A new method was developed to fabricate unique gold quasi-3D plasmonic nanostructures on poly(dimethylsiloxane) PDMS and 2D nanohole arrays on silicon as surface-enhanced Raman scattering (SERS) substrates using electron beam lithography (EBL) with negative tone resist Ma-N 2403 and soft lithography. The size and shape of nanopillars fabricated by EBL were well controlled via different beam conditions. An enhancement factor (EF) as high as 6.4 x 10(5) was obtained for 4-mercaptopyridine molecules adsorbed on the gold quasi-3D nanostructure array on PDMS with 400 nm diameter, 100 nm spacing and 300 nm depth, while no enhancement was observed for the gold 2D nanohole array on silicon with the same diameter and spacing. The experimental results were confirmed by finite-difference time-domain (FDTD) calculations. Furthermore, the calculated total electric fields showed that the strong SERS exhibited by the gold quasi-3D nanostructure arrays on PDMS is due to the strong localized electric fields at the gold-air interface of the bottom gold nanodisc. The strong and reproducible SERS spectroscopy for molecules adsorbed on precisely controlled gold quasi-3D nanostructure arrays on PDMS makes it possible for the integration of SERS-active nanopatterns into microfluidic devices as chemical and biological sensors with molecular specificity.

In a 5-year survey of nonpromyelocytic/nonmonocytic acute myeloid leukemias (AMLs) diagnosed in the University of Washington Hematopathology Laboratory, we identified 19 cases containing distinctive, cup-like nuclear indentation in 10% or more of the blasts ('AML-cuplike'). Fourteen of these cases (74%) demonstrated near-complete loss of HLA-DR expression, while the other five cases showed partial loss of HLA-DR. A total of 16 of the cases (84%) demonstrated internal tandem duplication (ITD) of the Flt3 gene. When compared to a selected set of AMLs lacking this nuclear morphology, AMLcuplike was significantly more likely to lack HLA-DR and CD34 expression, to express CD123 without CD133, to have a normal karyotype, and to harbor the Flt3 ITD. To characterize AMLcuplike in an unselected series of AMLs, we analyzed 42 consecutive nonpromyelocytic/nonmonocytic AMLs diagnosed in our laboratory during a 6-month period in 2002. Strikingly, in this unselected series, there was a statistically significant coincidence of invaginated nuclear morphology, loss of HLA-DR, and presence of the Flt3 ITD beyond that expected if these three features were unrelated, suggesting that AMLs with these three features may represent a distinct AML subset.

Reversible addition-fragmentation chain transfer (RAFT) polymerization was employed to prepare a nanoparticulate drug delivery system for chemotherapeutics. The nanoparticles contain a PEG “stealth” corona as well as reactive anhydride functionality designed for conjugating targeting proteins. The multifunctional carrier functionality was achieved by controlling the copolymerization of the hydrophobic monomer lauryl methacrylate (LMA), with a reactive anhydride functional methacrylate (TMA), and a large polyethyleneglycol methacrylate monomer (Mn~950 Da) (O950). RAFT polymerization kinetics of O950 were evaluated as a function of target degrees of polymerization (DP), initial chain transfer agent to initiator ratio ([CTA]o/[I]o), and solvent concentration. Excellent control over the polymerization was observed for target DPs of 25 and 50 at [CTA]o/[I]o ratio of 10 as evidenced by narrow and symmetric molecular weight distributions and the ability to prepare block copolymers. The TMA-functional copolymers were conjugated to the tumor targeting protein transferrin (Tf). The targeted copolymer was shown to encapsulate docetaxel at concentrations comparable to the commercial single vial formulation of docetaxel (Taxotere). In vitro cytotoxicity studies conducted in HeLa cells show that the Tf targeting enhances the cancer killing properties relative to the polymer encapsulated docetaxel formulation.