Real-time Detection of Active TB in HIV Exposed Children on CustomizedNanotrap
使用定制纳米陷阱实时检测 HIV 暴露儿童的活动性结核病
基本信息
- 批准号:9377004
- 负责人:
- 金额:$ 39.67万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2015
- 资助国家:美国
- 起止时间:2015-01-09 至 2018-12-31
- 项目状态:已结题
- 来源:
- 关键词:AbateAddressAdultAffectAgeAlgorithmsAliquotAntibodiesAntigensAntitubercular AgentsApplications GrantsAutomobile DrivingBacteriaBacterial DNABase SequenceBiological AssayBiological MarkersBiologyBiopsyBlindedBloodBlood CirculationBlood specimenCharacteristicsChildChildhoodClinicalClinical ChemistryClinical ManagementCommunicable DiseasesCommunitiesCouplesDetectionDevelopmentDiagnosisDiagnosticDiagnostic ProcedureDiagnostic testsDiseaseDrug resistance in tuberculosisEarly identificationEarly treatmentEvaluationExhibitsExtreme drug resistant tuberculosisGenus MycobacteriumGoalsGoldHIVHIV InfectionsHIV SeropositivityHealthHealthcareHumanIndividualInfectionInternationalKnowledgeLabelLifeLightLogistic RegressionsMALDI-TOF Mass SpectrometryMass Spectrum AnalysisMeasuresMethodsModalityMonitorMultidrug-Resistant TuberculosisMycobacterium tuberculosisNanotechnologyNational Institute of Allergy and Infectious DiseaseNaturePatientsPeptidesPerinatalPlasmaPredisposing FactorPreventionProbabilityProceduresPropertyProtocols documentationRadiology SpecialtyRecombinantsRecordsRegimenRespiratory Signs and SymptomsRiskRisk AssessmentRisk FactorsSamplingSensitivity and SpecificitySerumSignal TransductionSilicon DioxideSpecificitySpecimenSpinal PunctureStomachSymptomsTaxesTechniquesTechnologyTestingTherapeuticThoracic RadiographyTimeTreatment EfficacyTuberculin TestTuberculosisValidationVariantWorkbasecare burdenclinical Diagnosisclinical translationclinically relevantco-infectioncohortexperimental studyextensive drug resistanceglobal healthimprovedinsightinterestlight curvelymph nodesmultiplex detectionnanoporepatient populationpediatric patientspreventpublic health relevancerespiratoryresponsesample collectionscreeningtooltransmission processtuberculosis treatmentvalidation studiesvirtual
项目摘要
DESCRIPTION (provided by applicant): Tuberculosis (TB), particularly multidrug and extensively drug-resistant TB (M/XDR-TB), poses a significant, worldwide health threat to HIV-exposed children, as progression from infection to disease can occur rapidly and unpredictably. The current gold standard for TB diagnosis and treatment monitoring in children as well as adults relies heavily on time-consuming bacterial culturing or bacterial DNA detection (e.g. GeneXpert MTB/RIF) methods. Clinical diagnosis of childhood TB is especially challenging because of the paucibacillary (few bacteria) nature of the disease and difficulties in obtaining clinically relevant specimens. Even sample collection is itself an enormous task because it often requires invasive procedures (e.g., gastric aspiration, lymph node biopsy, and lumbar puncture). To minimize the destruction and health care burdens resulting from this infectious disease in vulnerable HIV-infected children, a specific and quantitative diagnostic test for active TB is needed for early identification and prevention of TB transmission. We have recently developed a biomarkers detection assay that couples the tunable properties of silica nanopore chips (referred to as Nanotrap ) to the detection capabilities of our benchtop matrix-assisted laser desorption/ionization time-of flight mass spectrometry (MALDI-TOF MS), which capitalizes on recent advances in clinical chemistry applied to MS that enables a different biomarkers detection modality not seen to date. Our preliminary studies reveal three major findings: (1) with the Nanotrap-MS platform, two TB biomarkers (CFP-10 and ESAT-6) can be detected in circulation at an incredibly low concentration (as little as 1.0 fmol), flagging the presence of possible infection well before any conventional technique can assess bacterial load; (2) we have used the platform to differentiate 51 HIV+/TB+ children from 27 HIV+/TB- children and 18 healthy controls simply by detecting the presence of CFP-10 and ESAT-6 in patients' blood, rather than performing burdensome bacterial isolation procedures, with 100% specificity and 94% sensitivity; and (3) perhaps most strikingly, the time between sample processing to answer, or diagnosis, is only half a day rather than the typical 4-6 week period required for conventional methods! In this proposal, we aim to advance the Nanotrap-MS platform much closer to full clinical translation by: a) establishing a simple but extremely accurate protocol to quantify the amount of CFP-10 and ESAT-6 in tandem in a small blood aliquot; b) performing a clinical validation study for Nanotrap- MS, using a large sample set collected from TB-infected children who may also be HIV carriers; and c) investigating the platform's feasibility in monitoring the (early) treatment efficacy of anti-TB therapies, as well as screening for the possible emergence of M/XDR-TB. Successful execution of the proposed studies will help to diminish the likelihood of or even prevent TB transmission, and improve clinical management of TB. Furthermore, the Nanotrap-MS platform has enormous potential not just for TB disease assessment, but it also has broad applications in virtually any clinical indication that manifests in biomarker release int circulation.
