Quantum Dot-based Qualitative and Quantitative Multiplex Strip Test for Malaria I

基于量子点的疟疾定性和定量多重试纸测试 I

• 批准号: 8302222
• 负责人: RUOBING WANG
• 金额: $ 29.47万
• 依托单位: OCEAN NANOTECH, LLC
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-01 至 2014-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8302222
• 关键词: Absorbent Pads; Affect; Agreement; Antibodies; Antigens; Biological; Biological Assay; Biological Markers; Blood Banks; Blood donor; Blood specimen; Caring; Cessation of life; Child; Color; Communicable Diseases; Country; Culicidae; Detection; Diagnosis; Diagnostic; Diagnostic tests; Disease; Drug resistance; Drug usage; Dyes; Exhibits; Fluorescence; Glutamate Dehydrogenase; Goals; Health Personnel; Human; Infection; Insecticide Resistance; Lactate Dehydrogenase; Lateral; Legal patent; Licensing; Life; Malaria; Measurement; Medicine; Membrane; Methods; Metric; Military Personnel; Oceans; Parasitemia; Parasites; Pathogen detection; Pharmaceutical Preparations; Phase; Plasmodium; Plasmodium falciparum; Property; Quantum Dots; Reader; Reagent Strips; Reliability of Results; Reproducibility; Sampling; Science; Side; System; Technology; Testing; Time; Travel; United States National Institutes of Health; Vaccines; Visual; Whole Blood; base; density; diagnostic accuracy; drug candidate; drug development; histidine-rich proteins; instrument; light intensity; multiplex detection; nanoparticle; novel; quantum; response; single molecule; vaccine candidate; vaccine development

DESCRIPTION (provided by applicant): Our goal is to develop easy to use, inexpensive, and sensitive quantum dots beads (QDBs) based strip test for multiplex diagnosis of human malaria infection called MAL-QDBTest" that can detect as low as 1 parasite/uL in a <20 min assay. The MAL-QDBTest" consists of 1) multiplexed strip test for qualitative visual detection (Fig. 1), 2) reagents for the strip test, and 3) an optional a handheld fluorescence reader called QD-Analyzer". The MAL-QDBTest" uses novel quantum dots beads in a multiplex strip test that is used both for a) qualitative detection using visual inspection and b) quantitative detection using the QD- Analyzer". The MAL-QDTest" uses novel quantum dots beads (QDBs) that can be used to differentiate a) Pfalciparum from Pvivax; b) detect other Plasmodia causing malaria; c) differentiate live from dead parasites through the detection of pGluDH; and d) quantify the number of parasites present with the use of the QD- Analyzer. It uses quantum dots beads (QDBs) which are nanoparticles (NPs) containing hundreds of quantum dots that exhibit color stability and high light intensity greater than organic dyes. Quantum confined properties of quantum dots with a few atoms to 10,000 atoms can enable single molecule detection. Interfaced with the QD-Analyzer, the QDB-based multiplex detection will provide higher sensitivity, greater reproducibility, lower detection limits, and increased diagnostic accuracy. The proposed multiplex MAL-QDBTest" uses patented QDBs that can be conjugated to selective and specific antibodies for the capture and detection of antigen biomarkers of malaria infection. To date, there is no existing malaria assay that uses QDBs which are sacs of hundreds of NPs that exhibit color stability and high light intensity that are 100% greater than organic dyes with the potential to detect a single molecule. There is a great need for developing better detection methods for malaria parasites because not only does current diagnosis suffer from sensitivity and reliability of results, these cannot detect lower than 100 parasites /uL may be fatal. The sensitivity of current rapid diagnostic tests may be >85% but only at 200 parasites/uL or higher. These cannot be used for drug/vaccine development that requires 1 parasite/uL detection. The proposed MAL-QDBTest" is anticipated to alleviate the diagnosis of > 500 million cases of malaria each year with 1-3 million deaths and the drug and vaccine development hurdles. Currently, there is no no licensed vaccine against this disease. In the US, malaria may re-emerge due to increased travel to endemic countries as well as the deployment of the >300,000 US military personnel worldwide. Furthermore, the number of blood donors who had been refused as a result of recent travel to endemic countries has been > 10% that may have caused shortage at blood banks around the country. Thus, there is a need to develop the proposed MAL-QDBTest" interfaced with the QD-Analyzer for fast, easy to use, reliable, quantitative, and inexpensive methods for malaria diagnosis and to quickly validate drug and vaccine candidates.

描述（由申请人提供）：我们的目标是开发易于使用、廉价和敏感的基于量子点珠（qdb）的条形试验，用于人类疟疾感染的多重诊断，称为MAL-QDBTest，可以在<20分钟的分析中检测到低至1个/uL的寄生虫。al - qdbtest“包括1)用于定性视觉检测的多路试纸（图1），2)用于试纸的试剂，以及3)可选的手持式荧光读取器，称为qd分析仪”。MAL-QDBTest“在多重条带测试中使用新型量子点珠，可用于a)使用目测进行定性检测，b)使用QD分析仪进行定量检测”。MAL-QDTest“使用新型量子点珠（qdb），可用于区分a) Pfalciparum和Pvivax；b)发现引起疟疾的其他疟原虫；c)通过检测pGluDH来区分活的和死的寄生虫；d)使用QD-分析仪量化存在的寄生虫数量。它使用量子点珠（qdb），这是一种包含数百个量子点的纳米颗粒（NPs），具有比有机染料更稳定的颜色和更高的光强。量子点的量子限制特性，从几个原子到10000个原子，可以实现单分子检测。与qd分析仪接口，基于qdb的多路检测将提供更高的灵敏度，更高的重现性，更低的检测限，并提高诊断准确性。拟议的多重MAL-QDBTest”使用获得专利的qdb，可以与选择性和特异性抗体结合，以捕获和检测疟疾感染的抗原生物标志物。迄今为止，还没有使用qdb的现有疟疾检测方法，qdb是由数百个NPs组成的囊，具有颜色稳定性和高光强，比有机染料高100%，具有检测单个分子的潜力。开发更好的疟疾寄生虫检测方法非常有必要，因为目前的诊断不仅灵敏度和结果的可靠性差，而且不能检测到低于100个/单位的寄生虫可能是致命的。目前快速诊断试验的灵敏度可达bb0 - 85%，但只能在200个寄生虫/ μ l或更高的情况下使用。这些不能用于需要1个寄生虫/uL检测的药物/疫苗开发。拟议的MAL-QDBTest"预计将减轻每年50亿疟疾病例的诊断，其中有100万至300万人死亡，并消除药物和疫苗开发障碍。目前，尚无针对这种疾病的许可疫苗。在美国，疟疾可能会再次出现，因为前往流行国家的旅行增加，以及在全球部署了30万美国军事人员。此外，由于最近前往流行国家旅行而被拒绝的献血者人数已达到10%，这可能导致全国各地血库出现短缺。因此，有必要开发与qd分析仪接口的MAL-QDBTest，以实现快速、易于使用、可靠、定量和廉价的疟疾诊断方法，并快速验证候选药物和疫苗。

项目成果

Immunochromatographic assay for ultrasensitive detection of aflatoxin B₁ in maize by highly luminescent quantum dot beads.

• DOI: 10.1021/am503517s
• 发表时间: 2014-08-27
• 期刊: ACS APPLIED MATERIALS & INTERFACES
• 影响因子: 9.5
• 作者: Ren, Meiling;Xu, Hengyi;Huang, Xiaolin;Kuang, Min;Xiong, Yonghua;Xu, Hong;Xu, Yang;Chen, Hongyu;Wang, Andrew
• 通讯作者: Wang, Andrew