A laser pointer driven microheater for precise local heating and conditional gene regulation in vivo. Microheater driven gene regulation in zebrafish

Background - Tissue heating has been employed to study a variety of biological processes, including the study of genes that control embryonic development. Conditional regulation of gene expression is a particularly powerful approach for understanding gene function. One popular method for mis-expressing a gene of interest employs heat-inducible heat shock protein (hsp) promoters. Global heat shock of hsp-promoter-containing transgenic animals induces gene expression throughout all tissues, but does not allow for spatial control. Local heating allows for spatial control of hsp-promoter-driven transgenes, but methods for local heating are cumbersome and variably effective. Results - We describe a simple, highly controllable, and versatile apparatus for heating biological tissue and other materials on the micron-scale. This microheater employs micron-scale fiber optics and uses an inexpensive laser-pointer as a power source. Optical fibers can be pulled on a standard electrode puller to produce tips of varying sizes that can then be used to reliably heat 20-100 μm targets. We demonstrate precise spatiotemporal control of hsp70l:GFP transgene expression in a variety of tissue types in zebrafish embryos and larvae. We also show how this system can be employed as part of a new method for lineage tracing that would greatly facilitate the study of organogenesis and tissue regulation at any time in the life cycle. Conclusion - This versatile and simple local heater has broad utility for the study of gene function and for lineage tracing. This system could be used to control hsp-driven gene expression in any organism simply by bringing the fiber optic tip in contact with the tissue of interest. Beyond these uses for the study of gene function, this device has wide-ranging utility in materials science and could easily be adapted for therapeutic purposes in humans

Optical biopsy identification and grading of gliomas using label-free visible resonance Raman spectroscopy.

Glioma is one of the most refractory types of brain tumor. Accurate tumor boundary identification and complete resection of the tumor are essential for glioma removal during brain surgery. We present a method based on visible resonance Raman (VRR) spectroscopy to identify glioma margins and grades. A set of diagnostic spectral biomarkers features are presented based on tissue composition changes revealed by VRR. The Raman spectra include molecular vibrational fingerprints of carotenoids, tryptophan, amide I/II/III, proteins, and lipids. These basic in situ spectral biomarkers are used to identify the tissue from the interface between brain cancer and normal tissue and to evaluate glioma grades. The VRR spectra are also analyzed using principal component analysis for dimension reduction and feature detection and support vector machine for classification. The cross-validated sensitivity, specificity, and accuracy are found to be 100%, 96.3%, and 99.6% to distinguish glioma tissues from normal brain tissues, respectively. The area under the receiver operating characteristic curve for the classification is about 1.0. The accuracies to distinguish normal, low grade (grades I and II), and high grade (grades III and IV) gliomas are found to be 96.3%, 53.7%, and 84.1% for the three groups, respectively, along with a total accuracy of 75.1%. A set of criteria for differentiating normal human brain tissues from normal control tissues is proposed and used to identify brain cancer margins, yielding a diagnostic sensitivity of 100% and specificity of 71%. Our study demonstrates the potential of VRR as a label-free optical molecular histopathology method used for in situ boundary line judgment for brain surgery in the margins

NASA SBIR abstracts of 1990 phase 1 projects

The research objectives of the 280 projects placed under contract in the National Aeronautics and Space Administration (NASA) 1990 Small Business Innovation Research (SBIR) Phase 1 program are described. The basic document consists of edited, non-proprietary abstracts of the winning proposals submitted by small businesses in response to NASA's 1990 SBIR Phase 1 Program Solicitation. The abstracts are presented under the 15 technical topics within which Phase 1 proposals were solicited. Each project was assigned a sequential identifying number from 001 to 280, in order of its appearance in the body of the report. The document also includes Appendixes to provide additional information about the SBIR program and permit cross-reference in the 1990 Phase 1 projects by company name, location by state, principal investigator, NASA field center responsible for management of each project, and NASA contract number

NONINVASIVE MULTIMODAL DIFFUSE OPTICAL IMAGING OF VULNERABLE TISSUE HEMODYNAMICS

Measurement of tissue hemodynamics provides vital information for the assessment of tissue viability. This thesis reports three noninvasive near-infrared diffuse optical systems for spectroscopic measurements and tomographic imaging of tissue hemodynamics in vulnerable tissues with the goal of disease diagnosis and treatment monitoring. A hybrid near-infrared spectroscopy/diffuse correlation spectroscopy (NIRS/DCS) instrument with a contact fiber-optic probe was developed and utilized for simultaneous and continuous monitoring of blood flow (BF), blood oxygenation, and oxidative metabolism in exercising gastrocnemius. Results measured by the hybrid NIRS/DCS instrument in 37 subjects (mean age: 67 ± 6) indicated that vitamin D supplement plus aerobic training improved muscle metabolic function in older population. To reduce the interference and potential infection risk on vulnerable tissues caused by the contact measurement, a noncontact diffuse correlation spectroscopy/tomography (ncDCS/ncDCT) system was then developed. The ncDCS/ncDCT system employed optical lenses to project limited numbers of sources and detectors on the tissue surface. A motor-driven noncontact probe scanned over a region of interest to collect boundary data for three dimensional (3D) tomographic imaging of blood flow distribution. The ncDCS was tested for BF measurements in mastectomy skin flaps. Nineteen (19) patients underwent mastectomy and implant-based breast reconstruction were measured before and immediately after mastectomy. The BF index after mastectomy in each patient was normalized to its baseline value before surgery to get relative BF (rBF). Since rBF values in the patients with necrosis (n = 4) were significantly lower than those without necrosis (n = 15), rBF levels can be used to predict mastectomy skin flap necrosis. The ncDCT was tested for 3D imaging of BF distributions in chronic wounds of 5 patients. Spatial variations in BF contrasts over the wounded tissues were observed, indicating the capability of ncDCT in detecting tissue hemodynamic heterogeneities. To improve temporal/spatial resolution and avoid motion artifacts due to a long mechanical scanning of ncDCT, an electron-multiplying charge-coupled device based noncontact speckle contrast diffuse correlation tomography (scDCT) was developed. Validation of scDCT was done by imaging both high and low BF contrasts in tissue-like phantoms and human forearms. In a wound imaging study using scDCT, significant lower BF values were observed in the burned areas/volumes compared to surrounding normal tissues in two patients with burn. One limitation in this study was the potential influence of other unknown tissue optical properties such as tissue absorption coefficient (µa) on BF measurements. A new algorithm was then developed to extract both µa and BF using light intensities and speckle contrasts measured by scDCT at multiple source-detector distances. The new algorithm was validated using tissue-like liquid phantoms with varied values of µa and BF index. In-vivo validation and application of the innovative scDCT technique with the new algorithm is the subject of future work

