Optical fiber biosensor is a kind of optical sensor, which has the characteristics of small size, high sensitivity, real-time online monitoring and so on. At the same time, as a sensing platform, the optical fiber itself has the properties of anti-electromagnetic interference, corrosion resistance, water resistance, high temperature resistance and so on. The optical fiber sensor system is mainly composed of a light source, an optical fiber, and a spectrometer, as shown in Figure 1A. Common light sources include tungsten halogen lamps, light-emitting diodes and pulsed xenon light sources, which cover a wide range of wavelengths, generally between hundreds and more than 2000 nanometers. There are many kinds of optical fibers, and their composition materials and structures are different according to their different uses. For example, it can be divided into quartz optical fiber, plastic optical fiber and composite optical fiber according to the different raw materials. According to the transmission mode, it can be divided into single-mode fiber and multimode fiber^[8]. Optical fibers are generally divided into three layers: a core with a high refractive index at the center, a cladding with a low refractive index in the middle, and a protective coating at the outermost layer. Since light is transmitted in the fiber by total internal reflection (TIR), this requires that the refractive index of the core must be greater than that of the cladding^[9]. Therefore, in terms of material selection, the core material is generally high-purity silicon dioxide, and the cladding material is mostly fluorine-doped silicon dioxide with a refractive index lower than that of the core. According to the different amount of fluorine doping, the refractive index distribution of the core and cladding can be slightly different. The outermost coating layer mainly plays a protective role to ensure the overall firmness and applicability of the optical fiber.

The sensitive response of the optical path inside the fiber core to the external environment is the basis for rapid detection of the target. In order to improve the interaction between light and fluid, a variety of optical fibers with different geometric modifications have been developed, as shown in Figure 1b. The common ones are U-bend optical fiber, D-type optical fiber, tapered optical fiber and end reflection optical fiber^[10]. U-structure fiber can be obtained by bending the fiber with a fixed bending diameter and burning it with a flame, which has been proved to significantly increase the penetration depth of the evanescent field in the bending region and outside the direction of light propagation, thus improving the sensitivity of the fiber^[11,12][13]. D-type fiber is generally treated by single-sided mechanical polishing, which only removes part of the cladding on one side of the fiber, and then further modifies the exposed flat side^[14,15]. The diameter of a geometrically modified fiber with a tapered structure is usually only a few microns, and the diameter of the fiber can be reduced by locally heating the fiber with a heat source and stretching the glass in both directions along the axis in a molten state^[16,17]. By adjusting the taper ratio, the taper length and the incident light angle, the evanescent wave can be fully exposed to the external medium, the penetration depth can be increased, and the sensitivity of the sensor can be improved^[18]. Light is transmitted unidirectionally in the above optical fibers with various structures, while the optical fiber based on end reflection relies on the reflection of light at the cut end of the optical fiber to obtain the signal. The evanescent wave sensor model is formed by modifying the polished end face to realize the detection of the target analyte^[19]. For different practical application scenarios, the choice of optical fiber is a key point to be concerned.

Optical fiber spectrometer is an important scientific instrument which uses optical fiber as a signal coupling device to analyze the spectrum of the substance to be measured. Because the incident light is in the whole band, the signal measurement is usually carried out by intensity detection or wavelength detection. The core configuration of a fiber spectrometer typically includes a grating, a slit, and a detector. The choice of grating depends on the spectral range as well as the resolution requirements. At present, most of the fiber spectrometers on the market can be configured with gratings of various specifications to achieve a wide spectral range. The height design of the slit has an important impact on the sampling sensitivity. A narrower slit can improve the resolution, but will lead to a reduction in the luminous flux. A wider slit can increase the sensitivity, but will sacrifice the resolution. With the development of technology, the slit height can be customized to meet different application scenarios. At present, the types of detectors can be roughly divided into CCD detectors, CMOS detectors and InGaAs detectors. For different types of optical fibers and the spectral range to be measured, the selection of the detector is also very important. The CCD detector is suitable for both the ultraviolet range and the near-infrared range; The CMOS detector has the advantages of low delay, fast response, high cost performance and high sensitivity in the ultraviolet band; InGaAs detector has very high sensitivity in the near infrared region.

