Quartz crystal microbalance studies of Al2O3 atomic layer deposition using trimethylaluminum and water at 125 degrees C.

Al(2)O(3) atomic layer deposition (ALD) growth with Al(CH(3))(3) (trimethylaluminum (TMA)) and H(2)O as the reactants was examined at the relatively low temperature of 125 degrees C using quartz crystal microbalance (QCM) measurements. The total Al(2)O(3) ALD mass gain per cycle (MGPC) and MGPCs during the individual TMA and H(2)O reactions were measured versus TMA and H(2)O exposures. The Al(2)O(3) MGPC increased with increasing H(2)O and TMA exposures at fixed TMA and H(2)O exposures, respectively. However, the TMA and H(2)O reactions were not completely self-limiting. The slower surface reaction kinetics at lower temperature may require very long exposures for the reactions to reach completion. The Al(2)O(3) MGPCs increased quickly versus H(2)O exposure and slowly reached limiting values that were only weakly dependent on the TMA doses. Small TMA exposures were also sufficient for the Al(2)O(3) MGPCs to reach different limiting values for different H(2)O doses. The TMA MGPCs increased for higher TMA exposures at all H(2)O exposures. In contrast, the H(2)O MGPCs decreased for higher TMA exposures at all H(2)O exposures. This decrease may occur from more dehydroxylation at larger hydroxyl coverages after the H(2)O exposures. The hydroxyl coverage after the H(2)O exposure was dependent only on the H(2)O exposure. The Al(2)O(3) MGPC was also linearly dependent on the hydroxyl coverage after the H(2)O dose. Both the observed hydroxyl coverage versus H(2)O exposure and the Al(2)O(3) ALD growth versus H(2)O and TMA exposures were fit using modified Langmuir adsorption isotherm expressions where the pressures are replaced with exposures. These results should be useful for understanding low-temperature Al(2)O(3) ALD, which is important for coating organic, polymeric, and biological substrates.

High-resolution (1)H NMR spectroscopy in organs and tissues using slow magic angle spinning.

It is shown that high-resolution (1)H NMR spectra of intact excised tissues and organs can be obtained by rotating the sample slowly about an axis at the magic angle of 54 degrees 44' with the external magnetic field. In this way tissue and cellular damage invoked by standard magic angle spinning (MAS) experiments, where spinning speeds of several kHz are typically employed, are minimized. Special RF pulse sequences, developed originally in solid state NMR, can be used to produce a spinning sideband-free isotropic spectrum. In this article the first results are shown of the brain, heart, liver, gluteus muscle, and kidney excised from mice using the 2D-phase-altered spinning sidebands (PASS) technique and employing MAS spinning speeds of 43-125 Hz. It was found that with slow sample spinning similar, and in some cases even better, spectral resolutions are obtained as compared with fast MAS.

An integrated confocal and magnetic resonance microscope for cellular research.

Complementary data acquired with different microscopy techniques provide a basis for establishing a more comprehensive understanding of health and disease at a cellular level, particularly when data acquired with different methodologies can be correlated in both time and space. In this Communication, a brief description of a novel instrument capable of simultaneously performing confocal optical and magnetic resonance microscopy is presented, and the first combined images of live Xenopus laevis oocytes are shown. Also, the potential benefits of combined microscopy are discussed, and it is shown that the a priori knowledge of the high-resolution optical images can be used to enhance the boundary resolution and contrast of the MR images.

In vivo MRI measurements of tumor growth induced by dichloroacetate: implications for mode of action.

