Biomedical Engineering Reference
In-Depth Information
Reichert, 1998; James
et al.
, 1998; Kane
et al.
, 1999; Ito,
1999; Folch and Toner, 2000
). Sometimes the patterned
surfaces will have regions that repel proteins
(''nonfouling'' compositions) while others may contain
covalently-linked cell receptor ligands (
Neff
et al.
, 1999;
Alsberg
et al.
, 2002; Csucs
et al.
, 2003; VandeVondele
et al.
, 2003
), or may have physically adsorbed cell ad-
hesion proteins (
McDevitt
et al.,
2002; Ostuni
et al.
,
2003
). There has also evolved a huge industry based on
''biochips'' that contain microarrays of immobilized,
single-stranded DNA (for genomic assays) or peptides or
proteins (for proteomic assays) (
Houseman and Mrksich,
2002; Lee and Mrksich, 2002
). The majority of these
microarrays utilize inorganic silica chips rather than
polymer substrates directly, but it is possible to in-
corporate functionality through chemical modification
with silane chemistries (
Puleo, 1997
) or adsorption of
a polymeric adlayer (
Scotchford
et al.
, 2003; Winkel-
mann
et al.
, 2003
). A variety of methods have been used
for the production of these patterned biochips, including
photocontrolled synthesis (
Ellman and Gallop, 1998;
Folch and Toner, 2000
), microfluidic fluid exposure
(
Ismagilov
et al.
, 2001
), and protection with adhesive
organic protecting layers that are lifted off after exposure
to the biomolecular treatment (
Jackman
et al.
, 1999
).
Table 3.2.16-2 Application of immobilized biomolecules and cells
Enzymes
Bioreactors (industrial, biomedical)
Bioseparations
Biosensors
Diagnostic assays
Biocompatible surfaces
Biosensors
Diagnostic assays
Affinity separations
Targeted drug delivery
Cell culture
Antibodies, peptides,
and other affinity
molecules
Thrombo-resistant surfaces
Drug delivery systems
Drugs
Lipids
Thrombo-resistant surfaces
Albuminated surfaces
Nucleic acid derivatives
and nucleotides
DNA probes
Gene therapy
Bioreactors (industrial)
Bioartificial organs
Biosensors
Cells
swollen they become hydrogels, and biomolecules may
be immobilized on the outer gel surface as well as within
the swollen polymer gel network. Examples of applica-
tions of these immobilized biological species are listed in
Table 3.2.16-2
. It can be seen that there are many diverse
uses of such biofunctional systems in both the medical
and biotechnology fields. For example, a number of
immobilized enzyme supports and reactor systems (
Table
3.2.16-3
) have been developed for therapeutic uses in
the clinic (
Table 3.2.16-4
) (De
Myttenaere
et al.
, 1967;
Kolff, 1979; Sparks
et al.
, 1969; Chang, 1972; Nose
et al.
,
1983, 1984
;
Schmer
et al.
, 1981; Callegaro and Denri,
1983
;
Lavin
et al.
, 1985; Sung
et al.
, 1986
).
Immoblized biomolecules and their uses
Many different biologically functional molecules can be
chemically or physically immobilized on polymeric sup-
ports (
Table 3.2.16-1
)(
Laskin, 1985; Tomlinson and
Davis, 1986
). When some of these solids are water-
Table 3.2.16-1 Examples of biologically active molecules
that may be immobilized on or within polymeric biomaterials
Drugs
Antithrombogenic
agents
Anticancer agents
Antibiotics
Contraceptives
Drug antagonists
Peptide, protein drugs
Ligands
Hormone receptors
Cell surface receptors
(peptides, saccharides)
Avidin, biotin
Nucleic acids,
nucleotides
Single or double-
stranded DNA, RNA
(e.g., antisense
oliogonucleotides)
Proteins/peptides
Enzymes
Immobilized cell ligands
Antibodies
Antigens
Cell adhesion molecules
''Blocking'' proteins
Cell interactions with foreign materials are usually me-
diated by a biological intermediate, such as adsorbed
Saccharides
Sugars
Oligosaccharides
Polysaccharides
Lipids
Fatty acids
Phospholipids
Glycolipids
Other
Conjugates or
mixtures of the above
Table 3.2.16-3 Bioreactors supports and designs
''Artificial cell'' suspensions
(microcapsules, RBC ghosts, liposomes, reverse micelles [w/o]
microspheres)
Biologic supports
(membranes and tubes of collagen, fibrin GAGs)
Synthetic supports
(porous or asymmetric hollow fibres, particulates, parallel plate
devices)
