## 2 Applications of Biosensors in Bacteria Detection
### Recognition of Bacteria Using Biosensors
#### 2.1.1 Optical Biosensors
SPR can be improved by imaging methods (iSPR) to get more details on the antibiotic binding process [21]. Surface-enhanced Raman scattering (SERS) improves the amplitude of a Raman spectrum manifold and has been applied in combination with other methods to detect bacterial cells in blood medium [23; 85]. SERS (surface-enhanced Raman spectroscopy) is a very sensitive technique [82; 85; 86]; it is able to distinguish different bacteria down to the single bacterium level [87; 88]. Especially with these enhancing strategies, SPR-based systems are still large, costly appliances which have not yet been adopted for point-of-care diagnostics [23]. Although Sprete SPR chips (Texas Instruments Inc., Dallas, TX, USA) have permitted the development of a miniaturized SPR-based biosensor, this still needs a microfluidic system and is thus confined to the research laboratory [23]. [PERSON] et al. developed an OWLS-based bacterial biosensor containing silicate in modified bacteria for the detection of stressors, environmental pollutants, and antibiotics [89]. [PERSON] et al. utilized the optical waveguide lightmode spectroscopy (OWLS) sensor for online monitoring of the adhesion of _E. coli_ K12 cells to the sensor surface with a novel waveguide design [90]. The so-called reverse symmetry waveguide employs waveguide substrates with refractive index lower than that of the aqueous cover media. This results in an increased and fine-tunable penetration depth of the monitoring evanescent optical field, fitted this way to the size of living cells [10; 91; 92]. Metal-clad waveguides also provide an enhanced evanescent field compared to conventional waveguide sensor designs [93; 94]. Such configurations are also termed metal-clad leaky waveguides (MCLW), where the increased sensitivity is due to the thin metal layer (8.5 nm) between substrate (glass) and spacer (silica) [95]. The design of the sensor allows the detection of whole bacteria (1-5 um). The limit of detection is about 1 \(\times\) 10\({}^{3}\) bacterial spores/mL [95; 96; 97; 98; 99]. Reflectometric interference Fourier transform spectroscopy (RIFTS) with porous silicon is an alternative way to detect bacteria. [PERSON] et al. detected _E. coli_ and _S. aureus_ in a real-time mode with a limit of detection (LOD) of about 10\({}^{3}\) cells/mL [100]. Another novel biosensing technique is the nanophotonic interferometric biosensor which provides a fast method for the identification of nosocomial pathogens for the diagnosis of infections [101]. One general problem with most of the biosensor assays (as well as the mechanical and electrochemical ones discussed in the following sections) is that quantification of the number of bacteria detected by the sensor relies on calibration, which in turn relies on sometimes questionable assumptions, although this might still be better than having to use labels. The elegant approach to quantifying particles, including protein molecules, that is uniquely available for OWLS [2; 3; 7; 102] cannot be applied to bacteria because they are too large, nor can the different, also elegant, approach to quantifying eukaryotic cell number and shape [8; 9; 10] be applied to bacteria because they are too small. [PERSON] and [PERSON] devised a heuristic solution to the problem [49] that can be applied when kinetic information is available.