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

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.