Indwelling biosensor for real-time chemotherapeutic blood level monitoring
用于实时化疗血浓度监测的留置生物传感器
基本信息
- 批准号:8839582
- 负责人:
- 金额:$ 22.19万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2014
- 资助国家:美国
- 起止时间:2014-12-01 至 2016-03-31
- 项目状态:已结题
- 来源:
- 关键词:AcuteAddressAdverse effectsAffectAnimalsArea Under CurveBindingBiosensing TechniquesBiosensorBloodBlood TestsBlood drug level resultBuffersCancer PatientCardiotoxicityCathetersCellsChemicalsChronicCisplatinClinicalClinical ResearchCytotoxic agentDNADataData CollectionDependenceDetectionDevelopmentDevicesDiagnosticDoseDose-LimitingDoxorubicinDrug ExposureDrug KineticsElectronicsEnsureEvolutionFinite Element AnalysisGeometryGoldHeartHourIV FluidIn VitroIndiumIndividualInfusion proceduresLaboratoriesLegal patentLettersLicensingLifeLigandsMalignant NeoplasmsMalignant neoplasm of lungManualsMeasurementMeasuresMetabolismMethodsMicrofluidicsModelingMonitorNeurosciencesNew Drug ApprovalsNon-Small-Cell Lung CarcinomaOverdosePatient MonitoringPatientsPharmaceutical PreparationsPhaseProcessProductionProteinsRNARiskSystemTechniquesTechnologyTestingTherapeuticTherapeutic UsesTimeTissuesTopotecanToxic effectVariantVenousWhole BloodWorkabstractingaptamerarmbasebiochipclinical applicationcostdesigndocetaxeldrug clearancefluid flowimprovedminimally invasivemulti-electrode arraysnovel strategiespersonalized medicinepoint of carepreclinical studypreventprototypepublic health relevancesample collectionsensorsmall moleculetooltrend
项目摘要
DESCRIPTION (provided by applicant): The Specific Aim of this proposal is to test the feasibility of developing a catheter-based, indwelling biosensor for the real-time, continuous monitoring of chemotherapeutic blood levels of lung cancer patients. A tool that continuously monitors blood drug levels in real-time will enable an unprecedented understanding of an individual patient's distinctive metabolism and clearance of drugs. This information is critically needed for three reasons: 1) to reduce drug dosing related toxicities, such as heart tissue damage, 2) to potentially improve efficacy of chemotherapeutics by ensuring patients maintain therapeutic drug blood levels, and 3) to facilitate development and approval of new drugs with narrow therapeutic ranges and high interindividual variability. The proposed tool will measure blood levels of chemotherapeutic drug doxorubicin every 5 seconds in flowing venous whole blood for real-time determination of blood levels and accurate calculation of cumulative drug exposure. Current methods require multiple, timely blood draws that are error prone and require manual labor for both sample collection and laboratory analysis. No point-of-care method is available to detect doxorubicin. The proposed work is based upon an existing doxorubicin microfluidic biosensor that works in whole blood for over 4 hours (Ferguson et al., 2013; see Plaxco letter of support). We propose to design and fabricate a biosensor that utilizes the advantageous fluidic dynamics of the existing system, but that is small enough to fit in an I.V. catheter in a patient's arm. Diagnostic Biochips has already developed a proprietary MEMS process for fabricating implantable multi-electrode arrays. We will accomplish our Specific Aim by: 1) using finite element analysis to model fluid flow in venous, flowing, whole blood to demonstrate a laminar boundary buffer layer at the sensor interface to prevent biofouling, 2) fabricate the optimized catheter design and functionalize the biosensor, and 3) develop electronics for point-of-care use. The test of feasibility will be the successful detection of doxorubicin in flowing whole blood for at least 8 hours at physiologically relevant concentrations (10 nM - 10 uM; Eksborg et al., 1985) in a device that with clinically implementable design (defined by similarity in size and geometry to existing I.V. catheters and acceptable levels of I.V fluid delivered). In Phase II, we will test our sensors in live animals and, using principles of robust design, turn our prototype into a commercial product.
