Science & Technology Program

• CBST researchers developed a prototype advanced microscope (OMX) for biological imaging with 2X better resolution than conventional systems. This instrument, developed at UCSF, is capable of structured illumination imaging and 4-color video rate imaging. Using structured illumination, biological images can be obtained that reveal structures never before seen with a light microscope. A more advanced system is planned that uses saturated structured illumination and gives 5 times better resolution than a conventional microscope. CBST plans to raise the funds to produce 10 of these prototype systems and make them available to the biological community.
• CBST researchers developed a new assay for botulinum toxin in milk. As part of a project to develop optical based assays, researchers funded by LLNL and CBST have developed a prototype immunoassay for botulinum toxin in raw milk that requires a minimum of sample preparation. Botulinum toxin poisoning occurs in dairy cattle and is a biosecurity concern. Present assays of milk require 48 hours and gold standard culture assays require 5-7 days but the optical fluorescent bead based assay developed at LLNL and CBST can be performed in a few minutes.
• CBST researchers have developed a non-invasive optical technique that may someday quantify the viability of transplant organs. In this country and worldwide there is a severe shortage of organs for transplant patients. This situation could be partially alleviated by using optical research performed by CBST scientists. In vivo optical scattering and autofluorescent optical signatures from exposed kidneys of laboratory rats were discovered to correlate with the condition of the kidney as it was controlled by modulating the blood supply to that organ.
• A CBST funded project has produced luciferin compounds that will now allow the development of novel protease in vivo assays. A synthetic chemist from LLNL working with a team of researchers at Stanford University have synthesized a key compound (amino-luciferin) that will now allow efficient attachment of peptides to the luciferin molecule. Luciferin reacts with the enzyme luciferase in transgenic mice to produce bioluminescent light. These substrate-reporter complexes will be used for drug screening and disease diagnosis applications.
• CBST researchers developed a new mathematical model of biological membranes. Building on the work of other groups, researchers at CBST have developed a new mathematical model of phospholipid bilayer membranes that allow efficient molecular dynamics calculations. Instead of taking into account each atom in the lipid molecules as is done in conventional MD calculations, these researchers have represented the molecules with only a few (5) individual segments. This model has now begun to explain novel features observed in another CBST project where uv light is used to produce persistent patterns of arbitrary shape.
• A CBST co-funded project has revealed the novel behavior of single helicase/nuclease enzymes (RecBCD) upon encountering a DNA Chi-sequence. Researchers co-funded by CBST and NIH have used a special optical microscope capable of tracking the motion of a single RecBCD enzyme along a single double-stranded DNA molecule as the enzyme (associated with genetic recombination) unwinds and disassociates the nucleotides. The rate of motion can be determined by these measurements and it was recently discovered by this group that when the enzyme encounters a special sequence (known as Chi) that the enzyme undergoes modification and then proceeds at a slower rate.
• CBST researchers are developing lensless aberration-free 3D x-ray imaging having the highest ever spatial resolution at that x-ray wavelength. CBST researchers in collaboration with other researchers from Stanford and the University of Uppsala are developing techniques that will enable the diffraction pattern and thus the structure of single protein molecules to be determined using the 4th generation FEL xray source, LCLS, at SLAC, expected to be operational in 2008. In preparation, new diffraction imaging techniques are being developed on existing synchrotrons. Recently a complex 2D object consisting of an arrangement of 50 nm spheres was imaged using only the diffraction pattern produced by this object. Novel reconstruction algorithms developed by CBST personnel were used to reconstruct an aberration free image with 10 nm resolution (2 times better than convention zone plate imaging). Now at the LBNL ALS synchrotron the imaging technique is being extended to 3D with the recent acquisition of data from complex three-dimensional objects. New algorithms are being developed to reconstruct the first ever 3D  images from these new data sets. It is hoped that this new form of imaging can be used for 3D imaging of biological samples with resolutions not previously obtained.
• CBST sponsored researchers have leveraged their projects into an addition $800k / year of extramural funding from NIH, DOD, and DOE. Several other grant applications are pending. In many cases, reviewers have commented that CBST sponsorship has been critical to awarding the grant. We expect our grant portfolio to increase at least 15-25%/year.

