3D carbon-nanotubes integrated microdevice for extracellular vesicle isolation and in situ sample preparation towards noninvasive pancreatic cancer diagnosis
用于细胞外囊泡分离和原位样品制备的 3D 碳纳米管集成微器件,用于非侵入性胰腺癌诊断
基本信息
- 批准号:9891982
- 负责人:
- 金额:$ 50.51万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-08-10 至 2024-07-31
- 项目状态:已结题
- 来源:
- 关键词:3-DimensionalAllelesBiological AssayBiological MarkersBlood CirculationCarbon NanotubesCellsClinicalCytolysisDNADNA BindingDNA Sequence AlterationDNA amplificationDNA purificationDefectDepositionDetectionDevicesDiagnosisDiagnosticEarly DiagnosisEventExcisionFeasibility StudiesFiltrationGenesGenomeGenomic DNAHigh PrevalenceImmuneIn SituKRAS2 geneMalignant NeoplasmsMalignant neoplasm of pancreasMeasuresMembrane LipidsMicrofluidic MicrochipsModelingMutationMutation DetectionNeoplasm Circulating CellsNeoplasm MetastasisNucleic AcidsOncogenesOperative Surgical ProceduresPancreasPatient-Focused OutcomesPatientsPatternPlasmaPreparationPrognostic MarkerProteinsRNAResearch PersonnelResolutionSamplingSensitivity and SpecificitySolidSourceStage at DiagnosisTechnologyThickTimeTissue SampleUltrafiltrationValidationVesicleatomic layer depositionbasecancer biomarkerscancer diagnosiscancer typecurative treatmentsdesigndiagnostic biomarkerdigitalds-DNAextracellular vesiclesforestimaging modalityimprovedinterdisciplinary collaborationliquid biopsymicrodevicemutantmutation assaymutational statusnanomaterialsnanometerneoplasticneoplastic cellnoninvasive diagnosisnucleic acid purificationoperationpancreatic cancer patientspancreatic tumorigenesisparticlerecruitsextheoriestumortumor DNAvesicular releasezirconium oxide
项目摘要
PROJECT SUMMARY
Pancreatic cancer is the deadliest solid malignancy with an abysmal overall 5-year survival less than 7%. Late
stage diagnosis is regarded as the most important factor contributing to the bleak patient outcome. Since
pancreatic neoplastic cells can take decades to metastasis, in theory, there is a large window for early diagnosis.
However, current early diagnosis often fails due to lack of sensitive and specific pancreatic biomarkers and
limitations on the spatial resolution of the imaging methods. Extracellular vesicles (EVs) are sub-micrometer
vesicles released by almost all the cells and are emerging as an attractive non-invasive liquid biopsy target for
clinical cancer diagnosis. Compared with other liquid biopsy materials, EVs are likely released by live cells and
contains much longer DNA fragments than circulating tumor DNA (ctDNA), and are more abundant than
circulating tumor cells (CTCs) to provide higher sensitivity and better clinical utility. Based on our preliminary
study on using carbon nanotube (CNT) forest as an unprecedented material for sub-micrometer particle isolation,
we propose a new CNT-integrated EV isolation and genome enrichment microdevice (CNT-iEVIGEM), which is
a continuous flow microfluidic device integrated with CNT forest. The self-regulating continuous-flow design
boosts the sample capacity and throughput of our previous CNT integrated device by 10 times and eliminates
clogging, while making the device immune to local CNT forest defects and maintaining high EV capture efficiency.
With additive fabrication of nanometer-thick functional zirconia on CNTs, the CNT-iEVIGEM can efficiently purify
EV DNA in situ. For pancreatic cancer diagnosis, we will develop a multiplex digital droplet PCR (ddPCR) assay
to detect KRAS mutations from EVs isolated from plasma by CNT-iEVIGEM. KRAS mutations are the most
prevalent pancreatic cancer mutations with over 90% occurrence. It is a major driver oncogene and often the
earliest event in pancreatic tumorigenesis. Using model samples of cancer-derived EVs spiked in healthy control
plasma, we will determine the detection limit as the lowest mutant allele fraction that can be detected
unambiguously. The assay will be validated with 75 plasma samples from stage IV pancreatic cancer patients
and 75 age-/sex- matched healthy donors. Then we will use this assay to investigate diagnosis of pancreatic
cancer at different stages, by recruiting 60 early stage (stage I + II) and 60 stage III pancreatic cancer patients.
