Technology applications Semiannual project report, 1 Jun. - 30 Nov. 1970
Biomedical technology applications and operational description of Application Team Program
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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.
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Chiral DOTA chelators as an improved platform for biomedical imaging and therapy applications
Despite established clinical utilisation, there is an increasing need for safer, more inert gadolinium-based contrast agents, and for chelators that react rapidly with radiometals. Here we report the syntheses of a series of chiral DOTA chelators and their corresponding metal complexes and reveal properties that transcend the parent DOTA compound. We incorporated symmetrical chiral substituents around the tetraaza ring, imparting enhanced rigidity to the DOTA cavity, enabling control over the range of stereoisomers of the lanthanide complexes. The Gd chiral DOTA complexes are shown to be orders of magnitude more inert to Gd release than [GdDOTA]¯. These compounds also exhibit very-fast water exchange rates in an optimal range for high field imaging. Radiolabeling studies with (Cu-64/Lu-177) also demonstrate faster labelling properties. These chiral DOTA chelators are alternative general platforms for the development of stable, high relaxivity contrast agents, and for radiometal complexes used for imaging and/or therapy.
60 APPLIED LIFE SCIENCES↗
TH-CD-207B-07: Noise Modeling of Single Photon Avalanche Diode (SPAD) for Photon Counting CT Applications
Purpose: Silicon photomultiplier (SiPM) has recently emerged as a promising photodetector for biomedical imaging applications. Due to its high multiplication gain (comparable to PMT), fast timing, low cost and compactness, it is considered a good candidate for photon counting CT. Dark noise is a limiting factor which impacts both energy resolution and detection dynamic range. Our goal is to develop a comprehensive model for noise sources for SiPM sensors. Methods: The physical parameters used in this work were based upon a test SPAD fabricated in 130nm CMOS process. The SPAD uses an n+/p-well junction, which is isolated from the p-substrate by a deep n-well junction. Inter-avalanche time measurement was used to record the time interval between two adjacent avalanche pulses. After collecting 1×106 counts, the histogram was obtained and multiple exponential fitting process was used to extract the lifetime associated with the traps within the bandgap. Results: At room temperature, the breakdown voltage of the SPAD is ∼11.4V and shows a temperature coefficient of 7.7mV/°C. The dark noise of SPAD increases with both the excess biasing voltage and temperature. The primary dark counts from the model were validated against the measurement results. A maximum relative error of 8.7% is observed at 20 °C with an excess voltage of 0.5V. The probabilities of after-pulsing are found to be dependent of both temperature and excess voltage. With 0.5V excess voltage, the after-pulsing probability is 63.5% at - 30 °C and drops to ∼6.6% at 40 °C. Conclusion: A comprehensive noise model for SPAD sensor was proposed. The model takes into account of static, dynamic and statistical behavior of SPADs. We believe that this is the first SPAD circuit simulation model that includes the band-to-band tunneling dark noise contribution and temporal dependence of the after-pulsing probability.
46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗
Size-separation of silver nanoparticles using sucrose gradient centrifugation
Size and shape distributions of nanoparticles can drastically contribute to the overall properties of nanoparticles, thereby influencing their interaction with different chemotherapeutic molecules, biological organisms and or materials and cell types. Therefore, to exploit the proper use of nanoparticles for various biomedical and biosensor applications, it is important to obtain well-separated monodispersed nanoparticles. However, gaining precise control over the morphological characteristics of nanoparticles during their synthesis is often a challenging task. Consequently, post-synthesis separation of nanoparticles is necessary. In the present study, we demonstrate the successful one-pot post-synthesis separation of anisotropic silver nanoparticles to near modispersities using sucrose density gradient sedimentation. The separation of the nanoparticles was evidenced based on optical confirmation, and spectrophotometric and transmission electron microscopy measurements. Our results clearly demonstrate the facile separation of anisotropic silver nanoparticles using sucrose density gradient sedimentation and can enable the use of nanoparticles for various biomedical applications.
