Phase Multiplexing-Based Molecular Imprint Biosensor

The precise biomolecular detection is crucial in medical diagnosis, biological research, and bioengineering. In this article, a phase multiplexing-based molecularly imprinted polymer biosensor (PM-MIPB) is proposed. It considers the high-throughput and nonlabeling detection mode by multiplexing without increasing the number of scanning and detecting elements, as well as the high specificity and affinity of molecular imprinting technology (MIT), to improve the throughput and accuracy of molecular detection. Phase multiplexing originates from phase-sensitive spectral-domain optical coherence tomography, where the low-coherence interferometric spectra with multiple optical path differences are spectrally analyzed to identify and extract the interferometric phases across these paths. Based on this principle, simultaneous quantitative detection and interaction analysis of multiple analytes can be realized by preparing multiple optical-path difference-encoded (also thickness-encoded) detection channels and simultaneously extracting the phases of the interfering signals. Furthermore, the PM-MIPB utilizes molecularly imprinted polymer as an alternative to antigen-antibody systems, creating selective recognition sites through specific template molecules to achieve highly selective, specific, and stable detection of target molecules. Theoretically, the PM-MIPB can simultaneously measure up to 255 biomolecules, with a detection speed of 0.025 s, recovery rate ranging from 95.65% to 103.41%, and sensitivity of $4.05\times 10^{-{3}}$ nm $\cdot $ mL/ $\mu $ g. By integrating phase multiplexing with molecular imprinting, the PM-MIPB meets the high demand for efficient, high throughput, and accurate biomolecular detection in the life science field.