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Drug-delivery vehicles have been used extensively to modulate the biodistribution of drugs for the purpose of maximizing their therapeutic effects while minimizing systemic toxicity. The release characteristics of the vehicle must be balanced with its encapsulation properties to achieve optimal delivery of the drug. An alternative approach is to design a delivery vehicle that preferentially releases its contents under specific endogenous (e.g., tissue pH) or exogenous (e.g., applied temperature) stimuli. In the present manuscript, we report on a novel delivery system with potential for triggered release using external beam radiation. Our group evaluated Zein protein as the basis for the delivery vehicle and used radiation as the exogenous stimulus. Proteins are known to react with free radicals, produced during irradiation in aqueous suspensions, leading to aggregation, fragmentation, amino acid modification, and proteolytic susceptibility. Additionally, we incorporated gold particles into the Zein protein matrix to create hybrid Zein–gold nanoparticles (ZAuNPs). Zein-only nanoparticles (ZNPs) and ZAuNPs were subsequently exposed to kVp radiation (single dose ranging from 2 to 80 Gy, fractionated doses of 2 Gy delivered 10 times) and characterized before and after irradiation. Our data indicated that the presence of gold particles within Zein particles was correlated with significantly higher levels of alterations to the protein, and was associated with higher rates of release of the encapsulated drug compound, Irinotecan. The aggregate results demonstrated a proof-of-principle that radiation can be used with gold nanoparticles to modulate the release rates of protein-based drug-delivery vehicles, such as ZNPs.

Canine lower urinary tract neoplasia is a clinically important disease process that has high mortality due to late stage diagnosis and poorly durable response to treatment. Non-invasive diagnostic techniques (e.g. dipstick test, urine cytology) currently have poor diagnostic value, while more invasive tests (e.g. cystoscopy and biopsy) are costly and often require general anesthesia. We have developed and herein describe a quantitative cytological analysis method based on the use of surface-enhanced Raman spectroscopy (SERS), for identifying cancerous transitional cells in urine using SERS biotags (SBTs) carrying the peptide PLZ4 (amino acid sequence cQDGRMGFc) that targets malignant transitional cells. By analyzing the ratio of the PLZ4-SBTs to an on board control we were able to show that transitional cells had significantly higher ratios (P < 0.05) in patients diagnosed with transitional cell carcinoma (TCC) than in healthy samples.

OTS964 is an inhibitor of T-lymphokine-activated killer cell-originated protein kinase (TOPK), a protein kinase important for mitosis and highly expressed in ovarian and lung cancers. This compound demonstrated potent anti-proliferative activity in a panel of cell lines positive for TOPK; however, when administered to mouse xenograft models, adverse hematopoietic toxicities were observed. To overcome this problem, OTS964 was encapsulated into liposomes and a liposomal formulation of OTS964 is now considered a lead candidate for clinical development. To support clinical development of this formulation, it is critically important to define assays that can easily distinguish between free and liposomal OTS964. Here, we develop a new assay to determine liposomal OTS964 encapsulation (percentage of drug associated with the liposomes) and OTS964 that is dissociated from the liposomes (percentage of drug released from liposomes) by monitoring the enhanced OTS964 fluorescence after its binding to albumin. The optical properties of OTS964 were investigated and three absorbance peaks were identified (235 nm, 291 nm, and 352 nm). Fluorescence was observed at 350 nm (excitation) and 470 nm (emission). Interestingly, the fluorescence of OTS964 increased 18-fold in the presence of serum proteins and more specifically albumin. This phenomenon was used to discriminate between the amounts of drug associated with the liposomes or released from the liposomes. Controls consisting of liposomal OTS964 permeabilized with saponins or octyl glucopyranoside served to confirm that drug release could be monitored by albumin-associated increases in fluorescence. The OTS964 liposomal formulation proved to be very stable with less than 10% release after 4 days in phosphate-buffered saline at 37 °C. The quantity of drug associated with the liposomal surface but not inside the liposomes could also be estimated using this approach. These studies present a novel approach to characterize liposomal release of OTS964, in real time and in a non-invasive manner while acquiring additional information about the spatial distribution of liposomal drug.