77 NANOSCIENCE AND NANOTECHNOLOGY↗
Replacing non-biomedical concepts improves embedding of biomedical concepts
Embeddings are semantically meaningful representations of words in a vector space, commonly used to enhance downstream machine learning applications. Traditional biomedical embedding techniques often replace all synonymous words representing biological or medical concepts with a unique token, ensuring consistent representation and improving embedding quality. However, the potential impact of replacing non-biomedical concept synonyms has received less attention. Embedding approaches often employ concept replacement to replace concepts that span multiple words, such as non-small-cell lung carcinoma, with a single concept identifier (e.g., D002289). Also, all synonyms of each concept are merged into the same identifier. Here, we additionally leveraged WordNet to identify and replace sets of non-biomedical synonyms with their most common representatives. This combined approach aimed to reduce embedding noise from non-biomedical terms while preserving the integrity of biomedical concept representations. We applied this method to 1,055 biomedical concept sets representing molecular signatures or medical categories and assessed the mean pairwise distance of embeddings with and without non-biomedical synonym replacement. A smaller mean pairwise distance was interpreted as greater intra-cluster coherence and higher embedding quality. Embeddings were generated using the Word2Vec algorithm applied to a corpus of 10 million PubMed abstracts. Our results demonstrate that the addition of non-biomedical synonym replacement reduced the mean intra-cluster distance by an average of 8%, suggesting that this complementary approach enhances embedding quality. Future work will assess its applicability to other embedding techniques and downstream tasks. Python code implementing this method is provided under an open-source license.
algorithms↗
Applicability Analysis of Validation Evidence for Biomedical Computational Models
Computational modeling has the potential to revolutionize medicine the way it transformed engineering. However, despite decades of work, there has only been limited progress to successfully translate modeling research to patient care. One major difficulty which often occurs with biomedical computational models is an inability to perform validation in a setting that closely resembles how the model will be used. For example, for a biomedical model that makes in vivo clinically relevant predictions, direct validation of predictions may be impossible for ethical, technological, or financial reasons. Unavoidable limitations inherent to the validation process lead to challenges in evaluating the credibility of biomedical model predictions. Therefore, when evaluating biomedical models, it is critical to rigorously assess applicability, that is, the relevance of the computational model, and its validation evidence to the proposed context of use (COU). However, there are no well-established methods for assessing applicability. In this paper, we present a novel framework for performing applicability analysis and demonstrate its use with a medical device computational model. The framework provides a systematic, step-by-step method for breaking down the broad question of applicability into a series of focused questions, which may be addressed using supporting evidence and subject matter expertise. The framework can be used for model justification, model assessment, and validation planning. While motivated by biomedical models, it is relevant to a broad range of disciplines and underlying physics. Finally, the proposed applicability framework could help overcome some of the barriers inherent to validation of, and aid clinical implementation of, biomedical models.
97 MATHEMATICS AND COMPUTING↗
An unsteady flow of magnetic nanoparticles as drug carrier suspended in micropolar fluid through a porous tapered arterial stenosis under non-uniform magnetic field and periodic body acceleration
A mathematical model has been developed for pulsatile flow of blood through a tapered arterial stenosis in a porous medium under the influence of non-uniform magnetic field and periodic body acceleration treating blood as micropolar fluid carrying iron oxide nanoparticles. The governing equations of the system are solved numerically using finite difference schemes. The effects of stenotic height, taper angle, micropolar parameters, magnetic field, porosity, pulsatility, and magnetic nanoparticles on the flow of blood are analysed, and the results are represented graphically. It is significant to note that the flow parameters such as wall shear stress and flow resistance increase with increase in stenotic height, tapering parameter, magnetic field, pulsatile Reynolds number, time period, particle concentration, and particle mass parameters. Wall shear stress decreases with the increasing values of coupling number and it shows opposite behaviour in the case of flow resistance. Also increase in Darcy number leads to decrease in wall shear stress and flow resistance. The significance of treating blood as micropolar fluid is that the rotation of particles is taken into account. Cardiovascular diseases occur mainly due to abnormal blood flow in the arteries. To normalize the blood flow in the arteries, analysis of parameters involved in the study is essential. Hence, the present study has various applications in biomedical sciences. The effects of nanoparticles on blood flow analysed in the study have significant applications in delivery of drugs for treating cancer.
