Time is critical when diagnosing sepsis, but the tests currently used to identify this disease can take up to 72 hours. Researchers at the Laboratory of Bionanophotonic Systems (BIOS) at École Polytechnique Fédérale de Lausanne (EPFL) have developed an optical biosensor that reduces sepsis diagnosis time from several days to a few minutes. The portable biosensor is based on nanoparticle-enhanced digital plasmonic imaging. The device employs an optical metasurface composed of a thin gold sheet containing arrays of billions of nanoholes. The metasurface concentrates light around the nanoholes to allow for precise biomarker detection. Sepsis biomarkers in a blood sample are detected using an LED and a standard CMOS camera. The portable device can detect biomarkers of sepsis in a few minutes. Courtesy of Alain Herzog/EPFL 2020. To perform a test, a solution of nanoparticles, designed to capture the biomarkers, is added to the sample, and this mixture is distributed onto the metasurface. “Any nanoparticles that contain captured biomarkers are trapped quickly by antibodies on the nanoholes,” researcher Alexander Belushkin said. When an LED is applied to the metasurface, the nanoparticles containing the biomarkers partially obstruct the light passing through the perforated metasurface. “These nanoscale interactions are imaged by the CMOS camera and digitally counted in real time at high precision,” said Filiz Yesilkoy, an EPFL researcher who is now an assistant professor at the University of Wisconsin-Madison. The CMOS images are used to rapidly determine whether disease biomarkers are present in a sample and, if so, in what concentration. Researcher Alexander Belushkin and Hatice Altug, head of BIOS. Courtesy of Alain Herzog/EPFL 2020. Because the biosensor uses plasmonics, it can be built from small, inexpensive components and still achieve an accuracy comparable to gold-standard laboratory methods, the researchers said. The device can be used to screen a large panel of biomarkers and could be adapted for the rapid diagnosis of a number of diseases. The device was installed at Vall d’Hebron University Hospital in Spain and tested with a range of patient samples with sepsis or noninfectious systemic inflammatory response syndrome (SIRS), as well as samples from healthy subjects. It was used to measure the blood serum levels of two sepsis-relevant biomarkers, procalcitonin and C-reactive protein. The results were validated against ultimate clinical diagnosis and currently used immunoassays, and showed that the device provided accurate and robust performance. The plasmonic imager enabled identification of procalcitonin levels typical of sepsis and SIRS patients in less than 15 minutes. The compact and low-cost device is a promising solution for assisting rapid and accurate on-site sepsis diagnosis. “There is an urgent need for such promising biosensors so that doctors can diagnosis sepsis accurately and quickly, thereby keeping patient mortality to a minimum,” Dr. Anna Fàbrega and Dr. Juan José González said. “We believe our low-cost, compact biosensor would be a valuable piece of equipment in ambulances and certain hospital wards,” Hatice Altug, the head of BIOS, said. The technology is patent-pending. The research was published in Small (www.doi.org/10.1002/smll.201906108).