Single Molecule with a Large Transistor – SiMoT cytokine IL-6 Detection Benchmarked against a Chemiluminescent Ultrasensitive Immunoassay Array

Early diagnosis and efficient treatments of oncological, neurological, inflammatory, and infectious diseases rely more and more on ultrasensitive detection of protein markers; the ultimate limit is a reliable immunoassay capable of single-protein detection. Among protein biomarkers, cytokines play a key role in clinical diagnosis as they are involved in developing many complex diseases and disorders, such as chronic inflammatory diseases including metabolic syndrome, neurodegenerative diseases, and cardiovascular diseases, along with autoimmune diseases and cancer. Herein, the improvement of a Single Molecule with Transistor (SiMoT) is reported based on an electrolyte-gated organic field-effect transistor applied for the detection of cytokine IL-6 in blood serum, reaching a limit-of-detection (LOD) of 1 ± 1 protein in a sample of 0.1 mL. The analytical performance levels are benchmarked against the Simoa Planar Array SP-X technology, a benchtop chemiluminescent array. After comprehensive optimization, Simoa SP-X by using a multivariate experimental design approach exhibits a LOD 10³ higher than SiMoT. The proposed SiMoT electronic assay is label-free, fast (30 min), and selective, paving the way for an ultra-sensitive point-of-care immunoassay platform enabling pre-symptomatic disease diagnosis.