High Throughput ◽  
Drug Screening ◽  
High Throughput Drug Screening

Therapeutic stratification of acute leukemia using high throughput drug screening

2020 ◽  
Author(s):  
S Bhatia ◽  
H Ahlert ◽  
N Dienstbier ◽  
J Schliehe-Diecks ◽  
M Sönnichsen ◽  
...  
Keyword(s):  
Acute Leukemia ◽  
High Throughput ◽  
Drug Screening ◽  
High Throughput Drug Screening

scholarly journals High-throughput drug screening identifies the ATR-CHK1 pathway as a therapeutic vulnerability of CALR mutated hematopoietic cells

2021 ◽  
Vol 11 (7) ◽  
Author(s):  
Ruochen Jia ◽  
Leon Kutzner ◽  
Anna Koren ◽  
Kathrin Runggatscher ◽  
Peter Májek ◽  
...  
Keyword(s):  
High Throughput ◽  
Drug Screening ◽  
Synthetic Lethality ◽  
Myeloproliferative Neoplasms ◽  
Hematopoietic Cells ◽  
Replication Stress ◽  
Phase Cell ◽  
Nuclear Staining ◽  
Wild Type ◽  
High Throughput Drug Screening

AbstractMutations of calreticulin (CALR) are the second most prevalent driver mutations in essential thrombocythemia and primary myelofibrosis. To identify potential targeted therapies for CALR mutated myeloproliferative neoplasms, we searched for small molecules that selectively inhibit the growth of CALR mutated cells using high-throughput drug screening. We investigated 89 172 compounds using isogenic cell lines carrying CALR mutations and identified synthetic lethality with compounds targeting the ATR-CHK1 pathway. The selective inhibitory effect of these compounds was validated in a co-culture assay of CALR mutated and wild-type cells. Of the tested compounds, CHK1 inhibitors potently depleted CALR mutated cells, allowing wild-type cell dominance in the co-culture over time. Neither CALR deficient cells nor JAK2V617F mutated cells showed hypersensitivity to ATR-CHK1 inhibition, thus suggesting specificity for the oncogenic activation by the mutant CALR. CHK1 inhibitors induced replication stress in CALR mutated cells revealed by elevated pan-nuclear staining for γH2AX and hyperphosphorylation of RPA2. This was accompanied by S-phase cell cycle arrest due to incomplete DNA replication. Transcriptomic and phosphoproteomic analyses revealed a replication stress signature caused by oncogenic CALR, suggesting an intrinsic vulnerability to CHK1 perturbation. This study reveals the ATR-CHK1 pathway as a potential therapeutic target in CALR mutated hematopoietic cells.

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