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© CEA Cadarache/DEN/DER/SPRC. The resource-renewable boiling water reactor (RBWR) is an innovative boiling water reactor that has the capability to breed or to burn transuranium elements (TRUs). Core characteristics of the RBWR of the TRU burner type were evaluated by two different core analysis methods. The RBWR core features an axially heterogeneous configuration, which consists of an internal blanket region between two seed regions, to achieve the TRU multi-recycling capability while maintaining a negative void reactivity coefficient. Axial power distribution of the TRU burner core tends to be more heterogeneous because the isotopic composition ratio of fertile TRUs to fissile TRUs becomes larger in the TRU burner-type core than in the breeder-Type core and the seed regions need to be axially shorter than that of the breeder-Type core. Thus core analysis of the TRU burner-type core is more challenging. A conventional diffusion calculation using nuclear constants prepared by two-dimensional lattice calculations was performed by Hitachi, while the calculation using nuclear constants prepared by three-dimensional calculations and axial discontinuity factors was performed by the University of Michigan to provide a more sophisticated treatment of the axial heterogeneity. Both calculations predicted similar axial power distributions except in the region near the boundary between fuel and plenum. Both calculations also predicted negative void reactivity coefficients throughout the operating cycle. Safety analysis was performed by Massachusetts Institute of Technology for the all-pump trip accident, which was identified as the limiting accident for the RBWR design. The analysis showed the peak cladding temperature remains below the safety limit. Detailed fuel cycle analysis by University of California, Berkeley, showed that per electrical power generated, the RBWR is capable of incinerating TRUs at about twice the rate at which they are produced in typical pressurized water reactors.

We demonstrate controlled transport of superparamagnetic beads in the opposite direction of a laminar flow. A permanent magnet assembles 200 nm magnetic particles into about 200 μm long bead chains that are aligned in parallel to the magnetic field lines. Due to a magnetic field gradient, the bead chains are attracted towards the wall of a microfluidic channel. A rotation of the permanent magnet results in a rotation of the bead chains in the opposite direction to the magnet. Due to friction on the surface, the bead chains roll along the channel wall, even in counter-flow direction, up to at a maximum counter-flow velocity of 8 mm s−1. Based on this approach, magnetic beads can be accurately manoeuvred within microfluidic channels. This counter-flow motion can be efficiently be used in Lab-on-a-Chip systems, e.g. for implementing washing steps in DNA purification.

An adhesion-based cell-separation device is developed for the extraction of rare cells from a cell mixture. The cell-separation principle mimics leukocyte recruitment from blood vessels in our body, where leukocytes are decelerated by antigen-antibody interaction at the sites of inflammation or injury. Separation of cell mixture can be accomplished by simply introducing the sample plug through an antibody-immobilized microchannel without any pre- or postprocessing. A new class of amino-functionalized parylene (diX AM) is employed in order to provide amino group on the channel-wall surface. The amount of immobilized biomolecules on diX AM surface is characterized through quartz-crystal-microbalance measurements. The number density of immobilized biotin is as large as , which indicates an amount of amino group enough to immobilize biotin and other biomolecules in a closely packed state. It is shown by the measurement of cell velocity in the CD31-coated diX AM microchannel that the flowing velocity of human endothelial cells are reduced by up to 70% due to specific adhesion of CD31 antigens and antibodies. The results are further analyzed by using a 2-D membrane-peeling model, with which the cell velocity can be estimated under different conditions of antibody number density and bulk mean velocity. Based on the experimental results, a cell-separation device for treating a 1- cell-mixture plug is designed and microfabricated. A mixture of human endothelial cells and leukocytes is successfully separated into plugs of each cell type within a shorter period of time as compared to conventional cell-separation methods which require sample preprocessing.

Massively parallel and individual DNA manipulation for analysis has been demonstrated by designing a fully self-assembled molecular system using motor proteins. DNA molecules were immobilized by trapping in a polyacrylamide gel replica, and were digested by a restriction enzyme, XhoI, for DNA analysis. One end of the lambdaDNA was modified with biotin and the other end was modified with digoxin molecules by fragment labeling and ligation methods. The digoxin-functionalized end was immobilized on a glass surface coated with anti-digoxigenin antibody. The biotinylated end was freely suspended and experienced Brownian motion in a buffer solution. The free end was attached to a biotinylated microtubule via avidin-biotin biding and the DNA was stretched by a kinesin-based gliding assay. A stretched DNA molecule was fixed between the gel and coverslip to observe the cleavage of the DNA by the enzyme, which was supplied through the gel network structure. This simple process flow from DNA manipulation to analysis offers a new method of performing molecular surgery at the single-molecule scale.