Index to 1984 NASA Tech Briefs, volume 9, numbers 1-4

Short announcements of new technology derived from the R&D activities of NASA are presented. These briefs emphasize information considered likely to be transferrable across industrial, regional, or disciplinary lines and are issued to encourage commercial application. This index for 1984 Tech B Briefs contains abstracts and four indexes: subject, personal author, originating center, and Tech Brief Number. The following areas are covered: electronic components and circuits, electronic systems, physical sciences, materials, life sciences, mechanics, machinery, fabrication technology, and mathematics and information sciences

Pathways to clinical CLARITY: volumetric analysis of irregular, soft, and heterogeneous tissues in development and disease

AbstractThree-dimensional tissue-structural relationships are not well captured by typical thin-section histology, posing challenges for the study of tissue physiology and pathology. Moreover, while recent progress has been made with intact methods for clearing, labeling, and imaging whole organs such as the mature brain, these approaches are generally unsuitable for soft, irregular, and heterogeneous tissues that account for the vast majority of clinical samples and biopsies. Here we develop a biphasic hydrogel methodology, which along with automated analysis, provides for high-throughput quantitative volumetric interrogation of spatially-irregular and friable tissue structures. We validate and apply this approach in the examination of a variety of developing and diseased tissues, with specific focus on the dynamics of normal and pathological pancreatic innervation and development, including in clinical samples. Quantitative advantages of the intact-tissue approach were demonstrated compared to conventional thin-section histology, pointing to broad applications in both research and clinical settings.</jats:p

Small business innovation research. Abstracts of completed 1987 phase 1 projects

Non-proprietary summaries of Phase 1 Small Business Innovation Research (SBIR) projects supported by NASA in the 1987 program year are given. Work in the areas of aeronautical propulsion, aerodynamics, acoustics, aircraft systems, materials and structures, teleoperators and robotics, computer sciences, information systems, spacecraft systems, spacecraft power supplies, spacecraft propulsion, bioastronautics, satellite communication, and space processing are covered

Design, Assembly, and Fabrication of Two-Dimensional Nanomaterials into Functional Biomimetic Device Systems

Diverse functioning biosystems in nature have inspired us and offered unique opportunities in developing novel concepts as well as new class of materials and devices. The design of bioinspired functional materials with tailored properties for actuation, sensing, electronics, and communication has enabled synthetic devices to mimic natural behavior. Among which, artificial muscle and electronic skin that enable to sense and respond to various environmental stimuli in a human-like way have been widely recognized as a significant step toward robotics applications. Polymer materials have previously been dominant in fabricating such functional biomimetic devices owing to their soft nature. However, lacking multifunctionality, handling difficulty, and other setbacks have limited their practical applications. Recently, versatile and high-performance two-dimensional (2D) materials such as graphene and its derivatives have been studied and proven as promising alternatives in this area. In this chapter, we highlight the recent efforts on fabrication and assembly of 2D nanomaterials into functional biomimetic systems. We discuss the structure-function relationships for the development of 2D materials–based biomimetic devices, their tailoring property features, and their variety of applications. We start with a brief introduction of artificial functional biomimetic materials and devices, then summarize some key 2D materials–based systems, including their fabrication, properties, advantages and demonstrations, and finally present concluding remarks and outlook

Fiber Optic-Based Pressure Sensing Surface for Skin Health Management in Prosthetic and Rehabilitation Interventions

Applied physic

NASA SBIR abstracts of 1991 phase 1 projects

The objectives of 301 projects placed under contract by the Small Business Innovation Research (SBIR) program of the National Aeronautics and Space Administration (NASA) are described. These projects were selected competitively from among proposals submitted to NASA in response to the 1991 SBIR Program Solicitation. The basic document consists of edited, non-proprietary abstracts of the winning proposals submitted by small businesses. The abstracts are presented under the 15 technical topics within which Phase 1 proposals were solicited. Each project was assigned a sequential identifying number from 001 to 301, in order of its appearance in the body of the report. Appendixes to provide additional information about the SBIR program and permit cross-reference of the 1991 Phase 1 projects by company name, location by state, principal investigator, NASA Field Center responsible for management of each project, and NASA contract number are included