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
基本信息
- 批准号:8358451
- 负责人:
- 金额:$ 223.5万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2012
- 资助国家:美国
- 起止时间:2012-09-17 至 2017-06-30
- 项目状态:已结题
- 来源:
- 关键词:AccountingAntineoplastic AgentsBiological AssayBiopsyBloodBlood CellsBlood CirculationBlood VolumeBlood specimenBody partCancer PatientCancer PrognosisCell SizeCellsCessation of lifeClinicDetectionDevelopmentDiagnosisDisseminated Malignant NeoplasmFDA approvedFiltrationGeneticInvadedLeadLeukocytesLiquid substanceMalignant NeoplasmsMechanical StressMethodsMicrofabricationMicrofluidicsMolecular ProfilingMonitorMutation DetectionNeoplasm MetastasisOutcomePatient IsolationPatientsPharmaceutical PreparationsPrimary NeoplasmProcessReactionRiskStagingSystemTechniquesTechnologyTestingTherapeuticTimeToxic effectTravelabstractingbasecancer diagnosiscancer typechemotherapyclinically relevantcostcost effectivedrug efficacyefficacy testingexperienceflexibilityimprovedminimally invasiveneoplastic cellnovel strategiespressurepublic health relevancetreatment planningtumor progression
项目摘要
DESCRIPTION (Provided by the applicant)
Abstract: The ability of metastatic cancer to release circulating tumor cells (CTCs) that travel through the blood and invade different parts of the body accounts for over 90% of cancer related deaths. New techniques for improved diagnosis and therapeutic strategies are desperately needed to improve patient outcomes in late stage metastatic cancer patients. One such technique involves the analysis of these CTCs through isolation from patient blood samples. Since molecular profiles of CTCs can be quite different from those of the primary tumor and more similar to the metastatic tumors, CTCs are better suited for metastatic cancer prognosis and diagnosis. Current CTC technologies have serious difficulties and limitations for clinic applications due to poor sensitivity and selectivity, high cost, and long processing times. CellSearchTM, the only current FDA approved system for CTC analysis, is only used for detection of CTCs and is not capable of preserving viable cells. The fundamental challenge with obtaining CTCs from blood samples is the fact that they are so rare, with only a few tumors cells occurring among billions of blood cells. Since tumor cells are almost always significantly larger than normal blood cells, size based separation has been demonstrated as an effective method for CTC capture. We have taken a novel approach to established microfiltration technology by implementing an array of flexible microsprings and using a regulated low pressure flow system to minimize the mechanical stresses experienced by cells during the filtration process. This is an efficient and cost effective system that is capable of the enrichment of viable CTCs from a clinically relevant blood volume of 7.5 mL in only 10 minutes. Despite achieving greater than 104 enrichment against leukocytes, the purity of the enriched cells is not sufficient for obtaining
clinically relevant genetic information. We propose the incorporation of a high throughput microfluidic system that will physically partition these cells for analysis on a single cell level.By exploiting this inherent advantage of microtechnology, a large volume of parallel reactions can be used to overcome the issues with purity. Genetic expression profiles and mutation detections may be used for improved diagnosis, and lead to the development of highly personalized therapy plans that are optimized for each patient. Furthermore, the use of microfluidics for multiwell partitioning of CTCs will be used to attempt the establishment of favorable conditions for the culture of CTCs, even at an initially low seeding number. Successful primary culture of CTCs will allow drug efficacy tests that may be used to assay potential drugs ex vivo without exposing a patient to the unnecessary cost or toxic effects of chemotherapy. These new approaches based on the analysis of viable CTCs represent a different approach that has not been proven. However, since this technological platform is applicable to almost every type of cancer, it could fairly quickly revolutionize the way that therapies are derived for metastatic cancer patients.
Public Health Relevance: The most deadly forms of cancer can release aggressive cells that circulate through the bloodstream and spread throughout the body. Microfabrication technology has been developed to effectively isolate these cells from a patient blood sample, allowing a minimally invasive "liquid biopsy" that may be performed often for monitoring tumor progression. This project explores the integration of a high throughput approach to analysis that will make it possible to test various anticancer drugs on these cells at no risk to the patient, and obtain genetic information that will be crucial to developing a highly personalized treatment plan.
描述(由申请人提供)
项目成果
期刊论文数量(20)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Separable Bilayer Microfiltration Device for Label-Free Enrichment of Viable Circulating Tumor Cells.
可分离双层微滤装置,用于无标记富集活循环肿瘤细胞。
- DOI:10.1007/978-1-4939-7144-2_6
- 发表时间:2017
- 期刊:
- 影响因子:0
- 作者:Hao,Sijie;Nisic,Merisa;He,Hongzhang;Tai,Yu-Chong;Zheng,Si-Yang
- 通讯作者:Zheng,Si-Yang
Highly sensitive DNA detection using cascade amplification strategy based on hybridization chain reaction and enzyme-induced metallization.
- DOI:10.1016/j.bios.2014.11.035
- 发表时间:2015-04-15
- 期刊:
- 影响因子:12.6
- 作者:Yu, Xu;Zhang, Zhi-Ling;Zheng, Si-Yang
- 通讯作者:Zheng, Si-Yang
Synthesis of Self-Assembled Multifunctional Nanocomposite Catalysts with Highly Stabilized Reactivity and Magnetic Recyclability.
- DOI:10.1038/srep25459
- 发表时间:2016-05-05
- 期刊:
- 影响因子:4.6
- 作者:Yu X;Cheng G;Zheng SY
- 通讯作者:Zheng SY
Point-of-care microdevices for blood plasma analysis in viral infectious diseases.
- DOI:10.1007/s10439-014-1044-2
- 发表时间:2014-11
- 期刊:
- 影响因子:3.8
- 作者:Yeh YT;Nisic M;Yu X;Xia Y;Zheng SY
- 通讯作者:Zheng SY
Construction of a high-performance magnetic enzyme nanosystem for rapid tryptic digestion.
- DOI:10.1038/srep06947
- 发表时间:2014-11-06
- 期刊:
- 影响因子:4.6
- 作者:Cheng G;Zheng SY
- 通讯作者:Zheng SY
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Siyang Zheng其他文献
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{{ truncateString('Siyang Zheng', 18)}}的其他基金
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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:
$ 223.5万 - 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:
$ 223.5万 - 项目类别:
3D carbon-nanotubes integrated microdevice for extracellular vesicle isolation and in situ sample preparation towards noninvasive pancreatic cancer diagnosis
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- 批准号:
9891982 - 财政年份:2019
- 资助金额:
$ 223.5万 - 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:
$ 223.5万 - 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
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10004593 - 财政年份:2018
- 资助金额:
$ 223.5万 - 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:
$ 223.5万 - 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:
$ 223.5万 - 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:
$ 223.5万 - 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:
$ 223.5万 - 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:
$ 223.5万 - 项目类别:
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