Label-Free Biochemical Sensing Using Processed Optical Fiber Interferometry: A Review

Abstract

Over the last 20 years, optical fiber-based devices have been exploited extensively in the field of biochemical sensing, with applications in many specific areas such as the food processing industry, environmental monitoring, health diagnosis, bioengineering, disease diagnosis, and the drug industry due to their compact, label-free, and highly sensitive detection. The selective and accurate detection of biochemicals is an essential part of biosensing devices, which is to be done through effective functionalization of highly specific recognition agents, such as enzymes, DNA, receptors, etc., over the transducing surface. Among many optical fiber-based sensing technologies, optical fiber interferometry-based biosensors are one of the broadly used methods with the advantages of biocompatibility, compact size, high sensitivity, high-resolution sensing, lower detection limits, operating wavelength tunability, etc. This Review provides a comprehensive review of the fundamentals as well as the current advances in developing optical fiber interferometry-based biochemical sensors. In the beginning, a generic biosensor and its several components are introduced, followed by the fundamentals and state-of-art technology behind developing a variety of interferometry-based fiber optic sensors. These include the Mach-Zehnder interferometer, the Michelson interferometer, the Fabry-Perot interferometer, the Sagnac interferometer, and biolayer interferometry (BLI). Further, several technical reports are comprehensively reviewed and compared in a tabulated form for better comparison along with their advantages and disadvantages. Further, the limitations and possible solutions for these sensors are discussed to transform these in-lab devices into commercial industry applications. At the end, in conclusion, comments on the prospects of field development toward the commercialization of sensor technology are also provided. The Review targets a broad range of audiences including beginners and also motivates the experts helping to solve the real issues for developing an industry-oriented sensing device.

Figure 1

A general pictorial representation of the biochemical sensor.

Figure 2

Schematic diagram of an optical fiber-based MZI. (a) The basic structure of a dual-arm-based MZI. In-line fiber-based MZI for different configurations using (b) long period grating (LPG), (c) fiber core mismatching, (d) air-hole collapsing of the photonic crystal fiber (PCF), (e) multimode fiber (MMF) segment, (f) thin core fiber (TCF) segment, and (g) micro/nanostructured fiber combinations.

Figure 3

Different experimental procedures for the fabrication of optical micro/nanofiber. (a) Schematic image of the flame and brush technique. (b) Fusion splicer-based tapering technique. (c) Schematic diagram of microfiber fabrication process using the chemical etching technique.

Figure 4

Graphene oxide-functionalized optical microfiber-based ultrasensitive and in situ DNA detection. (a) Schematic geometrical structure of a silica microfiber-based interferometer. (b) Schematic representation of the interaction between ssDNA chains and GO on the fiber surface by π–π stacking. (c) Experimental setup of the tapered fiber-based biochemical sensor. The inset shows images of the sensing probe. (d) Scanning electron microscope (SEM) image of GO immobilized fiber. The inset shows a magnified view of GO coating by transmission electron microscopy (TEM). (e) Output transmission spectra of the probe for different steps of GO coating process: (1) bared silica fiber after cleaning, (2) after APTES modification on the cleaned fiber surface, and (3) after GO surface immobilization on fiber. Reprinted with permission from ref (75). Copyright 2017 Royal Society of Chemistry.

Figure 5

(a) Schematic pictorial description of the biorecognizing synthesis process through GO interface formation on a microfiber surface. TEM images of (b) the GO interface and (c) biorecognizing element immobilization with the GO interface. AFM characterized 3D height view of the (d) silica microfiber surface, (e) microfiber after GO interface formation, and (f) microfiber after GO interface formation with anti-GABA molecules on it. The Z scales are 20 nm; the images have been second-order flattened to eliminate the substrate effect. The scan area was 4 μm × 4 μm. Reprinted with permission from ref (77). Copyright 2018 Royal Society of Chemistry.

Figure 6

Mach–Zehnder interferometric biosensor for BSA detection. (a) Schematic representation of a MZI-based biochemical sensor. (b) Schematic diagram of the FS laser-based micromachining system utilized to fabricate the in-fiber structure. The system includes an attenuator comprised of a polarizer (P) and half-wave plate (W) for controlling the laser power, a beam splitter (BS), a CCD camera, and an objective lens (MO) to focus the laser beam onto the fiber. (c) Variation of the dip wavelength shift for different concentrations of BSA samples. Reprinted with permission from ref (78). Copyright 2017 Optica.

Figure 7

Mach–Zehnder interferometric detection of microRNAs. (a) Schematic diagram of the probe construction process. (b) Functionalization of the sensing probe for microRNA. (c) The kinetic binding curves of different concentrations of miRNA-let7a. Reprinted with permission from ref (80). Copyright 2017 Elsevier.

Figure 8

Concatenated microfiber-based MZI for biosensing applications. (a) Schematic image of the concatenated microfiber. The first tapered region is channel-1 used for stable interference patterns, and the second tapered region is channel-2 coated with MIP and used for sensing purposes. The inset shows the microscopic images of the bare microfiber and MIP-coated probe. (b) Variation of interference dip wavelength shifts with the concentration of the sensing analyte (PM). (c) Selectivity performance of the sensor. The red bars represent the comparative shift for different structurally analogous analytes for the MIP-immobilized probe, while the green bars are the same for the NIP-coated probe. Reprinted with permission from ref (83). Copyright 2019 Elsevier.

