Significance In-situ spatial distribution acquisition of biochemical substances is particularly important for gas-liquid distribution monitoring, cell analysis, tumor detection, drug design, and other fields. Optical fiber biochemical sensors are ideal tools for biochemical detection due to their unmarked, in-situ, fast, and accurate properties. However, existing optical fiber biochemical sensors only obtain the content of a single point of biochemical substances, making it difficult to obtain the spatial distribution information. The distributed biochemical sensing method with hundreds or thousands of sensors continuously distributed along the optical fiber axis can achieve this goal. We start with quasi-distributed optical fiber biochemical sensing and comprehensively review the latest progress of distributed optical fiber biochemical sensing in gas sensing, refractive index (RI) sensing, and biochemical sensing. Finally, the development prospects and current challenges of distributed optical fiber biochemical sensors are discussed. The research on distributed optical fiber biochemical sensing is expected to lead the current study of single-point discrete optical fiber biochemical sensing to the multi-point continuous distribution development. Additionally, it has the potential to be a new powerful tool in fields such as chemistry, biology, and medicine. Progress For quasi-distributed biochemical sensing, the gas sensing development based on multiplexing mainly focuses on reducing noise and improving the limit of detection (LOD). With the deepening sensor research, the utilization of different sensors and the combination of multiple methods have greatly improved the quasi-distributed gas sensing accuracy, quantity, and efficiency. In terms of quasi-distributed fiber optic RI sensing, the RI sensitivity has greatly improved with the optimized sensor preparation process. Based on the multi-channel advantages, it is possible to achieve quasi-distributed RI sensing in multiple regions. However, due to the sensor size, quasi-distributed RI sensors cannot achieve spatial distribution recognition in solutions. Therefore, the research on distributed RI fiber optic sensors is very necessary. Quasi-distributed fiber optic biochemical sensing has achieved simultaneous sensing of multiple biological tissues or chemical substances. However, like quasi-distributed RI sensors, quasi-distributed fiber optic biochemical sensors cannot achieve position monitoring of biological tissues. This can be addressed in distributed fiber optic biochemical sensing. Compared to the quasi-distributed sensing, distributed gas sensing has clearer requirements in sensing distance and spatial resolution. Gain modules such as EDFA are gradually added to sensing systems for long-distance detection. Meanwhile, the sensing method has gradually changed from quasi-distributed multi-channel sensing with multiple gas cells to distributed single channel sensing with multiple gas cells. Additionally, distributed RI sensing improves its spatial resolution to the millimeter level, which is of significance for detecting concentration distribution and substance localization in solutions. However, due to the short development period of distributed RI sensing, there are still powerful development prospects in spatial resolution and sensitivity. For the newly developed distributed biochemical sensing, distributed biochemical research mainly focuses on pH measurement. With the improved spatial resolution, it is possible to achieve micro localization of biochemical substances such as tumor cells. The sensing spatial resolution of distributed biosensors based on OFDR can be improved to less than 100 micrometers or even a few micrometers. When the spatial resolution approaches cell size, fiber optic probes can be adopted for individual cell localization. We believe that these manifestations are essential for the localization and subsequent treatment of tumor cells. It can be foreseen that distributed biochemical sensors based on OFDR will become the most active research field in the entire distributed fiber optic biochemical sensing. Conclusions and Prospects We start with quasi-distributed fiber optic biochemical sensing and comprehensively review the latest progress of distributed fiber optic biochemical sensing in gas sensing, RI sensing, and biochemical sensing. Quasi-distributed fiber optic biochemical sensors are based on methods such as time division multiplexing, space division multiplexing, wavelength division multiplexing, and frequency division multiplexing, and they can be utilized to characterize the performance of multiple sensors in an optical system by multiplexing. These methods have advantages in measuring multiple gases, biochemical substances, or multi parameters. However, due to the sensor size and structure, it is hard to achieve high spatial resolution, such as distributed sensing at the micron level. The distributed fiber optic biochemical sensor based on OTDR or OFDR demodulates the backscatter in the optical fiber, which can not only obtain information about the biochemical substance contents but also obtain spatial distribution information of these contents. More importantly, OFDR and OTDR technologies can choose appropriate spatial resolution based on the differences of sensing targets. However, there are still many challenges in distributed fiber optic biochemical sensing at present. The first challenge to be addressed is the sensing sensitivity. Compared to traditional split and quasi-distributed sensing, the sensitivity of distributed sensors is still 1-2 orders of magnitude lower. Furthermore, how to improve the backscatter signal-to-noise ratio of sensing fibers is also a problem to be overcome currently. Although distributed RI sensing based on OFDR has gradually become a hot topic, it is currently limited by the evanescent field excitation method. Additionally, the relatively short sensing distance limits the application scenarios. Therefore, in future research, some sensitization methods of fiber optic single point biochemical sensors can be referenced, such as gold plating, silver plating, nanoparticles, and two-dimensional materials. Meanwhile, based on distributed RI sensing, it is necessary to further expand the research on distributed biochemical sensing by combining immune reactions, chain reactions, and other biochemical reactions. By utilizing the high spatial resolution characteristics of OFDR, it is ultimately possible to perceive the spatial distribution of biochemical substance contents in subcellular structures such as nucleic acids, DNA, ions, and enzymes. This will potentially become a powerful new tool in life sciences.