In an optical fiber, when the incident light strikes the interface between the core and the cladding, it will produce an electromagnetic wave that is exponentially attenuated by about one wavelength depth into the cladding, which is called the evanescent wave. The distance of the evanescent wave beyond the core-cladding interface is called the penetration depth. In the presence of a target in actual detection, the evanescent wave can be absorbed by molecules or atoms constituting the target within the effective penetration distance of the evanescent wave, and the concentration of the target is quantified according to the degree of absorption, so as to realize the accurate monitoring of the target^[20]. At present, the common evanescent wave optical fiber sensors are usually divided into surface plasmon resonance (SPR)/localized surface plasmon resonance (LSPR) sensors based on noble metal materials and optical fiber sensors based on fluorescence resonance energy transfer.

The principle of SPR optical fiber sensor is similar to that of LSPR optical fiber sensor, but it is different because of the different structure of the surface modified metal material. SPR optical fiber sensor usually deposits a certain thickness of gold, silver and other metal films on the optical fiber core, the evanescent wave generated at the interface between the fiber core and the metal interacts with the free electrons on the surface of the metal dielectric to excite the surface plasmon resonance, and the energy transfer occurs due to the mismatch between the evanescent wave and the surface plasmon, resulting in the resonance absorption peak^[21,22][23]. LSPR optical fiber sensor is usually modified with metal nanomaterials such as gold and silver on the core of the optical fiber. When the frequency of the evanescent wave matches the vibration frequency of the noble metal nanoparticles, the nanoparticles will have a strong absorption of photon energy, resulting in an enhanced local electromagnetic field and a more sensitive response to the target molecules^[24,25]. When the analyte interacts with the recognition site on the surface of the fiber core, the refractive index and the morphology of the nanoparticles in the local area change, which changes the position of the SPR or LSPR absorption peak, so that quantitative detection can be achieved according to the relationship between the deviation degree and the concentration of the target.

The principle of the fluorescence resonance energy transfer sensor is that a molecule modified with a fluorophore as a sensing element is fixed on a fiber core in advance, and a corresponding complementary sequence labeled with a quencher is combined with the sensing element,The fluorescence intensity is maintained at a low level, and when the target molecule is close to the complementary sequence, the fluorescence intensity is restored through the competitive binding relationship, and the quantitative detection is carried out according to the relationship between the concentration of the target substance and the fluorescence intensity^[27].

In recent years, with the innovation and development of detection methodology, the combination of biosensing strategy and optical fiber sensing technology to construct a new type of optical fiber biosensor can significantly improve the detection sensitivity and practicability of optical fiber sensing method. The interaction between the fiber core and the external modification is the basis of quantitative detection. The construction of different types of fiber optic biosensors mainly includes two processes: fiber pretreatment and core surface sensing strategy design. The pretreatment of the optical fiber is mainly to remove the cladding by physical or chemical methods, expose part of the fiber core as the sensing area, and activate it. And then modifying various specific recognition elements on the surface of the fiber core according to the type and application of the optical fiber biosensor to construct a sensing area. According to the different sensing elements and application scenarios, the types of optical fiber biosensors can be simply divided.

