High-throughput synthesis and characterization of nanocrystalline porphyrinic zirconium metal-organic frameworks.

We describe and employ a high-throughput screening method to accelerate the synthesis and identification of pure-phase, nanocrystalline metal-organic frameworks (MOFs). We demonstrate the efficacy of this method through its application to a series of porphyrinic zirconium MOFs, resulting in the isolation of MOF-525, MOF-545, and PCN-223 on the nanoscale.

A 99Tcm-labelled leukotriene B4 receptor antagonist for scintigraphic detection of infection in rabbits.

In a search for a rapid and accurate imaging agent for scintigraphic detection of infection and inflammation, an LTB4 receptor antagonist, 99Tcm-RP517, which contains the hydrazino nicotinamide moiety, has been developed recently. To study the in vivo behaviour of 99Tcm-RP517, rabbits with Escherichia coli infection were injected intravenously with 99Tcm-RP517. Gamma camera images were obtained and ex vivo bio-distribution was determined at several hours post-injection (p.i.). In a separate set of rabbits the choledochal duct was cannulated to quantitatively monitor the hepatobiliary clearance of the radiopharmaceutical. The receptor binding fraction of the radiolabelled RP517 exceeded 70%. Accumulation of 99Tcm-RP517 in the abscess was visualized as early as 1 h p.i. Due to rapid blood clearance (t1/2 alpha=18+/-0.6 min, t1/2 beta=6.5+/-0.4 h) and high abscess uptake, the abscess-to-muscle ratios increased with time from 7.0+/-2.3 at 1 h p.i. to 44.3+/-4.6 at 20 h p.i. The agent mainly cleared via the hepatobiliary route: 50% of the radiolabel was recovered in the small bowel at 1 h p.i., whereas 85% was found in cecum and sigmoid at 20 h p.i. In conclusion, 99Tcm-RP517 rapidly visualized E. coli abscesses in rabbits. The agent rapidly cleared from the blood, mainly via the hepatobiliary route. High abscess-to-background ratios were achieved. The accumulation in the intestines could limit the applicability of this agent for detecting infectious processes in the abdominal area. The development of a more hydrophilic analogue of 99Tcm-RP517 could improve the clinical applicability of this agent.

Synthesis of stable hydrazones of a hydrazinonicotinyl-modified peptide for the preparation of 99mTc-labeled radiopharmaceuticals.

Hydrazones of a 6-hydrazinonicotinyl-modified cyclic peptide IIb/IIIa receptor antagonist were prepared in order to protect the hydrazine moiety from reaction with trace aldehyde and ketone impurities encountered during the process of manufacturing and compounding lyophilized kits used in radiolabeling with (99m)Tc. Hydrazones were prepared by either a direct reaction of the 6-hydrazinonicotinyl-modified cyclic peptide with carbonyl compounds or by conjugation of the cyclic peptide with hydrazones of succinimidyl 6-hydrazinonicotinate. Stability of the hydrazones was evaluated by treatment with formaldehyde. Hydrazones derived from simple aliphatic aldehydes underwent an exchange reaction with formaldehyde, while hydrazones of aromatic aldehydes and ketones provided the greatest level of stability when challenged with formaldehyde. We have been successful in protecting 6-hydrazinonicotinyl-modified cyclic peptides from reacting with formaldehyde, while still allowing sufficient reactivity for radiolabeling with (99m)Tc. The hydrazones of succinimidyl 6-hydrazinonicotinate are convenient and general reagents for forming 6-hydrazinonicotinyl conjugates with amino-functionalized bioactive molecules.

Modal approximation for the electromagnetic field of a near-field optical probe.

A formalism is given in which the optical field generated by a near-field optical aperture is described as an analytic expansion over a complete set of optical modes. This vectoral solution preserves the divergent behavior of the near field and the dipolar nature of the far field. Numerical calculation of the fields requires only evaluation of a well behaved, one-dimensional integral. The formalism is directly applicable to experiments in near-field scanning optical microscopy when relatively flat samples are evaluated.

Near-field spectroscopy of the quantum constituents of a luminescent system.

Luminescent centers with sharp (<0.07 millielectron volt), spectrally distinct emission lines were imaged in a GaAs/AIGaAs quantum well by means of low-temperature near-field scanning optical microscopy. Temperature, magnetic field, and linewidth measurements establish that these centers arise from excitons laterally localized at interface fluctuations. For sufficiently narrow wells, virtually all emission originates from such centers. Near-field microscopy/spectroscopy provides a means to access energies and homogeneous line widths for the individual eigenstates of these centers, and thus opens a rich area of physics involving quantum resolved systems.

Polarization contrast in near-field scanning optical microscopy.

Recent advances in probe design have led to enhanced resolution (currently as significant as ~ 12 nm) in optical microscopes based on near-field imaging. We demonstrate that the polarization of emitted and detected light in such microscopes can be manipulated sensitively to generate contrast. We show that the contrast on certain patterns is consistent with a simple interpretation of the requisite boundary conditions, whereas in other cases a more complicated interaction between the probe and the sample is involved. Finally application of the technique to near-filed magneto-optic imaging is demonstrated.

Breaking the diffraction barrier: optical microscopy on a nanometric scale.

In near-field scanning optical microscopy, a light source or detector with dimensions less than the wavelength (lambda) is placed in close proximity (lambda/50) to a sample to generate images with resolution better than the diffraction limit. A near-field probe has been developed that yields a resolution of approximately 12 nm ( approximately lambda/43) and signals approximately 10(4)- to 10(6)-fold larger than those reported previously. In addition, image contrast is demonstrated to be highly polarization dependent. With these probes, near-field microscopy appears poised to fulfill its promise by combining the power of optical characterization methods with nanometric spatial resolution.

Catalyzed reporter deposition, a novel method of signal amplification. Application to immunoassays.

A novel signal amplification method, catalyzed reporter deposition (CARD), and its application to immunoassays is described. The method involves utilizing an analyte-dependent reporter enzyme (ADRE) to catalyze the deposition of additional reporter on the surface in a solid-phase immunoassay. In the examples described, deposition of reporter is facilitated by using a horseradish peroxidase (HRP) ADRE to catalyze the deposition of biotin labeled phenols. The deposited biotins are then reacted with streptavidin-labeled enzyme, thereby resulting in deposition of enzyme. Using the ADRE to catalyze the deposition of additional enzyme results in an amplification of the signal of the ADRE alone and improves the detection limit of the assay. The method is highly sensitive, simple, flexible, and easy to implement.

A stereoradiographic technique and its application to the evaluation of lung casts.

Stereoradiographs have been used on occasion for three-dimensional reconstruction and measurement of objects in radiology and radiotherapy. The lack of a good stereoradiographic technique has limited the uses of steroradiographic exposures. In this paper, the principle of the double-image is outlined and a method of applying this principle to stereoradiographic exposures is developed. A computer program has been developed from geometrical considerations to analyze the stereobronchogram and to calculate the dimensions of the objects in question. The applications of this technique are discussed and its use in evaluating lung casts is described.