Phage display for detection of biological threat agents

The essential element of any immuno-based detector device is the probe that binds analyte and, as a part of the analytical platform, generates a measurable signal. The present review summarizes the state of the art in development of the probes for detection of the biological threat agents: toxins, bacteria, spores and viruses. Traditionally, the probes are antibodies, which are isolated from sera of immunized animals or culture media of hybridomas. However, the “natural” antibodies may have limited application in the new generation of real-time field detectors and monitoring systems, where stress-resistant and inexpensive long-livers are required. Phage display is a newcomer in the detection area, whose expertise is development of molecular probes for targeting of various biological structures. The probes can be selection from about billion clone libraries of recombinant phages expressing on their surface a vast variety of peptides and proteins, including antigen-binding fragments of antibodies. The selection procedure, like kind of affinity chromatography, allows separating of phage binders, which are propagated in Escherichia coli bacterial cells and purified using inexpensive technology. Although phage display traditionally is focused more on development of medical preparations and studying molecular recognition in biological systems, there are some examples of its successful use for detection, which are presented in the review. To be used as probes for detection, peptides and antibodies identified by phage display are usually chemically synthesized or produced in bacteria. Another interesting aspect is using of the selected phage itself as a probe in detector devices, like sort of substitute antibodies. This idea is illustrated in the review by “detection” of β-galactosidase from E. coli with “landscape” phage displaying a dense array of peptide binders on the surface.