Mycotoxins are secondary metabolites produced by fungi that can cause poisoning in humans and animals, and can lead to serious public safety problems^[45]. Because mycotoxins are widely distributed in a variety of cereals and cereal products, food intake has become a routine route of human exposure to mycotoxins, which can lead to infection-related diseases or death^[46]. Common toxins include zearalenone (ZEN), deoxynivalenol, ochratoxin A (OTA), and aflatoxin. Therefore, it is very important to construct specific analytical methods for the rapid and accurate detection of mycotoxins in food^[42]. In recent years, thanks to the advantages of optical fiber sensors, there are more and more applications in the detection of mycotoxins. Xu et al. Constructed a portable and reusable LSPR-based fiber-optic biosensor for the detection of ZEN in beer, as shown in Fig. 6^[19]. First, the thiol group was modified on the end of the fiber by conventional silanization method, and then the gold nanoparticles were connected to the thiol group through Au-S bond, and the surface of the gold nanoparticles was modified by ZEN aptamer. The functionalized optical fiber was used as a sensing probe, and when the probe was immersed in different concentrations of ZEN solution, the ZEN would be selectively trapped, and the LSPR absorption peak would be red-shifted to different degrees. The linear range was 1 ~ 480 ng/mL, and the detection limit was 0. 102 ng/mL. By cutting and polishing the used fiber tip and repeating the modification process mentioned above, it can be simply and conveniently used for the next test. In addition, when beer is used as an actual sample to detect ZEN, the sample processing process is relatively simple, only the beer is degassed, and the ZEN standard solution is added after being diluted by the buffer solution, and the recovery rate is calculated to be 85% -102%, so the method has good detection reliability.

Lee et al. Designed a fiber-based LSPR sensing system for OTA detection^[47]. In the sensor, a gold nanorod is modified on a sulfhydryl functionalized optical fiber core, the surface of the gold nanorod is modified by an OTA aptamer through Au-S bond interaction, and when an optical fiber probe is immersed in an OTA sample solution,The combination of OTA and OTA aptamer makes the aptamer change from single-chain structure to G-quadruplex structure and leads to the increase of the refractive index of the gold nanorod surface, resulting in the red shift of the LSPR absorption peak. The developed sensor can directly determine the concentration level of OTA between 10 pM and 100 nM. Then grape was selected as the actual sample to be detected, and the developed sensor was immersed in the mixed solution of grape juice and buffer solution with the volume ratio of 1:1, and different concentrations of OTA were added to the test, and the results showed that the recovery rate was 85. 5% ~ 116.9%.

Song et al. Developed a two-color evanescent wave all-fiber detection system based on fluorescence resonance energy transfer to simultaneously detect aflatoxin M1 (AFM1) and OTA in milk, as shown in Fig. 7^[48]. The system is equipped with two lasers (635, 405 nm) for simultaneous acquisition of fluorescence signals at two wavelengths. The aptamers of AFM1 and OTA were labeled with two fluorophores (Cy5.5 and Alexa 405) with different excitation wavelengths, respectively, and their complementary sequences were labeled with the respective quenchers （BHQ₃ and Dabcyl). In the absence of a target, the aptamer hybridizes to a complementary sequence, resulting in fluorescence quenching due to the proximity of the fluorophore and the quencher. After the addition of the target, the target binds to the corresponding aptamer to form a stable complex structure, resulting in the recovery of fluorescence intensity. Under the optimal conditions, the system can simultaneously and selectively determine AFM1 and OTA in the range of 1 ng/L ~ 1 mg/L, and the detection limits of AFM1 and OTA are 21 and 330 ng/L, respectively. In the milk sample test, the standard solution of toxin was added to the mixed solution of pure milk sample and acetonitrile, fully shaken and refrigerated, and the supernatant was diluted with buffer by centrifugation, thus reducing the matrix effect and directly used for sensor testing. The results showed that the recoveries of AFM1 and OTA ranged from 71.28% to 116.7% and from 74.13% to 124.8%, respectively.

The development of biocoupling technology has led to the development of optical fiber biosensors, in which the receptor sensing element can be easily combined with other nanomaterials or signal molecules. When detecting various small molecular substances represented by biotoxins, the toxins can be easily captured by the aptamer modified on the optical fiber. Here, the optical fiber not only serves as a detection device, but also serves as a circulation device of the optical path, so that the equipment is simpler and more practical. However, it still has some problems, such as the binding time of the analyte to be tested is not fixed, and the pretreatment step of the optical fiber takes a long time. In the future, these shortcomings will be gradually overcome with the development of technology.