Dichloroacetate (DCA) is an important by-product of the chlorination of drinking water that produces liver cancer in rodents. Assessment of the risk that results from concentrations that occur in drinking water will be dependent upon the mode of action held responsible for these tumors. A study by Stauber and Bull [Stauber, A.J. and Bull, R. J (1997) Differences in phenotype and cell replicative behavior of hepatic tumors inducted by dichloroacetate (DCA) and trichloroacetate (TCA). Toxicol. Appl. Pharmacol. 144, 235-246] in mice treated with DCA demonstrated a lesion distribution that was skewed towards many small, altered foci of cells that are assumed to be precursor lesions [EPA, (1996). U.S. Environmental Protection Agency: Proposed Guidelines for carcinogen risk assessment; notice. Fed. Reg. 61, pp. 17960-10811]. The present study was designed to determine the extent to which the tumorigenic effects of DCA could be explained by its effect on tumor growth rates (i.e. tumor promoting activity). In vivo magnetic resonance imaging (MRI) allowed accurate determination of growth rates of individual lesions in mice that had been treated with DCA in drinking water at 2 g/l. Out of thirty treated mice, ten were found to have hepatic tumors detectable by MRI at 48 weeks of treatment. These tumor-bearing animals were assigned to two groups matched on the size of lesions observed by in vivo MR1. Treatment with DCA continued in one group of five mice and was stopped in the other. For both groups, tumor growth rates were determined by measuring changes in size of all lesions greater than 1 mm(3) in volume during a 14-day period. Removal of DCA treatment resulted in growth rates that could not be distinguished from zero across all lesion sizes represented in the sample. These data are in agreement with previous observations of DCAs effects on replication rates within tumors (Stauber and Bull, (1997)). Tumor growth rates observed in animals maintained on treatment decreased with lesion volume in a manner that is consistent with a stochastic Gompertz birth-death process proposed by Tan [Tan, W.Y. (1986) A stochastic Gompertz birth-death process. Stat. Prob. Lett. 4, 25-28]. Parameters of this model obtained by fitting measured growth rates were used to predict the lesion-size distribution expected after one year of DCA treatment. The shape of the predicted lesion-size distribution was similar to that observed by Stauber and Bull (Stauber and Bull, (1997)) in mice sacrificed after 40 weeks of DCA treatment. We conclude that the effects of DCA on the division and/or death rates of spontaneously initiated cells can account for the predominance of small lesions in DCA-treated animals.

1H dynamic nuclear polarization in supercritical ethylene at 1.4 T.

(1)H dynamic nuclear polarization (DNP) has been measured in supercritical ethylene in the pressure range 60-300 bar in an external field of 1.4 T. A single-cell sapphire tube was used as a high-pressure cell, and powdered 1,3-bisdiphenylene-2-phenyl allyl (BDPA) free radicals were added and distributed at the wall of the cell. At all pressures the dominant DNP mechanism was a positive Overhauser enhancement, caused by proton-electron contact interactions at the fluid/solid radical interface. The observed enhancements varied from 12 at 60 bar to 17 at 300 bar. Besides the Overhauser enhancement, small solid state and thermal mixing enhancements also were observed, indicating that part of the ethylene was adsorbed at the radical surface for a prolonged time. The impacts of the experimental conditions on the Overhauser enhancement factors are discussed, and enhancements of at least 40-60 are estimated when the EPR saturation factor and the leakage factor become maximal. These data indicate that DNP-enhanced NMR has the potential of extending the impact of NMR in research areas involving supercritical fluids.

1H DNP at 1.4 T of water doped with a triarylmethyl-based radical.

Recently a triarylmethyl-based (TAM) radical has been developed for research in biological and other aqueous systems, and in low magnetic fields, 10 mT or less, large (1)H dynamic nuclear polarization (DNP) enhancements have been reported. In this paper the DNP properties of this radical have been investigated in a considerably larger field of 1.4 T, corresponding to proton and electron Larmor frequencies of 60 MHz and 40 GHz, respectively. To avoid excessive microwave heating of the sample, an existing DNP NMR probe was modified with a screening coil, wound around the sample capillary and with its axis perpendicular to the electric component of the microwave field. It was found that with this probe the temperature increase in the sample after 4 s of microwave irradiation with an incident power of 10 W was only 16 degrees C. For the investigations, 10 mM of the TAM radical was dissolved in deionized, but not degassed, water and put into a 1-mm i.d. and 6-mm long capillary tube. At 26 degrees C the following results were obtained: (I) The relaxivity of the radical is 0.07 (mMs)(-1), in accordance with the value extrapolated from low-field results; (II) The leakage factor is 0.63, the saturation factor at maximum power is 0.85, and the coupling factor is -0.0187. It is shown that these results agree very well with an analysis where the electron-dipolar interactions are the dominant DNP mechanism, and where the relaxation transitions resulting from these interactions are governed by translational diffusion of the water molecules. Finally, the possibilities of combining DNP with magnetic resonance microscopy (MRM) are discussed. It is shown that at 26 degrees C the overall DNP-enhanced proton polarization should become maximal in an external field of 0.3 T and become comparable to the thermal equilibrium polarization in a field of 30 T, considerably larger than the largest high-resolution magnet available to date. It is concluded that DNP MRM in this field, which corresponds to a standard microwave frequency of 9 GHz, has the potential to significantly increase the sensitivity in NMR and MRI experiments of small aqueous samples doped with the TAM radical.

A compact respiratory-triggering device for routine microimaging of laboratory mice.

