MIPS Molecular Imaging Program at Stanford
Center for Cancer Nanotechnology Excellence Focused on Therapy Response

Stanford Environment

Clark CenterStanford University has made significant investments in several key areas that directly impact this CCNE-TR research proposal. Stanford University has strongly believed that its strengths in the School of Medicine, Engineering, and Humanities & Sciences (home of Chemistry Department) need to be leveraged towards advancing biomedical sciences. For this reason a key effort known as the Bio-X Program was established and a new building of 225,000 square feet known as the James H. Clark Center was constructed (see above figure). This was an investment of over $175 million in construction costs and infrastructure that brings together scientists from many disciplines including Chemistry, Applied Physics, Bioengineering, Computer Science, Developmental Biology, Molecular Pharmacology, Medicine, Surgery, and Radiology. All the Bio-X Program Scientists share a common goal to advance Biomedical Science. The CCNE-TR proposal will tremendously benefit from the environment at Stanford and the Bio-X that fosters highly multidisciplinary efforts including nanotechnology research. It is through the structure of the Bio-X program that many of the Stanford based researchers in this proposal were brought together (e.g., Drs. Gambhir, Rao, Dai, Wang, Felsher, Nolan). Dr. Matthew Scott, Director of the Bio-X Program, and Dr. Arthur Bienenstock, Stanford Dean of Research overseeing the Bio-X Program, are highly supportive of this CCNE-TR as it is the exact type of collaborative effort that the Bio-X would like to foster.

In 2001, Drs. Gary Glazer (chair of Radiology) and Philip Pizzo (Dean, School of Medicine) initiated a nation-wide search to bring leadership in multimodality molecular imaging of living subjects to Stanford. Dr. Gambhir was recruited and appointed as the Director of the Molecular Imaging Program at Stanford (MIPS) (http://mips.stanford.edu) and moved to Stanford in 2003. Dr. Gambhir, who was also appointed Head of Nuclear Medicine, immediately began recruitment of new faculty in molecular imaging and has already recruited 6 new MIPS faculty.

Drs. Glazer and Pizzo were supported in their efforts by the University as a whole, including Dr. John Hennessy (President, Stanford University), Dr. Sharon Long (Dean of Humanities and Sciences), Dr. Jim Plummer (Dean of Engineering), and Martha Marsh (President & CEO of Stanford Hospital), This same senior leadership is also highly supportive of the CCNE-TR as this grant is a perfect example of what the University leadership would like to see happen on campus .

Stanford University has made major commitments to the Molecular Imaging Program at Stanford (MIPS). The recruitment of Dr. Gambhir to Stanford was a top-down effort with significant commitments in new space, renovation of existing space, equipment, new faculty billets, startup packages for new faculty, and funds for infrastructure development. The University committed $45,000,000 in total towards the MIPS effort. Many different Departments and individuals were committed to ramping-up molecular imaging, therefore facilitating the recruitment of Dr. Gambhir.

Lucas BuildingConstruction of a new building of 14,000 net square feet (Lucas Expansion, see left) finished in February 2005. This building houses the new cyclotron facility, radiochemistry labs, chemistry labs, and cell/molecular biology labs. This was an investment of over $23,000,000 by Stanford University to ensure the proper infrastructure for Molecular Imaging Chemistry on campus in the form of space for the new Lucas Expansion building. In addition, approximately 7,000 square feet were allocated within the Clark Building to house a portion of the MIPS. Space was also committed to the Nuclear Medicine clinic (see support letter by Martha Marsh, Hospital CEO) to double its size from approximately 6,000 to 12,000 net sq. feet. This is existing space that we will finish renovating in 2007 and which will allow for a significant clinical component to the program. The renovated space will house 2 PET/CT's, 4 new SPECT/CT cameras, and 2 existing SPECT cameras.

Cancer CenterStanford is actively preparing a comprehensive cancer center grant for submission to the NCI in October 2009. This will be important for the CCNE-TR effort in cancer for the Medical School. Dr. Karl Blume (retired head of Bone Marrow Transplantation) has been championing the effort along with Dr. Irv Weissman, PI of the upcoming NCI proposal. Dean Philip Pizzo is very committed to cancer research and translation and a new clinical cancer center building has just been completed. Dr. Leibel from Memorial Sloan Kettering Cancer Center (MSKCC) has been appointed the Clinical Director. Dr. Gambhir serves on the Executive Committee for the cancer center to provide significant input into shaping its future. The comprehensive cancer center grant will have molecular imaging as a key component including both an imaging shared resource and a basic science program project focused on new molecular imaging probes/assays. Drs. Pizzo and Weissman are highly supportive of this CCNE-TR effort and will help us to leverage resources as needed (see support letters). The timing could not be better to fully integrate nanotechnology and molecular imaging into the cancer center vision on the medical campus.

