# Recent Lipid Membrane-Based Biosensing Platforms
## 2 The Electroanalytical Aspect of Lipid Membrane Biosensors  
The dynamic nature of the lipid organization into sheets provides the mechanisms for the translation of the biochemical information into an electric signal. The simplest set-up uses a lipid bilayer formed in a \(\upmu\)m-aperture between two electrolyte solutions (Figure 3A) under an external voltage. This organization is maintained through a careful balance between the bilayer and its surrounding micro-environment, expressed by certain membrane properties that are not easily accessible, yet controllable (to a certain extend) by lipid composition, electrolyte solution, pH, temperature, and the value of external voltage [10] thickness, surface charge density, fluidity, dipolar potential, and transmembrane potential. These properties collaborate to allow a small but measurable ion flux through the membrane; any alteration of any of these parameters alters membrane permeability and changes its electrostatics in a way analogous to the intensity of the cause of perturbation (i.e., the concentration of the target analyte). It follows that the mechanism of signal generation corresponding to an external stimulus involves manipulations of membrane permeability. Ionic flux through the membrane can be the result of a chemical gradient (Figure 3C); it depends on diffusion coefficients [2] and it can be thermodynamically driven by high mobility ions and  
Figure 3: The electroanalytical aspect of artificial bilayer lipid membranes: Simplified schematic of the experimental set-up (**A**); potential distribution across the bilayer (**B**); overview of the principle mechanisms for signal generation (**C–F**); and the main biosensing strategies employed (**a–c**). For details see text. the presence of a large number of ions on one electrolyte-membrane interface [5]. Higher values may be recorded in the presence of transient or permanent pores [10], induced by external voltage (electroporation) [11], surface charge density fluctuations [6], or molecular surface perturbations [8] (Figure 3D). Pore formation depends on lipid composition and molecular packing and fluidity of the bilayer [10]; it can be controlled by pH, temperature, and divalent cations. Lipophilic compounds, for example, are adsorbed onto the membrane surface to alter lipid packing that modifies ion fluxes (Figure 3A(a)); the phenomenon becomes more prominent if aggregation of the lipophilic molecules follows initial adsorption. In a complex mixture of species with slightly different partition coefficients (lipophilic species A and B in (Figure 3A(a)), discrimination is possible [12]. Further, antigen-antibody complementation on the membrane surface may induce changes in the interaction between the antibody and the lipid headgroups, also, resulting in transient pore formation [13] (Figure 3A(b)). Enzyme-based systems operate on similar principles, where the most common permeability regulator is surface charge density [14]. Notwithstanding, protein channels (e.g., gramicidin or alamethicin) that span the bilayer can provide the means for a vast ion flux increase (Figure 3E); channels can be controlled by electrolyte composition [15]. Similarly, carriers (e.g., valinomycin) can enhance permeability, provided a fluid bilayer is maintained (Figure 3F); mobility can be controlled by pH, ionic strength, and lipid composition [16] (Figure 3A(c)). As the bilayer, in its suspended architecture, forms two interfaces with the electrolyte, the alterations of potential across the bilayer can be monitored. The electric field of a bilayer is the sum of the potential drop across the membrane (transmembrane potential) due to chemical gradients between the two electrolyte interfaces, the potential drop in the diffuse part of the electrical double layer (surface potential) due to surface ionization and screening by electrolyte ions and the voltage drop across the interface (dipolar potential) due to the alignment of the electric dipole moments in the membrane-water interface (Figure 3B) [10].