are only able to recognize certain structural elements that have previously been characterized and prepared for. Function-based detectors, on the other hand, can react to previously uncharacterized structures that affect the monitored biological functions. Thus, function-based detectors are less specific or selective but have the potential for detecting the presence of unknown chemical and biological agents. Initially, research in this area focused on chemical toxicants; it is only recently that function-based techniques have been applied to the detection of biological warfare agents.

Currently, there are a wide variety of biosensing systems that could fall under the banner of functional. These include enzyme systems, ion channel/receptors, cells, and whole organisms.4Table 9.1 provides a basic comparison of various recognition elements and the level of information they can provide. Antibodies and synthetic ligands can be generated to recognize a specific epitope (structural element). These recognition elements can be highly specific or common to various target organisms. For example, a given monoclonal antibody may identify a specific Bacillus species, while another may recognize all Bacillus species. Similarly, nucleic acid-based identification sequences can be specific to the strain level, or they can be directed to conserved regions of particular genomes. Enzymes and cellular chemistries are modulated by compounds that affect their active site and thus modulate their function. Since modulation of most enzyme activities is accomplished by the natural substrate as well as structural analogs, the information generated is rather generic; e.g., inhibition of cholinesterase activity by various nerve agents. Similar restrictions of specific identification apply to receptors, cells, and whole organisms. These systems are valuable for providing functional information regarding potentially harmful material in the environment. While the ability to identify harmful material for which no specific assay exists is important, one must also consider the fact that the response of an isolated cell may or may not model the response of humans to the same challenge. Differential responses among multiple function-based sensing elements (e.g., different cell types) may provide fingerprints of various classes of compounds in much the same way that surface acoustic wave devices identify chemicals (see Chapter 8).

There is a very fine line dividing structure-based and function-based detection systems. In the following examples, hybrid systems exploit part of the functional process within a cell-based response system, even as they are targeted at a specific characterized function.

The canary-on-a-chip concept,5 which uses genetically engineered B cells or B lymphocytes with the appropriate antibody incorporated into the genome and displayed on the cell surface, is an example of a biosensing system that exhibits characteristics of a functional detector but is reliant on having a specific

TABLE 9.1 Type of Information Provided by Various Recognition Systems

Recognition Element

Functional Information

Specific Identificationa

Generic Detection and Classification



Nucleic acids


Synthetic ligands


Enzymes/cellular chemistry


Ion channel/receptors




Whole organisms


a Relies on a specific binding event (e.g., gene probe primer sets for a given organism or antibody antigen binding).


J. Pancrazio, Naval Research Laboratory. Presentation to the committee on September 26, 2002.


J.D. Harper, MIT Lincoln Laboratory. Discussions with the committee on June 13, 2002.

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