Development and validation of nanoparticle-mediated microfluidic profiling approach for rare cell analysis
用于稀有细胞分析的纳米颗粒介导的微流体分析方法的开发和验证
基本信息
- 批准号:9232705
- 负责人:
- 金额:$ 25.9万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2017
- 资助国家:美国
- 起止时间:2017-03-15 至 2020-02-28
- 项目状态:已结题
- 来源:
- 关键词:Alpha CellAntibodiesAutomationBenignBiochemicalBiological AssayBiological ModelsBlood CirculationBlood VolumeBlood specimenBreast Cancer PatientCancer CenterCancer DiagnosticsCancer PatientCell Adhesion MoleculesCell CountCell FractionCell SeparationCellsClinicalClinical ResearchCollaborationsCompanionsDetectionDevelopmentDevice or Instrument DevelopmentDevicesDiagnosisDiagnosticDiagnostic ProcedureDiseaseDisease ProgressionEngineeringEpithelialEpithelial CellsExhibitsGeneticGoalsHealth SciencesHeterogeneityHospitalsIndividualLeukocytesLondonMagnetic nanoparticlesMalignant neoplasm of prostateMediatingMembrane ProteinsMesenchymalMethodsMicrofluidic MicrochipsMicrofluidicsMolecularMolecular AnalysisMolecular GeneticsMolecular ProfilingMonitorNeoplasm Circulating CellsNeoplasm MetastasisPatientsPerformancePhenotypePopulationPrimary NeoplasmProcessProductionProteinsReportingResearchResearch PersonnelSamplingSensitivity and SpecificitySpecificityStagingStructureSurfaceSystemTechnologyTestingTimeUniversitiesValidationWhole BloodWorkassay developmentbasecancer cellcancer subtypescirculating cancer cellclinical decision-makingcommercializationeffective therapyepithelial to mesenchymal transitiongenetic analysisgenetic informationmagnetic fieldmalignant breast neoplasmmanufacturing scale-upmedical specialtiesmultidisciplinarynanoparticlenew technologynovel diagnosticsprototyperesearch clinical testingresponsetooltumortumor progressionuser-friendly
项目摘要
Project Summary:
Circulating tumour cells (CTC) are shed into the vasculature from primary tumours, and have been shown to
contribute to the formation of metastatic lesions in model systems. Monitoring these circulating cells therefore
presents, in principle, a means to monitor a tumour's metastatic potential in real time. Similar to the
heterogeneity of cellular subpopulations within an individual tumour, CTCs within an individual also exhibit
heterogeneity, containing subpopulations having varying relevance to the development of metastatic disease.
Recent studies show that specific subpopulations of CTCs possess metastatic potential, while other
subpopulations of circulating epithelial cells may be relatively benign.
Similarly, the levels of surface proteins on CTCs are heterogeneous and dynamic: they are observed to
change as a function of disease stage and response to therapy. In particular, the epithelial-mesenchymal
transition (EMT) appears to be a dynamic process in CTCs, and the markers that correspond to these two
states vary and contribute to the phenotypic heterogeneity of CTCs. Using a microfluidic device, the velocity
valley (VV) chip, that was developed in our group, we now have the ability to profile a CTC population from
blood samples and by sorting these cells based on expression of surface markers. This novel technology has
enabled us to capture and study CTCs within various ranges of EMT.
In this proposal, our goal is to fully develop the VV chip technology into a fully integrated device for CTC
population profiling, CTC detection, and molecular analysis. This will be accomplished through integration of
companion technologies allowing for sensitive on-chip electrochemical detection and genetic analysis of CTCs.
Manufacturing methods for the device will be investigated for production at high-scale. In addition,
automation for sample analysis and detection will be developed enabling the full realization of the device in a
clinical or research setting. Finally the device will be validated with clinical samples from prostate and breast
cancer patients.
This project will include the collaboration of a multidisciplinary team of six researchers and clinicians for device
development, manufacturing, and clinical testing. As a team, the researchers will work to develop and validate
this diagnostic platform. At the completion of this project a clinical research tool will be produced capable of
profiling a patient's CTC population and providing molecular and genetic information on the EMT for that
population in a single automated device with capture, profiling, and detection capabilities.
项目摘要:
循环肿瘤细胞(CTC)从原发性肿瘤中脱落到脉管系统中,已被证明
有助于模型系统中转移性病变的形成。因此,监测这些循环细胞
原则上,礼物是实时监测肿瘤转移潜力的一种手段。类似于
单个肿瘤内细胞亚群的异质性,个体内的CTC也表现出
异质性,其中包含与转移性疾病发展不同的亚群。
最近的研究表明,CTC的特定亚群具有转移性潜力,而其他
循环上皮细胞的亚群可能相对良性。
同样,CTC上的表面蛋白水平是异质和动态的:它们被观察到它们
随着疾病阶段和对治疗的反应而变化。特别是上皮 - 间质
过渡(EMT)似乎是CTC中的一个动态过程,与这两个相对应的标记
状态变化并有助于CTC的表型异质性。使用微流体设备,速度
谷(VV)芯片是在我们小组中开发的,我们现在有能力从
血液样本并根据表面标记的表达对这些细胞进行排序。这项新技术有
使我们能够在EMT的各个范围内捕获和研究CTC。
在此提案中,我们的目标是将VV芯片技术完全开发为CTC完全集成的设备
种群分析,CTC检测和分子分析。这将通过整合
伴随技术允许对CTC的敏感片上电化学检测和遗传分析。
该设备的制造方法将在高规模上进行生产。此外,
将开发用于样本分析和检测的自动化,以使设备在A中的完整实现
临床或研究环境。最后,该设备将通过前列腺和乳房的临床样品进行验证
癌症患者。
该项目将包括由六名研究人员和设备临床医生组成的多学科团队的合作
开发,制造和临床测试。作为一个团队,研究人员将努力开发和验证
这个诊断平台。该项目完成时
分析患者的CTC人群,并提供有关EMT的分子和遗传信息
具有捕获,分析和检测功能的单个自动化设备中的人群。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Shana O Kelley的其他文献
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{{ truncateString('Shana O Kelley', 18)}}的其他基金
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Functional genetic screening to elucidate novel mitochondrial DNA repair factors using organelle-targeted chemical probes
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