© 2015. We describe a near infrared (NIR) light-activated gene silencing method in undifferentiated human embryonic stem cell (hESC) using a plasmonic hollow gold nanoshell (HGN) as the siRNA carrier. Our modular biotin-streptavidin coupling strategy enables positively charged TAT-peptide to coat oligonucleotides-saturated nanoparticles as a stable colloid formation. TAT-peptide coated nanoparticles with dense siRNA loading show efficient penetration into a wide variety of hESC cell lines. The siRNA is freed from the nanoparticles and delivered to the cytosol by femtosecond pulses of NIR light with potentially exquisite spatial and temporal control. The effectiveness of this approach is shown by targeting GFP and Oct4 genes in undifferentiated hESC (H9). The accelerated expression of differentiation markers for all three germ layers resulting from Oct4 knockdown confirms that this method has no detectable adverse effects that limit the range of differentiation. This biocompatible and NIR laser-activated patterning method makes possible single cell resolution of siRNA delivery for diverse studies in stem cell biology, tissue engineering and regenerative medicine.

A reliable identification of cells on the basis of their surface markers is of great interest for diagnostic and therapeutic applications. We present a multiplexed labeling and detection strategy that is applied to four microparticle populations, each mimicking cellular or bacterial samples with varying surface concentrations of up to four epitopes, using four distinct biotags that are meant to be used in conjunction with surface enhanced Raman spectroscopy (SERS) instead of fluorescence, together with microfluidics. Four populations of 6 μm polystyrene beads were incubated with different mixtures, "cocktails" of four SERS biotags (SBTs), simulating the approach that one would follow when seeking to identify multiple biomarkers encountered in biological applications. Populations were flowed in a microfluidic flow-focusing device and the SERS signal from individual beads was acquired during continuous flow. The spectrally rich SERS spectra enabled us to separate confidently the populations by utilizing principal component analysis (PCA). Also, using classical least squares (CLS), we were able to calculate the contributions of each SBT to the overall signal in each of the populations, and showed that the relative SBT contributions are consistent with the nominal percentage of each marker originally designed into that bead population, by functionalizing it with a given SBT cocktail. Our results demonstrate the multiplexing capability of SBTs in potential applications such as immunophenotyping.

We present a sensitive and quantitative protein detection assay that can efficiently distinguish between specific and nonspecific target binding. Our technique combines dual affinity reagents with surface-enhanced Raman spectroscopy (SERS) and chemometric analysis. We link one Raman reporter-tagged affinity reagent to gold nanoparticles and another to a gold film, such that protein-binding events create a "hot spot" with strong SERS spectra from both Raman reporter molecules. Any signal generated in this context is indicative of recognition by both affinity labels, whereas signals generated by nonspecific binding lack one or the other label, enabling us to efficiently distinguish true from false positives. We show that the number of hot spots per unit area of our substrate offers a quantitative measure of analyte concentration and demonstrate that this dual-label, SERS-linked aptasensor assay can sensitively and selectively detect human α-thrombin in 1% human serum with a limit of detection of 86 pM.

We have combined a versatile and powerful route to deliver nucleic acids with peptide-based cell-specific targeting. siRNA targeting the polo-like kinase gene is in clinical trials for cancer treatment, and here we deliver this RNA selectively to cancer cells displaying the neuropilin-1 epitope using gold nanoshells. Release of the siRNA from the nanoparticles results from irradiation with a pulsed near-infrared laser, which also provides efficient endosomal escape within the cell. As a result, our approach requires 10-fold less material than standard nucleic acid transduction materials and is significantly more efficient than other particle-based methods. We also describe a particle–nucleic acid design that does not rely on modified RNA, thereby making the preparation of these materials more efficient and much less expensive. These improvements, when combined with control over when and where the siRNA is released, could provide the basis for diverse cell biological studies.

The water-soluble rhenium(I) complex fac-[Re(bpy)(CO)(3)(thp)](+) (1) [CF(3)SO(3)(-) salt; bpy = 2,2'-bipyridine, thp = tris(hydroxymethyl)phosphine] is both strongly luminescent and photoactive toward carbon monoxide release. It is stable in aerated aqueous media, is incorporated into cells from the human prostatic carcinoma cell line PPC-1, and shows no apparent cytotoxicity. Furthermore, the solvated Re(I) photoproduct of CO release (2) is also luminescent, a feature that allows one to track the transformation of 1 to 2 inside such cells using confocal fluorescence microscopy. In this context, 1 is a very promising candidate as a photoactivated CO releasing moiety (photoCORM) with potential therapeutic applications.

