Biomedical Engineering Reference
In-Depth Information
platform to maximize the biosensor sensitivity to the analyte. There have been quite a large
number and variety of physical and chemical attachment methods used in developing
biosensors and we will not review them here. However, we will focus on one of our major
thematic approaches in the Center for Intelligent Biomaterials, which has been to utilize
polymeric thin films bound to the biosensor platform surface to immobilize biological ele-
ments. We have utilized both conducting and nonconducting polymers in various thin-film
formats to carry out immobilizations of different biological elements. As an example, some
of these strategies have involved chemical synthesis of conducting polymers derivatized
with biotin, which functions as a pendant biological attachment site. In Figure 1.1a, a gen-
eral single-step reaction used widely to create derivatized conducting polythiophenes is
presented. In Figure 1.1b, we outline the two-step synthesis of a representative biotinylated
(B) polythiophene copolymer, B-PUMT, where the biotin is connected by an ester linkage
to the pendant CH
2
OH group on the thiophene polymer backbone (3). These biotin ligands
recognize and bind each of the four subunits of the tetrameric proteins streptavidin and
avidin with affinity constants approaching those of covalent bonds, around 10
15
per M (4).
These two proteins have been widely used to covalently derivatize many biological macro-
molecules, leading to an attachment system where multiple derivatized biological elements
can be immobilized upon the biotinylated polymer chain, following prior immobilization
of the polymer upon the surface of the chosen platform.
(a)
R
R
FeCl
3
S
S
n
C
11
H
23
(b)
C
11
H
23
CH
2
OH
FeCl
3
S
+
S
S
S
n
CH
2
OH
O
C
11
H
23
NH
NH
S
DCC
Pdp
DCM
+
S
HOOC(CH
2
)
4
n
CH
2
OH
S
C
11
H
23
S
S
n
S
CH
2
OOC(CH
2
)
4
NH
NH
FIGURE 1.1
Synthetic schemes for creating thiophene polymers: (a) general synthetic scheme for poly(3-alkylthiophenes) for
any alkyl (R)-derivatized monomer; (b) two-step synthesis of B-PUMT, biotinylated poly(3-undecylthiophene-
co-3-methanolthiophene). The biotin ligand (B) is added in the second esterification step. Reprinted with per-
mission from Marx, K.A., Samuelson, L.A., Kamath, M., Lim, J.O., Sengupta, S., Kaplan, D., Kumar, J., Tripathy,
S.K. (1994). Intelligent Biomaterials Based on Langmuir-Blodgett Monolayer Films. In: Birge, B.R., ed.
Molecular
and Biomolecular Electronics.
Advances in Chemical Series, Vol. 240, American Chemical Society Books,
Washington, D.C., 395-412. Copyright (1994) American Chemical Society.