The sensitivity and specificity of the assay at different stages will be measured with the mutation status in tissue
samples as the true values. The proposed study will pave the way for further clinical validation of the CNT-
iEVIGEM technology for cancer diagnosis. The EV isolation platform can also be used for other DNA mutations,
other EV cargos, and other cancer types as a non-invasive liquid biopsy technology.
项目总结
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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Siyang Zheng其他文献
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{{ truncateString('Siyang Zheng', 18)}}的其他基金
3D carbon-nanotubes integrated microdevice for extracellular vesicle isolation and in situ sample preparation towards noninvasive pancreatic cancer diagnosis
用于细胞外囊泡分离和原位样品制备的 3D 碳纳米管集成微器件,用于非侵入性胰腺癌诊断
- 批准号:
10460188 - 财政年份:2019
- 资助金额:
$ 50.51万 - 项目类别:
3D carbon-nanotubes integrated microdevice for extracellular vesicle isolation and in situ sample preparation towards noninvasive pancreatic cancer diagnosis
用于细胞外囊泡分离和原位样品制备的 3D 碳纳米管集成微器件,用于非侵入性胰腺癌诊断
- 批准号:
10669041 - 财政年份:2019
- 资助金额:
$ 50.51万 - 项目类别:
3D carbon-nanotubes integrated microdevice for extracellular vesicle isolation and in situ sample preparation towards noninvasive pancreatic cancer diagnosis
用于细胞外囊泡分离和原位样品制备的 3D 碳纳米管集成微器件,用于非侵入性胰腺癌诊断
- 批准号:
10231020 - 财政年份:2019
- 资助金额:
$ 50.51万 - 项目类别:
Lipid nanoprobe integrated microdevice for extracellular vesicle isolation and duplex sequencing based mutation detection for non-invasive lung cancer diagnosis
用于细胞外囊泡分离和基于双重测序的突变检测的脂质纳米探针集成微器件用于非侵入性肺癌诊断
- 批准号:
10004593 - 财政年份:2018
- 资助金额:
$ 50.51万 - 项目类别:
Carbon nanotube integrated microdevice for next generation sequencing based virus discovery
用于基于下一代测序的病毒发现的碳纳米管集成微器件
- 批准号:
10226147 - 财政年份:2018
- 资助金额:
$ 50.51万 - 项目类别:
Lipid nanoprobe integrated microdevice for extracellular vesicle isolation and duplex sequencing based mutation detection for non-invasive lung cancer diagnosis
用于细胞外囊泡分离和基于双重测序的突变检测的脂质纳米探针集成微器件用于非侵入性肺癌诊断
- 批准号:
10478149 - 财政年份:2018
- 资助金额:
$ 50.51万 - 项目类别:
Lipid nanoprobe integrated microdevice for extracellular vesicle isolation and duplex sequencing based mutation detection for non-invasive lung cancer diagnosis
用于细胞外囊泡分离和基于双重测序的突变检测的脂质纳米探针集成微器件用于非侵入性肺癌诊断
- 批准号:
10686287 - 财政年份:2018
- 资助金额:
$ 50.51万 - 项目类别:
Lipid nanoprobe integrated microdevice for extracellular vesicle isolation and duplex sequencing based mutation detection for non-invasive lung cancer diagnosis
用于细胞外囊泡分离和基于双重测序的突变检测的脂质纳米探针集成微器件用于非侵入性肺癌诊断
- 批准号:
10248377 - 财政年份:2018
- 资助金额:
$ 50.51万 - 项目类别:
Development of a Flexible Micro Spring Array device for viable circulating tumor
开发用于活循环肿瘤的柔性微弹簧阵列装置
- 批准号:
8303786 - 财政年份:2012
- 资助金额:
$ 50.51万 - 项目类别:
Integration of Flexible Micro Spring Array and High Throughput Microfluidics for
柔性微弹簧阵列和高通量微流体的集成
- 批准号:
8358451 - 财政年份:2012
- 资助金额:
$ 50.51万 - 项目类别:
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