A multiplexed, ratiometric method is described that can confidently distinguish between cancerous and noncancerous epithelial prostate cells in vitro. The technique is based on bright surface-enhanced resonance Raman scattering (SERRS) biotags (SBTs) infused with unique Raman reporter molecules, and carrying cell-specific peptides. Two sets of SBTs were used. One targets the neuropilin-1 (NRP-1) receptors of cancer cells through the RPARPAR peptide. The other functions as a positive control (PC) and binds to both noncancerous and cancer cells through the HIV-derived TAT peptide. Point-by-point 2D Raman maps of the spatial distribution of the two tags were constructed with subcellular resolution from cells simultaneously incubated with the two sets of SBTs. Averaging the SERRS signal over a given cell yielded an NRP/PC ratio from which a robust quantitative measure of the overexpression of the NRP-1 by the cancer cell line was extracted. The use of a local, on-cell reference produces quantitative, statistically robust measures of overexpression independent of such sources of uncertainty as variations in the location of the focal plane, the local cell concentration, and turbidity.

Understanding uptake and processing of nanomaterials by cells has implications for therapeutics and diagnostics. Although nanoparticle agents have been developed as proven imaging agents and promising drug-delivery vehicles, much remains to be learned regarding their internalization as local environmental sensors, even for the relatively simple case of pH determination at the nanoscale. Strategies for in vitro cell culture have been reported that use cargo-containing or dyelabeled nanoparticles with a cationic agent, which promotes binding to the cell membrane through an electrostatic interaction, inducing the cell membrane to wrap around the particle, which is then internalized through endocytosis. Nutrients and molecules that are not able to cross the membrane through active transport or diffusion and inorganic particles bigger than a few nanometers use this route. This complex process is also exploited in the uptake of nucleic acids, drugs and peptides, and of polymers for drug delivery, sensing and biocompatibility applications. Although promising efforts to monitor the interior pH in a cell after endocytosis of pHsensitive dual-color fluorescent polymers have been reported, issues of photostability and wavelength optimization remain. An ideal nanoprobe would be photostable, sensitive, and excitable with near-infrared (NIR) wavelengths at which cells and tissues are somewhat transparent and autofluorescence is minimized. A wide range of fluorescence-based materials have been developed as imaging agents and as local probes of the presence of specific biomarkers or of local environmental conditions. For example pH-sensitive fluorescence probes have been used to determine the time-dependent acidity of endosomes through a comparison of the intensity ratio between two

The temporal and spatial control over the delivery of materials such as siRNA into cells remains a significant technical challenge. We demonstrate the pulsed near-infrared (NIR) laser-dependent release of siRNA from coated 40 nm gold nanoshells. Tat-lipid coating mediates the cellular uptake of the nanomaterial at picomolar concentration, while spatiotemporal silencing of a reporter gene (green fluorescence protein) was studied using photomasking. The NIR laser-induced release of siRNA from the nanoshells is found to be power- and time-dependent, through surface-linker bond cleavage, while the escape of the siRNA from endosomes occurs above a critical pulse energy attributed to local heating and cavitation. NIR laser-controlled drug release from functional nanomaterials should facilitate more sophisticated developmental biology and therapeutic studies.

Organic molecular beam deposition is studied systematically at thermal and hyperthermal regimes aiming at investigating the role of molecular kinetic energy on the growth mechanism of pentacene submonolayers on SiO (x) /Si. We show that the kinetic energy of the impinging molecule (E (k) ) plays a crucial role in determining island structure and shape, distribution of island sizes, the crystalline quality of the first monolayer, and even the growth mode of subsequent layers. With increasing E (k) , the island structure changes from fractal to nonfractal, the shape becomes more anisotropic and the island size more uniform, pointing to correlated island growth. Moreover, while 3D island growth is observed for thermal organic molecular beam deposition, supersonic molecular beam deposition gives rise to layer-by-layer growth, at least for the first two layers. When E (k) a parts per thousand yen5.0 eV, the first monolayer is composed of large single crystalline domains which can extend over up to 10 mu m, inferred from comparing atomic force micrographs of height and net transverse shear force. In these growth conditions both the high surface diffusivity and energy redistribution play a major role. We propose a mechanism where the energy dissipation occurring during the molecule-surface collision leads to the reorientation of whole islands during island coalescence, resulting in the elimination of grain boundaries.

