PA22176, SBIR, Phase I, Lateral Flow Assay to Detect Malaria

PA22176，SBIR，第一阶段，侧向层析检测疟疾

• 批准号: 10697156
• 负责人: JOSEPH FRANCIS KREBS
• 金额: $ 24.88万
• 依托单位: ATTOGENE
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-30 至 2024-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10697156
• 关键词: PA22176; SBIR; Phase; Lateral; Flow

Summary/Abstract Malaria is a deadly disease transmitted by mosquito bites. Every year, many millions of people in developing areas are affected by this disease. Children under 5 are most vulnerable to malaria. Great strides have been made to develop vaccines and medicines to prevent and treat malaria. The number of annual malaria deaths has decreased by about 85% in the past 100 years. This said, malaria is still endemic in 78 countries. One of the great challenges to further eradication of this disease is detection of subclinical/asymptomatic infections, especially in large rural areas in the developing world. Molecular methods such as PCR or LAMP assays can detect these infections, but they require equipment and expertise which are best suited to the laboratory environment. Portable rapid antigen tests are generally well suited for use in remote areas, but they lack the required sensitivity to detect many low-level infections. Recent reports indicate that rapid antigen tests miss up to 98% of the subclinical cases identified using a LAMP assay on the same samples. Also, many malaria tests require extensive sample prep which is very difficult to perform in remote locations. The overall goal of this project is to create a rugged, portable lateral flow assay to detect malaria. These types of assays are well suited for field use because they do not require equipment and have a simple visual readout. Our test will use specially-engineered sample pads and cassette design to process blood samples within the device - this feature eliminates the need for complicated sample prep in the field. Unlike current rapid diagnostics based on antibody/antigen interactions, our assay utilizes a malarial biomarker (called hemozoin) to create a visual signal. Our test uses the iron atoms within the hemozoin to catalyze the labeling of gold nanoparticles. Our catalytic reaction scheme can generate many labeled particles from each analyte, thereby creating strong signal amplification. The signal amplification will greatly improve the detection sensitivity of our device compared other rapid diagnostic tests and permit detection of low-level subclinical infections in the field. We believe that our unique lateral flow assay device will be an important tool in the ongoing fight to eradicate malaria. Specific Aim #1: Construct a lateral flow test to detect hemozoin. Specific Aim #2: Develop an integrated lateral flow assay device to process blood samples and perform the test. Specific Aim #3: Detect infected cells in whole blood using a novel hemozoin-based lateral flow assay.

摘要/摘要 疟疾是一种致命的疾病，该疾病是由蚊虫叮咬传播的。每年，成千上万的人正在发展 该疾病的影响。 5岁以下的儿童最容易受到疟疾的影响。大步很大 开发疫苗和药物以预防和治疗疟疾。年疟疾死亡人数 在过去的100年中，已减少了约85％。也就是说，在78个国家，疟疾仍然是流行的。 进一步根除这种疾病的巨大挑战之一是检测亚临床/无症状 感染，特别是在发展中国家的大型农村地区。 PCR或LAMP等分子方法 测定可以检测到这些感染，但它们需要设备和专业知识，最适合 实验室环境。便携式快速抗原测试通常非常适合在偏远地区使用，但它们 缺乏所需的灵敏度来检测许多低级感染。最近的报告表明快速抗原测试 在同一样品上使用灯泡测定法确定的亚临床案例中，多达98％。还有许多疟疾 测试需要广泛的样品准备，这在远程位置很难执行。 该项目的总体目标是创建一个坚固的便携式横向流量测定法以检测疟疾。这些类型的 测定非常适合现场使用，因为它们不需要设备并具有简单的视觉读数。 我们的测试将使用特殊设计的样品垫和盒式设计来处理在 设备 - 此功能消除了对现场中复杂样品准备的需求。与电流快速不同 基于抗体/抗原相互作用的诊断方法，我们的测定法利用疟疾生物标志物（称为血元） 创建视觉信号。我们的测试使用血元中的铁原子催化金的标签 纳米颗粒。我们的催化反应方案可以从每个分析物中产生许多标记的颗粒，从而 创建强信号扩增。信号扩增将大大提高检测灵敏度 我们的设备比较了其他快速诊断测试，并允许检测到低级亚临床感染 场地。我们认为，我们独特的侧向流程设备将是持续争夺的重要工具 消除疟疾。 特定目标＃1：构建横向流程测试以检测血元。 特定目的＃2：开发一个集成的侧向流程设备来处理血液样本并执行 测试。 特定的目标＃3：使用新型基于血元的横向流量测定法检测全血中感染的细胞。