Preclinical Imaging Technology Center

Director: David Stout

<em>In vitro</em>

Figure 1: Graph showing the number of preclinical in vivo imaging studies/yr with each of the imaging modalities, along with the total. With the move to the CNSI building in January 2009, the Crump Institute now has its own cyclotron and radiochemistry lab. This is expected to dramatically increase the microPET studies.

<em>In vitro</em>

Figure 2: Photos of the imaging systems, display and data analysis work station and the Biosafety Cabinet work area in the Crump Institute.

The Crump Preclinical Imaging Technology Center is a Crump faculty laboratory facility that also acts in part as a shared resource for over 40 faculty from various departments on campus. In 2003, optical bioluminescent, microPET, microCT and autoradiography systems were brought together into a single integrated facility. New methods, equipment and infrastructure were created to make imaging simple and easy for the biological research. These improvements led to a huge increase in usage, from ~1200 studies per year to ~1000 per month (as shown in Figure 1). Our efforts enabled combined PET/CT fusion imaging, the ability to maintain a barrier at all times around immune compromised animals and development of ways to minimize variability in animal physiology during the studies to help isolate the changes observed to those of the study design. We have recently added a whole body and sectioning cryostats to further enhance our autoradiography capabilities.



Cyclotron and Radiochemistry Technology Center

Director: Clifton Shen

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Figure 1: Classes of molecules used to develop molecular imaging probes for PET.

The Cyclotron and Radiochemistry Technology Center consists of three major components. There is a RDS 111 cyclotron for production of commonly used radioisotopes in the application of PET such as carbon-11, nitrogen-13, oxygen-15 and fluorine-18 in particular. These isotopes can be further incorporated into molecular imaging probes in the second component, the radiochemistry laboratory. The radiochemistry facility is equipped with four Hotcells and six Minicells to accommodate high levels of radioactivity for remote controlled or automated syntheses of PET imaging probes. The third component of the Cyclotron and Radiochemistry Technology Center is an adjacent analytical laboratory fully equipped with HPLC-, GC-MS-, TLC-systems, etc. for quality control. All of the analytical instruments are coupled to radioactivity detectors for parallel detection of chemical and radiochemical purity of compounds. Adjacent to this facility an organic chemistry laboratory can be used for precursor and probe preparation.

The purpose of the technology center is the production of standard PET tracers including [18F]FDG, [18F]FLT, [18F]FAC, etc. to facilitate the work of the Small Animal Imaging Facility in a routine manner. In addition, the tech center is part of the discovery process for developing new PET imaging probes and assays. The various classes of molecules for PET molecular imaging probes are shown in Figure 1. Another scientific focus is the incorporation of microfluidic devices into the processes of radiosyntheses as a new, enabling technology.



Engineering and Prototyping Technology Center

Director: R. Michael Van Dam

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Figure 1: Examples of mechanical design and prototyping projects from the Engineering and Prototyping Technology Center. (a) Purification module for radiochemical syntheses; (b) Partially assembled radiochemical reactor modules; (c) Vial heater/cooler; (d) Experimental [18F]fluoride QC device (collaboration with Eric Chiou, UCLA Engineering); (e) Microwave radiosynthesis system; (f) Commercial pipetting robot modified to interface with IVMD microfluidic chips by the addition of a (g) tip holder and (h) custom tips.

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Figure 2: Examples of microfluidic projects from the Engineering and Prototyping Technology Center. (a-b) Lid and base for “injection molding” of PDMS microfluidic devices to control outer dimensions and shape; (c-d) Molds for simple pattern of microchannels machined in aluminum and stainless steel; (e) Quick-disconnect liquid trap interface; (f) Standardized chip connector for rapid and easy chip installation; (g) Polycarbonate manifold for interfacing with a PDMS microfluidic patch-clamp chip (collaboration with Jim Heath group, Caltech); (h) Microfluidic cell-culture chip holder prototype; (i) PDMS microfluidic radiolabeling; (j) PFPE chip for multi-step radiosynthesis; (k) Microchannel electrode test chip.

To have an impact in the world, promising technologies must eventually move out of the laboratory and into other research labs and clinics. The mission of the Engineering and Prototyping Technology Center is to facilitate transitions from proof-of-concept to working prototype. Working systems enable sharing of technology between engineers and research scientists, benefiting the science to which the technology is applied, as well as providing feedback for improvements to the technology itself.

The Engineering and Prototyping Technology Center comprises two laboratories in the new Crump Institute space in the CNSI Building: the Mechanical Prototyping Laboratory and the Micro/Nano Fabrication Laboratory. It brings together expertise and state-of-the-art facilities for mechanical design and engineering, precision machining, instrument prototyping and microfluidic device fabrication. The mechanical prototyping laboratory contains CAD workstations, a fully-equipped machine shop, and an assembly and testing area. Machines and tools are available to members of the Crump lnstitute, and two staff members with expertise in design, drafting, manual machining, and CNC machining are available to assist Crump Institute members to complete mechanical projects. The laboratory offers occasional courses in the use of design software, good design principles, designing for machining, tooling and workholding, and machining safety, as well as operation of specific machines. State-of-the-art equipment includes a CNC milling machine (Haas OM-2A), CNC lathe (Haas HPCL), manual mill (Bridgeport 12BR2J), drill press, vertical band saw, horizontal band saw, and grinder.

The Micro/Nano Fabrication laboratory is a class 1000 cleanroom located within the newly opened CNSI Integrated Systems Nanofabrication Cleanroom (ISNC). The lab contains equipment for microfluidic device fabrication from poly(dimethylsiloxane) (PDMS), glass, and other materials: fume hoods for solvent and acid/base processing, a photoresist spin-coater, PDMS mixer, PDMS vacuum degasser, PDMS spin-coater, programmable ovens, CCD-assisted hole-punching tool, zoom stereomicroscopes (Nikon SMZ-1000), oxygen plasma bonding system (Harrick PDC-001), corona discharge bonding system, and a microfluidic chip test station. A biosafety cabinet provides a sterile environment for preparation of cell culture chips. State-of-the-art facilities for processing and characterization of micro- and nano-devices are available on a shared basis in the ISNC (e.g. photolithography, reactive ion etching, metal deposition, stylus and optical profilometry, scanning electron microscopy, etc.). One staff member is available to assist with microfluidic chip design and fabrication and to provide training to members of the Crump Institute.

Future plans for this center are to establish expertise and develop facilities for electrical engineering, electronics, control system development and user-interface development. These final stages of prototyping are critical when a system is to be used in a different laboratory. Currently, assembly of electronic, pneumatic, fluidic, etc., integrated systems is carried out in the engineering area of Michael van Dam's laboratory.


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