Organic–inorganic nano-hybrids, synthesized by supersonic molecular beams of TiO2 clusters and copper-phthalocyanine (CuPc) molecules, have been used to develop gas-sensing devices. This approach allows tailoring the properties of the synthesized materials and the interface between clusters and organic molecules so that new functional materials with interesting sensing properties are obtained. Two-layer hybrid devices with different architectures have been realized on alumina substrates with gold interdigitated electrodes. The hybrid films show an increase in conductivity up to a factor 6 compared to the pure CuPc depending on the architecture used. The response in terms of changes in conductivity towards non-oxidizing (methanol) species has been tested at different working temperatures. The hybrids show much higher sensitivity and stability with respect to CuPc grown with the same technique and they are already quite responsive at temperatures (75 °C) where the nanostructured TiO2 sensors are not at all functional. We ascribe these promising performances to the contribution coming from the n-TiO2–CuPc interfaces generated by the deposition process and we envisage the ability of the supersonic beam approach to produce novel classes of nano-hybrids in a variety of functional nanostructures.

Surface enhanced Raman spectroscopy (SERS) is a powerful analytical technique that has been proposed as a substitute for fluorescence for biological imaging and detection but is not yet commercially utilized. The reason lies primarily in the lower intensity and poor reproducibility of most metal nanoparticle-based tags as compared to their fluorescence-based counterparts. Here, using a technique that scrupulously preserves the same number of dye molecules in both the SERS and fluorescence measurements, we show that SERS-based biotags (SBTs) with highly reproducible optical properties can be nanoengineered such that their brightness is at least equal to that of fluorescence-based tags.

Reliable identification and collection of cells from bodily fluids is of growing interest for monitoring patient response to therapy and for early detection of disease or its recurrence. We describe a detection platform that combines microfluidics with surface-enhanced Raman spectroscopy (SERS) for the identification of individual mammalian cells continuously flowing in a microfluidics channel. A mixture of cancerous and noncancerous prostate cells was incubated with SERS biotags (SBTs) developed and synthesized by us, then injected into a flow-focused microfluidic channel, which forces the cells into a single file. The spectrally rich SBTs are based on a silver nanoparticle dimer core labeled with a Raman-active small reporter molecule paired with an affinity biomolecule, providing a unique barcode whose presence in a composite SERS spectrum can be deconvoluted. Individual cancer cells passing through the focused laser beam were correctly identified among a proportionally larger number of other cells by their Raman signatures. We examine two deconvolution strategies: principal component analysis and classical least-squares. The deconvolution strategies are used to unmix the overall spectrum to determine the relative contributions between two SBT barcodes, where one SBT barcode indicates neuropilin-1 overexpression, while a second SBT barcode is more universal and indicates unspecific binding to a cell's membrane. Highly reliable results were obtained for all of the cell mixture ratios tested, the lowest being 1 in 100 cells.

© 2015 American Chemical Society. Mussel foot protein-1 (mfp-1) is an essential constituent of the protective cuticle covering all exposed portions of the byssus (plaque and the thread) that marine mussels use to attach to intertidal rocks. The reversible complexation of Fe3+by the 3,4-dihydroxyphenylalanine (Dopa) side chains in mfp-1 in Mytilus californianus cuticle is responsible for its high extensibility (120%) as well as its stiffness (2 GPa) due to the formation of sacrificial bonds that help to dissipate energy and avoid accumulation of stresses in the material. We have investigated the interactions between Fe3+and mfp-1 from two mussel species, M. californianus (Mc) and M. edulis (Me), using both surface sensitive and solution phase techniques. Our results show that although mfp-1 homologues from both species bind Fe3+, mfp-1 (Mc) contains Dopa with two distinct Fe3+-binding tendencies and prefers to form intramolecular complexes with Fe3+. In contrast, mfp-1 (Me) is better adapted to intermolecular Fe3+binding by Dopa. Addition of Fe3+did not significantly increase the cohesion energy between the mfp-1 (Mc) films at pH 5.5. However, iron appears to stabilize the cohesive bridging of mfp-1 (Mc) films at the physiologically relevant pH of 7.5, where most other mfps lose their ability to adhere reversibly. Understanding the molecular mechanisms underpinning the capacity of M. californianus cuticle to withstand twice the strain of M. edulis cuticle is important for engineering of tunable strain tolerant composite coatings for biomedical applications. (Chemical Equation Presented).

While a host of methods exist to deliver genetic materials or small molecules to cells, very few are available for protein delivery to the cytosol. We describe a modular, light-activated nanocarrier that transports proteins into cells by receptor-mediated endocytosis and delivers the cargo to the cytosol by light triggered endosomal escape. The platform is based on hollow gold nanoshells (HGN) with polyhistidine tagged proteins attached through an avidity-enhanced, nickel chelation linking layer; here, we used green fluorescent protein (GFP) as a model deliverable cargo. Endosomal uptake of the GFP loaded nanocarrier was mediated by a C-end Rule (CendR) internalizing peptide fused to the GFP. Focused femtosecond pulsed-laser excitation triggered protein release from the nanocarrier and endosome disruption, and the released protein was capable of targeting the nucleoli, a model intracellular organelle. We further demonstrate the generality of the approach by loading and releasing Sox2 and p53. This method for targeting of individual cells, with resolution similar to microinjection, provides spatial and temporal control over protein delivery.

