Biochip sensors for the rapid and sensitive detection of viral disease

Abstract

Recent advances in DNA and protein microarray methodology and the emerging technology of cell-based sensors have massively increased the speed and sensitivity with which we can detect viral infections. The advantages of the multi-parameter microarray technologies could be combined with the speed and sensitivity of cell-based systems to give 'cell-omic' sensors.

Figure 1

The structure of microarray experiments. (a) To obtain gene-expression profile data from a cDNA microarray, or chip, RNA is first extracted from an infected cell. The RNA is then reverse-transcribed and labeled ('sample preparation') and prepared RNA is hybridized to the chip. (b) Protein microarrays may have either antibodies or antigens arrayed as probes. Antibody probes can be used to detect antigens from an infected cell, and vice versa, following sample preparation and labeling. In both cases (a,b) the hybridized chip is scanned and the image processed to provide corresponding profiles.

Figure 2

The CANARY method (cellular analysis and notification of antigen risks and yields) [19]. B lymphocytes were engineered to express calcium-dependent bioluminescent aequorin in the cytosol as well as pathogen-specific antibodies on the cell surface. Ligation of the antibody by the pathogen causes an elevation in intracellular calcium ions, thus triggering emission of light from the aequorin within seconds of pathogen contact.

Figure 3

The concept of 'cell-omic sensors'. Cell-based detection systems can be combined with arrayed probes to allow multi-parameter analysis. By arraying cells in a monolayer on top of probes (such as antibodies), it would be possible to detect changes in multiple cellular components simultaneously. Components secreted from the cell or expressed on its surface could be detected directly by the probes; detection of intracellular components would require the use of more sophisticated techniques. Information would be collected directly from the underlying probes through detection systems positioned below the probes.