Due to the non-degradability, bioaccumulation and strong toxicity of heavy metal ions, the presence of heavy metals in food and environmental samples can lead to serious pollution and health problems^[46,49,50]. Some heavy metal ions, such as Pb²⁺, Hg²⁺ and Cd²⁺, can cause serious damage to the human body and even lead to a variety of diseases even at very low concentrations. Fiber optic biosensors have also become a convenient and effective method to detect heavy metal ions^[51]. Sadani et al. Designed a U-shaped optical fiber sensor based on LSPR for sensitive detection of heavy metal ions^[52]. Firstly, the optical fiber was silanized, and then bovine serum albumin (BSA) was immobilized on the surface of the optical fiber. The detection of mercury ions was realized by immobilizing the synthesized chitosan-coated gold nanoparticles on the BSA. The linear range was from 0.1 to 540 ppb. Fish and spinach samples were tested, and 1 G of each sample was neutralized with sodium hydroxide after being crushed, and then four different concentrations of mercury ions were added to the test, with an overall error of less than 15%.

Verma et al. Prepared a sensor based on surface plasmon resonance to detect cadmium ions, lead ions and mercury ions^[53]. In this sensing model, the surface of the fiber core is coated with a 40 nm silver film, a 10 nm antimony tin oxide (ITO) film, and a pyrrole/chitosan coating in turn. ITO can improve the sensitivity of the sensor and protect the silver film from oxidation, and the composite matrix formed by pyrrole and chitosan can be highly sensitive to heavy metal ions. The detection limits of cadmium ion, lead ion and mercury ion were 0. 256,0.440 and 0. 796 ppb, respectively. Based on the ability of mercury ion to specifically bind to thymine to form a T-Hg²⁺-T complex structure, Zhou et al. Developed an optical fiber biosensor based on fluorescence resonance energy transfer, as shown in Fig. 8^[49]. Quenching molecule labeled poly T base DNA strand (BQ-T14) and fluorescent molecule labeled poly A base DNA strand (CY-A14) were used as biological recognition element and signal reporter, respectively. When the sample does not contain the Hg²⁺, the two DNA molecular chains are hybridized, and the fluorescence signal intensity is low; When there is Hg²⁺ in the sample, due to the competitive binding between Hg²⁺ and BQ-T14, a stable T-Hg²⁺-T mismatch structure is formed, and then CY-A14 is excited by the evanescent wave on the fiber surface, and the fluorescence intensity increases, and the higher the concentration of Hg²⁺, the higher the fluorescence intensity. Under the optimal conditions, the detection period of a single sample did not exceed 10 min, and the detection limit of Hg²⁺ was 8. 5 nM. The recovery rate of commercial bottled water is between 89. 2% and 104. 7%, which proves that the sensor has sufficient precision and accuracy.

Antibiotics play an important role in the treatment of diseases caused by bacterial infections in animals and are widely used in animal husbandry^[54]. The use of high doses of antibiotics can lead to antibiotic residues in animal-derived foods, which will eventually enter the human body along the food chain and eventually affect human health, so it is very important to develop sensitive and effective methods to detect antibiotics in food quickly and accurately^[55].