Understanding the adsorption mechanisms of large molecules on metal surfaces is a demanding task. Theoretical predictions are difficult because of the large number of atoms that have to be considered in the calculations, and experiments aiming to solve the molecule-substrate interaction geometry are almost impossible with standard laboratory techniques. Here, we show that the adsorption of complex organic molecules can induce perfectly ordered nanostructuring of metal surfaces. We use surface X-ray diffraction to investigate in detail the bonding geometry of C60 with the Pt(111) surface, and to elucidate the interaction mechanism leading to the restructuring of the Pt(111) surface. The chemical interaction between one monolayer of C60 molecules and the clean Pt(111) surface results in the formation of an ordered SQR13xSQR13R13.9° reconstruction based on the creation of a surface vacancy lattice. The C60 molecules are located on top of the vacancies, and 12 covalent bonds are formed between the carbon atoms and the 6 platinum surface atoms around the vacancies. In-plane displacements induced on the platinum substrate are of the order of a few picometres in the top layer, and are undetectable in the deeper layers.

We report on the correlation between structural and electrical properties of pentacene thin film transistors fabricated by the novel supersonic molecular beam epitaxy (SuMBE) technique. We exploited the ability of SuMBE that, through the control on the molecular precursors in the beam, allows improving the quality in terms of structure and morphology of the semi-conducting thin films compared to the more standard OMBE growth. Different growth conditions were explored to find the better range of beam parameters improving the performance of the TFT device whereas the quality of the films grown was studied by atomic force microscopy. We show that the initial kinetic energy of the pentacene molecule strongly affects both the morphology of the films and the electrical properties of the devices that result to be strongly correlated. With our FET devices prepared, on SiO 2 /Si and top Au contact, we achieved the very promising field effect mobility larger than 0.5 cm 2 V −1 s −1 for films grown at room temperature at a pentacene kinetic energy of about 5.5 eV that are characterized by large crystalline grains (>2 μm).

This paper reports on the preparation, surface and electrical characterisation of titanium dioxide thin-films for highly selective gas sensor devices. Seeded supersonic beam deposition technique was used to prepare nanostructured thin films for gas sensors application. Two different typologies of sensors, prepared under different deposition conditions, were investigated. They showed gas-sensing properties comparable to most of the TiO 2 films realised with other more conventional techniques.

We present a silica nanoparticle (SNP) functionalized with polyphosphate (polyP) that accelerate the body’s natural clotting process. SNPs initiate the blood clotting system’s contact pathway; short-chain polyP accelerates the common pathway via rapid formation of thrombin. This enhances the overall blood-clotting system, both by accelerating fibrin generation and by facilitating the regulatory anticoagulation mechanisms essential for hemostasis. Analyzing the clotting properties of bare SNPs, bare polyP, and polyP-functionalized SNPs in plasma, demonstrates that attaching polyP to SNPs to form polyP-SNPs creates a substantially enhanced synergistic effect that lowers clotting time and increases thrombin production at low concentrations when compared to bare SNPs or polyP alone. PolyP-SNP even retains its clotting function at ambient temperature. The polyP-SNP system has the potential to significantly improve trauma treatment protocols and outcomes in hospital and prehospital settings.

There is considerable interest in using nanoparticles as labels or to deliver drugs and other bioactive compounds to cells in vitro and in vivo. Fluorescent imaging, commonly used to study internalization and subcellular localization of nanoparticles, does not allow unequivocal distinction between cell surface-bound and internalized particles, as there is no methodology to turn particles 'off'. We have developed a simple technique to rapidly remove silver nanoparticles outside living cells, leaving only the internalized pool for imaging or quantification. The silver nanoparticle (AgNP) etching is based on the sensitivity of Ag to a hexacyanoferrate-thiosulphate redox-based destain solution. In demonstration of the technique we present a class of multicoloured plasmonic nanoprobes comprising dye-labelled AgNPs that are exceptionally bright and photostable, carry peptides as model targeting ligands, can be etched rapidly and with minimal toxicity in mice, and that show tumour uptake in vivo.