62 RADIOLOGY AND NUCLEAR MEDICINE↗
An organic dye with very large Stokes-shift and broad tunability of fluorescence: Potential two-photon probe for bioimaging and ultra-sensitive solid-state gas sensor
Light-emitting nonlinear optical molecules, especially those with large Stokes shifts and broad tunability of their emission wavelength, have attracted considerable attention for various applications including biomedical imaging and fluorescent sensors. However, most fluorescent chromophores have only limited potential for such applications due to small Stokes shifts, narrow tunability of fluorescence emissions, and small optical nonlinearity in highly polar solvents. In this work, we demonstrate that a two-photon absorbing stilbene chromophore exhibits a large two-photon absorption action cross-section (ηδ = 320 GM) in dimethylsulfoxide (DMSO) and shows broad fluorescence tunability (125 nm) by manipulating the polarity of the surrounding medium. Importantly, a very large Stokes shift of up to 227 nm is achieved in DMSO. Thanks to these features, this chromophore can be utilized as a two-photon probe for bioimaging applications and in an ultrasensitive solid-state gas detector.
71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗
Effect of shells on photoluminescence of aqueous CdTe quantum dots
Graphical abstract: Size-tunable CdTe coated with several shells using an aqueous solution synthesis. CdTe/CdS/ZnS quantum dots exhibited high PL efficiency up to 80% which implies the promising applications for biomedical labeling. - Highlights: • CdTe quantum dots were fabricated using an aqueous synthesis. • CdS, ZnS, and CdS/ZnS shells were subsequently deposited on CdTe cores. • Outer ZnS shells provide an efficient confinement of electron and hole inside the QDs. • Inside CdS shells can reduce the strain on the QDs. • Aqueous CdTe/CdS/ZnS QDs exhibited high stability and photoluminescence efficiency of 80%. - Abstract: CdTe cores with various sizes were fabricated in aqueous solutions. Inorganic shells including CdS, ZnS, and CdS/ZnS were subsequently deposited on the cores through a similar aqueous procedure to investigate the effect of shells on the photoluminescence properties of the cores. In the case of CdTe/CdS/ZnS quantum dots, the outer ZnS shell provides an efficient confinement of electron and hole wavefunctions inside the quantum dots, while the middle CdS shell sandwiched between the CdTe core and ZnS shell can be introduced to obviously reduce the strain on the quantum dots because the lattice parameters of CdS is situated at the intermediate-level between those of CdTe and ZnS. In comparison with CdTe/ZnS core–shell quantum dots, the as-prepared water-soluble CdTe/CdS/ZnS quantum dots in our case can exhibit high photochemical stability and photoluminescence efficiency up to 80% in an aqueous solution, which implies the promising applications in the field of biomedical labeling.
36 MATERIALS SCIENCE↗
Boosting production yield of biomedical peptides
Nuclear magnetic resonance (NMR) technique is employed to monitor synthesis of biomedical peptides. Application of NMR technique may improve production yields of insulin, ACTH, and growth hormones, as well as other synthesized biomedical peptides.
Manatt, S. L.↗
Potential medical applications of TAE
In cooperation with scientists in the University of Washington Medical School, a microcomputer-based image processing system for quantitative microscopy, called DMD1 (Digital Microdensitometer 1) was constructed. In order to make DMD1 transportable to different hosts and image processors, we have been investigating the possibility of rewriting the lower level portions of DMD1 software using Transportable Applications Executive (TAE) libraries and subsystems. If successful, we hope to produce a newer version of DMD1, called DMD2, running on an IBM PC/AT under the SCO XENIX System 5 operating system, using any of seven target image processors available in our laboratory. Following this implementation, copies of the system will be transferred to other laboratories with biomedical imaging applications. By integrating those applications into DMD2, we hope to eventually expand our system into a low-cost general purpose biomedical imaging workstation. This workstation will be useful not only as a self-contained instrument for clinical or research applications, but also as part of a large scale Digital Imaging Network and Picture Archiving and Communication System, (DIN/PACS). Widespread application of these TAE-based image processing and analysis systems should facilitate software exchange and scientific cooperation not only within the medical community, but between the medical and remote sensing communities as well.
