EAGER: Rapid and Sensitive Drug Testing for COVID-19

由于对抗新冠肺炎大流行的疫苗还需要几个月到几年的时间才能接种，目前对感染患者的治疗主要集中在抗病毒药物上。然而，像许多导致严重发病率和死亡率的病毒一样，冠状病毒可能会发生变异并产生抗药性。有效的治疗可能需要多种有效药物的供应。目前有数以千计的候选药物，但目前的一个瓶颈是药物测试，这需要在细胞培养中生长病毒，这是一个劳动密集型、低敏感性和耗时的过程，可能需要长达一周的时间才能完成。这个急切的项目利用细胞和病毒培养中的微观流体流动来提高灵敏度和速度，潜在地将测试时间减少到一天。该项目旨在确定抗新冠肺炎病毒药物测试的最佳条件，这将扩大有效治疗感染患者的机会。测试抗病毒药物的金标准是空斑试验，它直接衡量药物对细胞培养中传染性病毒颗粒的产生和传播的影响。然而，斑块测试是劳动密集型的，药物测试的敏感性有限，而且可能需要一周的时间。作为另一种选择，拥有病毒学和流体动力学专业知识的团队将推进更快、更灵敏的检测。这种方法利用了流动增强的感染传播和自动定量成像，他们将优化冠状病毒药物测试。这项技术利用了横扫受感染细胞的微尺度流动，加强了感染的传播；在细胞培养井中，径向流动自发地产生于每口井中心附近流体表面的强化蒸发冷却，从而驱动自然对流。该项目可能在十分之一的时间内将候选药物与新冠肺炎进行测试的敏感度提高10到100倍。这种加速测试可以帮助有效地识别显著降低持续大流行及其可能再次出现的发病率和死亡率的药物。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

With vaccines against the COVID-19 pandemic still months-to-years away, current treatments for infected patients focus on anti-viral drugs. However, like many viruses that cause serious morbidity and mortality, coronaviruses can mutate and develop drug resistance. Effective treatment may require the availability of multiple effective drugs. Thousands of drug candidates are available, but a current bottleneck is drug testing, which entails virus growth in cell cultures, a labor intensive, low sensitivity, and time-consuming process that can take up to a week to perform. ThIs EAGER project exploits microscopic fluid flows in cell and virus cultures to enhance sensitivity and speed, potentially reducing test times to one day. The project aims to identify best conditions for testing of drugs against the COVID-19 virus, which will expand opportunities to effectively treat infected patients.The gold standard for testing anti-viral drugs is the plaque assay, which gives direct measures of drug effect on the production and spread of infectious virus particles in the cell culture. However, the plaque assay is labor-intensive, limited in sensitivity for drug testing, and it can take a week to perform. As an alternative, a team with expertise in virology and fluid dynamics will advance a faster, more sensitive assay. The approach exploits flow-enhanced infection spread and automated quantitative imaging, which they will optimize for coronavirus drug testing. The technology exploits microscale flows that sweep across infected cells, enhancing the spread of infection; in cell-culture wells, radial flows spontaneously arise from enhanced evaporative cooling at the fluid surface near the center of the each well, driving natural convection. The project may enable a 10-to100-fold higher sensitivity in one-tenth the time for testing drug candidates against COVID-19. Such accelerated testing could help efficiently identify drugs that significantly reduce morbidity and mortality from the ongoing pandemic and its possible re-emergence.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.