TABLE 7.1 Transduction Modes in Biosensors

Transduction Mode and Device

Observed Output

Optical

 

Fiber-optic and planar devices utilizing absorption, fluorescence, scattering, polarization, reflectivity, and/or interference of light

Changes in wavelength, intensity, emission profile, reflectivity, fringe patterns, polarization state, and refractive index.

Electrochemical

 

Potentiometric devices (e.g., ion-selective electrodes), amperometric devices, and conductometric devices

Changes in voltage, current, impedance and/or resistance.

Gravimetric

 

Acoustic wave devices, magnetic acoustic resonator sensors

Changes in mass and surface viscosity through shifts in frequency or phase of resonant vibrations.

Thermal

 

Thermistor devices

Changes in temperature through shifts in electrical output.

Magnetic

 

Magnetic field detectors

Changes in magnetic properties of paramagnetic particle reporters.

In many ways, structure-based biosensors mirror the highly effective in vivo processes that enable living organisms to respond appropriately to their environment. For example, cells respond rapidly and specifically to other cells, bacteria, viruses, hormones and other molecules and do so in proportion to the concentration of those signaling agents. In these signal transduction systems, the cell produces and displays its molecular recognition elements on its surface, embedded in its membrane. Each such element binds a specific target, usually to an extent that reflects the amount that is present. The binding activates a "reporter" function—usually a conformational change in the membrane-embedded molecular recognition molecule itself—that is then either detected directly or leads to a change in the molecular balance in the cell. Some structure-based sensors are modeled after biological systems, but are simpler, retaining only the specific binding components of the biological system. In general, they are easily replicated independent of the organisms (see Table 7.2 for some examples). The most common types of structure-based biosensors are immunosensors, which employ antibodies or antibody fragments as the recognition elements.1 Antibodies are proteins that are generated within organisms to bind molecules (antigens) that the organism recognizes as foreign. Thus, they will bind to the surfaces of potentially dangerous viruses, cells, or nonbiological chemicals. Given that vertebrates produce in excess of 1011 different antibodies, it is highly likely that one or more antibodies can be found to bind any given target.

Antibodies have historically been produced by inoculating animals (often rabbits) with the target analyte of interest and isolating the antibodies from the serum or the specific cells that generate them. This is a relatively costly and laborious process, and methods have recently been developed for generating antibodies in vitro, without the inoculation of vertebrates. For example, methods have been developed for generating antibodies on the surface of a bacteriophage,2 and a library of 109 human antibody fragments has been generated on the surface of yeast.3 Once these libraries of antibodies are

1  

B. Hock. 1997. Antibodies for immunosensors: A review. Analytica Chimica Acta 347:177-186.

P.B. Luppa, L.J. Sokoll, and D.W. Chan. 2001. Immunosensors: Principles and applications to clinical chemistry. Clin. Chem. Acta 314:1-26.

2  

I. Benhar. 2001. Biotechnological applications of phage and cell display. Biotechnology Advances 19:1-33.

3  

M.J. Feldhaus, R.W. Siegel, L.K. Opresko, J.R. Coleman, T.M. Feldhaus, Y.A. Yeung, J.R. Cochran, P. Heinzelman, D. Colby, J. Swers, C. Graff, H.S. Wiley, and K.D. Wittrup. 2003. Flow-cytometric isolation of human antibodies from a nonimmune Saccharomyces cerevisiae surface display library. Nature Biotechnology 21:163-170.



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