Fahy, J. Ben↗
Advances in metal–organic framework-based hydrogel materials: preparation, properties and applications
Although metal–organic frameworks (MOFs) with intriguing physiochemical properties have recently attracted increasing attention of researchers, MOFs have not adequately achieved various applications due to their instability and unsatisfactory processability. Hence, MOF-based composites as well as structurally novel MOFs have been established to solve this challenge. Recently, some efforts have been made for the development of MOF-based hydrogels. They exhibit excellent properties compared to initial MOFs in many ways (e.g., mechanical strength, absorption capacity and total pore volume). In this review, the up-to-date research progress of MOF-based hydrogels will be briefly summarized. Here, we mainly focus on expounding the classification of MOF-based hydrogels and their related synergistic effects. As to details, we will provide a conspectus of laconic and latest approaches for the synthesis of MOF-based hydrogels, focusing on composite systems, mechanism research, and stability. In addition, the applications of MOF-based hydrogels have been widely discussed, particularly in the environmental, energy and medical aspects. It is hoped that the detailed description of this review can help researchers working on MOF-based hydrogels to develop more novel composite materials and investigate their wider application.
37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
Design and Analysis of Shape Memory Spring Tires for Martian and Lunar Rover Vehicles
Shape memory alloys (SMAs) have played an important role in various innovative engineering and medical applications, such as aerospace actuators, vibration damping devices, and coronary stents. In applications, shape memory alloys are commonly utilized in two fundamentally different ways: (i) making use of the superelasticity/ pseudoelasticity (SE/PE) phenomena, as in applications in biomedical engineering, and (ii) taking advantages of the shape memory effect (SME), as is used for actuators. Their ability to act in such vastly different capacities is mainly due to their unique capability to recover large amounts of deformation produced by either applied stresses or temperature changes. One recent emerging application in use of SMAs has been in the area of non-pneumatic tire designs for Martian or Lunar roving vehicles. These vehicles require tires that are capable of traversing rugged terrain while withstanding extreme temperatures and atmospheric conditions. Inspired by the flexible wire mesh tires used on three Lunar Roving Vehicle (LRV) missions to the Moon on Apollo 15, 16, and 17, a new compliant tire technology was developed by the NASA Glenn Research Center (GRC) and Goodyear Tire & Rubber, known as the Spring Tire. The Spring Tire consists of several hundred coiled springs woven into a flexible mesh and formed into the shape of a tire. Like the LRV wire mesh tires, the original Spring Tires were made from spring steel and were prone to permanent deformation when undergoing high localized loads. Later, a new iteration of this technology was invented, known as the ‘Superelastic Tire’. This new technology incorporated the use of superelastic SMA springs, which could effectively undergo approximately 30 times more reversible deformation than the steel spring. It also provided even greater durability and allowed for more flexibility in design, such as the use of other structural forms to reduce mass or increase load carrying capacity. Because of the unique nature of both the SMA material and the complex interactions between the springs, designing Spring Tires for a specific application requires extensive effort. Historically, design decisions have relied on full-scale empirical testing; however, this is very expensive and time consuming, especially when multiple iterations are needed. Therefore, developing a large-scale, robust, and predictive numerical model entailing complex spring interactions and the shape memory material behavior within a tire construct is the first essential step towards a successful design program. The current work focuses on implementation of the user-defined Shape Memory Alloy (SMA) model, otherwise known as SMA-GVIPs, in the Finite Element analysis (FEA) program ABAQUS for large-scale simulations of the GRC-developed Spring Tires made of SMA. The novelty of this work lies in the thorough, detail-oriented, and computationally efficient finite element analysis of full-scale SMA tires. A well-thought material characterization plan followed by model validation and a systemic sensitivity study on SMA tires has never been reported in the previous literature. The main objective of this study is to help the team improve and optimize the structural design of the SMA tires through in-depth numerical analysis and sensitivity studies. Various design variables (wire diameter, coil diameter, pitch, bead angle, and number of springs) were varied to study their influence on the global load-displacement response of the tire construct. A detailed investigation of the three-dimensional stress states was also carried out to enhance our understanding of the local changes as the tire goes through global deformation. It was concluded that a robust numerical model with a good predictive capability, together with a thoughtfully crafted sensitivity study can result in improved design iterations required to reach a desired tire performance while, significantly reducing manufacturing, labor and testing expenses. A summary of the Finite Element (FE) model construction will be presented together with a description of the user-defined SMA model, characterization process, experimental results, model validation, and numerical sensitivity study results.
