A
central focus of the Bio-Microelectronics and Nanotechnologies portion
of the CEB is aimed at developing technologies for sensing, actuation,
information extraction and processing, and computing at the molecular
scale. This is central to the CEB vision of dissecting, monitoring,
and controlling processes at the molecular level to achieve real-time
information processing, computation, and control in complex systems.
These complex systems include environmental systems (waste water treatment,
water purification, etc.), food quality testing, biomedical applications
(e.g. implantable medical devices), in situ process control, space and military monitoring and
detection, and any other systems where awareness and control at the
molecular level will provide revolutionary new capabilities.
Two
parallel and complementary research paths are being pursued. The first
path involves the coupling of genetically engineered whole cells with
advanced integrated circuit (IC) and sensor technology. This approach
was pioneered by members of CEB with the invention of the Bioluminescent
Bioreporter Integrated Circuit (BBIC) (Fig. 1). Information is sensed
at the molecular level by the cells through the modulation of genetic
regulation. In the simplest approach, this information is then communicated
to the IC where it is further processed and transmitted.
While
this BBIC sensor approach has and will continue to generate research
interest and funding, we now know that this is much too limited use
of the total information processing capabilities of the cells. Microorganisms
survive in a wide variety of harsh environments by processing information
and arriving at decisions (what to metabolize, what to transport into
the cell, where to locate or attach, etc.) that are conducive to cell
survival. Even in simple cells this is a tremendously complex operation
involving memory (DNA, genes), sensing and feedback (promoters, regulatory
proteins), interconnectivity (quorum sensing), chemical production (gene
expression), the formation and dissolution of groups (biofilms), self-assembly
and self-replication, and even locomotion. These cells sense and respond
to their environment at the molecular level. In the CEB, research is
being pursued that will allow us to access and use these extraordinary
capabilities in bio-microelectronic devices.
Specifically,
the approach for the development of bio-microelectronic devices is focused
in the following six areas:
1.
Establish an on-chip environment for cells
2.
Establish two-way communication between cells and the chip.
3.
Engineer cells to perform information processing functions
that can be communicated to the chip.
4.
Develop algorithms that exploit the information processing
schemes of the cells.
5.
Develop methods to parse information processing problems
into biological and silicon components.
6.
Integrate and package items 1-4 above into bio-microelectronic
devices.
Nanobiotechnology
is the development of nanostructured materials that interface with biological
systems, or the development of nanostructured devices that mimic biological
function. These devices will lead to a fundamental understanding of chemical and biological
systems at the nanometer scale, and new devices for the sensing and
control at the molecular scale.
In collaboration with groups at ORNL, CEB researchers have developed methods
to deterministically grow organized arrays of carbon nanofibers (CNFs).
These CNFs have diameters of a few nanometers, can be nanometers to
microns long, and can have nanometer-scale center-to-center spacing.
Furthermore, CNFs are electrically conductive, and can be chemically
derivatized. There are a variety of applications for these devices in
nanoelectronics, flat-panel displays, and advanced lithography. However,
in this research, two very promising nanobiotechnology applications
of CNFs will be developed: (1) nanoscale probes for real-time
mapping of intracellular molecular species with extremely high spatial
resolution and real-time gene expression
determination (Fig. 2); and (2) cellular mimics that use closely-spaced
CNFs as diffusion barriers (Fig. 3).
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Fig. 2. A densely populated, vertically-aligned carbon
nanofiber array comprised of 20 nm diameter fibers several microns in
length (left). Note the vastly improved spatial coverage the array can
provide for probing cells, as compared to traditional electrophysiological
techniques (patchclamping at right). Spatial resolution and dynamic
response to chemical stimulus at individual probes should also show
vast improvements over traditional methods as probe response is dominated
by boundary layer phenomena that only occur at the interface between
the probe and the measurement volume, which, due to the CNF’s
small diameter, is an exceptionally small region.
Fig.
3. Densely packed CNF array that may act as an engineered diffusion
barrier in cellular mimics.
For more
information contact Gary Sayler or Mike Simpson.