描述(由申请人提供):结核病(TB),特别是耐多药和耐药结核病(M/XDR-TB),对艾滋病毒暴露儿童构成重大的全球健康威胁,因为从感染到疾病的进展可能会迅速发生,并且目前儿童和成人结核病诊断和治疗监测的金标准严重依赖耗时的细菌培养或细菌 DNA 检测(例如 GeneXpert MTB/RIF)方法。儿童结核病的临床诊断尤其具有挑战性,因为该疾病具有少杆菌(很少的细菌)性质,并且难以获取临床相关标本,甚至样本采集本身也是一项艰巨的任务,因为它通常需要侵入性操作(例如胃抽吸、淋巴结活检)。 (活组织检查和腰椎穿刺)为了最大限度地减少这种传染病对易受艾滋病毒感染的儿童造成的破坏和医疗保健负担,需要对活动性结核病进行特异性和定量的诊断测试,以便及早识别和预防结核病。我们最近开发了一种生物标志物检测分析,将二氧化硅纳米孔芯片(称为 Nanotrap)的可调特性与我们的台式基质辅助激光解吸/电离飞行时间质谱 (MALDI-TOF MS) 的检测能力结合起来。 ),它利用了应用于 MS 的临床化学的最新进展,实现了迄今为止未见过的不同生物标志物检测模式,我们的初步研究揭示了三个主要发现:(1)使用 Nanotrap-MS 平台,发现了两种 TB。可以在循环中以极低的浓度(低至 1.0 fmol)检测到生物标志物(CFP-10 和 ESAT-6),在任何传统技术评估细菌负荷之前就标记出可能感染的存在(2);该平台只需检测患者血液中是否存在 CFP-10 和 ESAT-6,即可将 51 名 HIV+/TB+ 儿童与 27 名 HIV+/TB- 儿童和 18 名健康对照区分开来,而无需进行繁琐的细菌分离程序具有 100% 的特异性和 94% 的灵敏度;(3) 也许最引人注目的是,样本处理到回答或诊断之间的时间仅为半天,而不是传统方法所需的典型 4-6 周!根据该提案,我们的目标是通过以下方式使 Nanotrap-MS 平台更接近全面的临床转化: a) 建立一个简单但极其准确的方案来量化小份血液中 CFP-10 和 ESAT-6 的含量 b) )执行一个Nanotrap-MS 的临床验证研究,使用从结核病感染儿童(也可能是艾滋病毒携带者)收集的大量样本;c) 调查该平台在监测抗结核疗法(早期)治疗效果方面的可行性,以及筛查可能出现的耐多药/广泛耐药结核病将有助于减少甚至预防结核病传播的可能性,并改善结核病的临床管理。此外,Nanotrap-MS 平台不仅具有巨大的潜力。对于结核病评估,但它也广泛应用于几乎所有体现在循环中生物标志物释放的临床适应症中。
项目成果
期刊论文数量(0)
专著数量(0)
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会议论文数量(0)
专利数量(0)
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Tony Y. Hu其他文献
Serum-Based Diagnosis of Pediatric Tuberculosis by Assay of Mycobacterium tuberculosis Factors: a Retrospective Cohort Study
通过结核分枝杆菌因子测定对小儿结核病进行血清诊断:一项回顾性队列研究
- DOI:
- 发表时间:
2020 - 期刊:
- 影响因子:9.4
- 作者:
Yifan He;Christopher J. Lyon;D. Nguyen;Chang Liu;W. Sha;E. Graviss;Tony Y. Hu - 通讯作者:
Tony Y. Hu
Microsoft Word-pbaa041.docx
Microsoft Word-pbaa041.docx
- DOI:
10.1038/leu.2014.102 - 发表时间:
2020 - 期刊:
- 影响因子:11.4
- 作者:
Xuerong Chen;Tony Y. Hu - 通讯作者:
Tony Y. Hu
IP-MS Analysis of ESX-5 and ESX-1 Substrates Enables Mycobacterial Species Identification
ESX-5 和 ESX-1 底物的 IP-MS 分析可实现分枝杆菌菌种鉴定
- DOI:
- 发表时间:
2020 - 期刊:
- 影响因子:0
- 作者:
Qingbo Shu;Meena U Rajagopal;Jia Fan;Lingpeng Zhan;Xiangxing Kong;Yifan He;Suwatchareeporn Rotcheewaphan;Christopher J. Lyon;W. Sha;A. Zelazny;Tony Y. Hu - 通讯作者:
Tony Y. Hu
2D metal carbides and nitrides (MXenes) for sensors and biosensors.
