## 2 Applications of Biosensors in Bacteria Detection
### Bacteriophage in Biosensors  
Bacteriophages are viruses of bacteria; they only infect bacteria and do not attack animal or human cells. Bacteriophages are ubiquitous in all natural environments and they are the most abundant living entities. They differ from each other in structure and physicochemical properties and are highly specific, recognizing only bacteria of one species or even only one particular strain [47; 204]. Their recognition specificity is due to binding to a specific receptor on the bacterial surface. After recognition and binding, they inject their DNA into the bacterial cells. Bacteriophages are already being used in novel technologies to achieve fast recognition of pathogenic bacteria, particularly by using bacteriophage-based probes [47; 205]. It is possible to isolate bacteriophages against any target bacterium. New real-time detection systems to recognize antibiotic-resistant bacteria would need to be developed as well; bacteriophages can be effectively used in different biosensors as recognition elements even for detection of these resistant pathogens [47]. Only a few commercial appliances detect antibiotic-resistant bacteria with bacteriophage-based technology (e.g., the blood culture test for MRSA/MSSA developed by MicroPhase Inc. [47] can be used as a clinical aid in combination with other laboratory tests to recognize MRSA from samples from patients; it is based on the bacteriophage amplification method and has a low detection limit (\(6\times 10^{5}\) CFU/mL) with waiting for 5 h to get the result). Commercial devices using bacteriophage amplification have been developed by BIOTEC Laboratories Ltd. for detection and testing of antibiotic resistance of _M. tuberculosis_ in sputum [47; 206; 207]. Another US FDA-approved system is the xTAG Gastrointestinal pathogen panel (GPP) by Luminex Molecular Diagnostics [47]. The panel is for the identification and detection of multiple viral, parasitic, and bacterial nucleic acids in human stool samples from patients with symptoms of gastroenteritis or infectious colitis. Multiple pathogens, for instance _S. typhimurium_, are included in the. The method is based on the reverse transcription-polymerase chain reaction (RT-PCR/PCR) with a low detection limit of 2.3 \(\times\) 10\({}^{5}\) CFU/mL and a 24 h detection time in case of _S. typhimurium_[47]. A few of the antibiotic-resistant bacteria from the Centers for Disease Control (CDC) list have counterpart bacteriophages, but to our knowledge phage-based detection assays have not yet been developed [47]. In the work of [PERSON] et al., a penicillin-binding protein (PBP 2a) antibody-conjugated latex beads were utilized to create a biosensor to discriminate between methicillin-resistant (MRSA) and methicillin-sensitive (MSSA) _S. aureus_[208; 209; 210]. Lytic bacteriophages are formed into phage spheroids by contact with a water-chloroform interface [208]. When lytic phages are transformed into spheroids, they retain their strong lytic activity and show high bacterial binding ability. Phage spheroid monolayers were transferred to the surface of the biosensor by the Langmuir-Blodgett (LB) method where they were examined by a quartz crystal microbalance with dissipation tracking (QCM-D) to measure bacteria-phage binding [208]. Bacteria-spheroid binding results in reduced resonance frequency and a rise in dissipation energy for both MSSA and MRSA strains. The sensors are then exposed to the penicillin-binding protein-antibody latex beads after the bacterial binding. MRSA responds to PBP 2a antibody beads, but sensors with MSSA gave no response. Biosensors whose ability to detect resistant bacteria has been demonstrated are summarized in Table 2.