RNA interference (RNAi), a process that controls the flow of genetic information in cells, has been recognized for its potential in cancer therapeutic applications and stem cell differentiation rel...

We review the concept of superresolution optical fluctuation imaging (SOFI), discuss its attributes and trade-offs (in comparison with other superresolution methods), and present superresolved images taken on samples stained with quantum dots, organic dyes, and plasmonic metal nanoparticles. We also discuss the prospects of SOFI for live cell superresolution imaging and for imaging with other (non-fluorescent) contrasts.

SERS biotags are made from polymer-encapsulated silver nanoparticle dimers infused with unique Raman reporter molecules, and carry peptides as cell recognition moieties. We demonstrate their potential use for early and rapid identification of malignant cells, a central goal in cancer research. SERS biotags (SBTs) can be routinely synthesized and simultaneously excited with a single, low intensity laser source, making the determination of the relative contribution of the individual SBTs to the overall spectrum tractable. Importantly for biomedical applications, SERS employs tissuepenetrating lasers in the red to near-infrared range resulting in low autofluorescence. We have previously described a multiplexed, ratiometric method that can confidently distinguish between cancerous and noncancerous epithelial prostate cells in vitro based on receptor overexpression. Here we present the progress towards the application of this quantitative methodology for the identification of cancer cells in a microfluidic flow-focusing device. Beads are used as cell mimics to characterize the devices. Cells (and beads) are simultaneously incubated with two sets of SBTs while in suspension (simulating cells’ capture from blood), then injected into the device for laser interrogation under flow. Each cell event is characterized by a composite Raman spectrum, deconvoluted into its single components to ultimately determine their relative contribution. We show that using SBTs ratiometrically can provide cell identification insensitive to normal causes of uncertainty in optical measurements such as variations in focal plane, cell concentration, autofluorescence, and turbidity.

We report on a multiplexed, ratiometric method that can confidently distinguish between cancerous and non-cancerous epithelial prostate cells in vitro, as demonstrated by a double blind experiment. The technique is based on bright SERRS biotags (SBTs) infused with unique Raman reporter molecules, and carrying cell-specific peptides. Two sets of SERRS biotags were used. One targets the neuropilin-1 (NRP) receptors of cancer cells through the RPARPAR peptide. The other functions as a positive control (PC) and binds to both non-cancerous and cancer cells through the HIV derived TAT peptide. Averaging the SERRS signal over a given cell yielded an NRP/PC ratio from which a robust quantitative measure of the overexpression of the NRP-1 by the cancer cell line was extracted. The use of a local, on-cell reference produces quantitative, statistically robust measures of overexpression independent of such sources of uncertainty such as variations in the location of the focal plane, the local cell concentration and turbidity.

Nanorattles consisting of hydrophilic, rare-earth-doped NaYF(4) shells each containing a loose magnetic nanoparticle were fabricated through an ion-exchange process. The inner magnetic Fe(3)O(4) nanoparticles are coated with a SiO(2) layer to avoid iron leaching in acidic biological environments. This multifunctional mesoporous nanostructure with both upconversion luminescent and magnetic properties has excellent water dispersibility and a high drug-loading capacity. The material emits visible luminescence upon NIR excitation and can be directed by an external magnetic field to a specific target, making it an attractive system for a variety of biological applications. Measurements on cells incubated with the nanorattles show them to have low cytotoxicity and excellent cell imaging properties. In vivo experiments yield highly encouraging tumor shrinkage with the antitumor drug doxorubicin (DOX) and significantly enhanced tumor targeting in the presence of an applied magnetic field.

The alpha-quatertiophene is widely considered an interesting material for the realization of organic electronics and opto-electronics. Compared to other oligothiophenes, the performances of transistors based on this compound are limited by its kind of growth on the typical materials used for device realization. Here we show that via seeded supersonic beams we can lead to a nice improvement of both morphological and electrical properties of the film grown, through a better control of the initial state of the precursor in the vapor phase. Using the high kinetic energy achievable in the supersonic beams, we increase the dimensions of the grains and the coalescence of different islands, limiting the grain boundary formation. As consequence, the performance of the realized field effect transistors is enhanced of one order of magnitude.

Supersonic molecular beam deposition (SuMBE) is a thin film growth method for organic semiconducting molecules that gives unprecedented control oil morphology and structure by tuning the kinetic energy of the impinging molecules. This is the key factor by which we could control the growth of high quality films showing state of the art electrical properties for pentacene films. We show that exploiting such ability to control structure and morphology of the films one could tailor the gas response of the organic thin film transistors. We envisage the potential of such devices in applications where the transistor configuration offers new strategic opportunities as in gas sensing and in microfluidics.