CBST Scientific Workshops

• Medical Applications of Biophotonics (San Antonio, TX; Feb 26-27; principal sponsor; this is a major opportunity for this MSI)
• CBST Workshop on Biophysics (Davis, CA; Dec ‘03; principal organizer)
• From Biosecurity Defense to Cancer Offense: Applying biosecurity technologies to cancer research, detection, and therapy (Stockton, CA; Feb 29; co-organized)
• NIBIB/DOE Workshop on Biomedical Imaging: Optical & X-Ray Technologies (Bethesda, MD; Feb 10-11; co-organized)
• Biological Applications of the LCLS (Palo Alto, CA; March 15; principal sponsor)
• Major presentations on CBST at Photonics West / SPIE, LEOS, BioLight

Knowledge Transfer Program

• Sacramento Angel Student Poster Award for Best Commercialization Analysis. CBST students were teamed with Graduate School of Management (GSM) students to determine the commercialization potential of specific CBST technologies. The Sacramento Angels (an Industry Partner) sponsored the contest and supplied mentors for each of the teams. A panel of investors and corporate partners selected the winning team. This team was awarded $5,000 by the Sacramento Angels to assist in the commercialization of the technology.
• Sacramento Life Sciences Summit 2004 featuring the CBST 2004 Technology Showcase & Governor’s Life Science Summit Panel. The Life Science Summit enabled CBST to showcase highlights of the Science and Technology, Education, and Knowledge Transfer programs and explore how these programs could impact regional economic development. It provided a forum to expose CBST to over 400 researchers, corporations, and investors. In addition, CBST continues to serve on the blue ribbon Governor’s Life Science Summit panel. This distinction recognizes CBST as a key organization that understands not only trends in technology, but also understands what factors influence regional economic growth.
• Launch of Professional Society Collaborations Effort. This effort was designed to form alliances with professional societies in order to provide education to companies and professionals. It was especially designed for companies and individuals who had a background in photonics and were interested in exploring the Biophotonics market sector. During its first year of existence, over 20,000 professionals were exposed to CBST and the field of Biophotonics.
• Analysis of Industrial Demand for Technicians Skilled in Biophotonics. This joint effort between Education and Knowledge Transfer was initiated to determine the present and future demands by industry for technicians trained in Biophotonics. The study is being conducted in conjunction with Technical Vocation Institute (TVI) based in Albuquerque, New Mexico. The feedback from industry will be used to design curriculum at the community college level.
• Association for Distance Education Conference (ADEC), Demonstration of First IP Broadband Trial. CBST and its industry partners SBC and Tandberg tested the first IP broadband system at ADEC in Pasadena, CA. This system remotely linked Sacramento, Pasadena, Denver, and Davis. The ADEC conference was focused on new techniques and technologies to facilitate distance learning. Participation in this  event assisted in further establishing CBST as an institute that is on the cutting edge of new technologies for distance learning and knowledge exchange.
• Joint Collaborations with the Center for Adaptive Optics (CfAO). Vision Science technologies from CfAO were presented along with CBST technologies at the Sacramento Life Sciences Summit in March 2004. Both groups are exploring joint research and commercialization opportunities. An example of potential integrated projects would be to combine adaptive optics with CBST’s structured illumination technology.
• CBST Newsletter and Web Site. Both the web site and newsletter were designed to provide information on Biophotonics to the public-at-large. This was a key step in establishing the CBST “brand” as the main source for information on Biophotonics. The Newsletter was specifically designed to provide highlights of Science and Technology, Education, and Knowledge Transfer. The web site has been registered with major search engines. In addition, a web space for collaboration (collaboratory) is currently under construction to provide interaction among Biophotonics professionals. In short, the Center’s Web is turning into a set of arenas for collaboration and conversation.
• Bridging Commercialization through Industry Partners. CBST was an invited presenter at two key conferences conducted by industry partners Technology Ventures Corporation and NANOSIG: First California Equity Capital Symposium and Bridging Commercial Applications of Nano- BioTechnology. Approximately 200 attendees, 1/3rd investors, discussed steps required to commercialize early stage Biophotonics technologies. These forums also offered the opportunity for CBST’s industry partners to expose their technologies to investors.

Leadership & Management Highlights

• New Building for CBST home finally broke ground in March 2004. Move-in slated for August 2005. The first floor of this 40,000 square foot state-of-the-art building will provide the permanent home to CBST.
• CBST Televideo network serves as enabler of monthly Director's Televideo Meetings involving all the NSF STC’s. The CBST televideo network infrastructure enables all of the STC Directors and managing Directors to have a monthly televideo meeting. The monthly format includes approximately 30 minutes of business items and a one-hour presentation by a Center Director of their Center. This provides opportunities to interact scientifically, televise courses, discuss education opportunities/projects as well as address admin/management issues.