Integrated ImageXpress Micro Confocal High Content Screening System
Integrated ImageXpress Micro Confocal High Content Screening System
批准号:
10175498
负责人:
Joshua A. Bauer
金额:
$79.9万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2021
资助国家:
美国
项目状态:
已结题
起止时间:
2021-06-15 至 2022-05-31
关键词:
3-DimensionalAcademiaAutomationBiochemicalBiological AssayBiologyBiomedical ResearchCell LineCellsChemicalsClinicalComplexDevicesDiseaseDisease modelDrug CombinationsDrug ScreeningDrug toxicityEquipmentFluorescenceFunctional disorderGuide RNAImageIncubatorsIndustryInstitutesIntentionLibrariesMeasuresMethodsMicroscopeMissionMolecularOpen Reading FramesOrganoidsPatientsPhenotypePreclinical TestingRNA InterferenceResistanceRobotRoboticsRouteScientific Advances and AccomplishmentsServicesSmall Interfering RNASpeedSystemTechnologyTherapeuticTissuesVendorVirus Replicationarmbasecellular imagingclinically relevantconfocal imagingdesigndrug candidatedrug discoverydrug mechanismfunctional genomicshigh throughput screeninghuman diseaseimaging capabilitiesimaging systemin vitro Modelinduced pluripotent stem cellinnovative technologiesinstrumentinstrumentationmeetingsnovel therapeuticsresponsescreeningsmall moleculestem cellstherapeutic developmentthree dimensional structurethree-dimensional modeling
中文摘要
项目总结
英文摘要
PROJECT SUMMARY
In the last 20 years, both academia and industry have significantly shifted from target-based drug discovery to
phenotypic screening. An unmet need in the biomedical research enterprise has long been human disease
models with reliable translational content that can be used to screen small molecule or RNAi/gRNA/ORF libraries
for desirable phenotype changes. Recent advances in culturing organoids or 3D tissue derived from patient or
progenitor cells provide opportunities for meeting this challenge. It is widely accepted that drug discovery using
such in vitro models represents an accelerated route to pre-clinical testing of drug candidates because organoids
and 3D structures more closely resemble the complex physiopathology of diseased tissue than cultured cell lines
or biochemical assays. An ongoing challenge in the field is the upgrading of instrumentation, technology, and
methods to visualize and measure components and features (phenotypes) in responses to molecular treatment
within these 3D models.
The Vanderbilt Institute of Chemical Biology and Vanderbilt High-throughput Screening (VHTS) facility is a well-
established academic drug discovery center that uses innovative technologies to advance scientific and clinical
therapeutic discoveries. Currently, the VHTS facility has an automated fluorescence-based microscope for high-
content imaging (HCI) and phenotypic screening that is integrated with a robot arm and incubator, which allow
for automated live and fixed cell imaging in micro-titer plates. Studies that have utilized this system include iPSC-
derived cell screens, functional genomics screens (siRNA, ORF), mechanisms of viral replication, drug toxicity
studies, drug screens for novel therapeutic development, drug mechanisms of action and resistance, and drug
combination studies. However, due to the lack of confocal imaging capability, this system is severely inadequate
for imaging and measuring features within organoids and 3D structures. In addition, the current vendor no longer
supports service of the robot arm and incubator. Therefore, it is critical to acquire a new automated HCI system,
complete with robotic equipment, in order to enable state-of-the-art high-throughput phenotypic screening
approaches to disease biology and drug discovery using organoids and 3D structures. The proposed HCI drug
discovery system will center on a Molecular Devices (MD) ImageXpress Micro Confocal HCI system, with
integration of a Precise Automation PreciseFlex PF400 robot arm and Liconic automated incubator. This
combination of instruments will allow for high-throughput phenotypic screening at every desired level and
capacity. We note that MD has committed to designing the most robust automated microscope instrument with
the intention of implementing optimization for both speed and accuracy specifically for HCI of 3D structures and
organoids. The proposed system would add significant value to the already established Vanderbilt clientele, as
well as, to the mission of VICB and VHTS facility in drug discovery using disease models with strong potential to
identify therapeutic strategies with clinical relevance.
期刊论文(1)
专著(0)
科研奖励(0)
会议论文
DOI:
10.1021/acscentsci.1c01058
发表时间:
2022-03-23
期刊:
ACS central science
影响因子:
18.2
作者:
[Fricke N, Raghunathan K, Tiwari A, Stefanski KM, Balakrishnan M, Waterson AG, Capone R, Huang H, Sanders CR, Bauer JA, Kenworthy AK]
通讯作者:
Kenworthy AK
Automated Compound Storage and Retrieval System
-
批准号:10415712
-
项目类别:
-
资助金额:$74.14万
-
财政年份:2022
-
负责人:Joshua A. Bauer
-
依托单位:
Cancer Pharmacologist and HTS Scientist
-
批准号:9220043
-
项目类别:
-
资助金额:$11.58万
-
财政年份:2016
-
负责人:Joshua A. Bauer
-
依托单位:
Cancer Pharmacologist and HTS Scientist
-
批准号:10491133
-
项目类别:
-
资助金额:$21.9万
-
财政年份:2016
-
负责人:Joshua A. Bauer
-
依托单位:
Cancer Pharmacologist and HTS Scientist
-
批准号:9353738
-
项目类别:
-
资助金额:$11.58万
-
财政年份:2016
-
负责人:Joshua A. Bauer
-
依托单位:
Cancer Pharmacologist and HTS Scientist
-
批准号:9766086
-
项目类别:
-
资助金额:$11.58万
-
财政年份:2016
-
负责人:Joshua A. Bauer
-
依托单位:
Cancer Pharmacologist and HTS Scientist
-
批准号:10693286
-
项目类别:
-
资助金额:$21.9万
-
财政年份:2016
-
负责人:Joshua A. Bauer
-
依托单位:
Cancer Pharmacologist and HTS Scientist
-
批准号:10320283
-
项目类别:
-
资助金额:$21.9万
-
财政年份:2016
-
负责人:Joshua A. Bauer
-
依托单位:
Identification of druggable targets for triple-negative breast cancer
-
批准号:7615211
-
项目类别:
-
资助金额:$5.01万
-
财政年份:2009
-
负责人:Joshua A. Bauer
-
依托单位:
海外基金