Large-surface-area diamond (111) crystal plates for applications in high-heat-load wavefront-preserving X-ray crystal optics.

Fabrication and results of high-resolution X-ray topography characterization of diamond single-crystal plates with large surface area (10 mm × 10 mm) and (111) crystal surface orientation for applications in high-heat-load X-ray crystal optics are reported. The plates were fabricated by laser-cutting of the (111) facets of diamond crystals grown using high-pressure high-temperature methods. The intrinsic crystal quality of a selected 3 mm × 7 mm crystal region of one of the studied samples was found to be suitable for applications in wavefront-preserving high-heat-load crystal optics. Wavefront characterization was performed using sequential X-ray diffraction topography in the pseudo plane wave configuration and data analysis using rocking-curve topography. The variations of the rocking-curve width and peak position measured with a spatial resolution of 13 µm × 13 µm over the selected region were found to be less than 1 µrad.

Pericentral activity of alpha-fetoprotein enhancer 3 and glutamine synthetase upstream enhancer in the adult liver are regulated by ß-catenin in mice.

UNLABELLED: We previously showed that mouse alpha-fetoprotein (AFP) enhancer 3 activity is highly restricted to pericentral hepatocytes in the adult liver. Here, using transgenic mice, we show that the upstream enhancer of the rat glutamine synthetase gene is also active, specifically in pericentral regions. Activity of both enhancers is lost in the absence of ß-catenin, a key regulator of zonal gene expression in the adult liver. Both enhancers contain a single, highly conserved T-cell factor/lymphoid enhancer factor binding site that is required for responsiveness to ß-catenin. We also show that endogenous AFP messenger RNA levels in the perinatal liver are lower when ß-catenin is reduced. CONCLUSION: These data identify the first distinct zonally active regulatory regions required for ß-catenin responsiveness in the adult liver, and suggest that postnatal AFP repression and the establishment of zonal regulation are controlled, at least in part, by the same factors.

Ultrathin single crystal diamond nanomechanical dome resonators.

We present the first nanomechanical resonators microfabricated in single-crystal diamond. Shell-type resonators only 70 nm thick, the thinnest single crystal diamond structures produced to date, demonstrate a high-quality factor (Q ≈ 1000 at room temperature, Q ≈ 20 000 at 10 K) at radio frequencies (50-600 MHz). Quality factor dependence on temperature and frequency suggests an extrinsic origin to the dominant dissipation mechanism and methods to further enhance resonator performance.

Surface functionalization of thin-film diamond for highly stable and selective biological interfaces.

Carbon is an extremely versatile family of materials with a wide range of mechanical, optical, and mechanical properties, but many similarities in surface chemistry. As one of the most chemically stable materials known, carbon provides an outstanding platform for the development of highly tunable molecular and biomolecular interfaces. Photochemical grafting of alkenes has emerged as an attractive method for functionalizing surfaces of diamond, but many aspects of the surface chemistry and impact on biological recognition processes remain unexplored. Here we report investigations of the interaction of functionalized diamond surfaces with proteins and biological cells using X-ray photoelectron spectroscopy (XPS), atomic force microscopy, and fluorescence methods. XPS data show that functionalization of diamond with short ethylene glycol oligomers reduces the nonspecific binding of fibrinogen below the detection limit of XPS, estimated as > 97% reduction over H-terminated diamond. Measurements of different forms of diamond with different roughness are used to explore the influence of roughness on nonspecific binding onto H-terminated and ethylene glycol (EG)-terminated surfaces. Finally, we use XPS to characterize the chemical stability of Escherichia coli K12 antibodies on the surfaces of diamond and amine-functionalized glass. Our results show that antibody-modified diamond surfaces exhibit increased stability in XPS and that this is accompanied by retention of biological activity in cell-capture measurements. Our results demonstrate that surface chemistry on diamond and other carbon-based materials provides an excellent platform for biomolecular interfaces with high stability and high selectivity.

Sex-specific parent-of-origin allelic expression in the mouse brain.

