Automated High-purity Exosome isolation-based AD diagnostics system (AHEADx)
基于自动化高纯度外泌体分离的 AD 诊断系统 (AHEADx)
基本信息
- 批准号:10738697
- 负责人:
- 金额:$ 78.88万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-09-01 至 2028-05-31
- 项目状态:未结题
- 来源:
- 关键词:AccelerationAcousticsAddressAffectAlzheimer disease detectionAlzheimer disease screeningAlzheimer&aposs DiseaseAlzheimer&aposs disease diagnosisAlzheimer&aposs disease diagnosticAlzheimer&aposs disease pathologyAlzheimer&aposs disease patientAlzheimer&aposs disease testAlzheimer&aposs disease therapeuticAlzheimer&aposs disease therapyAlzheimer’s disease biomarkerBehavioralBenchmarkingBiological MarkersBiometryBloodBlood - brain barrier anatomyBrain PathologyBrain imagingCerebrospinal FluidClinicalClinical ResearchCommunicationComputer softwareDetectionDevelopmentDevicesDiagnosisDiagnostic ProcedureDiagnostic testsDiseaseDisease ProgressionEarly DiagnosisEarly treatmentEconomic BurdenElectronicsFutureHealthcareImpairmentIntuitionLanguageLibrariesLiquid substanceLongitudinal StudiesMachine LearningMemory impairmentMethodsMicroRNAsMolecularMonitorNanoPillarNeurodegenerative DisordersNucleic AcidsOpticsPatient-Focused OutcomesPatientsPerformancePersonsPhysiologicalPlasmaPositron-Emission TomographyProteinsResearchResearch PersonnelRiskSamplingSourceSpecificitySpeechSpeedSpinal PunctureStandardizationSymptomsSystemTechniquesTechnologyTestingTherapeuticTimeUnited StatesUniversitiesValidationWhole Bloodaccurate diagnosisamplification detectionbiomaterial compatibilityclinical applicationclinical diagnosiscognitive abilitycostcost efficientdiagnostic platformdiagnostic toolexosomeextracellular vesiclesfunctional declineglobal healthhealth economicsimaging modalityimprovedinventionliquid biopsymedical schoolsminimally invasivenanophotonicnanoplasmonicnanoscalenovelphotonicsplasmonicspoint of carepoint-of-care diagnosticspre-clinicalprototyperesponsescreeningtooltraffickingtreatment responsetreatment strategy
项目摘要
PROJECT SUMMARY
Alzheimer’s disease (AD) is a severe neurodegenerative illness that destroys cognitive abilities causing memory
impairment, difficulties with speech and language, behavioral changes, functional decline, and significant
impairment. AD affects an estimated 13.8 million people in the United States and 50 million worldwide, imposing
a significant economic burden and global health crisis. While many researchers are working towards developing
a cure for the disease, there is currently no objective, point-of-care diagnostic test for the early diagnosis of AD,
significantly limiting screening efforts for clinical studies and delaying treatment for patients suffering from early
AD pathology. The current standard methods for AD diagnosis involve expensive PET imaging methods that
irradiate the patient and cerebrospinal fluid biomarker tests, which are invasive and require a lumbar puncture.
Recently, exosomes (30-150 nm extracellular vesicles) have been identified as a possible tool for AD diagnosis,
attributed to their ubiquitous presence in biofluids, their ability to pass through the blood-brain-barrier, and their
rich library of AD-relevant physiological information present in the molecular cargo they carry, making them prime
candidates for use as biomarkers. However, the clinical application of exosomes is hindered by slow, inefficient
techniques for exosome isolation and the absence of standardized exosomal biomarker detection and analysis.
Thus, an automated, highly sensitive, fast, and efficient system that can isolate exosomes from biofluids and
analyze the miRNAs and proteins they contain will significantly improve early-stage AD diagnosis efforts. In this
R01 project, we will develop an Automated High-purity Exosome isolation-based AD diagnostics system
(AHEADx) to address the limitations of current technologies. The proposed AHEADx platform includes two units:
(1) a rapid (<1 min), high-yield (>90%), and high-purity (>90%) acoustic Bessel beam-based separation unit to
isolate and enrich exosomes from whole blood, and (2) a rapid (<6 mins), highly sensitive photonic PCR and
immuno-PCR (~1 copy/µL for nucleic acids and ~5 copies/µL for proteins, respectively) utilizing a plasmonic
nanopillar array to enable on-chip thermocycling and multiplexed exosomal screening of combined panels of
AD-relevant biomarkers. Our rapid and precise AHEADx platform will provide a simple, minimally invasive liquid
biopsy to detect molecular AD biomarkers with ultrahigh accuracy and sensitivity in early-stage AD patients,
allowing for an effective diagnostic method of AD screening for earlier treatment before the onset of severe
symptoms of the disease and enable long-term studies on AD development and progression. Additionally, the
proposed technology will accelerate the discovery of new exosomal miRNA and protein AD biomarkers and help
to elucidate the mechanisms in which exosome trafficking and transport contribute to AD pathology. With these
advantages, our AHEADx platform can potentially exceed current clinical standards in AD diagnostics,
addressing a significant need in the field and providing a compelling platform for earlier, accurate, and sensitive
detection of AD and long-term studies on the effects of novel AD therapeutics.
