Two-Dimensional Multi-Stage Isotachophoretic Technology for Multiplex Analysis of Cancer Exosomes and Proteins Marker Panel
用于癌症外泌体和蛋白质标记物组多重分析的二维多级等速电泳技术
基本信息
- 批准号:10322022
- 负责人:
- 金额:$ 16.88万
- 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
- 起止时间:2021-01-01 至 2023-12-31
- 项目状态:已结题
- 来源:
- 关键词:3D PrintAddressAdoptedAntibodiesAntigensAreaBehaviorBindingBiologicalBloodBlood CirculationCD44 geneCancer PatientCancer PrognosisCancerousCationsCell secretionCellsCellular PhoneClinicalCommunicationConsumptionDeath RateDetectionDevicesDiagnosisDiseaseDistalEarly DiagnosisEpidermal Growth Factor ReceptorExhibitsHematopoietic NeoplasmsImmuneImmune TargetingLeadLiquid substanceMalignant NeoplasmsMembraneMethodsMicroRNAsMicrofluidicsModelingNeoplasm MetastasisNormal CellPaperPathologic ProcessesPatientsPlasma ProteinsPlayPoint of Care TechnologyPopulationPrimary Health CareProcessPrognosisProteinsQuality of lifeResearchRoleSamplingSchemeScreening for cancerSensitivity and SpecificitySerumSerum ProteinsSignaling MoleculeSurvival RateTechniquesTechnologyTestingTimeTissuesTranslatingTranslational ResearchTumor MarkersTumor-Derivedbasebiomarker panelcancer biomarkerscancer cellcancer diagnosiscell typeclinical diagnosisclinical prognosisclinically significantcostcost effectivedesignearly screeningexosomeextracellularextracellular vesiclesimprovedinterdisciplinary approachliquid biopsymalignant breast neoplasmminiaturizemultiplex assayneoplastic cellnoninvasive diagnosisnovelnovel strategiespoint of careprotein biomarkersrapid techniquesuccesssurvivintooltranslational potentialtumortumor growthtumor progressiontwo-dimensional
项目摘要
Abstract
Exosomes are small-sized (30–120 nm) extracellular vesicles. They are secreted by most cell types and play
important roles in extracellular communication in normal and pathological processes. The exosomes derived
from cancers shuttle signaling molecules (e.g. proteins and miRNAs) from parental cancer cells and tissue to
distal recipient cells to reprogram the recipient cells and promote tumor growth and metastasis. Therefore,
circulating tumor-derived exosomes carrying signature protein markers of the tumor hold great potential as
invaluable liquid biopsy tools for the noninvasive diagnosis of early-stage cancers. Despite their potential clinical
significance, translating disease-derived exosomes into point-of-care (POC) applications for the early diagnosis
of cancers is hampered by a critical technical barrier: lack of a cost-effective POC approach capable of the
simultaneous analysis of specific exosomes and their content markers in clinical samples. Although a number of
methods for exosome isolation and characterization have been developed, either they are singly functionalized,
nonspecific, laborious, or time-consuming, or they lack the robustness to be adopted as a cost-effective POC
technique. Therefore, there is an urgent need for an effective, precise, easy to use, low-cost approach to
multiplex POC sample analysis to detect trace levels of specific populations of exosomes released by specific
cancer cells at an early stage and comprehensively profile the cancer markers carried by the exosomes. This
application aims to fill the gap by taking a multidisciplinary approach to developing a novel, disposable two-
dimensional paper-based multistage isotachophoresis (ITP) technology platform capable of the simultaneous
analysis of specific target exosomes and exosomal proteins in a cost-effective way. Our objective is to develop
an integrated paper-based isotachophoretic platform on which: 1) anionic cascade ITP is used to deplete high-
abundance plasma proteins and enrich target exosomes before their capture and analysis; 2) a second ITP
process simultaneously analyzes multiplex exosomal proteins released by lysing the exosomes captured in the
first ITP process; and 3) a miniaturized smartphone-based detection module quantifies the target exosomes and
protein markers captured by novel graded-binding test lines. We expect that integrating effective
isolation/identification of specific exosomes with multiplex analysis of their contents in a cost-effective modular
platform will provide a robust POC approach to advancing basic and clinical translational research on disease-
derived exosomes. Exosomes derived from breast cancer will be used as model targets to validate our
technology. The success of this project will not only provide a clinically compatible POC tool for tracking specific
exosomes and markers for early screening for cancers, but also prompt research on the profile analysis of
exosomal markers for the precision diagnosis of other diseases. Therefore, the technique may have broad
translational potential in managing patients with malicious diseases and improving their quality of life.