The key role of the pentacene kinetic energy (E-k) in the early stages of growth on SiOx/Si is demonstrated: islands with smooth borders and increased coalescence differ remarkably from fractal-like thermal growth. Increasing E-k to 6.4 eV, the morphology evolves towards higher density of smaller islands. At higher coverage, coalescence grows with E-k up to a much more uniform, less defected monolayer. The growth, interpreted by the diffusion mediated model, shows the critical nucleus changing from 3 to 2 pentacene for E-k > 5-6 eV. Optimal conditions to produce single crystalline films are envisaged.

Polymorphism in the growth of titanyl phthalocyanine films on dielectric substrates has been systematically studied by UV absorption and micro-Raman analyses, correlating structure and optical properties. We explored different growth regimes as a function of substrate temperature and growth rate using hyperthermal seeded supersonic beams. We identify and discuss specific signatures in micro-Raman spectra specifically correlated to the different phases and demonstrate the unprecedented ability of growing crystalline films and controlling the relative abundance of the different phases (amorphous, phase I, and phase II) by the beam parameters. We envisage the very promising perspective of controlling polymorphism at low temperatures via supersonic beam growth, paving the way for better performing devices.

Addition/Correction pubs.acs.org/Biomac Correction to “Tough Coating Proteins: Subtle Sequence Variation Modulates Cohesion” Saurabh Das, Dusty R. Miller, Yair Kaufman, Nadine R. Martinez Rodriguez, Alessia Pallaoro, Matthew J. Harrington, Maryte Gylys, Jacob N. Israelachvili,* and J. Herbert Waite* Downloaded by UNIV OF CALIFORNIA SANTA BARBARA on September 10, 2015 | http://pubs.acs.org Publication Date (Web): June 17, 2015 | doi: 10.1021/acs.biomac.5b00759 Biomacromolecules, 2015, 16 (3), 1002−1008. DOI:10.1021/bm501893y F igure 3 caption corrected. Corrections highlighted in bold. Figure 3. pH dependence of Fe 3+ -mediated cohesion between two symmetric mfp-1 (Mc) films. Representative force vs distance plot showing the interaction between two symmetric mfp-1 (Mc) films deposited at 50 μg/mL in 0.1 M sodium acetate buffer, pH 5.5, 0.25 M KNO 3 , and 1 mM bis− tris with C Fe 3+ = 0 (gray) and 10 μM (blue) at pH 5.5. The cohesion between the mfp-1 (Mc) films was preserved after increasing the pH to 7.5 (magenta). (b) Representative force vs distance plot showing the interaction between two symmetric mfp-1 (Me) films deposited at 20 μg/mL in 0.1 M sodium acetate buffer, pH 5.5, 0.25 M KNO 3 , and 1 mM bis−tris with C Fe 3+ = 0 (gray) and 10 μM (blue) at pH 5.5. The surfaces showed a weak bridging cohesion (W c < 0.2 mJ/m 2 ) after increasing the pH to 7.5 (magenta). It should be noted that C Fe 3+ is the concentration of ferric cation in the bulk solution between the surfaces. Flushing with buffer at pH 7.5 removes iron from the bulk solution, however, to the extent that the preadsorbed protein films already had some bound Fe 3+ , the Dopa−Fe 3+ complexes will be present in them. Published: June 17, 2015 © 2015 American Chemical Society DOI: 10.1021/acs.biomac.5b00759 Biomacromolecules 2015, 16, 2254−2254

Recently, supersonic molecular-beam epitaxy (SuMBE) was invented as an alternative method for the deposition of organic material, using higher kinetic energies for deposition than conventional organic molecular-beam epitaxy (OMBE). Using titanyl phthalocyanine (TiOPc) as a model substance, we show that the SuMBE deposition results in increased crystal quality of the deposited material. This is induced by the high kinetic energy of the molecular-beam in SuMBE, which leads to increased molecular mobility on the surface, resulting in larger crystal sizes and higher crystal quality. Alternatively, similar films as made by OMBE can be deposited by SuMBE at lower substrate temperatures. This temperature reduction may be of interest for the deposition of stacked organic devices on underlying heat sensitive layers, as they are quite common in organic electronic devices.

