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Biomedical subjects

David D Nolte

Publications and source records attributed to David D Nolte.

4 recordsLinked to original sources

Fourier-domain holographic optical coherence imaging of tumor spheroids and mouse eye.

Fourier-domain holography (FDH) has several advantages over image-domain holography for optical coherence imaging of tissue. Writing the hologram in the Fourier plane significantly reduces background arising from reference light scattered from the photorefractive holographic film. The ability to use FDH is enhanced by the use of a diffuse target, such as scattering tissue, rather than specular targets, because the broader angular distribution from diffuse targets is transformed into a relatively uniform distribution in the Fourier plane. We demonstrate significantly improved performance for Fourier-domain optical coherence imaging on rat osteogenic sarcoma tumor spheroids and mouse eye. The sensitivity is documented at -95 dB.

Algorithms↗

Holographic optical coherence imaging of rat osteogenic sarcoma tumor spheroids.

Holographic optical coherence imaging is a full-frame variant of coherence-domain imaging. An optoelectronic semiconductor holographic film functions as a coherence filter placed before a conventional digital video camera that passes coherent (structure-bearing) light to the camera during holographic readout while preferentially rejecting scattered light. The data are acquired as a succession of en face images at increasing depth inside the sample in a fly-through acquisition. The samples of living tissue were rat osteogenic sarcoma multicellular tumor spheroids that were grown from a single osteoblast cell line in a bioreactor. Tumor spheroids are nearly spherical and have radial symmetry, presenting a simple geometry for analysis. The tumors investigated ranged in diameter from several hundred micrometers to over 1 mm. Holographic features from the tumors were observed in reflection to depths of 500-600 microm with a total tissue path length of approximately 14 mean free paths. The volumetric data from the tumor spheroids reveal heterogeneous structure, presumably caused by necrosis and microcalcifications characteristic of some human avascular tumors.

Animals↗

Fourier-domain holography in photorefractive quantum-well films.

Fourier-domain holography (FDH) is investigated as a candidate for holographic optical coherence imaging to produce real-time images of structure inside living tissue and turbid media. The effects of spatial filtering, the background intensity distributions, and the role of background noise in determining dynamic range are evaluated for both FDH and image-domain holography (IDH). The grating washout effect in FDH (edge enhancement) is removed by use of a vibrating diffuser that consequently improves the image quality. By comparing holographic images and background images of FDH and IDH we show that FDH provides a higher dynamic range and a higher image quality than IDH for this specific application of imaging diffuse volumetric objects.

Equipment Design↗

High-speed label-free detection by spinning-disk micro-interferometry.

Spinning-disk interferometers are a new class of analytic sensors to detect immobilized biomolecules with high speed and high sensitivity. The disks are composed of a large number of surface-normal self-referencing interferometers, analogous to an optical CD, but operating on the principle of microdiffraction quadrature that achieves sensitive linear detection of bound molecules. The surface-normal structures have a small footprint of only 20 microm each, allowing potential integration to over a million interferometric elements per disk. We have fabricated interferometric microstructures on silicon and on dielectric mirror disks to demonstrate the basic principles of the BioCD. We have detected the presence of immobilized anti-mouse IgG and the specific binding of 10 femtomol of mouse IgG at a sampling rate of 100 kilo-samples/s, while also demonstrating negligible non-specific binding. This technique provides a label-free method that could potentially screen hundreds to thousands of proteins per disk.

Biosensing Techniques↗