**2. Biochemical measurands in healthcare**

The optimum properties of optical fibers such as higher sensitivity and low limit of detection are the crucial parameters, but in addition, the selectivity is also an important concept in biochemical measurement. The selectivity or specificity is important to avoid the interference of other biomolecules or biomarkers presented in targeted analytes. There are two approaches based on which the selectivity of biosensor can be attained. The first approach is to use special material fibers such as chalcogenide glasses, fluoride or silver halide glasses [28]. These fibers are transparent to IR wavelength, and on the contrary, biomolecules pursue the highly absorption features [29, 30]. However, the use of chalcogenide fibers is not useful because of their potential toxicity and still an effort is required to improve their responses towards biomolecules [28]. In second approach, there is indirect sensing of analytes by placing a biochemical layer over the sensing region. The biochemical layer changes the optical properties on the basis of surrounding RI. Such biosensors provide the quantitative and qualitative information of the chemical reagent under examinations. The chemical layer over the sensing region means the wavelength of output optical signal is managed by the properties of biochemical layer instead of absorption spectra. The sensitivity of such biosensors is depends on the length of sensing area, amount of EW and optical properties of the coated biochemical layer [31].

#### **2.1 Chemical optical Fiber sensors**

The diagnosis of biomolecules present in human bodies can be detected in two phase such as in gases or in liquid. In gas phase, the analysis can be done by analyzing the gases exhaled from skin or breath. In liquid phase, the analysis of biomolecules can be done by testing the samples such as urine, saliva, blood, sweat and tears.

#### *2.1.1 Diagnosis in gas phase*

The biomarkers released from human bodies are useful to develop the noninvasive techniques. The diagnosis of these biomarkers is important to find the presence of disease [32, 33]. The breath sniffing method is useful to analyze the patient suffering from renal failure in rats [34] and lung cancer detection [35]. Oxygen and carbon dioxide are the two gases that are routinely checked in clinical applications. The detection of these two gases was also performed by using optical fiber sensor by using pH indicator separated with well separated with emission bands [36]. Ammonia is one of the major component that affects the body

metabolism and can disturb the functioning of kidney and liver [37, 38]. In normal conditions, the ammonia releases from body skin from slight alkaline blood and its detection is used to diagnose the disease related to kidney and liver [39]. The ammonia diagnosis was carried out by using optical fiber sensors. Initially, the detection was done by employing pH detector based on indications [40]. Since then, reflector sensor tips [41], EW based fiber grating [42], and lossy mode resonance (LMR) [43] were reported. The sensitivity and limit of detection of such optical fiber sensor was extremely good in comparison of existing works.

The diagnosis of various organic compound is hardly done at clinical level, but number of studies were reported. Although, the optical fiber sensors for the detection of organic compounds are not very sensitive [44]. An EW based optical fiber sensor was put forwarded for the detection of gas exhaled from human skin [45]. The proposed sensor is also capable of analyzing the physiological changes by applying a pattern recognition technique. The optical fiber sensors have also been utilized for the diagnosis of humidity, which is one of the important factor in case of critical conditions [46]. The increase in humidity in human bodies leads to the dryness in mucosa and cause difficulties in breathing. However, instead of such critical need, the optical fiber based humidity sensors cannot be used in medical applications because of slow response and recovery time.

#### *2.1.2 Diagnosis in liquid phase*

The diagnosis of biomarkers present in human bodies can be done by measuring the pH of liquid. The pH of liquid present in stomach is varies from 1.3 to 3.5, and of urine and pancreas is from 8.0 to 8.8 [47]. A tilted FBG based sensor structure was reported to detect the pH of human body fluids [48]. The sensor is working on the basis of coated polymer films whose thickness varies according to the variation of body fluid concentration and leads to the change in optical properties of the signal. Despite of reported articles, the pH sensors have been utilized *in vivo* applications and are commercially provided by the Ocean Optics [49] and PreSens [50] with enough capabilities to be utilized in medical applications.

The pH detection in bio-fluids is also useful to detect the presence of drugs which will be helpful for pharmaceuticals and could be a milestone to develop therapeutic aids for human and animals [51]. The detection of antibiotics in human blood stream can be a useful step to prevent the overdose or to provide the effective dose for specific disorder. A LPG based vancomycin sensor was reported which can be used to treat some severe gram-positive infections [52]. The sensor is capable of detecting the very low concentration of antibiotics present in blood stream which were at the concentration of 10 nM with high specificity towards other biomolecules. Similarly, propofol is an anesthetic usually used in surgery and in regular use in intensive care units. Therefore, the detection of presence of propofol in human body is also an important factor, and a work was put forwarded for its detection while employing the optical fibers [53]. The reported work demonstrated a strong linearity with whole blood samples of human bodies.

#### **3. Characterization and analysis process of optical fiber biosensors**

The different geometries of optical fiber sensors should need to be characterized before involving them in sensing of biomolecules. The development of optical fiber biosensors involves four different process such as fiber geometries, used nanoparticles, detection of biomolecules and sensing analysis of developed sensor

probes. Therefore, this section presents a brief discussion of about the necessary characterization of optical fiber sensors at all the steps.
