AUTHOR=Lin Sheng-Wen , Shen Ching-Fen , Liu Ching-Chuan , Cheng Chao-Min TITLE=A Paper-Based IL-6 Test Strip Coupled With a Spectrum-Based Optical Reader for Differentiating Influenza Severity in Children JOURNAL=Frontiers in Bioengineering and Biotechnology VOLUME=9 YEAR=2021 URL=https://www.frontiersin.org/journals/bioengineering-and-biotechnology/articles/10.3389/fbioe.2021.752681 DOI=10.3389/fbioe.2021.752681 ISSN=2296-4185 ABSTRACT=

Influenza virus infection is a major worldwide public health problem. Influenza virus infections are associated with a high hospitalization rate in children between the ages of 5 and 14. The predominant reason for poor influenza prognosis is the lack of any effective means for early diagnosis. Early diagnosis of severe illness is critical to improving patient outcome, and could be especially useful in areas with limited medical resources. Accurate, inexpensive, and easy-to-use diagnostic tools could improve early diagnosis and patient outcome, and reduce overall healthcare costs. We developed an interleukin-6 paper-based test strip that used colloidal gold-conjugated antibodies to detect human interleukin-6 protein. These complexes were captured on a paper-based test strip patterned with perpendicular T lines that were pre-coated with anti-human interleukin-6 antibodies. Applied serum samples interacted with these antibodies and presented as colored bands that could be read using a spectrum-based optical reader. The full-spectrum of the reflected light interleukin-6 protein signal could be obtained from the spectral optics module, and the standard could be used to quantitatively analyze interleukin 6 level in serum. We retrospectively evaluated 10 children (23 serum samples) with severe influenza virus infections, 26 children (26 serum samples) with mild influenza virus infections, and 10 healthy children (10 serum samples). Our system, the combined use of a paper-based test strip and a spectrum-based optical reader, provided both qualitative and quantitative information. When used with the optical reader, the detection limit was improved from a qualitative, naked-eye level of 400 pg/ml to a quantitative, optical reader level of 76.85 pg/ml. After monitoring serum interleukin-6 level via our system, we found a high correlation between our system results and those obtainable using a conventional sandwich enzyme-linked immunosorbent assay method (Rho = 0.706, p < 0.001). The sensitivity and specificity for differentiating between severe and mild influenza using our combined method (test strip coupled with optical reader) were 78.3 and 50.0%, respectively. When interleukin-6 was combined with serum C-reaction protein, the sensitivity and specificity were 85.7 and 95.5%, and the receiver operating characteristic area-under-the-curve was quite high (AUC = 0.911, p < 0.001). The potential advantages of our system, i.e., a paper-based test strip coupled with a spectrum-based optical reader, are as follows: 1) simple user operation; 2) rapid turnaround times–within 20 min; 3) high detection performance; and, 4) low-cost fabrication.