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have emerged, capable of transducing the often highly sensitive and specific
responses of cellular matrices for biosensing in environmental, medical, and in-
dustrial applications [20]. The demands of these systems have driven advances
in cellular immobilization and encapsulation techniques, enabling improved in-
teraction of the biological matrix with its environment while providing nutrient
and respiratory requirements for prolonged viability of the living matrices [51].
Predominantly, such devices feature a single interface between the bulk
biomatrix and transducer. However, advances in lithography, micromachin-
ing, and micro-/nanoscale synthesis provide broader opportunities for inter-
facing whole-cell matrices with synthetic elements. Advances in engineered,
patterned, or directed cell growth are now providing spatial and temporal con-
trol over cellular integration within microscale and nanoscale systems [34].
Perhaps the best defined integration of cellular matrices with electronically
active substrates has been accomplished with neuronal patterning. Topograph-
ical and physicochemical patterning of surfaces promotes the attachment and
directed growth of neurites over electrically active substrates that are used to
both stimulate and observe excitable cellular activity [64]. With the proper use
of emerging techniques in the directed synthesis and assembly of nanoscale
elements, the direct interface to smaller regions of individual cells and even
subcellular molecular components are possible.
To date, the largest body of work is with microscale systems, as biosensors
have incorporated cells with integrated circuits (IC) and microelectromechan-
ical systems (MEMS). More recent efforts have pushed toward the molecular-
scale interface between cells and synthetic components required for the types
of systems ultimately envisioned here. In this chapter we review these efforts
to integrate cells as components into microscale and nanoscale systems.
MICROSCALE SYSTEMS
Numerous demonstrations of the integration of cells into ICs, MEMS, or other
microscale devices have been reported. These include microelectrode arrays
for measuring action potentials from neuronal networks [58], a cell cartridge
device that interfaces neurons or cardiomyocytes to an IC transducer [17], an
IC transistor array that records electrical activity from on-chip cardiomyocyte
cultures [33], an IC that both stimulates and records electrical activity from
on-chip neurons [64], and many others. All these devices face similar issues
regarding the incorporation of cells, which are very different from the other
materials found in microscale devices. Our work has included extensive devel-
opment of a whole-cell/IC sensor device we have coined the
bioluminescent
bioreporter integrated circuit
(BBIC) [56, 57]. We present the BBIC as one
example that illustrates the issues involved in the incorporation of the cells into
microscale systems.
