Self-referenced Digital Spectral Chromatic Local Surface Plasmon Resonance in Ultrasensitive Severe Sepsis Interleukin-6 Detection

Clinical monitoring of cytokines, such as interleukin-6 (IL-6), enables a timely diagnosis and can significantly improve patient prognosis. In this study, we developed a rapid, label-free, ultrasensitive, and low matrix-effect method called chromatic digital nanoplasmon-metry (cDiNM) to detect IL-6 in human blood plasma. Utilizing a multiple filter configuration, two nonadjacent specific transmission wavelength bands are extracted. One is centered within the full-width-at-half-maximum (fwhm) range where the local surface plasmon resonance (LSPR) response of the 80 nm gold nanoparticles (AuNPs) is strongest, while the other band is narrowed and blue-shifted from the peak to a region with minor intensity change. Scattering images of AuNPs passing through these two bands are then captured simultaneously and independently via the red and green channels of a color scientific complementary metal–oxide–semiconductor (sCMOS) camera. This configuration allows every AuNPs’ spectral chromatic image contrast to be a self-referenced subtractive analysis LSPR and facilitates evaluation of their changes induced by the IL-6 binding across numerous individual AuNPs. This method achieves IL-6 detection in blood plasma within 45 min, requiring only 0.5 mL of a 10-fold diluted, label-free sample, with a limit of detection and quantification (LOD and LOQ) of less than 19.2 and 87.8 fg/mL, respectively, and a recovery rate of 96%. In summary, cDiNM provides rapid and accurate IL-6 monitoring with promising potential for clinical application in sepsis patient care.