Statement of the Problem: Combining biological with electronic components is a very challenging approach because it allows the design of ultra-small biosensors with unsurpassed specificity and sensitivity. However, many biomolecules lose their structure and/or function when randomly immobilized on inorganic surfaces. Hence, there is a strong need for robust self-assembling biomolecules, which attract great attention as surfaces and interfaces can be functionalized and patterned in a bottom-up approach. Methodology: Crystalline cell surface layer (S-layer) proteins, which constitute the outermost cell envelope structure of bacteria and archaea, are very promising and versatile components in this respect for the fabrication of biosensors. S-layer proteins show the ability to self-assemble in-vitro on many surfaces and interfaces to form a crystalline two-dimensional protein lattice. The S-layer lattice on the outside of a biosensor turns out to be a piece of the interface engineering connecting the bioreceptor to the transducer interface, which may cause signal enhancement. The S-layer lattice as ultrathin, exceptionally permeable structure with useful gatherings in a very much characterized spatial dissemination and direction and a general enemy of fouling qualities can fundamentally bring the cutoff up as far as assortment and simplicity of bioreceptor immobilization, smallness and arrangement of particle course of action, specificity, and sensitivity. In addition, emulating the supramolecular building standard of archaeal cell envelopes, containing a plasma film and an appended S-layer grid permit the creation of S-layer bolstered lipid layers. In the last mentioned, film dynamic peptides and layer proteins can be reconstituted and used as profoundly delicate bioreceptors. Biosensor-related examination has gained colossal ground in the course of recent decades, in light of the fact that the development in gadgets, nanolithography, nanobiotechnology, biomimetics, and manufactured science prompted effective courses for consolidating natural frameworks with silicon innovation. Biosensors are per definition devices, which use a biological recognition element that is retained in direct spatial contact with the transduction system or, in simplified terms, a device that changes over a physical or natural occasion into a quantifiable, for the most part electrical sign. The biosensing component or bioreceptor is every now and again an organically determined or biomimetic material, such as living cell, tissue, compound, film protein, layer dynamic peptide (e.g., ionophore), immune response, nucleic corrosive, and natural delicate components that are made by genetic engineering. The analyte, which binds in a highly specific manner to the bioreceptor may be amongst other ions, nucleic acids, and other organic molecules from cell cultures, human and food samples, and pollutants from environmental samples.