Point-of-care diagnostics: recent developments in a pandemic age

Abstract

In this review, we provide an overview of developments in point-of-care (POC) diagnostics during the COVID-19 pandemic. We review these advances within the framework of a holistic POC ecosystem, focusing on points of interest - both technological and non-technological - to POC researchers and test developers. Technologically, we review design choices in assay chemistry, microfluidics, and instrumentation towards nucleic acid and protein detection for severe acute respiratory coronavirus 2 (SARS-CoV-2), and away from the lab bench, developments that supported the unprecedented rapid development, scale up, and deployment of POC devices. We describe common features in the POC technologies that obtained Emergency Use Authorization (EUA) for nucleic acid, antigen, and antibody tests, and how these tests fit into four distinct POC use cases. We conclude with implications for future pandemics, infectious disease monitoring, and digital health.

Figure 1.. Overview of the POC diagnostics ecosystem in a pandemic age.

All technology and non-technology components play a role in determining the systems integration (i.e., use case) of POC diagnostic devices. Adapted from reference 2 with permission from American Chemical Society.

Figure 2.. Images of selected industry examples of SARS-CoV-2 POC tests.

Nucleic acid tests (A-C), antigen tests (D-F), antibody tests (G-I). A) Lucira Health CHECK-IT COVID -19 Test. Adapted from reference 278 with permission from Elsevier. B) Visby Medical COVID-19 Point-of-Care Test. Taken from www.visbymedical.com with permission from Visby Medical C) Cue Health Cue COVID -19 Test. Taken from www.cuehealth.com with permission from Cue Health D) Ellume COVID-19 Home Test. Credit to Ellume E) Luminostics Clip COVID Rapid Antigen Test. Credit to Luminostics. Inc. F) LumiraDx SARS-CoV-2 Ag Test. Credit to LumiraDx G) Assure Tech Assure COVID-19 IgG/IgM Rapid Test Device. Credit to Assure Tech. H) NOW Diagnostics ADEXUSDx COVID-19 Test. Adapted from reference 279 with permission from Elsevier. I) JoysBio SARS-CoV-2 IgG/Neutralizing Antibody Rapid Test Kit. Taken from en.joysbio.com with permission from JoysBio.

Figure 3.. Timeline of OTC tests approved by the FDA from 1990 to 2020.

Data from FDA’s OTC database

Figure 4.. Overview of IVD’s that have received FDA EUA

A) Total number of IVD’s issued EUA by the FDA during previous declarations of the EUA pathway. Note: IVD’s that have had their EUA revoked are included in the analysis, and all listed pathogens here have current EUAs except H1N1 (designated with *). B) Breakdown of current SARS-CoV-2 IVDs that have received EUA by assay type (nucleic acid, antigen, antibody) and authorized setting to run the test. See ESI for more information on methods for data compilation.

Figure 5.. Unofficial chart demonstrating relationships between company history, government funding (NIH, BARDA, DoD), and time to first EUA.

A) Year of company founding versus time (months) to company’s initial FDA EUA from declaration of public health emergency on February 4^th, 2020. B) Year of company founding versus US Federal funding in millions of dollars C) US Federal funding versus time to initial FDA EUA from declaration of public health emergency. Note: The date of company founding for Abbott uses the founding date of Alere, which originally developed the POC technologies (BinaxNOW and ID NOW) and was acquired by Abbott in 2017. See ESI for more information on methods for data compilation and Supplementary Table 3 for specific tests included in the analysis.

Figure 6:. POC use cases, decoupling cost from infrastructure.

A) Graphical representation of uses cases in 2x2 grid, with each use case assigned a representative color, and icon describing example settings B) Graphical representation of use cases using consumer electronics analogy C) General description and main design considerations for each use case D) Examples of SARS-CoV-2 POC diagnostics ideal for each use case (based on technology). Adapted from reference 2 with permission from American Chemical Society. This figure has been designed using icons made by Freepik, Eucalyp, and xnimrodx from Flaticon.com.

Figure 7:. Breaking down the POC diagnostic platforms that have received FDA EUA by their use case.

Note: platforms with multiple tests approved (e.g., for SARS-CoV-2 and panel including Influenza/RSV) were only counted once in this analysis. Use case analysis was based on ideal fit for underlying technology with Supplementary Table 4 outlining the specific tests included in each category. Cepheid GeneXpert was counted for both centralized and decentralized healthcare due to various instrument sizes available.