Biomedical Engineering Reference
In-Depth Information
could find unique applications such as providing novel structural scaffolds to create
unique reporter systems in biosensors. Synthetic DNAs have also been shown to possess
self-assembly properties that result in micrometer-scale arrays with nanoscale features
(190). A DNA self-assembly system proceeding by cooperative binding at multiple weak
domains has been proposed as a Turing universal biomolecular computing system (191).
In this device, computations are carried out using the nanoscale DNA 2- or 3-D self-assem-
bly or 'tiling' properties of short DNAs, representing the algorithmic basis for the device.
Progress in this area will require, among other advances, methods to reduce errors in self-
assembly, a way to extend 2- to 3-D self-assembly, and methods to connect nanoelectron-
ics to nanometer-scale DNA assemblies. Other types of nanoscale DNA and nucleic acid
self-assembly are being investigated for biosensors. For example, DNA hybridization can
mediate the assembly of nanosuperstructures formed from gold nanoparticles (192) or
inorganic nanocrystals (193). Via analyte nucleic acid cohybridization to different short
single-stranded DNAs immobilized on different particles, the transition to assembled
nanoparticle structures producing optical changes could sensitively indicate the presence
of a specific analyte nucleic acid of interest. Lastly, in an interesting new system called
hybridization chain reaction, a DNA hybridization system self-assembles to form double
helical segments when an initiator nucleic acid strand is sensed—the analyte (194). This is
capable of functioning in a biosensor as an amplifying transducer when coupled to
aptamer nucleic acid triggers.
Other creative approaches with potential applications to biosensors involve the design
and formation of supramolecular structures via the self-assembly of carefully designed
molecular units possessing complementary, favorably interacting functional groups. For
example, from the Stoddart lab, large organic molecules such as polyrotaxanes and cate-
nanes have been demonstrated to form a variety of interlocked and threaded structures. A
specific example of one complex topologically linked system they have synthesized is the
five-ring interlocked structure aptly named Olympiadone (195). These supramolecular
structures often do not themselves involve biological macromolecules. However, they
could be used as scaffolding for incorporating biological macromolecules or as actuator
components of biosensors. Another interesting example is a chiral molecular motor that
can be caused to rotate about an internal double bond in a mechanism driven by light.
When the molecule is incorporated into a liquid crystal, the light-driven motor perturbs
the liquid crystal phase. By controlling the motion of the molecular motor, the resulting
color of the liquid crystal can be controlled over the entire visible spectrum (196). By cou-
pling some analyte detection scheme to this molecular motor, the system could serve as
the optical output for a biosensor.
We believe that the complete set of evolved intelligent properties that living cells pos-
sess holds great promise in the future for the increasing incorporation of specific cell types
into biosensors. This fact has resulted in our most recent biosensor focus being on the use
of living cells attached to the piezoelectric QCM platform. The cell QCM biosensor sys-
tems have allowed us to propose novel ways in which they could be used to screen small-
molecule drugs that differentially affect the cellular cytoskeleton, as well as to be
potentially able to discriminate normal from cancerous cells contained in human biopsy
samples (96,98). Also, we described the application of specific applied electrochemical
potentials to the isolated ECM from normal ECs, to release specific biological factors.
When applied to surface wounds, these factors enhanced nearly twofold the rate of
wound healing in a mouse model system (107,108).
In the last few years, our most recent research direction at the Center for Intelligent
Biomaterials at the University of Massachusetts has been to employ novel computational
strategies to understand the intelligent properties of specific biological molecules. We
have particularly focused on analyzing DNA and DNA-sequence-specific protein