A partial-body plethysmograph was developed for measuring the respiratory flow of anesthetized mice during routine microimaging experiments performed in the close confines of an 89-mm-diameter, vertical-bore magnet. Respiratory flow patterns were used for synchronizing conventional T2-weighted spin-echo imaging with the respiratory cycle, thereby, significantly reducing motion-induced artifacts and increasing observed liver lesion contrast.

Quantitative 1H MRI and MRS microscopy of individual V79 lung tumor spheroids.

In this Communication 1H MRI and MRS microscopy experiments of individual V79 lung tumor spheroids with diameters between 550 and 650 micrometer are reported. The results have been used to determine the T1, T2, and D values as well as the concentrations of water, total choline, creatine/phosphocreatine, and mobile lipids in the viable rims and in the necrotic centers.

Dynamic nuclear polarization of nitrogen-15 in benzamide.

A 15N dynamic nuclear polarization (DNP) experiment is reported in which a 15N DNP enhancement factor of approximately 2.6 x 10(2) is obtained on free radical doped samples of 99% 15N labeled benzamide. The free radicals BDPA (1:1 complex of alpha, gamma-bisdiphenylene-beta-phenylallyl with benzene) and DPPH (2,2-Di(4-tert-octylphenyl)-1-picrylhydrazyl) are used as dopants and the spin relaxation effects of adding these dopants are studied by means of changes in proton and nitrogen T1 values of the samples. The combination in solids of a very low natural abundance, 0.37%, a small gyromagnetic ratio, and a long spin-lattice relaxation time for 15N nuclei create severe sensitivity problems that, in large part, are ameliorated by the signal enhancement observed in the 15N DNP experiment on samples containing free electrons.

An investigation of rat mammary healthy and R3230AC tumor tissues and cells by means of solid-state 13C NMR.

The first results are shown of a low temperature 13C solid-state, cross-polarization magic angle spinning (CPMAS) NMR study of R3230AC rat mammary carcinoma transplanted into female Fischer rats. Intact, healthy mammary tissues and tumor tissues, quickly frozen at -78 degrees C after excision, were examined, as were normal epithelial cells and tumor cells extracted from these tissues. The experiments were performed at -100 degrees C and -40 degrees C. The solid-state 13C NMR spectrum of the healthy tissue is dominated by the triacylglycerols present in the adipose tissue. The solid-state spectra of the other compounds differ significantly from the spectrum of the healthy tissue, and are dominated by the phospholipids and the large molecular weight proteins, for a major part present in the membranes. The spectra of the tumor tissues and the tumor cells were very similar, in accordance with the fact that the tumor tissues consisted of 80-90% tumor cells. The spectrum of the normal cells shows the same general features as those of the tumor tissue and tumor cells, but also exhibits some significant differences. The main difference at -100 degrees C is that, in the tumor samples, the relative intensity of the resonance line arising at 30 ppm, which is due to methylene chains, is reduced. At -40 degrees C this intensity is further reduced in the tumor samples, whereas the spectrum of the normal cells remains unaltered. It is tentatively concluded that the spectral differences between the normal and the malignant cells are due to changes in mobilities occurring in the cells after tumorigenesis, and that compared with normal epithelial cells the tumor cells contain an increased amount of mobile methylene chains. These differences virtually disappear if the samples are preserved at temperatures equal to or above 4 degrees C, emphasizing the importance of sample preservation at low temperatures, and hence of the solid-state NMR approach to investigate structures and dynamics in cells before and after tumor formation.

EPR and 1H and 13C dynamic nuclear polarization studies of a molecularly doped polymer: bisphenol A polycarbonate doped with trianisylamine and trianisylaminium perchlorate.

We have investigated the EPR and DNP behavior of a molecularly doped polymer modeling those used to transport electronic charge in electrophotography. The EPR spectra show no evidence of the superexchange reported for a closely related system based on tri-p-tolylamine. The difference may be due to larger charge-transfer matrix elements in the latter system. An unambiguous interpretation of the observed 1H DNP was rendered difficult by the unanticipated asymmetry of the EPR spectra. We report extensive data on the "three-spin" effect evident in the DNP-enhanced 13C NMR spectra, and comment on its potential for characterizing polymer interfaces.

N.m.r. relaxation and images of human breast tumours in vitro.

It is found that fat and non-fatty tissue in dissected samples of the mamma differ in their T1/T2 ratios. This opens the possibility of locating tumours by n.m.r. imaging, because they have a lower fat content than their surroundings. By means of a sensitive point method, samples were scanned with a resolution of about 0.4 mm X 0.4 mm. The similarity between the shape of a tumour in an n.m.r. and in an X-ray image of a thin section of mamma tissue is quite convincing.