Nanotechnology Infrastructure


NanotechnologyUncommon in the world, Stanford has world-class nanotechnology infrastructure centrally located at the Science and Engineering Quadrangle but adjacent to the School of Medicine. The two communities are physically and intellectually connected via the Clark Center and the Bio-X Program. The Stanford Nanofabrication Facility (SNF)(see above figure) in the Paul Allen Center for Integrated Systems, just next to the Clark Center, is a 10,000 square foot, Class 100 clean-room housing a complete suite of over 75 processing tools for the micro- and nano- fabrication of devices. A full-time staff of engineers and technicians provide equipment and process support to keep the facility operational 24 hours a day, 7 days a week. SNF, in partnership with twelve other university facilities across the country, form NSF's National Nanotechnology Infrastructure Network (NNIN), which is committed to providing nanofabrication resources to researchers across the country, in industry as well as academia. As one of the original Network sites, SNF now has over ten years of experience as an open user facility. Over 600 lab members are registered at SNF. Of the approximately 200 lab members who used SNF on average each month in 2004, about 15 came from non-Stanford academic institutions and 50 from industrial organizations. About 30 new researchers join SNF each month. Although more traditionally known for its strengths in silicon device fabrication, SNF has expanded its capabilities to serve other disciplines as well. Specifically, SNF now supports a large cadre of internal and external users with interests in biology, chemistry, MEMS, optics, and physics in addition to the traditional areas of electronics, materials, and process characterization. SNF lab members routinely develop processes requiring 10 to 15 or more patterning steps and hundreds of individual process steps. Thus, the SNF has extensive infrastructure for operating a large lab, training new researchers, and allowing them to fabricate complex devices. Of particular relevance to the CCNE-TR and its Core 2 Facility are e-beam, for nanopattern definition, and nanoimprint, for nanopattern transfer and replication. Existing in-house e-beam capability consists of:

  • The 30keV Hitachi H-700 F11, a fast-write, 100 MHz system that can reproducibly direct-write features down to 80 nm in size.
  • The Raith 150 high-resolution system that produces drawn features as small as 30 nm.

Through the Network, SNF also has access to more advanced tools, such as the Leica VB6 at Cornell's Nanofabrication Facility and the Jeol 9300 at Georgia Tech. These tools are for electron-beam lithography used in nanofabrication. Valued at $5M, they represent the very best of top-down approaches to nanofabrication, as opposed to bottom-up nanofabrication with chemical synthesis. Still, SNF recognizes the need to improve its own e-beam capability and so is in the process acquiring a state-of-the-art, direct write e-beam system that offers both the required nanoscale resolution and write speed. However, even with the most advanced tools, e-beam is limited by extremely long processing time and the kinds of materials that can be direct-written. Nanoimprinting methods, though, allow high-fidelity, fast transfer or replication of nanopatterns obtained by direct-write e-beam into a broad range of materials. SNF has recently acquired an EV Group MA 620 Nanoimprint system and is in the process of developing protocols for its use and for fabricating nano-imprint stamps.

As part of Stanford Advanced Materials Initiative, Stanford Nanocharacterization Lab (SNL) is established to raise private and public funds to maintain a state of the art facility for nanomaterials characterization. The SNL already operates as a successful user facility within the Stanford University community. Our system works well for a wide range of users such as materials scientists, mechanical and electrical engineers, physicists, chemists, biologists, etc. Major private donations have been obtained towards SNL reconstruction in which we plan on including a capability for remote access, so that off-site users can team with in-house staff to obtain results without the necessity of travel to the host location. We expect a high degree of utilization then by the researchers developing the nano-scale structures. One additional point worth noting is the synergy that is provided by the new SNL design. The new layout (available 10/05) is shown above. The microscopes, surface analysis and X-ray equipment will all exist side-by-side in an open working environment. Accordingly, researchers carrying out measurements with one piece of advanced equipment will encounter, and likely engage with, their counterparts working on a quite different analytical strategy. This is anticipated to lead to significant cross-fertilization of ideas, not only within our own projects but also with others. We have already experienced several occasions on which this transfer of ideas has substantially benefited and indeed developed a new research approach, and this will undoubtedly occur increasingly in the forthcoming laboratory set-up.

The directors of Stanford Nanofabrication Facility and Stanford Nanocharacterization Labs will serve as leaders of Core 2 and Core 1, respectively. Furthermore, Stanford School of Engineering has recently taken steps to significantly expand faculty billets in Materials Science and Chemical Engineering, which will inevitably greatly benefit our research enterprise in nanotechnology.

The combination of investments by Stanford University in the Bio-X Program, MIPS, the Cancer Center, the Stanford Nanofabrication Facility, and the Advanced Materials Initiative will tremendously help this CCNE-TR proposal to be successful. This is because the infrastructure that has been invested by the University is highly suited for interdisciplinary research such as that proposed in this CCNE-TR, and the link to ongoing efforts in clinical cancer care are ideal.

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