This work was supported in part by the Cancer Prevention and Research Institute of Texas (RP140021-P5), a Julia Jones Matthews Cancer Research Scholar CPRIT research training award (RP140106, CMW), and the National Institutes of Health (P30-CA016672).

NOTE: (Phantom Design) Two 3 ml chambers were machined out of Ultem and fitted with PEEK tubing (1.5875 mm OD and 0.762 mm ID) for injection and exhaust. The Chambers were placed in a 50 ml centrifuge tube filled with water (Figure 1). To avoid signal voids created by bubbles, the chambers and the lines were pre filled with deionized water (dH2O).
1. Solution Preparation
<ol>
	<li>Prepare 1 L buffer solution (81.3 mM Tris pH 7.6, 203.3 mM NaCl). Weigh out 11.38 g Trizma preset crystals pH 7.6 and 11.88 g NaCl and dissolve in 1 L of dH2O.</li>
	<li>Prepare 50 mM NADH solution. Weigh out 17.8 mg of &#946;-nicotinamide adenine dinucleotide (NADH), reduced dipotassium salt and dissolve in 280 &#181;l of the buffer solution that was prepared in step one.</li>
	<li>Prepare 250 U/ml Enzyme solution. Weigh out 78.75 activity units of lactate dehydrogenase (LDH) and dissolve in 315 &#181;l buffer from step one.</li>
	<li>Prepare pyruvic acid mix. Weigh out 21.4 mg Ox063 trityl radical and dissolve in 1.26 g (~1 ml) [1-13C] pyruvic acid.</li>
	<li>Prepare dissolution media (40 mM Tris pH 7.6, 40 mM NaOH, 0.27 mM EDTA and 50 mM NaCl). Weigh out 5.96 g of Trizma preset crystals pH 7.6, 1.6 g of NaOH, 0.1 g ethylenediaminetetraacetic acid disodium salt dehydrate (EDTA) and 2.9 g NaCl and dissolve in 1 L dH2O.</li>
	<li>Prepare 1:10 gadoteridol solution (50 mM). Mix 1 &#181;l of gadoteridol in 9 &#181;l of dH2O. Preparation of 8 M [13C] urea. Weigh out 1.465 5 [13C] urea and dissolve in 3 ml dH2O.</li>
</ol>
2. Preparation of Hyperpolarized Pyruvate
<ol>
	<li>In a sample cup for a Dynamic Nuclear Polarization (DNP) system, pipette 0.3 &#181;l of the gadoteridol solution and 13 mg (~10 &#181;l) of the pyruvic acid solution.</li>
	<li>Briefly stir this mixture in the sample cup with the pipette tip.</li>
	<li>Insert Sample into the DNP system.
	<ol>
		<li>Ensure the door to the DNP system is closed. Begin the sample insertion process by clicking the insert sample button on the DNP system console. On the sample wizard select normal sample and press next.</li>
		<li>Keeping the sample cup vertical gently place the insertion rod over the top of the sample cup. When prompted, open the DNP system and insert the cup into the variable temperature insert (VTI) using the insertion rod.</li>
		<li>Pull on the plunger at the end of the sample insertion rod to release the sample in the variable temperature index. Remove the sample insertion rod from the system and click the next button on the DNP system console.</li>
	</ol>
	</li>
	<li>Initiate the polarization.
	<ol>
		<li>Click the start polarization button on the DNP system console. In the RINMR software type .HYPERSENSENMR to launch polarization monitoring software. Set build up configuration to 1 and press enter. Then click solid build up.</li>
		<li>Set the location and name of the save file. Select the profile for 13-C in the drop down tab on the DNP system console and click next. Check the box to sample during the buildup, set sample time to 300 sec and click finish.</li>
	</ol>
	</li>
	<li>Measure out 3.85 g (~4 ml) of the dissolution media either by volume with a 5 ml syringe or by weight using a scale.</li>
</ol>
3. Preparation of the Enzyme Phantom
<ol>
	<li>Fill a microcentrifuge tube with ~3 ml [13C] urea solution and place it in the 50 ml centrifuge tube. Fill the 50 ml centrifuge tube with dH2O.</li>
	<li>Pre-fill the two enzyme chambers and the lines with dH2O by injecting ~3 ml dH2O into the injection lines of the phantom, taking care to flush any bubbles formed.</li>
	<li>Place the phantom in the center of the magnet with easy access to the injection lines. Ensure that there is some container to catch the liquid that will vent out to the exhaust line.</li>
	<li>Prepare high activity enzyme mixture (17.14 mM NADH, 44.57 U/ml LDH). Mix together 240 &#181;l NADH solution, 125 &#181;l LDH solution and 335 &#181;l buffer and keep in a 3 ml syringe that can be attached to the injection line. 