用于传感器和生物传感器的二维金属碳化物和氮化物 (MXene)。
- DOI:
10.1016/j.bios.2021.113943 - 发表时间:
2022-01-01 - 期刊:
- 影响因子:12.6
- 作者:
S. Alwarappan;N. Nesakumar;Da;Tony Y. Hu;Chen - 通讯作者:
Chen
Monocrystalline Labeling Enables Stable Plasmonic Enhancement for Isolation-Free Extracellular Vesicle Analysis.
单晶标记可实现稳定的等离子体增强,用于免分离的细胞外囊泡分析。
- DOI:
10.1002/smll.202204298 - 发表时间:
2022-11-10 - 期刊:
- 影响因子:13.3
- 作者:
Shu Wang;Wenshu Zheng;Ruixuan Wang;Lili Zhang;Li Yang;Tao Wang;Julian G. Saliba;Sutapa Ch;ra;ra;Chen;Christopher J. Lyon;Tony Y. Hu - 通讯作者:
Tony Y. Hu
Tony Y. Hu的其他文献
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{{ truncateString('Tony Y. Hu', 18)}}的其他基金
Multiplexed detection of cell-free M. Tuberculosis DNA and its drug-resistant variants in blood
血液中无细胞结核分枝杆菌 DNA 及其耐药变异体的多重检测
- 批准号:
10639855 - 财政年份:2023
- 资助金额:
$ 39.67万 - 项目类别:
A nanopore biosensor for leveling Mtb antigens in blood
用于平衡血液中 Mtb 抗原的纳米孔生物传感器
- 批准号:
10646134 - 财政年份:2022
- 资助金额:
$ 39.67万 - 项目类别:
Quantification of brain-derived extracellular vesicle microRNAs in blood by a liposome-mediated CRISPR assay for traumatic brain injury detection
通过脂质体介导的 CRISPR 测定对血液中脑源性细胞外囊泡 microRNA 进行定量,用于检测创伤性脑损伤
- 批准号:
10575436 - 财政年份:2022
- 资助金额:
$ 39.67万 - 项目类别:
Digital Nanoplasmonic Quantification of Tumor-derived Extracellular Vesicles in Plasma Microsamples
血浆微样品中肿瘤源性细胞外囊泡的数字纳米等离子体定量
- 批准号:
10461970 - 财政年份:2020
- 资助金额:
$ 39.67万 - 项目类别:
Digital Nanoplasmonic Quantification of Tumor-derived Extracellular Vesicles in Plasma Microsamples
血浆微样品中肿瘤源性细胞外囊泡的数字纳米等离子体定量
- 批准号:
10684737 - 财政年份:2020
- 资助金额:
$ 39.67万 - 项目类别:
Digital Nanoplasmonic Quantification of Tumor-derived Extracellular Vesicles in Plasma Microsamples
血浆微样品中肿瘤源性细胞外囊泡的数字纳米等离子体定量
- 批准号:
10269902 - 财政年份:2020
- 资助金额:
$ 39.67万 - 项目类别:
Digital Nanoplasmonic Quantification of Tumor-derived Extracellular Vesicles in Plasma Microsamples
血浆微样品中肿瘤源性细胞外囊泡的数字纳米等离子体定量
- 批准号:
10684737 - 财政年份:2020
- 资助金额:
$ 39.67万 - 项目类别:
Direct quantitation of the circulating Mtb-peptidome for pediatric TB management
直接定量循环 Mtb 肽组用于儿科结核病管理
- 批准号:
9333558 - 财政年份:2017
- 资助金额:
$ 39.67万 - 项目类别:
Detecting pathogen and host factors on extracellular vesicles for pediatric TB diagnosis and management
检测细胞外囊泡上的病原体和宿主因子,用于儿童结核病的诊断和管理
- 批准号:
10753281 - 财政年份:2017
- 资助金额:
$ 39.67万 - 项目类别:
Multiplexed quantification of circulating peptidomic signatures for EBOLA early diagnosis
用于埃博拉早期诊断的循环肽组特征的多重定量
- 批准号:
9387209 - 财政年份:2017
- 资助金额:
$ 39.67万 - 项目类别:
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