A concentration gradient generator on a paper-based microfluidic chip coupled with cell culture microarray for high-throughput drug screening

2016 ◽  
Vol 18 (1) ◽  
Author(s):  
Bo Hong ◽  
Peng Xue ◽  
Yafeng Wu ◽  
Jingnan Bao ◽  
Yon Jin Chuah ◽  
...  
Keyword(s):  
Cell Culture ◽  
High Throughput ◽  
Drug Screening ◽  
Microfluidic Chip ◽  
Concentration Gradient ◽  
Gradient Generator ◽  
High Throughput Drug Screening

Methods for advanced hepatocyte cell culture in microwells utilizing air bubbles

Lab on a Chip ◽  
2015 ◽  
Vol 15 (4) ◽  
pp. 1032-1037 ◽  
Author(s):  
Vasiliy N. Goral ◽  
Sam H. Au ◽  
Ronald A. Faris ◽  
Po Ki Yuen
Keyword(s):  
Cell Culture ◽  
High Throughput ◽  
Drug Screening ◽  
Specific Cell ◽  
Air Bubbles ◽  
Cytotoxicity Assays ◽  
High Throughput Drug Screening ◽  
Cellular Microenvironments ◽  
Substantial Control

We present a number of novel and unique methods for advanced cell culture in microwells utilizing air bubbles to provide substantial control over cellular microenvironments and organization in order to achieve specific cell-based applications, and an easy way for high throughput drug screening and cytotoxicity assays.

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.

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

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 A Microfluidic Spheroid Culture Device with a Concentration Gradient Generator for High-Throughput Screening of Drug Efficacy

Molecules ◽  
2018 ◽  
Vol 23 (12) ◽  
pp. 3355 ◽  
Author(s):  
Wanyoung Lim ◽  
Sungsu Park
Keyword(s):  
High Throughput ◽  
Concentration Gradient ◽  
High Throughput Screening ◽  
3D Cell Culture ◽  
Drug Efficacy ◽  
Cancer Drug ◽  
Spheroid Culture ◽  
Gradient Generator ◽  
Micro Channels

Three-dimensional (3D) cell culture is considered more clinically relevant in mimicking the structural and physiological conditions of tumors in vivo compared to two-dimensional cell cultures. In recent years, high-throughput screening (HTS) in 3D cell arrays has been extensively used for drug discovery because of its usability and applicability. Herein, we developed a microfluidic spheroid culture device (μFSCD) with a concentration gradient generator (CGG) that enabled cells to form spheroids and grow in the presence of cancer drug gradients. The device is composed of concave microwells with several serpentine micro-channels which generate a concentration gradient. Once the colon cancer cells (HCT116) formed a single spheroid (approximately 120 μm in diameter) in each microwell, spheroids were perfused in the presence of the cancer drug gradient irinotecan for three days. The number of spheroids, roundness, and cell viability, were inversely proportional to the drug concentration. These results suggest that the μFSCD with a CGG has the potential to become an HTS platform for screening the efficacy of cancer drugs.

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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