Genomic imprinting results in preferential gene expression from paternally versus maternally inherited chromosomes. We used a genome-wide approach to uncover sex-specific parent-of-origin allelic effects in the adult mouse brain. Our study identified preferential selection of the maternally inherited X chromosome in glutamatergic neurons of the female cortex. Moreover, analysis of the cortex and hypothalamus identified 347 autosomal genes with sex-specific imprinting features. In the hypothalamus, sex-specific imprinted genes were mostly found in females, which suggests parental influence over the hypothalamic function of daughters. We show that interleukin-18, a gene linked to diseases with sex-specific prevalence, is subject to complex, regional, and sex-specific parental effects in the brain. Parent-of-origin effects thus provide new avenues for investigation of sexual dimorphism in brain function and disease.

Proteasome regulation of ULBP1 transcription.

Killer lymphocytes recognize stress-activated NKG2D ligands on tumors. We examined NKG2D ligand expression in head and neck squamous cell carcinoma (HNSCC) cells and other cell lines. HNSCC cells typically expressed MHC class I chain-related gene A (MICA), MICB, UL16-binding protein (ULBP)2, and ULBP3, but they were uniformly negative for cell surface ULBP1 and ULBP4. We then studied how cancer treatments affected NKG2D ligand expression. NKG2D ligand expression was not changed by most cancer-relevant treatments. However, bortezomib and other proteasome inhibitor drugs with distinct mechanisms of action dramatically and specifically up-regulated HNSCC ULBP1 mRNA and cell surface protein. Proteasome inhibition also increased RNA for ULBP1 and other NKG2D ligands in nontransformed human keratinocytes. Proteasome inhibitor drugs increased ULBP1 transcription by acting at a site in the 522-bp ULBP1 promoter. Although the DNA damage response pathways mediated by ATM (ataxia-telangiectasia, mutated) and ATR (ATM and Rad3-related) signaling had been reported to up-regulate NKG2D ligand expression, we found that ULBP1 up-regulation was not inhibited by caffeine and wortmannin, inhibitors of ATM/ATR signaling. ULBP1 expression in HNSCC cells was not increased by several ATM/ATR activating treatments, including bleomycin, cisplatin, aphidicolin, and hydroxyurea. Ionizing radiation caused ATM activation in HNSCC cells, but high-level ULBP1 expression was not induced by gamma radiation or UV radiation. Thus, ATM/ATR signaling was neither necessary nor sufficient for high-level ULBP1 expression in human HNSCC cell lines and could not account for the proteasome effect. The selective induction of ULBP1 expression by proteasome inhibitor drugs, along with variable NKG2D ligand expression by human tumor cells, indicates that NKG2D ligand genes are independently regulated.

Patellofemoral arthroplasty with a custom-fit femoral prosthesis.

We reviewed the outcomes of a series of patellar arthroplasty operations with custom-fit femoral prostheses to examine the effectiveness of this procedure in relieving pain and restoring function in the knee. Twenty-two patellofemoral arthroplasty operations were performed in 21 patients (mean age, 48.6 years) at 2 institutions between 1994 and 2002. All patients had advanced patellofemoral arthritis and had undergone an average of 2.5 previous patellofemoral operations. The prosthesis, consisting of a custom-fit chrome cobalt trochlear component and an all-polyethylene patellar button, was implanted in a procedure designed to minimize bone resection. Patients later underwent three-view radiography of the knee to confirm that the prosthesis was positioned correctly. One patient required revision of an undersized patellar button 18 months postoperatively, and 2 other patients had postoperative arthrofibrosis necessitating arthroscopic debridement. No patient required revision of the trochlear component, and no loosening or migration of any component has been found since the first procedure was performed. However, the polyethylene patellar button has worn in 3 patients, and the patella broke in 1 patient. An average of 60 months postoperatively, patients used the Western Ontario and McMaster Universities Osteoarthritis Index to rate their preoperative and present joint pain, stiffness, and function. Patients' mean overall ratings (potential range, 24-96) were significantly lower for their present symptoms (28.4) than for their preoperative symptoms (63.4). Mean scores on each subscale also decreased: from 13.0 to 5.5 for pain, from 5.4 to 2.4 for stiffness, and from 45.0 to 20.6 for function. We conclude that, in carefully selected patients, patellofemoral arthroplasty with a custom-fit prosthesis is a viable surgical treatment for isolated patellofemoral arthritis.

CVD-diamond external cavity Raman laser at 573 nm.