Shrivastav et al. Proposed a method to detect erythromycin in milk and honey by combining molecular imprinting technology with optical fiber sensing method^[56]. Firstly, the sensing area of the fiber core was coated with a silver layer by thermal evaporation, and then the polymer nanoparticles with erythromycin as the template were coated on the silver-coated area by dip-coating method to prepare the binding sites for specific recognition of erythromycin. When the erythromycin molecule enters the imprinted binding site and through non-covalent binding, it causes the refractive index of the nanoparticle layer to change, thereby shifting the absorption wavelength to an extent proportional to the analyte concentration. Honey samples and milk samples were treated in the same way. They were diluted in water according to the ratio of weight to volume of 1:5. The diluted samples were filtered with a filter membrane and spiked for later use. The recovery rate was 98.2% ~ 102.0%, and the detection limit was 1.62 nM. The chemiluminescent optical fiber sensor developed by Nie et al. Realizes the multiple analysis of chloramphenicol, sulfadiazine and neomycin with different concentrations in milk samples by controlling the length of the optical fiber sensing area and the number of optical fibers, as shown in Figure 9^[57]. Tang et al. Designed a fiber-optic biosensor based on target binding to promote fluorescence quenching for on-line continuous specific detection of kanamycin^[58]. In this sensor system, the fluorophore-labeled kanamycin aptamer is prone to form an intermolecular multimeric structure (M-Apt) in the absence of antibiotics, while the binding of the aptamer to kanamycin leads to the destruction of M-Apt and the formation of kanamycin-aptamer-hairpin structure (Kana-Apt). The photoinduced electron transfer between the fluorophore and kanamycin partially quenches the fluorescence of the hairpin structure, and thanks to the ability of GO to efficiently bind to single-stranded DNA, the introduced GO quenches the fluorescence of free single-stranded DNA, reduces the background of the sensor, and further quenchs the fluorescence of Kana-Apt. Unbound aptamer in solution binds to unlabeled aptamer immobilized on the fiber, and the fluorescence signal increases, and the intensity is inversely proportional to the concentration of kanamycin, with a linear range of 200 nM to 200 μM and a detection limit of 26 nM.

In order to achieve real-time automatic monitoring of streptomycin (STR), Zhu et al. Established a sandwich-type fluorescent biosensor based on separated aptamer (SPA)^[59]. First, one fragment of the STR-specific separation aptamer, SPA1_STR, was immobilized on the optical fiber by covalent binding, and the other fragment, SPA2_STR, modified with Cy5.5 fluorophore, was mixed with the sample. Due to the presence of STR, SPA2_STR forms a stable composite structure with the STR captured by SPA1_STR. The evanescent wave excites Cy5.5 on SPA2_STR to produce a fluorescence signal, and the fluorescence intensity reflects the concentration level of STR. The sensor is sensitive in the range of 60 – 526 nM with a detection limit as low as 33 nM.

The abuse of pesticides can also lead to the residues of environmental pollutants and metabolites, which are likely to flow into the human body along with the food chain, so it is necessary to detect pesticide residues conveniently and quickly^[42,60]. Miliutina et al. Developed an optical fiber sensor fixed with a metal-organic framework (MOF-5) layer to detect organophosphorus pesticides, which was tested with fenitrothion in water, as shown in Figure 10^[61]. First, a gold film of about 40 nm is deposited on the fiber core by vacuum sputtering, and then a MOF-5 layer with high affinity for pesticides is deposited on the gold surface. When the sensor is immersed in an organophosphorus pesticide solution, the target will fill the gaps in the MOF-5 layer, resulting in an increase in the refractive index of the MOF-5 surface and a change in the wavelength of the plasma absorption band.The detection limit of pesticide can be as low as 10 pM, which is much lower than the detection limit 14552 of the traditional gas chromatography in the national standard (standard number: GB/T 14552-2003), and the sensing response time is affected by the concentration of pesticide, the higher the concentration, the faster the response, which can save time and cost to a greater extent. Atrazine (ATZ), as one of the most common herbicides in the world, has a high risk of carcinogenesis and poses a serious threat to human health. Long et al. Developed an optofluidic biosensing platform to detect ATZ^[62]. First, the hapten-carrier conjugate ATZ-bovine serum albumin (ATZ-BSA), which was used as a recognition element, was covalently coupled to the surface of the fiber, and then the Anti-ATZ monoclonal antibody (anti-ATZ-MAb), which was highly specific for ATZ, was bound to the ATZ-BSA. Because Anti-ATZ-Mab was modified with Cy5.5 fluorophore in advance, the evanescent wave excited the fluorophore to produce a fluorescence signal, and the intensity of the fluorescence signal was positively correlated with the concentration of ATZ. The final detection limit was 0. 06 μg/L, which was lower than the detection limit of 0. 25 μg/L in the national standard of liquid chromatography/mass spectrometry (standard number: GB/T 21925-2008), and had high application significance.

