## 2 Applications of Biosensors in Bacteria Detection
### Strategies to Reduce and Control Bacterial Adhesion on Sensing Surfaces  
One of the most decisive steps which precedes the harmful effect of bacterial infection on implants is microbial adhesion. It is very difficult to mechanically remove a mature biofilm or kill its bacteria [211]. Thus, inhibiting the bacterial surface-sensing mechanism and the subsequent initial binding events to surfaces is necessary to prevent biofilm-associated problems [211; 212]. Efforts have been made to reduce adhesion using specific surface coatings (e.g., hydrophilic and antimicrobial coatings) [213; 214]. Contradictory results from such treatments initiated a more theoretical approach in understanding the interactions involved in bacterium adhesion. A surface chemistry approach based on the DLVO theory describes two potential boundaries: the secondary and primary minima as a bacterium approaches a surface [215; 216]. In this model, the bacterial cells are considered to be large particles and van der Waals and electrostatic interactions are taken into account. If the bacterium can surpass the energy barrier between the secondary and primary minimum (depending on the ionic strength), the cell can reach the surface (i.e., stays in the primary minimum). Although this simple model can explain irreversible adsorption as a function of ionic strength, the natural complexity of the adhesion cannot be covered and explained in full depth (Figure 2). Furthermore, at physiological ionic strengths the electrostatic \begin{table}
\begin{tabular}{c c c c c c} \hline \hline
**Biosensor Type** & **Bacteria** & **Resistance** & **Limit of Detection** & **Assay Time** & **Ref.** \\ \hline Micromechanical & _E. coli_ & & & & 1 h (active growth) & \\ oscillators & (XL1-Blue) & Kanamycin, tetracycline & (50 pg/Hz) & 2 h & [PERSON] et al. [30] \\ \hline Biofunctionalized & & & Gentamicin, ciprofloxacin, ampicillin, cefritazone, sulfamethboxazol-trimethoprim & & & \\ screen-printed & & & & & \\ electrochemical & & & & & \\ sensor (ES) & & & & & \\ \hline  & MRSA, MSSA & & & & \\  & (_S.ureus_), & & & & \\  & _B. anthracis_, & & & & \\ QCD-D (with phage & _S. typhimurium_, & Penicillin-binding protein & \(10^{4}\) CFU/mL (phage capture in case of _S._ & 16 min/sample (spheroid-bacteria time-to-answer) & [PERSON] et al. [184] \\ spheroids) & _S. flexneri_, & antibody latex beads & _aureus_) & & \\  & _Y. enterica_, & _K.Pneumonia_, _B._ & & & \\  & _subtilis_ & & & & \\ \hline Magnesium zinc & & & & \(4.8\times 10^{4}\) to & \\ oxide (MZO) nano-structuremodified & _E. coli_ and & Ampicillin and & \(0.9\times 10^{4}\) CFU/mL (for & \\  & _S. cerevisiae_ & tetracycline (_E. coli_), amphotericin B and & ampicillin sensitive & \\  & (MZO) nano-QCM & & & & \\  & (_S. cerevisiae_) & & & & \\  & & & & \\  & & & & \\ \hline Electrochemical & & & Kanamycin, tetracyclin, erythromycin & \(7.1\times 10^{3}\) CFU/mL & \(\sim\)20 min & [PERSON] et al. [176] \\ impedance & _E. coli_ K-12 & & erythromycinogen & & \\ spectroscopy (ES) & & & & & \\ \hline Bead-based biosensor & _E. coli_ (ATCC & & & \\ via fluorescence & 25922 and 6937) & Ceftazidine, levofloxacin & \(5\times 10^{4}\) CFU/ mL & 60 min & [PERSON] et al. [179] \\ imaging & & & & & \\ \hline  & & & & & \\ LSPR & _P. aeruginosa, E. coli_ & Ceftazidime, cefotaxime, ampicillin, levofloxacin, doxycycline & 0.5 ug/mL in 5\% human serum (ceftazidine). & 3 h & [PERSON] et al. [178] \\  & & & levofloxacin, doxycycline & 10\% CFU/mL (used & \\  & & & bacteria concentration) & \\ \hline \hline \end{tabular}
\end{table} 
Table 2: Summary of biosensors reported as capable of detecting antibiotic resistance. interactions are negligible in comparison with electron donor-acceptor interactions [217]. In an extension to DLVO theory, [PERSON] et al. suggested an additional term, the Lewis acid-base (AB) interactions, which account for hydrogen bonding upon close approach of bacteria and substrate surfaces [218]. This XDLVO theory has been tested and improved over the years and is useful for predicting adhesion reversibility [219].