Recent progress in diamond growth via chemical vapor deposition (CVD) has enabled the manufacture of single crystal samples of sufficient size and quality for realizing Raman laser devices. Here we report an external cavity CVD-diamond Raman laser pumped by a Q-switched 532 nm laser. In the investigated configuration, the dominant output coupling was by reflection loss at the diamond's uncoated Brewster angle facets caused by the crystal's inherent birefringence. Output pulses of wavelength 573 nm with a combined energy of 0.3 mJ were obtained with a slope efficiency of conversion of up to 22%.

A mechanism for crystal twinning in the growth of diamond by chemical vapour deposition.

A model for the formation of crystal twins in chemical vapour deposited diamond materials is presented. The twinning mechanism originates from the formation of a hydrogen-terminated four carbon atom cluster on a local {111} surface morphology, which also serves as a nucleus to the next layer of growth. Subsequent growth proceeds by reaction at the step edges with one and two carbon atom-containing species. The model also provides an explanation for the high defect concentration observed in 111 growth sectors, the formation of penetration and contact twins, and the dramatic enhancement in polycrystalline diamond growth rates and morphology changes when small amounts of nitrogen are added to the plasma-assisted growth environments.

Direct photopatterning and SEM imaging of molecular monolayers on diamond surfaces: mechanistic insights into UV-initiated molecular grafting.

We have used X-ray photoelectron spectroscopy (XPS), infrared reflection-absorption spectroscopy, and field-emission scanning electron microscopy (SEM) to investigate the formation of single- and two-component molecular patterns by direct photochemical grafting of alkenes onto hydrogen-terminated diamond surfaces using sub-band gap 254 nm ultraviolet light. Trifluoroacetamide-protected 1-aminodec-1-ene (TFAAD) and 1-dodecene were used as model systems for grafting. Illumination with sub-band gap light can induce several different kinds of excitations, including creation of mobile electrons and holes in the bulk and creation of radicals at the surface and in the adjacent fluid, which induce grafting of the alkenes to the surface. SEM images of patterned molecular layers on nanocrystalline diamond surfaces reveal sharp transitions between functionalized and nonfunctionalized regions consistent with diffraction-limited excitation. However, identical experiments on type IIb single-crystal diamond yield a significantly more extended transition region in the molecular pattern. These data imply that the spatial resolution of the direct molecular photopatterning is affected by diffusion of charge carriers in the bulk of the diamond samples. The molecular contrast between surfaces with different terminations is consistent with the expected trends in molecular electron affinity. These results provide new mechanistic insights into the direct patterning and imaging of molecular monolayers on surfaces.

Direct electrical detection of antigen-antibody binding on diamond and silicon substrates using electrical impedance spectroscopy.

The integration of biological molecules with semiconducting materials such as silicon and diamond has great potential for the development of new types of bioelectronic devices, such as biosensors and bioactuators. We have investigated the electrical properties of the antibody-antigen modified diamond and silicon surfaces using electrical impedance spectroscopy (EIS). Frequency dependent measurements at the open-circuit potential show: (a) significant changes in impedance at frequency >10(4) Hz when the surface immobilized IgG was exposed to anti-IgG, and (b) only little or no change when exposed to anti-IgM. Mott-Schottky measurements at high frequency (200 kHz) show that the impedance is dominated by the space charge layer of the semiconducting substrates. Silicon surfaces modified in a similar manner to the diamond surface are compared; n-type and p-type samples show complementary behavior, as expected for a field effect. We also show it is possible to directly observe antigen-antibody interaction at a fixed frequency in real time, and with no additional labeling.

Electrical bias dependent photochemical functionalization of diamond surfaces.

Diamond is an excellent substrate for many sensing and electronic applications because of its outstanding stability in biological and aqueous environments. When the diamond surface is H-terminated, it can be covalently modified with organic alkenes using wet photochemical methods that are surface-mediated and initiated by the ejection of electrons from the diamond. To develop a better understanding of the photochemical reaction mechanism, we examine the effect of applying an electrical bias to the diamond samples during the photochemical reaction. Applying a 1 V potential between two diamond electrodes significantly increases the rate of functionalization of the negative electrode. Cyclic voltammetry and electrochemical impedance measurements show that the 1 V potential induces strong downward band-bending within the diamond film of the negative electrode. At higher voltages a Faradaic current is observed, with no further acceleration of the functionalization rate. We attribute the bias-dependent changes in rate to a field effect, in which the applied potential induces a strong downward band-bending on the negative electrode and facilitates the ejection of electrons into the adjacent fluid of reactant organic alkenes. We also demonstrate the ability to directly photopattern the surface with reactant molecules on length scales of <25 microm, the smallest we have measured, using simple photomasking techniques.

