Sample-free onsite detection of cocaine using microneedles via laser-treated skin
使用微针通过激光处理的皮肤对可卡因进行无样品现场检测
基本信息
- 批准号:9044652
- 负责人:
- 金额:$ 22.36万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2016
- 资助国家:美国
- 起止时间:2016-08-15 至 2018-07-31
- 项目状态:已结题
- 来源:
- 关键词:Accident and Emergency departmentAdministratorAnimalsAreaBindingBiologicalBiological AssayBiological MarkersBloodBlood specimenBoxingCapillary PermeabilityCessation of lifeClinicClinicalCocaineCocaine-Related DisordersCollectionColorCommunitiesCountryCrimeDNAData AnalysesDermalDermisDetectionDevicesDiagnosisDimensionsDoseDrug ControlsDrug abuseEconomicsEmergency SituationEmergency department visitEngineeringEquipmentEthical IssuesFamily suidaeFeedbackFluorescein-5-isothiocyanateFluorescenceGeneral HospitalsGoalsGoldGrantHemoglobinHeroinHospitalsHumanIllicit DrugsIn SituIn VitroInstitutesLabelLasersLeadLengthLightLightingMarijuanaMassachusettsMeasurementMeasuresMedicalMethodsModificationMusNeedlesOrangesPainlessPenetrationPharmaceutical PreparationsPhasePlasmaPoliciesProtocols documentationPublic HealthRattusReaction TimeResearchRiskRodentSalivaSamplingSensitivity and SpecificitySeriesShapesSkinSmall Business Innovation Research GrantSmall Business Technology Transfer ResearchSpecificitySpecimenSurfaceTechnologyTestingTransdermal substance administrationUnited StatesUnited States National Institutes of HealthUrinalysisUrineVariantVisitWorkplaceanalytical methodanimal facilityaptamerbasebenzoylecgoninecocaine usecommercializationcostcyanine dye 5designdrug testingdrugged drivingexperienceimprovedin vitro Assayin vitro testingin vivoinjuredminimally invasivenovelpreventproduct developmentprotocol developmentpublic health relevancereceptorsample collectionscreeningsensorsignal processingsocialspecific biomarkerssuccess
项目摘要
DESCRIPTION (provided by applicant): The abuse of illicit drugs such as cocaine, marijuana and heroin remains a critical public health concern throughout the country and is associated with staggering economic and social consequences. Cocaine remains the most frequently recorded illicit drug in emergency hospital visits and the leading cause of drug- related deaths in
the United States. Since as high as 23% of fatally injured drivers were found positive results in drug tests, the Office of National Drug Control Policy emphasizes the major concern of drugged driving in the United States. Urinalysis is the most common type of cocaine test, though urine collection has challenged its practicality. There are other biological specimen-based cocaine tests that have been explored such as blood and saliva tests but are not practical since blood samples need high-level medical administrators and specialized analytic equipment. Another alternative is the minimally invasive diagnosis through skin using surface modified microneedles (MNs). However, since concentrations of most blood biomarkers in the skin are too low to be captured by the MN array, the test suffers from low sensitivity and high variation. Here we propose a novel probe-MN-based assay in conjunction of using brief laser illumination on a tiny skin area to accumulate blood biomarker, such as cocaine into the upper dermis. This sample accumulation method enables the biomarker to be readily detected and quantified in situ using the probe-MNs inserted into the laser- treated skin. The objective for the STTR Phase I is to characterize and validate sensitivity and specificity of the probe-MN array in vitro and in vivo, and compare detection reliability with conventional analysis of cocaine in plasma and in urine samples. The specific aims are as follows: Aim 1: Determine optimal design of cocaine-specific binding MN probe and characterize cocaine assay in vitro. We will develop a protocol of surface modification of MNs with Cy3-labeled cocaine-specific aptamer and Cy5- labeled neutralizer. Length of the MNs ranging from 50 - 300um will be optimized based on iterative feedback from in vivo test. Sensitivity, specificity, and response time of the MNs array will be evaluated by in vitro tests. Aim 2: Demonstrate the feasibility and consistence of upper dermal cocaine detection in mice and rats. The cocaine-specific MN probe will be evaluated in mice and rats to demonstrate feasibility of the proposed minimally invasive MN-based cocaine detection in conjunction of using a brief illumination of a clinically safe dose of laser on the skin. Sensitiviy, specificity, and reliability will be determined with respect to conventional assays of plasma and urinalysis of cocaine. The ultimate goal of the entire STTR project is to develop and commercialize the minimally invasive, sample- free, in situ cocaine detection toolkit consisting of
device and cocaine-specific probe-MN arrays for prompt onsite cocaine detection in humans in community, work places, or emergency rooms and clinics.
描述(申请人提供):滥用非法药物,如可卡因、大麻和海洛因,仍然是全国一个严重的公共卫生问题,并与惊人的经济和社会后果有关。可卡因仍然是#年急诊中记录最频繁的非法药物,也是与药物有关的死亡的主要原因。
美国。由于高达23%的致命受伤司机在药检中呈阳性结果,国家药物管制政策办公室强调了美国对醉酒驾驶的主要关注。尿检是最常见的可卡因测试类型,尽管尿液采集对其实用性提出了挑战。还有其他以生物标本为基础的可卡因测试,如血液和唾液测试,但不实用,因为血液样本需要高水平的医疗管理人员和专门的分析设备。另一种选择是使用表面修饰微针(MNS)通过皮肤进行微创诊断。然而,由于皮肤中大多数血液生物标记物的浓度太低,无法被MN阵列捕获,因此该测试存在灵敏度低和变异性高的问题。在这里,我们提出了一种新的基于探针的MN检测方法,结合在微小皮肤区域使用短暂的激光照射,以积累血液生物标记物,如可卡因到真皮上部。这种样品积累方法使得使用插入到激光处理的皮肤中的探针-MN能够容易地在原位检测和定量生物标记物。STTRI阶段的目标是表征和验证探针-MN阵列在体外和体内的敏感性和特异性,并将检测可靠性与血浆和尿样中可卡因的常规分析进行比较。具体目的如下:目的1:确定可卡因特异性结合MN探针的优化设计,并对可卡因体外检测方法进行表征。我们将开发一种用Cy3标记的可卡因特异性适配子和Cy5标记的中和剂来修饰MNS的方案。根据体内试验的迭代反馈,将优化50-300um范围内的MN的长度。MNS阵列的敏感性、特异性和响应时间将通过体外测试进行评估。目的:验证小鼠和大鼠上皮可卡因检测方法的可行性和一致性。可卡因特异的MN探针将在小鼠和大鼠身上进行评估,以证明拟议的基于MN的微创可卡因检测的可行性,并结合使用临床安全剂量的激光对皮肤进行短暂照射。对于可卡因的常规血浆和尿液分析,将确定其敏感性、特异性和可靠性。整个STTR项目的最终目标是开发和商业化微创、无样本、原位可卡因检测工具包,包括
设备和可卡因特定探针-MN阵列,用于在社区、工作场所或急诊室和诊所对人体进行快速现场可卡因检测。
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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