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.

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.