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3.4 Antibody-based immunosensors       59




                  immobilization platforms where bio receptors are set on. The second part is the biore-
                  ceptors, the antibody or aptamer that is on the surface where the modified electrodes
                  exist. The system can be used after modification. The mechanism of this technique is
                  based on the interactions between the immobilized bioreceptors and proteins inside
                  the sample. And the reactions between them, like antibody-antigen or aptamer-anti-
                  gen labeled with enzyme or an electroactive compound create measurable signals.
                  In order to obtain good results from this technique, other factors such as pH, buffers,
                  temperature, concentration of nanostructures, monomers and incubation times with
                  aptamers, tumor markers, antibodies should be considered [38–40].
                     Optical immunosensors is another immunosensor technique that its sensor
                  response to light modified upon binding of specific antigen. In this technique an
                  optical sensor uses light for stimulation and then is able to detect alterations in the
                  power of light as it passes through or refracts from a sampling system in relation to
                  Ab/Ag binding. Optical immunosensors include surface plasmon resonance (SPR)
                  based sensors, fiber-optic sensors (FOS) and various fluorescence-based sensors.
                  Like electrochemical immunosensor these technique has some disadvantages that
                  now using nanoparticles such as carbon nanotube has developed its efficiency it bio-
                  marker detection in body fluids.
                     Piezoelectric immunosensor operation is based on the conversion of physical or
                  mechanical changes into electrical energy and vice versa. The commonest piezoelec-
                  tric sensor is the quartz crystal microbalance (QCM). With this sensor when antibody
                  or antigen is immobilized on the crystal surface, their bonding can be measured elec-
                  trically. Development in this technique has increased its popularity. In 2017, Su et al.
                  have developed a new biosensor based on the piezoelectric ceramic to detect cancer
                  biomarkers. It uses two piezoelectric resonators in order to decrease the environmen-
                  tal influence such as temperature. This device has shown high sensitivity in detection
                  of cancer markers prostate-specific antigen (PSA) and α-fetoprotein (AFP) and also
                  it’s detection is faster than using only one piezoelectric ceramic [41].
                     As it is said, biosensor immunoassay is an attractive assay for biomarker detec-
                  tion because it has a high sensitivity.  The performance of any immunosensor is
                  largely  dependent  on  the  type  of  antibody,  and  the  associated  antibody  immobi-
                  lization approach used to determine the sensor. Antibodies play a crucial role in
                  delineating the sensitivity and specificity of an immunosensor. A necessary factor
                  in immunosensor sensitivity is the immobilization strategy used with the antibody
                  or biorecognition ligand [42]. Several studies have demonstrated the enhancement
                  in antigen-binding activity by oriented antibody immobilization on a sensor surface.
                  By production of recombinant antibody fragments, because of their small size, they
                  are more stable and can be easily genetically changed to have highly oriented immo-
                  bilization on the sensor surface. Recombinant antibodies show significant additional
                  promise for the generation of antibody-based sensors with many novel applications
                  in cancer diagnostics. In 2016 Spain et al. have introduced a sensitive electrochemi-
                  cal immunosensor that use recombinant scVF as a receptor on electrocatalytic plati-
                  num nanoparticle in order to detect PSA in serum sample. This device has detected
                  a high concentration of PSA without need of any other techniques such as PCR or
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