Sub-monolayer Biolasers: Lower Gain, Higher Sensitivity

Biomarker detection is the key to identifying health risks. However, designing sensitive biosensors in a single-use mode for disease diagnosis remains a major challenge. Here, we report sub-monolayer biolasers with remarkable repeatability for ultrasensitive and disposable biomarker detection. The biolaser sensors are designed by employing the telecom optical fibers as distributed optical microcavities and pushing the gain molecules down to the sub-monolayer level. We observe a status transition from the monolayer biolaser to the sub-monolayer biolaser by tuning the specific conjugation. By reducing the fluorophores down to the threshold density (~ 3.2 x 10-13 mol/cm2), we demonstrate an ultimate sensitivity of sub-monolayer biolaser with six orders of magnitude enhancement compared with the monolayer biolasers. We further achieved ultrasensitive immunoassay for Parkinson's disease biomarker, alpha-synuclein, with a lower limit of detection of 0.32 pM in serum. This biosensor with massive fabrication capability at ultralow cost provides a general method for the ultrasensitive disposable biodetection of disease biomarkers.