shape memory alloys↗
Biomedical Polar Research Workshop Minutes
This workshop was conducted to provide a background of NASA and National Science Foundation goals, an overview of previous and current biomedical research, and a discussion about areas of potential future joint activities. The objectives of the joint research were: (1) to develop an understanding of the physiological, psychological, and behavioral alterations and adaptations to extreme environments of the polar regions; (2) to ensure the health, well-being, and performance of humans in these environments; and (3) to promote the application of biomedical research to improve the quality of life in all environments.
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Femtosecond laser three-dimensional micro- and nanofabrication
The rapid development of the femtosecond laser has revolutionized materials processing due to its unique characteristics of ultrashort pulse width and extremely high peak intensity. The short pulse width suppresses the formation of a heat-affected zone, which is vital for ultrahigh precision fabrication, whereas the high peak intensity allows nonlinear interactions such as multiphoton absorption and tunneling ionization to be induced in transparent materials, which provides versatility in terms of the materials that can be processed. More interestingly, irradiation with tightly focused femtosecond laser pulses inside transparent materials makes three-dimensional (3D) micro- and nanofabrication available due to efficient confinement of the nonlinear interactions within the focal volume. Additive manufacturing (stereolithography) based on multiphoton absorption (two-photon polymerization) enables the fabrication of 3D polymer micro- and nanostructures for photonic devices, micro- and nanomachines, and microfluidic devices, and has applications for biomedical and tissue engineering. Subtractive manufacturing based on internal modification and fabrication can realize the direct fabrication of 3D microfluidics, micromechanics, microelectronics, and photonic microcomponents in glass. These microcomponents can be easily integrated in a single glass microchip by a simple procedure using a femtosecond laser to realize more functional microdevices, such as optofluidics and integrated photonic microdevices. The highly localized multiphoton absorption of a tightly focused femtosecond laser in glass can also induce strong absorption only at the interface of two closely stacked glass substrates. Consequently, glass bonding can be performed based on fusion welding with femtosecond laser irradiation, which provides the potential for applications in electronics, optics, microelectromechanical systems, medical devices, microfluidic devices, and small satellites. This review paper describes the concepts and principles of femtosecond laser 3D micro- and nanofabrication and presents a comprehensive review on the state-of-the-art, applications, and the future prospects of this technology.
71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗
Proceedings of Synthetic Biology: Engineering, Evolution and Design (SEED) Conference 2015
Synthetic Biology is an emerging discipline that seeks to accelerate the process of engineering biology. As such, the tools are broadly applicable to application areas, including chemicals and biofuels, materials, medicine and agriculture. A characteristic of the field is to look holistically at cellular design, from sensing and genetic circuitry to the manipulation of cellular processes and actuators, to controlling metabolism, to programming multicellular behaviors. Further, the types of cells that are manipulated are broad, from in vitro systems to microbes and fungi to mammalian and plant cells and living animals. Many of the projects in synthetic biology seek to move biochemical functions across organisms. The field is highly interdisciplinary with faculty and students spread across departments that focus on engineering (biological, chemical, electrical, mechanical, civil, computer science) and basic science (biology and systems biology, chemistry, physics). While there have been many one-off workshops and meeting on synthetic biology, the 2014 Synthetic Biology: Engineering, Evolution and Design (SEED) was the first of an annual conference series that serves as a reliable place to pull together the involved disciplines in order to organize and exchange advances in the science and technology in the field. Further, the SEED conferences have a strong focus on industry, with many companies represented and actively participating. A number of these companies have started major efforts in synthetic biology including large companies (e.g., Pfizer, Novartis, Dow, Dupont, BP, Total), smaller companies have recently gone public (e.g., Amyris, Gevo, Intrexon), and many start-ups (e.g., Teslagen, Refactored Materials, Pivot, Genomatica). There are a number of loosely affiliated Synthetic Biology Centers, including ones at MIT, Boston