抽象的
外泌体是小尺寸(30-120 nm)的细胞外囊泡。它们由大多数细胞类型分泌并发挥作用
在正常和病理过程中细胞外通讯中发挥重要作用。衍生的外泌体
癌症将信号分子(例如蛋白质和 miRNA)从亲本癌细胞和组织传递到
远端受体细胞对受体细胞进行重新编程并促进肿瘤生长和转移。所以,
携带肿瘤特征蛋白标记物的循环肿瘤来源的外泌体具有巨大的潜力
用于早期癌症无创诊断的宝贵液体活检工具。尽管它们具有潜在的临床
意义重大,将疾病来源的外泌体转化为护理点(POC)应用以进行早期诊断
癌症的治疗受到关键技术障碍的阻碍:缺乏具有成本效益的 POC 方法
同时分析临床样本中的特定外泌体及其含量标记物。尽管有一些
外泌体分离和表征的方法已经开发出来,它们要么是单一功能化的,
非特异性、费力或耗时,或者缺乏作为具有成本效益的 POC 的稳健性
技术。因此,迫切需要一种有效、精准、易用、低成本的方法
多重 POC 样本分析可检测特定外泌体释放的痕量水平
早期阶段的癌细胞并全面分析外泌体携带的癌症标志物。这
该应用旨在通过采取多学科方法来开发一种新颖的一次性双
三维纸基多级等速电泳 (ITP) 技术平台,能够同时进行
以经济有效的方式分析特定目标外泌体和外泌体蛋白。我们的目标是发展
一个集成的纸基等速电泳平台,其上:1) 阴离子级联 ITP 用于耗尽高
在捕获和分析之前丰富血浆蛋白并富集目标外泌体; 2) 第二个 ITP
该过程同时分析通过裂解捕获的外泌体释放的多重外泌体蛋白
第一个 ITP 流程; 3) 基于智能手机的小型化检测模块可量化目标外泌体并
由新型分级结合测试线捕获的蛋白质标记。我们期望整合有效的
通过经济高效的模块对其内容物进行多重分析来分离/鉴定特定的外泌体
平台将提供强大的 POC 方法来推进疾病的基础和临床转化研究
衍生的外泌体。来自乳腺癌的外泌体将用作模型靶标来验证我们的研究
技术。该项目的成功不仅将提供一种临床兼容的 POC 工具,用于跟踪特定的
用于癌症早期筛查的外泌体和标记物,同时也促进了对癌症特征分析的研究
用于其他疾病精确诊断的外泌体标记物。因此,该技术可能具有广泛的
在管理恶性疾病患者和改善他们的生活质量方面具有转化潜力。
项目成果
期刊论文数量(1)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Exosomes as Powerful Engines in Cancer: Isolation, Characterization and Detection Techniques.
- DOI:10.3390/bios11120518
- 发表时间:2021-12-16
- 期刊:
- 影响因子:0
- 作者:Saad MG;Beyenal H;Dong WJ
- 通讯作者:Dong WJ
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{{ truncateString('WEN-JI DONG', 18)}}的其他基金
Paper-Based Nucleic Acid Amplification Test for Rapid Diagnosis of Hepatitis C Viral Infection
纸基核酸扩增测试快速诊断丙型肝炎病毒感染
- 批准号:
10558611 - 财政年份:2022
- 资助金额:
$ 16.88万 - 项目类别:
Paper-Based Nucleic Acid Amplification Test for Rapid Diagnosis of Hepatitis C Viral Infection
纸基核酸扩增测试快速诊断丙型肝炎病毒感染
- 批准号:
10430557 - 财政年份:2022
- 资助金额:
$ 16.88万 - 项目类别:
Structural Kinetics of Thin Filament Regulation at Single Molecule Level
单分子水平细丝调控的结构动力学
- 批准号:
8445988 - 财政年份:2013
- 资助金额:
$ 16.88万 - 项目类别:
Structural Kinetics of Thin Filament Regulation at Single Molecule Level
单分子水平细丝调节的结构动力学
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8690957 - 财政年份:2013
- 资助金额:
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