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. 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 high-density arrays of mammalian cells expressing de-fined genes, could be the basis for future high-throughput cell-based protein sensing platforms.
The artificial insertion of receptor-like molecules in the cell membrane is an attractive alternative to cell transformation with genes expressing membrane-bound antibodies. This generic approach is called Molecular Identification through Membrane Engineering (MIME). Interaction of MIME cells with viral particles can trigger changes to the cell membrane potential that are measured by appropriate microelectrodes, according to the principle of the Bioelectric Recognition Assay (BERA). BERA is a biosensory method based on a unique combination of a group of cells, whose immobilization in the matrix preserves their physiological functions and measures the expression of the cell interaction with viruses, through the change in electrical properties. In this way, when a positive sample is added to the probe, a characteristic, ‘signature-like’ change in electrical potential occurs upon contact between the virus and the gel matrix. BERA has been used for the detection of viruses in humans (Hepatitis B and C viruses, herpes viruses), animals (prion protein, foot and mouth disease, blue tongue virus) and plants (tobacco and cucumber viruses) in a remarkably specific, rapid (1–2 minutes), reproducible and cost-efficient fashion. The sensitivity of the virus detection with BERA is equal or even better than with advanced immunological, cytological and molecular techniques, such as the reverse transcription polymerase chain reaction (RT-PCR).
The BERA biosensor diagnostic system is currently available as a desktop, laboratory-scale prototype that can be operated by both expert and lay users. The commercialization process of the device includes engineering for a more compact, stand-alone unit. The system comprises a consumable miniature biosensor (with integrated circuitry, an immobilization matrix and virus-specifically responding cells), a data acquisition system and a PC (desktop or laptop). One of the major advantages of BERA is the extended storability of the disposable sensors, which is also documented by other research groups. So far, more than 35000 sensors have been used for screening worldwide.
Since BERA measurements are essentially electric signals, they can be instantly evaluated by means of specific software either on site (stand alone devices) or via an Internet site. Desktop devices with Internet-based evaluation are targeted to small clinic and doctors' office screening tests in the USA and European Union. On site assays are related to portable BERA field test kits, which are ideal for clinical testing in developing countries and military applications. In this way, BERA and MIME cell sensors lay the foundation for a fully operational global biothreat monitoring network.