Biosensors Involved in Drug Discovery - Biosensors and Biosensor Kinetics - page 92

function of the ARC-704 concentration (in m g/mL) in solution, (c) the binding rate coeffi-
cient, k 2 , for a dual-fractal analysis as a function of the fractal dimension, D f2 , (d) the disso-
ciation rate coefficient, k d , as a function of the fractal dimension, D fd , (e) the affinities, K 1
and K 2 , as a function of the ratio of fractal dimensions, D f1 / D fd and D f2 / D fd , respectively,
(f) the ratio of the binding rate coefficients, k 2 / k 1 , as a function of the ratio of fractal dimen-
sion, D f2 / D f1 , for the binding of inorganic phosphate ion (P i ) in solution to a rhodamine-PBP
phosphate biosensor ( Okoh et al., 2006 ), (g) the binding rate coefficient, k , for a single-fractal
analysis as a function of MET-AMC concentration in solution to the cSPA charging assay
( Forbes et al., 2007 ), and (h) the binding rate coefficient, k , for a single-fractal analysis
as a function of the fractal dimension, D f , or the degree of heterogeneity that exists on the
biosensor chip surface.
The three different examples presented in this chapter, emphasize that the degree of hetero-
geneity that exists on the biosensor surface does significantly affect, in general, the rate coef-
ficient and affinity values, and subsequently the kinetics in general. These are just a few of
the representative examples available in the literature. More such studies are required to
determine whether the binding and the dissociation rate coefficient(s), and subsequently
the affinity values are sensitive to their respective fractal dimensions on the biosensor chip
surface with regard to drug discovery.
A better understanding of all possible parameters that influence the kinetics of binding and
dissociation of different analyte-receptor systems on biosensor surfaces is critical. This will
be of considerable assistance, for example, to help select the correct drug of choice from a
list of possible candidates. More often than not, the influence of diffusion and heterogeneity
on the biosensor surface is neglected. As indicated in this chapter and elsewhere in the topic,
the degree of heterogeneity significantly influences, in general, the binding as well as the dis-
sociation kinetics occurring on biosensor surfaces. It would behove the practicing
biosensorists to start paying more attention to this aspect of kinetics on biosensor surfaces.
One may perhaps argue that the influence of diffusional limitations may be minimized or
perhaps even be eliminated if the biosensor is run properly.
In fact, ideally one should really analyze separately the influence of the degree of heteroge-
neity and the diffusional aspects on the kinetics of analyte-receptor reactions occurring on
biosensor surfaces. This is not possible at the present time by the manner in which the fractal
analysis is done. If one is able to separate the influence of diffusional limitations and hetero-
geneities on the biosensor surface, and analyze the influence of each on the analyte-receptor
reactions occurring on biosensor surfaces, then one may be able to better manage these
analyte-receptor interactions to advantage. This should very significantly impact the different
biosensor performance parameters such as sensitivity, selectivity, and stability, and permit
one to optimize these parameters in desired directions for the different analyte-receptor
reactions occurring on biosensor surfaces.