TABLE 7.2 Molecular Recognition Systems for Biosensing

Molecular Recognition Element

Target Inhibitor

Comments

Single-stranded DNA

Complementary sequence of DNA

DNA hybridization is the basis for DNA biochip arrays and DNA amplification methods such as polymerase chain reaction (PCR), which are used for trace detection.

Antibody (a protein)

Proteins, carbohydrates, small organic molecules, etc.

Basis for immunoassays and immunosensors. Whole antibodies and parts of antibodies can now be developed in vitro.

Peptide (small part of a protein)

Proteins, carbohydrates, small organic molecules, etc.

Analogous to antibodies but much smaller and developed in vitro.

Enzyme (a protein)

Substrate (such biochemicals as urea, glucose, acetic acid).

Catalyzes the conversion of the substrate to a detectable product.

Lectin (a protein)

Carbohydrate

Lectins bind to polysaccharides on cell surfaces. Lectins typically bind to at least several types of organisms. This approach is expected to be most useful for sample preparation and general biodetection rather than for specific pathogen identification.

Receptor (a protein)

Proteins, carbohydrates, small molecules

In nature, receptors are often embedded in the membranes of cells. Ligand binding to a receptor causes a conformational change in the receptor that triggers detectable intracellular events.

Aptamer (a nucleic acid sequence)

Proteins, small organic molecules, etc.

Recognition is analogous to ligand-receptor binding, in contrast to sequence-specific hybridization between complementary strands of DNA.

Small molecules

Proteins, cells, etc.

Recognition is analogous to the interaction between an antibody and small antigen molecule; however, the small molecule is used as the molecular recognition element, and a biomolecule such as a protein on the surface of a cell is the target.

Imprinted polymers

Proteins, small organic molecules, whole cells, etc.

Under development but not yet proven for biodetection.

generated, high-throughput selection processes can be used to select the cells that contain antibodies that selectively bind the antigens of interest, and the selected cells can then be used to rapidly generate large quantities of the antibodies for sensor development. There is potential for these types of high-throughput in vitro methods to generate low-cost molecular recognition reagents for biothreat detection.

In addition to antibodies, a wide variety of other molecular recognition elements can be used for biosensing,4 some of which are summarized in Table 7.2. Many of these molecular recognition elements are proteins (e.g., enzymes, lectins, receptors), but some other types of molecular recognition elements under development may have properties (e.g., greater temperature and chemical stability) that make them better suited for use in environmental biosensors than are proteins. In the sections below, the committee describes the key features required for structure-based detection of biothreats, discusses some structure-based biosensor systems that have been investigated for biothreat detection, and highlights the areas that are promising and/or need development in order to achieve reliable operation in detect-to-warn situations, which will require rapid, reliable, and sensitive detection.

4  

S.S. Iqbal, M.W. Mayo, J.G. Bruno, B.V. Bronk, C.A. Batt, and J.P. Chambers. 2000. A review of molecular recognition technologies for detection of biological threat agents. Biosensors and Bioelectronics 15:549-578.



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