Open Development and Clinical Validation of Multiple 3D-Printed Nasopharyngeal Collection Swabs: Rapid Resolution of a Critical COVID-19 Testing Bottleneck

Abstract

27The SARS-CoV-2 pandemic has caused a severe international shortage of the nasopharyngeal 28 swabs that are required for collection of optimal specimens, creating a critical bottleneck 29 blocking clinical laboratories' ability to perform high-sensitivity virological testing for SARS-CoV-30 2. To address this crisis, we designed and executed an innovative, cooperative, rapid-response 31 translational-research program that brought together healthcare workers, manufacturers, and 32 scientists to emergently develop and clinically validate new swabs for immediate mass 33 production by 3D printing. We performed a multi-step preclinical evaluation on 160 swab 34 designs and 48 materials from 24 companies, laboratories, and individuals, and shared results 35 and other feedback via a public data repository (http://github.com/rarnaout/Covidswab/). We 36 validated four prototypes through an institutional review board (IRB)-approved clinical trial that 37 involved 276 outpatient volunteers who presented to our hospital's drive-through testing center 38 with symptoms suspicious for COVID-19. Each participant was swabbed with a reference swab 39 (the control) and a prototype, and SARS-CoV-2 reverse-transcriptase polymerase chain 40 reaction (RT-PCR) results were compared. All prototypes displayed excellent concordance with 41 the control (κ=0.85-0.89). Cycle-threshold (Ct) values were not significantly different between 42 each prototype and the control, supporting the new swabs' non-inferiority (Mann-Whitney U 43[MWU] p>0.05). Study staff preferred one of the prototypes over the others and the control swab 44 overall. The total time elapsed between identification of the problem and validation of the first 45 prototype was 22 days. Contact information for ordering can be found at http://printedswabs.org. 46Our experience holds lessons for the rapid development, validation, and deployment of new 47 technology for this pandemic and beyond. 48 on June 9, 2020 by guest

SARS-CoV2 Testing: The Limit of Detection Matters

“…Of the 27,098 tests performed on 20,076 patients over the testing period, 6,037 tests were positive (22%), representing 4,774 unique patients. Analysis of repeats within 6 or 12 hours of each other (7) demonstrated high repeatability of Ct values over these short time windows ( R 2 0.70 and 0.63, n=25 and 51, respectively), supporting the validity of this quantitative measure as a basis for assessment of viral load in patients (Fig. 1).…”

Pandemic printing: a novel 3D‐printed swab for detecting SARS ‐CoV‐2

“…Our work builds on recent work in the United States, where evaluation of four 3D‐printed swab prototypes found no differences between control and 3D‐printed swabs with respect to the detection of SARS‐CoV‐2 . The authors of the US study also employed an iterative design process, with close collaboration between academic, clinical, and industrial partners, but health care providers and participants both preferred standard swabs to the 3D‐printed swabs.…”

“…We employed an iterative design process that incorporated feedback from clinical and engineering researchers. Based on initial specifications published by investigators in the United States, four initial prototype designs were printed. Printing was undertaken using selective laser sintering (SLS) technology (feature resolution, 80 μm) and PA2200 medical grade biocompatible nylon 12 as source material.…”

A Comparison Efficacy Study of Commercial Nasopharyngeal Swabs versus a Novel 3D Printed Swab for the Detection of SARS-CoV-2

“…Our data were similar to another comparison study between a commercial nasopharyngeal swab, a repurposed urogenital cleaning swab and four printed 3D prototypes with Cohen's kappa coefficients ranging from 0.85 to 0.90. [8] There are other prototypes of printed 3D swabs being tested. Manufacturing companies (Carbon, Redwood City, CA; Formlabs, Somerville, MA; Markforged, Watertown, MA;) currently manufacture and distribute 3D printed nasopharyngeal swabs for the purpose of detecting COVID-19, but efficiency data were not provided.…”