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Research » BioMicroElectronics and NanoBioTechnology


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:

  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).

For more information, contact Gary Sayler or Michael Simpson.


Current Research
 

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.