Semiconductor surface-induced 1,3-hydrogen shift: the role of covalent vs zwitterionic character.

X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared spectroscopy (FTIR) are used to compare the reaction of 1,2-cyclohexanedione (1,2-CHD) with Si(001) and diamond(001) surface dimers under ultra-high-vacuum conditions. 1,2-CHD is known to undergo a keto-enol tautomerization, with the monoenol being the primary equilibrium species in the solid and gas phases. XPS and FTIR data demonstrate that 1,2-CHD reacts with diamond(001) through the OH group of the monoenol, resulting in only one O atom being bonded to the surface. In contrast, XPS and FTIR data suggest that both oxygen atoms in the 1,2-CHD molecule bond via Si-O-C linkages to the Si(001) surface dimer, and that the molecule undergoes an intramolecular 1,3-H shift. While the Si(001) and diamond(001) surfaces are both comprised of surface dimers, the diamond(001) dimer is symmetric, with little charge separation, whereas the Si(001) dimer is tilted and exhibits zwitterionic character. The different reaction products that are observed when clean Si(001) and diamond(001) surfaces are exposed to 1,2-CHD demonstrate the importance of charge separation in promoting a 1,3-H shift and provide new mechanistic insights that may be applicable to a variety of organic reactions.

Adsorption of acrylonitrile on diamond and silicon (001)-(2 x 1) surfaces: effects of dimer structure on reaction pathways and product distributions.

Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS) are used to compare the reaction of acrylonitrile with Si(001) and C(001) (diamond) surfaces. Our results show that reaction with Si(001) and C(001) yield very different product distributions that result from fundamental differences in the ionic character of these surfaces. While acrylonitrile reacts with the C(001) surface via a [2 + 2] cycloaddition reaction in a manner similar to nonpolar molecules such as alkenes and disilenes, reaction with the Si(001) surface occurs largely through the nitrile group. This work represents the first experimental example of how differences in dimer structure lead to very different chemistry for C(001) compared to that for Si(001). The fact that Si(001) reacts with the strongly polar nitrile group of acrylonitrile indicates that the zwitterionic character of this surface controls its reactivity. C(001) dimers, on the other hand, behave more like a true molecular double bond, albeit a highly strained one. Consequently, while alternative strategies will be necessary for chemical modification of Si(001), traditional schemes from organic chemistry for functionalization of alkenes and disilenes may be available for building molecular layers on C(001).

Electrical properties of diamond surfaces functionalized with molecular monolayers.

Recent studies have shown that semiconductor surfaces such as silicon and diamond can be functionalized with organic monolayers, and that these monolayer films can be used to tether biomolecules such as DNA to the surfaces. Electrical measurements of these interfaces show a change in response to DNA hybridization and other biological binding processes, but the fundamental nature of the electrical signal transduction has remained unclear. We have explored the electrical impedance of polycrystalline and single-crystal diamond surfaces modified with an organic monolayer produced by photochemical reaction of diamond with 1-dodecene. Our results show that, by measuring the impedance as a function of frequency and potential, it is possible to dissect the complex interfacial structure into frequency ranges where the total impedance is controlled by the molecular monolayer, by the diamond space-charge region, and by the electrolyte. The results have implications for understanding the ability to use molecularly modified semiconductor surfaces for applications such as chemical and biological sensing.

Photochemical functionalization of hydrogen-terminated diamond surfaces: a structural and mechanistic study.