University, UCSD, UCSF, UC-Berkeley, Imperial College, Oxford, and ETH. SEED 2015 will serve as the primary meeting at which international synthetic biology centers and related infrastructure (synthesis/software/foundries) meet to discuss technology, standards, and education. SEED2015 will be the second in an annual series of meeting held to bring researchers from industry and academia in the area of Synthetic Biology. The first SEED conference was highly successful, attracting 285 attendees with varying backgrounds from academia, industry and government. The SEED series provides leadership in the development of the field of synthetic biology and serves to broaden the participants in the field by appealing to broad sectors in industry and providing a means for young investigators and those outside of the field to participate. Further, the series closely integrates with groups such as the SBCC to provide a means by which the synthetic biology community can communicate with policy makers. Further, we will pursue making the meeting the center for the exchange of educational materials as centers for synthetic biology emerge globally. Proceedings will be published each year in the journal ACS Synthetic Biology. After each SEED meeting, surveys are distributed to assess the success of the conference and to help guide changes year-to-year. The diverse application areas further extend the expertise needed from people in areas such as plant biology, agriculture and soil science, environmental science, medicine, and the chemical industry. These areas could have a widespread impact on society in a number of ways. For example, the CRISPR/Cas9 system that serves to immunize bacteria from phage has provided the fundamental chemistry that is used to edit the genomes of diverse organisms, including human stem cells, crop plants, and livestock animals.
09 BIOMASS FUELS↗
Continuous injection synthesis of indium arsenide quantum dots emissive in the short-wavelength infrared
With the emergence of applications based on short-wavelength infrared light, indium arsenide quantum dots are promising candidates to address existing shortcomings of other infrared-emissive nanomaterials. However, III–V quantum dots have historically struggled to match the high-quality optical properties of II–VI quantum dots. Here we present an extensive investigation of the kinetics that govern indium arsenide nanocrystal growth. Based on these insights, we design a synthesis of large indium arsenide quantum dots with narrow emission linewidths. We further synthesize indium arsenide-based core-shell-shell nanocrystals with quantum yields up to 82% and improved photo- and long-term storage stability. We then demonstrate non-invasive through-skull fluorescence imaging of the brain vasculature of murine models, and show that our probes exhibit 2–3 orders of magnitude higher quantum yields than commonly employed infrared emitters across the entire infrared camera sensitivity range. Finally, we anticipate that these probes will not only enable new biomedical imaging applications, but also improved infrared nanocrystal-LEDs and photon-upconversion technology.
37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
Data-Driven and Multiscale Modeling of DNA-Templated Dye Aggregates
Dye aggregates are of interest for excitonic applications, including biomedical imaging, organic photovoltaics, and quantum information systems. Dyes with large transition dipole moments (μ) are necessary to optimize coupling within dye aggregates. Extinction coefficients (ε) can be used to determine the μ of dyes, and so dyes with a large ε (>150,000 M –1 cm –1 ) should be engineered or identified. However, dye properties leading to a large ε are not fully understood, and low-throughput methods of dye screening, such as experimental measurements or density functional theory (DFT) calculations, can be time-consuming. In order to screen large datasets of molecules for desirable properties (i.e., large ε and μ), a computational workflow was established using machine learning (ML), DFT, time-dependent (TD-) DFT, and molecular dynamics (MD). ML models were developed through training and validation on a dataset of 8802 dyes using structural features. A Classifier was developed with an accuracy of 97% and a Regressor was constructed with an R2 of above 0.9, comparing between experiment and ML prediction. Using the Regressor, the ε values of over 18,000 dyes were predicted. The top 100 dyes were further screened using DFT and TD-DFT to identify 15 dyes with a μ relative to a reference dye, pentamethine indocyanine dye Cy5. Two benchmark MD simulations were performed on Cy5 and Cy5.5 dimers, and it was found that MD could accurately capture experimental results. The results of this study exhibit that our computational workflow for identifying dyes with a large μ for excitonic applications is effective and can be used as a tool to develop new dyes for excitonic applications.
77 NANOSCIENCE AND NANOTECHNOLOGY↗