Cell-Based Biosensors in Proteomic Analysis

In recent years there has been a rapid increase in the number of diagnostic applications based on biosensors, including live, intact cells, tissues, organs or whole organisms. Whole cells provide multipurpose catalysts, particularly in processes that require the participation of a number of enzymes in sequence. However, the sensitivity and reliability of these sensors is often limited by the signal transduction mechanisms and by non-specific interferences, due both to analyte and environmental variations.

In similar fashion to DNA and protein microarrays, which deliver multiplex detection via the high-density spatial arrangement of molecular recognition elements, arrays of cells at high-density can form the basis of cell-based sensors with extremely high-throughput capability. The expression of receptors of interest within these arrays could yield cell-based sensors with defined specificities. In addition, transfected cell microarrays composed of highdensity arrays of mammalian cells expressing defined genes, could be the basis for future high-throughput cell-based protein sensing platforms. Such cellular arrays could be used for the detection of molecular interactions in functional proteomics in vitro, to the testing of proteins in functional studies in living cells. Microarrays with ordered cell arrangements of GFP-producing or luminescent bacteria may be used as an integral part of future biosensors. Recent and representative applications in this direction include (i) the profiling of antibody specificities and protein interactions with genetically engineered human immune cells, (ii) cells containing surface antibodies, specific to antigens of different pathogens and (iii) cell proliferation/metabolism sensors dedicated to screening for drug candidates and drug kinetic analysis.