描述(由申请人提供):本提案的具体目的是测试开发基于导管的留置生物传感器的可行性,用于实时、连续监测肺癌患者的化疗血液水平。一种实时连续监测血液药物水平的工具将使人们能够前所未有地了解个体患者独特的药物代谢和清除。由于以下三个原因,迫切需要这些信息:1)减少药物给药相关毒性,如心脏组织损伤,2)通过确保患者维持治疗药物血液水平来潜在地改善化疗药物的疗效,以及3)促进具有窄治疗范围和高个体间变异性的新药的开发和批准。所提出的工具将在流动的静脉全血中每5秒测量化疗药物阿霉素的血液水平,以实时确定血液水平并准确计算累积药物暴露。目前的方法需要多次、及时的抽血,这是容易出错的,并且需要手工劳动来进行样品收集和实验室分析。没有即时检测方法可用于检测阿霉素。所提出的工作是基于现有的多柔比星微流体生物传感器,其在全血中工作超过4小时(Ferguson等人,2013;见Plaxco支持信)。我们建议设计和制造一种生物传感器,利用现有系统的有利流体动力学,但这是小到足以适应在静脉导管在病人的手臂。诊断生物芯片已经开发出一种专有的MEMS工艺制造植入式多电极阵列。我们将通过以下方式实现我们的特定目标:1)使用有限元分析对静脉流动全血中的流体流动进行建模,以证明传感器界面处的层流边界缓冲层可防止生物污染,2)制造优化的导管设计并使生物传感器功能化,以及3)开发用于护理点的电子产品。可行性测试将是在生理相关浓度下在流动的全血中成功检测阿霉素至少8小时(10 nM - 10 μ M; Eksborg et al.,1985),该装置具有临床可实施的设计(通过与现有静脉导管的尺寸和几何形状的相似性以及输送的静脉液体的可接受水平来定义)。在第二阶段,我们将在活体动物中测试我们的传感器,并使用稳健设计的原则,将我们的原型转化为商业产品。
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)
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Brian Glenn Jamieson其他文献
Brian Glenn Jamieson的其他文献
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{{ truncateString('Brian Glenn Jamieson', 18)}}的其他基金
Microfabricated tool for integrated PK/PD studies of CNS drugs
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- 批准号:
9042433 - 财政年份:2015
- 资助金额:
$ 22.19万 - 项目类别:
Indwelling Biosensor for real-time chemotherapeutic blood level monitoring
用于实时化疗血液浓度监测的留置生物传感器
- 批准号:
9251900 - 财政年份:2014
- 资助金额:
$ 22.19万 - 项目类别:
Indwelling Biosensor for real-time chemotherapeutic blood level monitoring
用于实时化疗血液浓度监测的留置生物传感器
- 批准号:
9056221 - 财政年份:2014
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$ 22.19万 - 项目类别:
Neural Probe for high spatial and temporal resolution detection of cocaine and su
用于可卡因和苏的高空间和时间分辨率检测的神经探针
- 批准号:
8705485 - 财政年份:2013
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$ 22.19万 - 项目类别:
Neural probe for high spatial and temporal resolution detection of cocaine and GA
用于高空间和时间分辨率检测可卡因和 GA 的神经探针
- 批准号:
8685390 - 财政年份:2013
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$ 22.19万 - 项目类别:
Microfabricated Neural Probe for the Rapid Detection of Multiple Neurochemicals I
用于快速检测多种神经化学物质的微型神经探针 I
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8453739 - 财政年份:2013
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$ 22.19万 - 项目类别:
Neural Probe for high spatial and temporal resolution detection of cocaine and su
用于可卡因和苏的高空间和时间分辨率检测的神经探针
- 批准号:
8592748 - 财政年份:2013
- 资助金额:
$ 22.19万 - 项目类别:
Microfabricated Neural Probe for the Rapid Detection of Multiple Neurochemicals I
用于快速检测多种神经化学物质的微型神经探针 I
- 批准号:
8739598 - 财政年份:2013
- 资助金额:
$ 22.19万 - 项目类别:
Neural probe for high spatial and temporal resolution detection of cocaine and GA
用于高空间和时间分辨率检测可卡因和 GA 的神经探针
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8650813 - 财政年份:2013
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