Hydrogen-terminated diamond surfaces can be covalently modified with molecules bearing a terminal vinyl (C=C) group via a photochemical process using sub-band-gap light at 254 nm. We have investigated the photochemical modification of hydrogen-terminated surfaces of nanocrystalline and single-crystal diamond (111) to help understand the structure of the films and the underlying mechanism of photochemical functionalization. A comparison of the rates of photochemical modification of single-crystal diamond and nanocrystalline diamond films shows no significant difference in reactivity, demonstrating that the modification process is not controlled by grain boundaries or other structures unique to polycrystalline films. We find that both single-crystal and polycrystalline hydrogen-terminated diamond samples exhibit negative electron affinity and are functionalized at comparable rates, while oxidized surfaces with positive electron affinity undergo no detectable reaction. Gas chromatography-mass spectrometry (GC-MS) analysis shows the formation of new chemical products in the liquid phase that are formed only when the alkenes are illuminated in direct contact with H-terminated diamond, while control experiments with other surfaces and in the dark show no reaction. Our results show that the functionalization is a surface-mediated photochemical reaction and suggest that modification is initiated by the photoejection of electrons from the diamond surfaces into the liquid phase.

Interfacial electrical properties of DNA-modified diamond thin films: intrinsic response and hybridization-induced field effects.

We have investigated the frequency-dependent interfacial electrical properties of nanocrystalline diamond films that were covalently linked to DNA oligonucleotides and how these properties are changed upon exposure to complementary and noncomplementary DNA oligonucleotides. Frequency-dependent electrical measurements at the open-circuit potential show significant changes in impedance at frequencies of >10(4) Hz when DNA-modified diamond films are exposed to complementary DNA, with only minimal changes when exposed to noncomplementary DNA molecules. Measurements as a function of potential show that at 10(5) Hz, the impedance is dominated by the space-charge region of the diamond film. DNA molecules hybridizing at the interface induce a field effect in the diamond space-charge layer, altering the impedance of the diamond film. By identifying a range of impedances where the impedance is dominated by the diamond space-charge layer, we show that it possible to directly observe DNA hybridization, in real time and without additional labels, via simple measurement of the interfacial impedance.

Shallow donors with high n-type electrical conductivity in homoepitaxial deuterated boron-doped diamond layers.

Diamond is a unique semiconductor for the fabrication of electronic and opto-electronic devices because of its exceptional physical and chemical properties. However, a serious obstacle to the realization of diamond-based devices is the lack of n-type diamond with satisfactory electrical properties. Here we show that high-conductivity n-type diamond can be achieved by deuteration of particularly selected homo-epitaxially grown (100) boron-doped diamond layers. Deuterium diffusion through the entire boron-doped layer leads to the passivation of the boron acceptors and to the conversion from highly p-type to n-type conductivity due to the formation of shallow donors with ionization energy of 0.23 eV. Electrical conductivities as high as 2omega(-1) x cm(-1) with electron mobilities of the order of a few hundred cm2 x V(-1) x s(-1) are measured at 300 K for samples with electron concentrations of several 10(16) x cm(-3). The formation and break-up of deuterium-related complexes, due to some excess deuterium in the deuterated layer, seem to be responsible for the reversible p- to n-type conversion. To the best of our knowledge, this is the first time such an effect has been observed in an elemental semiconductor.

DNA-modified nanocrystalline diamond thin-films as stable, biologically active substrates.

Diamond, because of its electrical and chemical properties, may be a suitable material for integrated sensing and signal processing. But methods to control chemical or biological modifications on diamond surfaces have not been established. Here, we show that nanocrystalline diamond thin-films covalently modified with DNA oligonucleotides provide an extremely stable, highly selective platform in subsequent surface hybridization processes. We used a photochemical modification scheme to chemically modify clean, H-terminated nanocrystalline diamond surfaces grown on silicon substrates, producing a homogeneous layer of amine groups that serve as sites for DNA attachment. After linking DNA to the amine groups, hybridization reactions with fluorescently tagged complementary and non-complementary oligonucleotides showed no detectable non-specific adsorption, with extremely good selectivity between matched and mismatched sequences. Comparison of DNA-modified ultra-nanocrystalline diamond films with other commonly used surfaces for biological modification, such as gold, silicon, glass and glassy carbon, showed that diamond is unique in its ability to achieve very high stability and sensitivity while also being compatible with microelectronics processing technologies. These results suggest that diamond thin-films may be a nearly ideal substrate for integration of microelectronics with biological modification and sensing.