Rapid Quantum Magnetic IL-6 Point-of-Care Assay in Patients Hospitalized with COVID-19

Abstract

Interleukin-6 (IL-6) has been linked to several life-threatening disease processes. Developing a point-of-care testing platform for the immediate and accurate detection of IL-6 concentrations could present a valuable tool for improving clinical management in patients with IL-6-mediated diseases. Drawing on an available biobank of samples from 35 patients hospitalized with COVID-19, a novel quantum-magnetic sensing platform is used to determine plasma IL-6 concentrations. A strong correlation was observed between IL-6 levels measured by QDTI10x and the Luminex assay (r = 0.70, p-value < 0.001) and between QDTI80x and Luminex (r = 0.82, p-value < 0.001). To validate the non-inferiority of QDTI to Luminex in terms of the accuracy of IL-6 measurement, two clinical parameters—the need for intensive care unit admission and the need for mechanical intubation—were chosen. IL-6 concentrations measured by the two assays were compared with respect to these clinical outcomes. Results demonstrated a comparative predictive performance between the two assays with a significant correlation coefficient. Conclusion: In short, the QDTI assay holds promise for implementation as a potential tool for rapid clinical decision in patients with IL-6-mediated diseases. It could also reduce healthcare costs and enable the development of future various biomolecule point-of-care tests for different clinical scenarios.

Keywords: COVID-19; ICU; IL-6; Luminex; QDTI; diagnostics; mechanical ventilation.

Figure 1

(a) Immunocomplex containing two magnetic beads covalently bonded to antibody tags specific to different epitopes of the target protein analyte. Arrows indicate the different magnetic properties of magnetic beads A and B, which are superparamagnetic and ferromagnetic, respectively. (b) Schematic of the quantum diamond microscope featuring a synthetic diamond chip with a thin layer of NV centers, a laser beam to excite NV center fluorescence, a high-resolution objective lens to collect the fluorescence onto a camera, and an electromagnet to apply different bias magnetic fields to the magnetic beads in the sample. (c) An immunocomplex containing both magnetic bead A and bead B is identified by overlapping magnetic dipole signals (light + dark lobes) in the separated bead A and bead B detection channels (blue and green images, respectively).

Figure 2

Example IL-6 assay calibration curve (squares). Assay signal is the fraction of beads contained in analyte-bound immunocomplexes. The solid line is a four-parameter logistic fit with 1/y² weighting.

Figure 3

Scatter plot matrix displaying associations between IL-6 concentrations between QDTI instrument and Luminex assay. High correlations were observed between the IL-6 concentrations (A) between QDTI10x and QDTI80x (r = 0.90, p-value < 0.001) and (B) between the Luminex and QDTI10x (r = 0.70, p-value < 0.001) and (C) between the Luminex and QDTI80x (r = 0.82, p-value < 0.001).

Figure 4

Distribution of QDTI10x, QDTI80x, and Luminex assay by ICU and intubation status. The dashed vertical lines represent median assay values. Y-axis represents density.

Figure 4

Distribution of QDTI10x, QDTI80x, and Luminex assay by ICU and intubation status. The dashed vertical lines represent median assay values. Y-axis represents density.

Figure 5

Luminex (red), QDTI10x (green), and QDTI80x (blue). (A) ROC for patients admitted to the ICU. (B) ROC for patients requiring intubation.