Ultrasensitive detection of interleukin-6 enabled by three-dimensional spatial amplification

Accurately measuring interleukin-6 (IL-6) levels is crucial in both clinical medicine and research due to its role in various physiological and pathological processes. We present proof-of-concept of a novel three-dimensional (3D) spatial amplification method for developing highly sensitive and miniaturized IL-6 biosensors. We designed an IL-6 immunosensor platform utilizing a unique 3D microfluidic structure fabricated with femtosecond-pulsed laser processing. This design features a porous transducer element with over 4500 microcavities, thereby increasing the reaction area by 13-fold compared to traditional 2D designs while maintaining transparency. By combining this 3D structure with a competitive antigen-antibody reaction, the sensor achieved an exceptional limit of detection of 0.27 pg/mL for IL-6 in human blood samples. Additionally, we demonstrated effective control of liquid flow within the porous element using a reduction of pressure and centrifugation speeds. This 3D spatial amplification method offers a promising approach for developing highly sensitive and compact IL-6 biosensors. Such miniaturized sensors hold potential for point-of-care testing devices, enabling convenient and timely IL-6 analysis.