The synthesis of new chiral auxiliaries, 7-alkyl substituted cis-1-amino-2-indanol derivatives, was established by the Diels–Alder reaction of 1-substituted dienes with cyclopentenone followed by the asymmetric epoxidation of the resulting indene derivatives and then the Ritter reaction. These bulky cis-aminoindanol derivatives are very effective as chiral auxiliaries and nitrogen sources in the asymmetric 6π-azaelectrocyclization. The corresponding 4-alkyl derivative was also prepared using a similar method.

The RBWR (resource-renewable boiling water reactor) is an innovative BWR that has a capability to breed and burn trans-uranium elements (TRUs) using a multi-recycling process. The RBWR can be used as a long-term energy supply, and it reduces the negative environmental impact that TRUs cause as they are otherwise long-lived radioactive wastes. Various design concepts of the RBWR core have been proposed. The RBWR-AC is a break-even reactor and the RBWR-TB and RBWR-TB2 are TRU burners. The RBWR-TB is designed to burn TRUs from the RBWR-TB itself and to burn almost all the TRUs by repeating their recycling. The RBWR-TB is assumed to be applied for a nuclear power phase-out scenario. The RBWR-TB2 is intended to burn TRUs from LWR spent fuels. The RBWR-TB2 is assumed to be applied for reducing the amount of TRUs to be managed in storage facilities. The RBWR cores achieve their TRU multi-recycling capability under the constraint that the void reactivity coefficient must be negative by introducing the parfait core concept. This chapter reviews details of the specific design and core characteristics of the RBWR.

We develop a versatile biomolecule immobilization method using amino-functionalized parylene, and examine the surface density of antibody immobilized on the parylene surface by using quartz crystal microbalance (QCM). We also demonstrate label-free cell sorting for the extraction of rare cells from a limited amount of sample. The sorting principle is based on cell-type specific adhesion with the aid of high-density surface-immobilized antibodies. Continuous lateral separation is also successfully achieved with antibody-immobilized oblique micro grooves in a micro channel.

The β-ray spectra of individual fission products were calculated by using the β-decay data assuming every β-decay to be allowed transition. For the nuclides without measured decay data the β-feeding function was evaluated with the gross theory of β-decay and the β-ray spectrum was calculated from the function. The measured decay data were also supplemented with the data calculated by the gross theory for the excitation energy range above the highest measured excitation energy level. The β-ray spectra from aggregate fission products after a burst fission were calculated by using the β-ray spectrum and the atom number of each fission product nuclide and they were compared with the ones measured for thermal neutron induced fission of 235U, 239Pu and 241Pu at Oak Ridge National Laboratory. The spectrum calculations showed excellent agreement with the measured data at shorter cooling times than 10s when many short-lived nuclides without measured decay data contributed considerably to the spectrum.

The stereocontrolled synthetic procedure for the preparation of 2,4,5-trisubstituted 2,5-chiral 1,2,5,6-tetrahydropyridines was established using a one-pot asymmetric azaelectrocyclization protocol; the generality of this protocol was demonstrated by synthesizing the title compounds with various aryl and alkenyl substituents at the C-2 position.

We report development of a novel label-free continuous cell separation method for the extraction of rare cells from a limited amount of sample. The separation method is based on specific adhesion between target cells and antibody immobilized on oblique micro grooves etched into the channel wall. Due to asymmetric adhesive force, cross-flow displacement of the target cells is induced. Label-free lateral separation of micro beads as the cell model has been successfully achieved. Cross-flow displacement of human umbilical-vein endothelial cells (HUVEC) with the CD31 antibody is also demonstrated.

We present a novel microfluidic platform using laminar-flow magnetophoresis for combined continuous extraction and purification of DNA. All essential unit operations (DNA binding, sample washing and DNA elution) are integrated on one single chip. The key function is the motion of magnetic beads given by the interplay of laminar flow and time-varying magnetic field. The time for extraction was 1 minute. The device is a central part of a complete biochemical system for continuous monitoring of cell-growth in bioreactors. The novel platform allows continuous purification of DNA, but is also applicable to purification of RNA, proteins or cells, including their subsequent real-time analysis in general.

