The critical role of engineering in the rapid development of COVID-19 diagnostics: Lessons from the RADx Tech Test Verification Core.

Engineering plays a critical role in the development of medical devices, and this has been magnified since 2020 as severe acute respiratory syndrome coronavirus 2 swept over the globe. In response to the coronavirus disease 2019, the National Institutes of Health launched the Rapid Acceleration of Diagnostics (RADx) initiative to help meet the testing needs of the United States and effectively manage the pandemic. As the Engineering and Human Factors team for the RADx Tech Test Verification Core, we directly assessed more than 30 technologies that ultimately contributed to an increase of the country's total testing capacity by 1.7 billion tests to date. In this review, we present central lessons learned from this "apples-to-apples" comparison of novel, rapidly developed diagnostic devices. Overall, the evaluation framework and lessons learned presented in this review may serve as a blueprint for engineers developing point-of-care diagnostics, leaving us better prepared to respond to the next global public health crisis rapidly and effectively.

Don't forget about human factors: Lessons learned from COVID-19 point-of-care testing.

During the COVID-19 pandemic, the development of point-of-care (POC) diagnostic testing accelerated in an unparalleled fashion. As a result, there has been an increased need for accurate, robust, and easy-to-use POC testing in a variety of non-traditional settings (i.e., pharmacies, drive-thru sites, schools). While stakeholders often express the desire for POC technologies that are "as simple as digital pregnancy tests," there is little discussion of what this means in regards to device design, development, and assessment. The design of POC technologies and systems should take into account the capabilities and limitations of the users and their environments. Such "human factors" are important tenets that can help technology developers create POC technologies that are effective for end-users in a multitude of settings. Here, we review the core principles of human factors and discuss lessons learned during the evaluation process of SARS-CoV-2 POC testing.

The RADx Tech Test Verification Core and the ACME POCT in the Evaluation of COVID-19 Testing Devices: A Model for Progress and Change.

Faced with the COVID-19 pandemic, the US system for developing and testing technologies was challenged in unparalleled ways. This article describes the multi-institutional, transdisciplinary team of the "RADxSM Tech Test Verification Core" and its role in expediting evaluations of COVID-19 testing devices. Expertise related to aspects of diagnostic testing was coordinated to evaluate testing devices with the goal of significantly expanding the ability to mass screen Americans to preserve lives and facilitate the safe return to work and school. Focal points included: laboratory and clinical device evaluation of the limit of viral detection, sensitivity, and specificity of devices in controlled and community settings; regulatory expertise to provide focused attention to barriers to device approval and distribution; usability testing from the perspective of patients and those using the tests to identify and overcome device limitations, and engineering assessment to evaluate robustness of design including human factors, manufacturability, and scalability.

Multiplexed detection of lectins using integrated glycan-coated microring resonators.

We present the systematic design, fabrication, and characterization of a multiplexed label-free lab-on-a-chip biosensor using silicon nitride (SiN) microring resonators. Sensor design is addressed through a systematic approach that enables optimizing the sensor according to the specific noise characteristics of the setup. We find that an optimal 6 dB undercoupled resonator consumes 40% less power in our platform to achieve the same limit-of-detection as the conventional designs using critically coupled resonators that have the maximum light-matter interaction. We lay out an optimization framework that enables the generalization of our method for any type of optical resonator and noise characteristics. The device is fabricated using a CMOS-compatible process, and an efficient swabbing lift-off technique is introduced for the deposition of the protective oxide layer. This technique increases the lift-off quality and yield compared to common lift-off methods based on agitation. The complete sensor system, including microfluidic flow cell and surface functionalization with glycan receptors, is tested for the multiplexed detection of Aleuria Aurantia Lectin (AAL) and Sambucus Nigra Lectin (SNA). Further analysis shows that the sensor limit of detection is 2 × 10(-6) RIU for bulk refractive index, 1 pg/mm(2) for surface-adsorbed mass, and ∼ 10 pM for the glycan/lectins studied here.

Detection of avian influenza virus using an interferometric biosensor.

An interferometric biosensor immunoassay for direct and label-less detection of avian influenza through whole virus capture on a planar optical waveguide is described. The assay response is based on index of refraction changes that occur upon binding of virus particles to unique antigen-specific (hemagglutinin) antibodies on the waveguide surface. Three virus subtypes (two H7 and one H8) in buffer solution were tested using both monoclonal and polyclonal capture antibodies. The real-time response of the antigen-antibody interaction was measured and was shown to be concentration-dependent, with detection limits as low as 0.0005 hemagglutination units per milliliter. A simple sandwich assay was shown to further increase the biosensor response.

Can false memories spontaneously recover?

Can false memories that were suppressed at one time spontaneously recover at a later time? Fuzzy trace theory and activation-monitoring theory predict that false memories in the Deese, Roediger, and McDermott (DRM) procedure become substantially reduced as list learning progresses because participants employ a memory-editing process. It follows that if the editing process is rendered less effective, false memories should spontaneously recover. We found that after DRM lists were well learned and false recognition to critical words was substantially reduced by multiple study-test trials, those false memories spontaneously recovered when participants were either rushed or delayed on a retest. We attributed the reduction in false recognition over trials to a memory-editing process that suppresses false recognition as participants gradually learn which words were in the lists and which words, though similar, were not. Rushing or delaying the participants on a retest made it more difficult for them to edit their memory, and false memories spontaneously returned.