Figure 9

Thin-core optical fiber-based biochemical sensor. (a) Schematic of the experimental setup for probe characterization. (b) Sequential steps for functionalizing the sensing probe. (c) Transmission spectra of the proposed TCFMZI before (solid line) and after (dashed line) the immobilization of (PEI/PAA)n multilayer films with different numbers of bilayers. (d) tSelectivity performance of the proposed TCFMZI-based DNA sensors for a different kinds of target ssDNA detection. Reprinted with permission from ref (87). Copyright 2013 Royal Society of Chemistry.

Figure 10

Immunoglobulin G sensor using thin core fiber-based MZI. (a) Schematic image of the sensing probe consisting of a TCF sandwiched between two SMFs. (b) Simulative transmission characterization of the proposed FOB for different refractive index media. (c) Transmission spectra for different concentrations value of IgG. (d) Linear relationship of the dip wavelength shift for different concentration of IgG. Reprinted with permission from ref (89). Copyright 2018 Elsevier.

Figure 11

(a) Schematic construction of a basic Michelson interferometer. (b) Modified form of an in-line fiber-based Michelson interferometer.

Figure 12

Sensitive detection of glucose using a microfiber-based MI. (a) Schematic diagram of the GOD immobilization process on a multimode microfiber. (b) Transmission interference spectra for different concentrations of glucose solution. (c) Linear relationship between wavelength shift and sample concentration. Detected transmittance spectra for (d) horse serum and (e) calf serum. Reprinted with permission from ref (95). Copyright 2018 Elsevier.

Figure 13

Optofluidic fiber-based biochemical sensor using a MI. (a) Schematic experimental setup consisting of a common broadband source coupled with two optical spectrum analyzers (OSA). (b) Systematic probe functionalization process. (c) Schematic structure of the fabricated probes. Reprinted with permission from ref (96). Copyright 2016 Elsevier.

Figure 14

In-line dual-core fiber-based MI for biochemical sensing. (a) Schematic experimental setup with a magnified view of the dual-core fiber. (b) Transmission characteristics curve for different binding times between anti-IgG and IgG. (c) Variation of the dip wavelength shift for different binding times. Reprinted with permission from ref (99). Copyright 2018 Elsevier.

Figure 15

Schematic representation of a fiber-optic Sagnac interferometer.

Figure 16

High-sensitivity microfiber-based SI for DNA detection. (a) Schematic experimental setup for probe characterization. (b) Elliptical high-birefringence (Hi-Bi) microfiber cross-sectional view and simulative intensity distributions profile of the x- and y-polarized transverse modes. (c) Output transmission spectrum of the probe at each stage of surface functionalization. (d) Performance of the sensor for constant concentration value of matched and mismatched (ssDNAA and ssDNAB) DNA. Reprinted with permission from ref (101). Copyright 2017 Optica.

Figure 17

A high-birefringence (Hi-Bi) microfiber Sagnac interferometer biochemical sensor using the Vernier effect. (a) Schematic experimental setup of measurement. (b) Transmission spectra of the sensor for different concentrations of BSA solutions. (c) Experimental data for the shift with a linear fit. Reprinted with permission from ref (102). Copyright 2018 MDPI.

Figure 18

Glucose sensing using a PCF-based SI biochemical sensor. (a) Experimental setup for probe characterization. (b) Output spectra of the sensor for different concentrations of sensing analyte (glucose). (c) Experimental data and corresponding linear shift. Reprinted with permission from ref (103). Copyright 2017 Elsevier.

Figure 19

High-sensitivity free SI-based biochemical sensor using an exposed core microstructure optical fiber. (a) Schematic experimental setup for probe characterization. The inset shows the microscopic view of the ECF cross-section. (b₁–b₃) Geometry of the theoretical simulation and the simulated electric field intensity distribution profiles of the x- and y-polarized fundamental modes. (c) Sequential steps of the probe functionalization procedure. (d) Biochemical sensing process. (e) Wavelength shift of the transmission spectra for each working step. Reprinted with permission from ref (104). Copyright 2018 Elsevier.

Figure 20

(a) Extrinsic FPI sensor made by forming an external air cavity. (b) Intrinsic FPI sensor formed by two reflecting components, R1 and R2, along with a fiber.

Figure 21

Schematic experimental setup and sensing mechanism of a C-type fiber-based Fabry–Perot interferometer for all-fiber qPCR. Reprinted with permission from ref (125). Copyright 2020 Elsevier.

Figure 22

Fiber optic Fabry–Perot interferometer-based biochemical immunosensor. (a) Schematic presentation of the sensing probe with a microscopic view. (b) Spectral response of the probe during the layer-by-layer functionalization process. (c) Spectral response for different IgG concentrations. Reprinted with permission from ref (127). Copyright 2013 Elsevier.

Figure 23

Fiber optic FPI sensor for microorganism detection. (a) Schematic experimental setup and basic working principle. (b) Microscopic image of the sensing probe. (c) Transmission interference spectra of the fabricated sensor. Reprinted with permission from ref (128). Copyright 2016 Elsevier.

Figure 24

Schematic representation of a biolayer interferometry (BLI) based biochemical sensor.