BioMicroElectronics and NanoBioTechnology
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:
- Establish an on-chip environment for cells
- Establish two-way communication between cells and the chip.
- Engineer cells to perform information processing functions that can be communicated to the chip.
- Develop algorithms that exploit the information processing schemes of the cells.
- Develop methods to parse information processing problems into biological and silicon components.
- 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).
For more information, contact Gary Sayler or Michael Simpson.
Current Research
- Electrically Inducible Genes
- DNA Delivery via Carbon Nanofibers
- BBIC Devices, Networks, and Sensing
- Microfluidic Devices for Specific Analyte Detection
- Ecotoxicology of C60 Fullerenes in Zebrafish
- Real-time Bioreporter Sensor and Therapeutic Effector Loop for Monitoring Physiological Fluctuations
Figure 1. This photograph shows maximally-induced bioluminescent bacteria on a CMOS microluminometer to form bioluminescent bioreporter integrated circuits (BBICs). All the light for this photograph was provided by the bacteria (45-minute exposure time).
Figure 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.
Figure 3. Densely packed CNF array that may act as an engineered diffusion barrier in cellular mimics.