Foodborne pathogens pose a serious threat to human health. After eating food containing foodborne pathogenic microorganisms, human beings are prone to nausea, vomiting, diarrhea and other symptoms, and even cause serious organ damage or cancer^[63]. Common pathogens include Campylobacter, non-typhoid Salmonella, Shiga toxin-producing Escherichia coli, Listeria monocytogenes and so on^[64,65]. Due to the disadvantages of traditional detection methods, such as long detection time, low sensitivity, complex and expensive instruments, it is of great significance to construct new biosensors for qualitative and quantitative detection of these pathogens^[66].

Cui et al. Developed a quantum dot immunofluorescence biosensor for the detection of Staphylococcus aureus, as shown in Figure 11. The sensor has both high specificity of antigen-antibody interaction and high sensitivity and stability of quantum dot fluorescence^[67]. After silanization of the optical fiber, the anti-Staphylococcus aureus polyclonal antibody was first immobilized on the surface of the probe to specifically capture Staphylococcus aureus, and when Staphylococcus aureus was captured, the monoclonal anti-Staphylococcus aureus antibody was combined with the captured Staphylococcus aureus again to form a double antibody sandwich structure. Biotin-labeled goat anti-mouse IgG antibody was then combined with mouse monoclonal antibody. Finally, streptavidin-labeled QDs were introduced for fluorescence labeling by specific binding between biotin and streptavidin. The signal cascade amplification of the biotin-streptavidin-quantum dot system can significantly enhance the fluorescence signal to improve the sensitivity, and the fluorescence intensity is significantly linearly and positively correlated with the logarithm of the concentration of Staphylococcus aureus in the range of 10³~10⁷CFU/mL, and the detection limit reaches 1×10³CFU/mL. Fang et al. Proposed a novel two-color fluorescent aptamer sensor for simultaneous detection of Escherichia coli O157: H7 and Salmonella typhimurium^[27]. Firstly, hydrofluoric acid was used to etch a conical optical fiber probe with a nanoporous layer of 50 ~ 100 nm, and Cy3-labeled Escherichia coli O157: H7 aptamer sensor (Cy3-apt-E) and Cy5.5-labeled Salmonella typhimurium aptamer sensor (Cy5.5-apt-S) were used as biological recognition elements and signal reporters, respectively. When the mixture of the two sensors and the two bacteria is introduced to the surface of the probe, the free Cy3-apt-E and Cy5.5-apt-S can enter the nanoporous layer of the optical fiber and be excited by the evanescent wave to generate fluorescence,However, Cy3-apt-E and Cy5.5-apt-S, which bind to two kinds of bacteria respectively, can not be excited because the size of bacteria is too large to enter the nanopore layer, so the relationship between the number of bacteria and the fluorescence intensity can be used to quantitatively detect pathogenic bacteria. Ultimately, the detection limits for E. Coli O157: H7 and S. Typhimurium were 340 and 180 CFU/mL, respectively. The recoveries of E. coli O157: H7 and Salmonella typhimurium were 82. 1% -97. 4% and 73% -89. 6%, respectively, when the samples were sterilized and directly added with different amounts of bacteria for fluorescence signal detection.

To sum up, when the optical fiber biosensor detects the above harmful substances, different sensing processes can be designed for different targets. By modifying aptamers, antibodies, enzymes and other molecules on the surface of optical fibers, combined with fluorescence, LSPR effect, nucleic acid amplification and other strategies, a diversified sensing platform suitable for precise detection of various food pests can be constructed, and its detection sensitivity and specificity can also be guaranteed. With the development of materials with better performance and more innovative detection methodologies, fiber optic biosensors are expected to become a detection technology with great practical application value, which is widely used in food safety, environmental monitoring and other fields.