Early identification of illnesses like dementia and cancer before they cause severe, irreversible symptoms is crucial for public health and can lower morbidity and death rates. It is challenging to accurately estimate the incredibly low concentrations of biomarkers in the early stages of a disease.
a, Submonolayer whispering-gallery biolasers on telecom optical fibers. b, Sensitivity as a function of the surface density of gain molecules. c, Comparison of the sensing performance of four types of biolasers. Image Credit: Chaoyang Gong, Xi Yang, Shui-Jing Tang, Qian-Qian Zhang, Yanqiong Wang, Yi-Ling Liu, Yu-Cheng Chen, Gang-Ding Peng, Xudong Fan, Yun-Feng Xiao, Yun-Jiang Rao, and Yuan Gong
Over the past 20 years, optical microcavities have become a powerful platform for biological investigation, magnifying optical signals with significant cavity feedback. However, for single-use biosensors, the great reliance on delicate fabrication techniques and the necessary coupling need is particularly undesirable.
Scientists at the Key Laboratory of Optical Fiber Sensing and Communications (Ministry of Education of China), School of Information and Communication Engineering, University of Electronic Science and Technology of China, Chengdu, China, and Associates have created submonolayer biolasers on optical fiber as ultrasensitive and disposable biosensors.
Their work was published in the journal Light Science & Application. Using optical fiber microcavities with ultrahigh Q-factors of 106, dispersed over an amazing 10 km, they achieved mass manufacturing of the submonolayer biolasers at a minimal cost.
Unlike passive microcavities, free-space optics makes it easy to pump and detect submonolayer biolasers. This eliminates the need for critical waveguide coupling and, more importantly, opens the door to developing ultrasensitive single-use biosensors.
More astonishingly, they showed that the submonolayer biolaser exhibits a six-order-of-magnitude improvement in the lower limit of detection (LOD) compared to the monolayer biolaser by pushing the gain molecules down to the threshold density. Additionally, the group showed how their submonolayer biolaser might be used for clinical diagnosis.
They used the submonolayer biolaser to find a lower limit of detection (LOD) of 0.32 pM for a Parkinson's disease (PD) biomarker in serum. The concentration of α-syn in the serum of people with Parkinson's disease is almost three orders of magnitude higher than this result. With its ultimate sensitivity, the suggested approach has considerable potential for high-throughput clinical diagnostics.
Scientists summarize the mechanism of submonolayer biolaser as, “We found that the submonolayer biolaser with optical gain slightly above the lasing threshold has the highest sensitivity. This phenomenon can be explained by the contribution of the gain molecules in lasing action. For example, when 10,000 gain molecules participate in lasing, the average contribution of each molecule is 1/10,000.”
“Once we decrease the gain molecules to 100, the average contribution of each molecule will increase to 1/100. The binding of one analyte molecule on the optical fiber will increase one more binding site for a gain molecule. Therefore, a higher sensitivity can be expected with biolaser with fewer gain molecules,” they quoted.
“We chose commercial optical fiber as microcavity to demonstrate this hypothesis. The geometry and surface properties of optical fiber were well controlled during the fiber drawing process. The optical fiber can be regarded as distributed microcavities with highly reproducible performance,” they said.
Scientists added, “Meanwhile, the price of optical fiber is very low, making disposable sensors possible. For example, the price of SMF-28e optical fiber used in our experiment is about $ 0.5 per meter. The submonolayer laser is fabricated with a fiber segment about 2 cm long, corresponding to a neglectable cost of about $ 0.01.”
Scientists forecasted, “The submonolayer biolaser is a general sensing platform, which can be employed to detect types of biomarkers. The single-use laser-based biosensors with ultrahigh sensitivity could enable cost-effective and early diagnosis of major diseases.”
Journal Reference:
Gong, C., et.al., (2023) Submonolayer biolasers for ultrasensitive biomarker detection. Light: Science & Applications. doi.org/10.1038/s41377-023-01335-8.