Microscopy with ultraviolet surface excitation for wide-area pathology of breast surgical margins.

Intraoperative assessment of breast surgical margins will be of value for reducing the rate of re-excision surgeries for lumpectomy patients. While frozen-section histology is used for intraoperative guidance of certain cancers, it provides limited sampling of the margin surface (typically <1  %   of the margin) and is inferior to gold-standard histology, especially for fatty tissues that do not freeze well, such as breast specimens. Microscopy with ultraviolet surface excitation (MUSE) is a nondestructive superficial optical-sectioning technique that has the potential to enable rapid, high-resolution examination of excised margin surfaces.

Tissue-engineered microenvironment systems for modeling human vasculature.

The high attrition rate of drug candidates late in the development process has led to an increasing demand for test assays that predict clinical outcome better than conventional 2D cell culture systems and animal models. Government agencies, the military, and the pharmaceutical industry have started initiatives for the development of novel in-vitro systems that recapitulate functional units of human tissues and organs. There is growing evidence that 3D cell arrangement, co-culture of different cell types, and physico-chemical cues lead to improved predictive power.

Innovations in preclinical biology: ex vivo engineering of a human kidney tissue microperfusion system.

Kidney disease is a public health problem that affects more than 20 million people in the US adult population, yet little is understood about the impact of kidney disease on drug disposition. Consequently there is a critical need to be able to model the human kidney and other organ systems, to improve our understanding of drug efficacy, safety, and toxicity, especially during drug development. The kidneys in general, and the proximal tubule specifically, play a central role in the elimination of xenobiotics.

Simultaneous 3D imaging of morphology and nanoparticle distribution in single cells with the Cell-CT technology.

The Cell-CT is an optical projection tomography microscope (OPTM) developed for high resolution 3D imaging of single cells based on absorption stains and brightfield microscopy. In this study we demonstrate the use of the Cell-CT in multi-color mode for simultaneous imaging of cellular 3D morphology and the 3D distribution of nanoparticle clusters in the cytoplasm. The ability to image cellular processes in relation to cellular compartments with a non-fluorescence 3D technology opens new perspectives for molecular research.

Three-dimensional imaging of single isolated cell nuclei using optical projection tomography.

A method is presented for imaging single isolated cell nuclei in 3D, employing computed tomographic image reconstruction. The system uses a scanning objective lens to create an extended depth-of-field (DOF) image similar to a projection or shadowgram. A microfabricated inverted v-groove allows a microcapillary tube to be rotated with sub-micron precision, and refractive index matching within 0.

Direct measurement of single synthetic vertebrate thick filament elasticity using nanofabricated cantilevers.

Thick filaments are generally thought to be effectively inextensible. Here we use novel nanofabricated cantilevers to carry out the first direct force-elongation measurements on single vertebrate thick filaments. Cantilevers are ideal for these experiments: force ranges are from pico- to micronewtons, specimens can be visualized during the experiment, and attachment surfaces are in the same plane as the filament.

Fluorescence anisotropy near-field scanning optical microscopy (FANSOM): a new technique for nanoscale microviscometry.

A near-field scanning optical microscope system was implemented and adapted for nanoscale steady-state fluorescence anisotropy measurement. The system as implemented can resolve approximately 0.1 cP microviscosity variations with a resolution of 250 nm laterally in the near field, or approximately 10 microm when employed in a vertical scanning mode.