Biosensors & Bioelectronics 15 (2000) 651–662
Analyte-receptor binding and dissociation kinetics for biosensor
applications: a fractal analysis
Anand Ramakrishnan, Ajit Sadana *
Chemical Engineering Department, Uni6ersity of Mississippi, P.O. Box
1848
, Mississippi, MS
38677
-
1848
, USA
Received 4 April 2000; received in revised form 11 September 2000; accepted 6 October 2000
Abstract
A fractal analysis of confirmative nature only is presented for analyte-receptor binding and dissociation kinetics for biosensor
applications. Data taken from the literature may be modeled, in the case of binding using a single-fractal analysis or a dual-fractal
analysis. The dual-fractal analysis represents a change in the binding mechanism as the reaction progresses on the surface.
Relationships are presented for the binding and dissociation rate coefficients as a function of their corresponding fractal
dimension, D
f
or the degree of heterogeneity that exists on the surface. When analyte-receptor binding or dissociation is involved,
an increase in the heterogeneity on the surface (increase in D
f
) leads to an increase in the binding and in the dissociation rate
coefficient. It is suggested that an increase in the degree of heterogeneity on the surface leads to an increase in the turbulence on
the surface owing to the irregularities on the surface. This turbulence promotes mixing, minimizes diffusional limitations, and
leads subsequently to an increase in the binding and in the dissociation rate coefficient (Martin S.J., Granstaff, V.E., Frye, G.C.,
Anal. Chem., 65, (1991) 2910). The binding and the dissociation rate coefficient are rather sensitive to the degree of heterogeneity,
D
f,bind
and D
f,diss
, respectively, that exists on the biosensor surface. For example, the order of dependence on D
f,bind
is 19.2 for the
binding rate coefficient, k
bind
for the binding of 0.03 –1.0 mM SH-2L
d
in solution to 2C TCR immobilized on a surface plasmon
resonance (SPR) biosensor (Corr, M., Salnetz, A.E., Boyd, L.F., Jelonek, M.T., Khilko, S., Al-Ramadi, B.K., Kim, Y.S., Maher,
S.E., Bothwell, A.L.M., Margulies, D.H., Science, 265, (1994) 946). The order of dependence on D
f,diss
is −6.22 for the
dissociation rate coefficient, k
diss
for the dissociation of 250– 1000 nM Sophora japonica agglutinin (SJA)-lactose complex from the
SPR surface. In general, the technique is applicable to other reactions occurring on different types of surfaces, such as cell-surface
reactions. © 2000 Elsevier Science S.A. All rights reserved.
Keywords
:
Analyte-receptor; Biosensor; Fractal analysis; Binding; Dissociation
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1. Introduction
Understanding biological processes at the molecular
level requires two basic approaches: structural and
functional analysis. A promising area in the investiga-
tion of biomolecular interactions is the development of
biosensors. These biosensors are finding application in
the areas of biotechnology, physics, chemistry,
medicine, aviation, oceanography, and environmental
control. These sensors or biosensors may be utilized to
monitor the analyte-receptor reactions in real time
(Myszka et al., 1997), besides some techniques like the
surface plasmon resonance (SPR) biosensor do not
require radiolabeling or biochemical tagging (Jonsson
et al., 1991), are reusable, have a flexible experimental
design, provide a rapid and automated analysis, and
have a completely integrated system. Besides, the SPR
in combination with mass spectrometry (MS) exhibits
the potential to provide a proteomic analysis (Williams
and Addona, 2000). In addition to evaluating affinities
and interactions the SPR can also be utilized to deter-
mine unknown concentrations, determination of specifi-
city, kinetic analysis, check for allosteric effects, and for
comparing binding patterns of different species.
There is a need to characterize the reactions occur-
ring at the biosensor surface in the presence of diffu-
sional limitations that are inevitably present in these
types of systems. It is essential to characterize not only
* Corresponding author. Tel.: +1-601-2327023; fax: + 1-601-
2327023.
E-mail address
:
cmsadana@olemiss.edu (A. Sadana).
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