We report the development of a micro cell sorter for extraction of rare cells from a limited amount of sample. The separation principle is based on specific adhesion with the aid of surface-immobilized antibodies. Antibody-immobilized channel walls are fabricated with a versatile technique using functionalized parylene. Performance of the cell sorter is characterized through cell velocity measurements, in which deceleration of positive cells up to 60% is observed. Cell separation with a mixture containing positive and negative cells is also demonstrated.

This paper reports the characterization of adhesion-based cell velocity regulation in a prototype microfabricated cell separation device for regenerative medicine. The principle of cell sorting is based on immunoreaction for accurate recognition of target stem cells. Target-cell specific antibody is immobilized on the micro channel wall to form a selectively adhesive surface, where a new class of functionalized parylene is used as the surface material for antibody immobilization. The flowing velocity of sample cells in a prototype microfabricated cell separation column is examined under the microscope. The measurement results show that the cell velocity is reduced by 400% due to the effect of antigen/antibody interaction.

This paper reports a novel microfluidic-chip based platform using "phase-transfer magnetophoresis" enabling continuous biomolecule processing. As an example we demonstrate for the first time continuous DNA extraction from cell lysate on a microfluidic chip. After mixing bacterial Escherichia coli culture with superparamagnetic bead suspension, lysis and binding buffers, DNA is released from cells and captured by the beads. These DNA carrying beads are continuously transported across the interfaces between co-flowing laminar streams of sample mixture, washing and elution buffer. Bead actuation is achieved by applying a time-varying magnetic field generated by a rotating permanent magnet. Flagella-like chains of magnetic beads are formed and transported along the microfluidic channels by an interplay of fluid drag and periodic magnetic entrapment. The turnover time for DNA extraction was approximately 2 minutes with a sample flow rate of 0.75 µl s(-1) and an eluate flow rate of 0.35 µl s(-1). DNA recovery was 147% (on average) compared to bead based batch-wise extraction in reference tubes within a dilution series experiment over 7 orders of magnitude. The novel platform is suggested for automation of various magnetic bead based applications that require continuous sample processing, e.g. continuous DNA extraction for flow-through PCR, capture and analysis of cells and continuous immunoassays. Potential applications are seen in the field of biological safety monitoring, bioprocess control, environmental monitoring, or epidemiological studies such as monitoring the load of antibiotic resistant bacteria in waste water from hospitals.

We report the development of a label-free continuous cell sorting method based on specific adhesivity between cells and surface-immobilized adhesion molecules. The separation of cells is induced by cross-flow adhesive force on micron-sized stripes with adhesion molecules immobilized on the surface. In order to accurately form the adhesive stripes on a microchannel wall, 1 µm wide micro-grooves are fabricated at a certain angle with respect to the flow direction using direct electron-beam lithography. Amino-functionalized parylene is used as the groove surface material, and streptavidin is immobilized on the entire surface, resulting in a surface with periodic adhesive patterns. The effectiveness of the proposed cell sorting principle is verified by flow-through experiments using functionalized particles as model cells. Measurements of the motion of biotin-coated microparticles show that the particles decelerated by specific adhesivity are displaced in the cross-flow direction. The observed cross-flow displacement is around 0.8% of the streamwise travelling distance. It is also shown that the rate of cross-flow displacement is independent of the flow rate or the stripe angle. Finally, it is demonstrated that a mixture of streptavidin- and biotin-coated microparticles can be completely separated after flowing over a 20 mm long patterned surface. The proposed label-free continuous lateral separation scheme has a wide range of potential applications for separation of cells which could not be distinguished by size or separated using dielectric forces.

Mikrofluidik-Plattform zur kontinuierlichen Aufreinigung von Biomolekulen M. Karle (E-Mail: marc.karle@hsg-imit.de), Dr. J. Miwa, Dr. S. Haeberle, Dr. G. Roth, Prof. Dr. R. Zengerle, Dr. F. von Stetten HSG-IMIT, Wilhelm-Schickard-Strase 10, D-78052 Villingen-Schwenningen, Germany Lehrstuhl fur Anwendungsentwicklung, Institut fur Mikrosystemtechnik (IMTEK), Universitat Freiburg, Georges-Kohler-Allee 106, D-79110 Freiburg, Germany DOI: 10.1002/cite.200950483

The stereocontrolled synthetic procedure for the preparation of 2,4,5-trisubstituted 2,5-chiral 1,2,5,6-tetrahydropyridines was established using a one-pot asymmetric azaelectrocyclization protocol; the generality of this protocol was demonstrated by synthesizing the title compounds with various aryl and alkenyl substituents at the C-2 position.