Pilot study for low-cost, rapid, and accessible infectious disease diagnostics via alpha particle detection

通过阿尔法粒子检测进行低成本、快速且易于获得的传染病诊断的试点研究

• 批准号: 10440761
• 负责人: Travis S. Schlappi
• 金额: $ 7.75万
• 依托单位: KECK GRADUATE INST OF APPLIED LIFE SCIS
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-01-12 至 2023-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10440761
• 关键词: Alpha Particles; Antibodies; Bacteria; Binding; Blood; COVID detection; COVID-19 pandemic; Cellular Phone; Cerium; Chemicals; Communicable Diseases; Detection; Devices; Diagnostic Equipment; Diagnostic Procedure; Diagnostic tests; Diarrhea; Disease; Disease Management; Electronics; Elements; Equipment; Evaluation; Event; Feces; Funding; Future; Goals; Gold; Government; Healthcare; Healthcare Systems; Home; Immunoassay; In Vitro; Institution; Isotopes; Knowledge; Label; Lateral; Legal; Licensing; Liquid substance; Methods; Nucleic Acid Amplification Tests; Nucleic Acids; Optics; Organism; Pathogenicity; Patients; Persons; Pilot Projects; Plutonium; Pregnancy Tests; Proteins; Public Health; RNA; Radioactive; Radioisotopes; Radiology Specialty; Regulation; Research; Reverse Transcriptase Polymerase Chain Reaction; Sampling; Signal Transduction; Source; Surface; Symptoms; Temperature; Testing; Time; Treatment outcome; Urine; Virus; Work; antigen test; base; clinical diagnostics; clinical practice; communicable disease diagnosis; cost; detection limit; detection method; detector; diagnostic technologies; disease diagnostic; disease transmission; experimental study; improved; in-vitro diagnostics; instrument; interest; lens; nanoGold; nanoparticle; novel diagnostics; pandemic preparedness; particle detector; pathogen; prevent; prototype; respiratory; seal; sensor; test strip; user-friendly

The following contains proprietary/privileged information that Travis Schlappi and Kevin Hickerson request not be released to persons outside the government, except for purposes of review and evaluation. Summary: Diagnosis of infectious disease is less effective when the diagnostic test does not meet one or more of the necessary standards of affordability, accessibility, and accuracy. The shortcomings of current diagnostic methods have been apparent in the COVID-19 pandemic, where some tests are accurate, but not affordable or accessible (e.g. RT-PCR tests that detect COVID RNA in a centralized lab), while other tests have become more accessible and affordable, but have low accuracy (e.g. rapid antigen tests). The high false negative rate of rapid antigen tests precludes their ability to limit disease transmission as asymptomatic carriers that test negative continue infecting others; therefore, RT-PCR or other nucleic acid (NA) tests remain the preferred testing method. This tradeoff of high accuracy with high cost, high complexity, and slow turnaround time, or low accuracy with low cost, low complexity, and fast turnaround time is an unsolved problem in medical diagnostics. The critical barrier to making progress is that the bacteria, viruses, NAs, or proteins of interest exist in the respiratory, blood, stool, or urine sample in too low of a concentration to be directly detected. To achieve sufficient sensitivity, current methods therefore amplify the pathogenic organism or amplify a target biomolecule coming from the pathogen. Even with recent advances, these amplification methods still require many steps and costly instruments to purify the target molecule from the sample and perform amplification. The goal of the proposed project is to do a pilot study for developing a new diagnostic technology that does not require target amplification, but instead detects radiologically labeled biomolecules with high sensitivity, low cost, and widespread accessibility. The proposed principle is similar to a sandwich immunoassay commonly found on lateral flow strips, such as at-home pregnancy tests. In Aim 1, nanoparticles of naturally abundant elements that have functionally identical radioisotopes will be formulated and characterized. The results from these experiments will inform which radioisotope is well-suited to be used in an integrated device. In Aim 2, a prototype will be developed for a radioactive particle detector from inexpensive, commercially available electronics, such as a CMOS sensor from a smartphone. The final detection device will be significantly simpler and cheaper than currently available tests because the multiple fluid handling and temperature control steps typically required for target purification and/or enzymatic amplification are avoided. If this pilot study proves successful, future work will develop an in vitro diagnostic device to detect infectious disease that satisfies all ASSURED criteria (affordable, sensitive, specific, user-friendly, rapid, equipment-free, deliverable). Clinical practice, disease management, pandemic preparedness, and healthcare of citizens around the globe would be transformed with rapid (<5 min), affordable (<$5), sensitive, and accessible tests for infectious diseases.

以下内容包含 Travis Schlappi 和 Kevin Hickerson 要求不得公开的专有/特权信息 向政府以外的人员发布，但出于审查和评估的目的除外。 概括： 当诊断测试不符合一项或多项要求时，传染病的诊断效果较差 负担能力、可及性和准确性的必要标准。目前诊断技术的缺陷 方法在 COVID-19 大流行中已经很明显，其中一些测试是准确的，但价格昂贵或价格昂贵 易于获取（例如，在集中实验室中检测新冠病毒 RNA 的 RT-PCR 测试），而其他测试则变得更加容易 容易获得且负担得起，但准确性较低（例如快速抗原测试）。快速检测假阴性率高 抗原检测妨碍了他们作为检测呈阴性的无症状携带者限制疾病传播的能力 继续感染他人；因此，RT-PCR 或其他核酸 (NA) 检测仍然是首选检测 方法。这种高精度与高成本、高复杂性和慢周转时间或低精度的权衡 低成本、低复杂性和快速周转时间是医疗诊断中尚未解决的问题。关键的 取得进展的障碍是细菌、病毒、NA 或感兴趣的蛋白质存在于呼吸道、血液、 粪便或尿液样本的浓度太低，无法直接检测。为了达到足够的灵敏度， 因此，当前的方法放大了致病生物体或放大了来自病原体的目标生物分子。 病原。即使取得了最新进展，这些扩增方法仍然需要许多步骤且成本高昂 从样品中纯化目标分子并进行扩增的仪器。拟议的目标 项目是进行一项试点研究，开发一种不需要目标放大的新诊断技术， 而是以高灵敏度、低成本和广泛的方式检测放射标记的生物分子 可达性。所提出的原理类似于侧流试纸条上常见的夹心免疫测定法， 例如在家进行妊娠测试。在目标 1 中，天然丰富元素的纳米颗粒具有功能性 相同的放射性同位素将被配制和表征。这些实验的结果将告诉我们哪些 放射性同位素非常适合在集成设备中使用。在目标 2 中，将开发一个原型 放射性粒子探测器由廉价的市售电子产品制成，例如 CMOS 传感器 智能手机。最终的检测设备将比目前可用的测试更简单、更便宜 因为目标纯化和/或通常需要多个流体处理和温度控制步骤 避免了酶促扩增。如果这项试点研究成功，未来的工作将开发一种体外 用于检测传染病的诊断设备，满足所有 ASSURED 标准（经济实惠、灵敏、特异性、 用户友好、快速、无需设备、可交付）。临床实践、疾病管理、流行病 全球公民的准备和医疗保健将通过快速（<5 分钟）、负担得起的方式发生转变 （< 5 美元）、敏感且易于使用的传染病检测。