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

以下包含Travis Schlappi和Kevin Hickerson要求的专有/特权信息 发布给政府以外的人，但出于审查和评估的目的除外。 摘要： 当诊断试验不符合以下一项或多项时，传染病的诊断就不那么有效了 可负担性、可及性和准确性的必要标准。当前诊断方法的缺陷 方法在新冠肺炎大流行中已经很明显，一些测试是准确的，但负担不起或 可访问的(例如，在中央实验室中检测COVID RNA的RT-PCR测试)，而其他测试已变得更多 可获得和负担得起，但准确度较低(例如快速抗原测试)。FAST的高假阴性率 抗原检测排除了他们作为检测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)检测仍然是首选的检测方法 方法。这种在高精度与高成本、高复杂性和慢周转时间或低精度之间的权衡 低成本、低复杂度、快速周转时间是医学诊断领域尚未解决的问题。关键人物 取得进展的障碍是呼吸道、血液中存在感兴趣的细菌、病毒、NAS或蛋白质， 粪便或尿样的浓度太低，无法直接检测到。为了获得足够的灵敏度， 因此，目前的方法是扩增病原体或扩增来自 病原体。即使有了最近的进展，这些扩增方法仍然需要许多步骤和昂贵的费用 从样品中提纯目标分子并进行扩增的仪器。建议的目标是 该项目将进行一项试点研究，以开发一种不需要靶标扩增的新诊断技术， 而是检测高灵敏度、低成本和广泛应用的放射性标记生物分子 可访问性。所提出的原理类似于通常在横向流条上发现的夹心免疫分析， 例如在家中进行怀孕测试。在目标1中，含有天然丰富元素的纳米颗粒具有 将制定和表征相同的放射性同位素。这些实验的结果将告诉我们 放射性同位素非常适合用在集成设备中。在目标2中，将开发一个原型，用于 来自廉价、商用电子产品的放射性粒子探测器，例如来自 一部智能手机。最终的检测设备将比目前可用的测试更简单、更便宜 因为目标提纯和/或 避免了酶促扩增。如果这项初步研究被证明是成功的，未来的工作将开发出一种体外 检测传染病的诊断设备，满足所有保证标准(负担得起、敏感、特异、 用户友好、快速、无需设备、可交付)。临床实践、疾病管理、大流行 全球公民的准备和医疗保健将以快速(&lt；5分钟)、负担得起的方式发生变化 (&lt；5美元)，敏感的，可获得的传染病检测。

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.