项目摘要
阿尔茨海默氏病(AD)是一种严重的神经退行性疾病,其破坏认知能力,导致记忆
损伤,言语和语言困难,行为变化,功能下降,以及显著
损伤AD影响美国估计1380万人和全世界5000万人,
严重的经济负担和全球健康危机。虽然许多研究人员正在努力开发
治愈该疾病,目前没有客观的,即时诊断测试用于AD的早期诊断,
严重限制了临床研究的筛查工作,并延迟了患有早期乳腺癌的患者的治疗。
AD病理学目前用于AD诊断的标准方法涉及昂贵的PET成像方法,
对患者进行照射和脑脊液生物标志物检测,这是侵入性的,需要进行腰椎穿刺。
最近,外泌体(30-150 nm的细胞外囊泡)已被鉴定为用于AD诊断的可能工具,
这归因于它们在生物流体中的普遍存在,它们穿过血脑屏障的能力,以及它们的
它们携带的分子货物中存在丰富的AD相关生理信息库,
用作生物标志物的候选物。然而,外泌体的临床应用受到缓慢、低效
用于外泌体分离的技术和标准化外泌体生物标志物检测和分析的缺乏。
因此,提供了一种自动化的、高灵敏度的、快速的和有效的系统,其可以从生物流体中分离外来体,
分析它们所包含的miRNAs和蛋白质将显著改善早期AD诊断工作。在这
R 01项目,我们将开发一种基于高纯度Exosome分离的AD诊断系统
(AHEADx)解决当前技术的局限性。拟议的AHEADx平台包括两个单元:
(1)快速(<1分钟)、高产率(>90%)和高纯度(>90%)基于贝塞尔声束的分离单元,
从全血中分离和富集外泌体,和(2)快速(<6分钟)、高灵敏度光子PCR和
免疫PCR(核酸约1拷贝/μL,蛋白质约5拷贝/μL),利用等离子体
纳米柱阵列,以使芯片上热循环和多重外泌体筛选的组合面板
AD相关生物标志物。我们快速精确的AHEADx平台将提供一种简单、微创的液体
活检以检测早期AD患者中具有较高准确性和灵敏度的分子AD生物标志物,
允许AD筛查的有效诊断方法,以便在严重疾病发作之前进行早期治疗,
该方法可以有效地改善疾病的症状,并能够对AD的发展和进展进行长期研究。另夕h
提出的技术将加速发现新的外泌体miRNA和蛋白质AD生物标志物,
阐明外泌体运输和转运促进AD病理学的机制。与这些
优势,我们的AHEADx平台有可能超过AD诊断的当前临床标准,
满足该领域的重大需求,并提供一个引人注目的平台,
AD的检测和新型AD治疗剂效果的长期研究。
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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Tony Jun Huang其他文献
Tony Jun Huang的其他文献
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{{ truncateString('Tony Jun Huang', 18)}}的其他基金
Acoustofluidic Separation of Placental Nanovesicle Subpopulations in Obstetrical Diseases
产科疾病胎盘纳米囊泡亚群的声流分离
- 批准号:
10625490 - 财政年份:2021
- 资助金额:
$ 78.88万 - 项目类别:
Development of a digital acoustofluidic system for automating liquid handling in biomedical research
开发用于生物医学研究中液体处理自动化的数字声流系统
- 批准号:
10405571 - 财政年份:2021
- 资助金额:
$ 78.88万 - 项目类别:
Development of a digital acoustofluidic system for automating liquid handling in biomedical research
开发用于生物医学研究中液体处理自动化的数字声流系统
- 批准号:
10175836 - 财政年份:2021
- 资助金额:
$ 78.88万 - 项目类别:
Development of a digital acoustofluidic system for automating liquid handling in biomedical research
开发用于生物医学研究中液体处理自动化的数字声流系统
- 批准号:
10689706 - 财政年份:2021
- 资助金额:
$ 78.88万 - 项目类别:
Development of a digital acoustofluidic system for automating liquid handling in biomedical research
开发用于生物医学研究中液体处理自动化的数字声流系统
- 批准号:
10795366 - 财政年份:2021
- 资助金额:
$ 78.88万 - 项目类别:
Acoustofluidic Separation of Placental Nanovesicle Subpopulations in Obstetrical Diseases
产科疾病胎盘纳米囊泡亚群的声流分离
- 批准号:
10418609 - 财政年份:2021
- 资助金额:
$ 78.88万 - 项目类别:
AFS/SERS Saliva-based SARS-CoV-2 Earliest Infection and Antibodies Detection
AFS/SERS 基于唾液的 SARS-CoV-2 最早感染和抗体检测
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10320991 - 财政年份:2020
- 资助金额:
$ 78.88万 - 项目类别:
AFS/SERS Saliva-based SARS-CoV-2 Earliest Infection and Antibodies Detection
AFS/SERS 基于唾液的 SARS-CoV-2 最早感染和抗体检测
- 批准号:
10266399 - 财政年份:2020
- 资助金额:
$ 78.88万 - 项目类别:
Enabling Efficient, Fast, Biocompatible Exosome Separation via Acoustofluidics
通过声流控技术实现高效、快速、生物相容性的外泌体分离
- 批准号:
10171868 - 财政年份:2019
- 资助金额:
$ 78.88万 - 项目类别:
Enabling Efficient, Fast, Biocompatible Exosome Separation via Acoustofluidics
通过声流控技术实现高效、快速、生物相容性的外泌体分离
- 批准号:
10456734 - 财政年份:2019
- 资助金额:
$ 78.88万 - 项目类别:
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