Hybrid organic-inorganic gas sensing devices have been developed by means of supersonic beam co-deposition of titania clusters and copper phthalocyanine. This technique allows controlling the cluster size and structure as well as the kinetic properties of organic precursors, thus enabling both the room-temperature growth of nanocrystalline Ti02 and its functionalization. Particularly the high kinetic energy transferred to the organic molecules is exploited to enhance reactivity at the interface between the two counterparts, resulting in the synthesis of a new material with interesting gas sensing properties. The hybrid devices show improved performances as to stability and sensitivity towards oxidizing and even nonoxidizing gases, which IS a remarkable result for metal-phthalocyanine based sensors. The role of the organic-inorganic interface in the development of such characteristics is briefly discussed.

Supersonic beams of organic molecules seeded in light carrier gases are a viable method to control the deposition of highly ordered thin films, to activate kinetically chemical reactions to functionalize surfaces or to synthesize hybrid compounds. The advantage of supersonic molecular beam deposition (SuMBE) with respect to the more standard OMBE/OMBD method is the control of the energetic parameters of the precursors that we have shown to give an unprecedented control on structural, morphological and hence functional properties in the deposition of organic thin films. The basic mechanism is envisaged to be a sort of local annealing activated by the kinetic energy of the molecules that collides with the surface. Depending on the molecular precursor used and on the kinetic energy achievable this same method can be exploited to activate reactivity at the surface and hence to synthesize different structures. Here we report on a few examples including the deposition of highly ordered organic thin films of pentacene, the synthesis of SiC at moderate temperatures and the functionalization of inorganic nanostructured materials such as TiO2.

Surface-enhanced Raman spectroscopy (SERS) biotags (SBTs) that carry peptides as cell recognition moieties were made from polymer-encapsulated silver nanoparticle dimers, infused with unique Raman reporter molecules. We previously demonstrated their potential use for identification of malignant cells, a central goal in cancer research, through a multiplexed, ratiometric method that can confidently distinguish between cancerous and noncancerous epithelial prostate cells in vitro based on receptor overexpression. Progress has been made toward the application of this quantitative methodology for the identification of cancer cells in a microfluidic flow-focusing device. Beads are used as cell mimics to evaluate the devices. Cells (and beads) are simultaneously incubated with two sets of SBTs while in suspension, then injected into the device for laser interrogation under flow. Each cell event is characterized by a composite Raman spectrum, deconvoluted into its single components to ultimately determine their relative contribution. We have found that using SBTs ratiometrically can provide cell identification in flow, insensitive to normal causes of uncertainty in optical measurements such as variations in focal plane, cell concentration, autofluorescence, and turbidity.

We show that pentacene field-effect transistors, fabricated by supersonic molecular beams, have a performance strongly depending on the precursor's kinetic energy (KE). The major role played by KE is in achieving highly ordered and flat films. In the range KE3.5-6.5 eV, the organic field effect transistor linear mobility increases of a factor 5. The highest value (1.0 cm2 V-1 s-1) corresponds to very uniform and flat films (layer-by-layer type growth). The temperature dependence of mobility for films grown at KE>6 eV recalls that of single crystals (bandlike) and shows an opposite trend for films grown at KE5.5 eV.

Cluster supersonic beams have been previously shown to be a viable method to produce nanostructures by assembling them on a substrate in a controlled way. Control of precursors properties in the beam efficiently determine morphology, structure of films and their functional properties. Sensors based on cluster assembled TiO/sub 2/ show remarkable properties (sensitivity, response time and selectivity). We expand this approach to organic functionalization of nanostuctured oxides in a co-deposition scheme combining supersonic sources of organics (SuMBE) and of oxides (MPCS). Characterization of the properties of films and of the precursors will be discussed. This opens the perspective of using a co-deposition process combining metal (oxides) clusters and organic molecules to produce hybrid "decorated" nanostructures that could combine the inorganic stability and the molecular selectivity to produce a novel generation of gas sensors. The performance of the first prototype will also be presented.

Crystalline silicon carbide (SiC) and silicon (Si) biocompatibility was evaluated by directly culturing three mammalian cell lines on these semiconducting substrates. Cell proliferation and adhesion quality were studied using MTT [3- (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assays and fluorescent microscopy. The reported results show that SiC is indeed a more biocompatible substrate than Si. The surface wettability of SiC and Si samples was evaluated through static contact angle measurements, which provided interesting information regarding the influence of different cleaning procedures on the SiC surfaces. The cell proliferation data are discussed in light of the contact angle measurements results. This joint analysis leads to interesting conclusions that may help to uncover the main factors that define a semiconductor's biocompatibility.