	NOTE: Once combined with the 500 &#181;l of 40 mM pyruvate from the DNP system, the final phantom volume will be 1.2 ml with concentrations of 16.7 mM Pyruvate, 10 mM NADH, and 26 U/L LDH in a tris buffered solution with pH ~ 7.5.</li>
	<li>Prepare low activity enzyme mixture (17.14 mM NADH 26.79 U/ml LDH) Mix together 240 &#181;l NADH solution, 75 &#181;l LDH solution and 385 &#181;l buffer and keep in a separate 3 ml syringe that can be attached to the injection line. 
	NOTE: Once combined with the 500 &#181;l of 40 mM pyruvate from the DNP system the final phantom volume will be 1.2 ml with concentrations of 16.7 mM Pyruvate, 10 mM NADH, and 15.625 U/L LDH in a tris buffered solution with pH ~ 7.5.</li>
</ol>
4. Run Any Quality Assurance (QA) and Positioning Scans
<ol>
	<li>Initial positioning.
	<ol>
		<li>Load a new FLASH positioning scan in operation mode [1H] TX/RX Volume mode. Change set up dimensions to 2: Spectrometer Control Tool -&#62; Edit GS -&#62; Setup Dimensions -&#62; 2. Press GSP on the Spectrometer Control and move phantom until centered in the magnet. Press STOP then Press GOP on the Spectrometer Control.</li>
	</ol>
	</li>
	<li>Pilot Scan.
	<ol>
		<li>Load a new TriPiolt positioning scan in operation mode [1H] TX/RX Volume mode. Position Slice: Scan Control -&#62; Slice Tool- &#62; move slices (hold M key click and drag; select slice to move with the slice package slider).</li>
		<li>Wobble 1H Coil: Spectrometer Control Tool - &#62; Acq -&#62; Wobble. Tune and match 1H coil behind the magnet and press STOP. While holding the shift key press the traffic light on the scan control window.</li>
	</ol>
	</li>
</ol>
5. Radial Echo Planar Spectral Imaging Scan Setup
<ol>
	<li>Load a new radial echo planar spectroscopic imaging (radEPSI) scan in operation mode [13C] TX/RX Volume mode. Position Slice: Slice Tool on the Scan control and move slices (hold M key click and drag; select slice to move with the slice package slider).</li>
	<li>Wobble 13C Coil by clicking Spectrometer Control Tool - &#62; Acq -&#62; Wobble. Set the receiver gain to 1,000-2,000 on the Spectrometer.</li>
	<li>Perform the final system check. Depending on the sequence, observe carbon 13 signal from the urea chamber in a scout protocol. 
	NOTE: This ensures that the system is set up properly before beginning the irreversible dissolution process.</li>
</ol>
6. Run Dissolution
<ol>
	<li>When the pyruvate has attained &#62;90% polarization (~ 1 hr), the solutions and phantom are ready, and the scan is configured click the run dissolution button on the DNP system console.</li>
	<li>When prompted move the dissolution stick into its operating position and inject dissolution media. Close the DNP system and click the finished button on the DNP system console. Move dissolution stick back to resting position when prompted then click finish.</li>
	<li>When the DNP system delivers the hyperpolarized pyruvate (~ 2 min after heating starts) withdraw 500 &#181;l of the pyruvate solution into each the high and low enzyme concentration solution syringes. Slowly (~10 sec) inject each syringe into an injection line. 
	NOTE: Scanning could have been initiated prior to injection or anytime up to 3 min post injection depending on the scan protocol used.</li>
</ol>
7. Image Processing
NOTE: This phantom was designed for use with many imaging strategies. See Figure 2, as an example of how the rad-EPSI images were processed using Matlab.
<ol>
	<li>Load raw data from the fid file. Reshape the data to match the number of projections, read out points, echoes and account for data stored as real and imaginary pairs. Separate out the even and odd echo points.</li>
	<li>Fourier transform either the even or odd echoes along the echo dimensions. Visually identify the frequency bands for pyruvate and lactate. For simplicity the absolute value of the spectrum was used.</li>
	<li>Separate each metabolite band and Fourier transform along the frequency encode direction to yield isolated sinograms for each metabolite. Inverse radon transform the separate sinograms to produce image of either lactate or pyruvate.</li>
</ol>

<ol>
	<li>Merritt, M. E., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Hyperpolarized+13C+allows+a+direct+measure+of+flux+through+a+single+enzyme-catalyzed+step+by+NMR.">Hyperpolarized 13C allows a direct measure of flux through a single enzyme-catalyzed step by NMR.</a> Proceedings of the National Academy of Sciences of the United States of America 104. 104, 19773-19777 (2007).</li><li>Rodrigues, T. B., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Magnetic+resonance+imaging+of+tumor+glycolysis+using+hyperpolarized+13C-labeled+glucose.">Magnetic resonance imaging of tumor glycolysis using hyperpolarized 13C-labeled glucose.</a> Nature medicine. 20, 93-97 (2014).</li><li>Day, S. E., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Detecting+tumor+response+to+treatment+using+hyperpolarized+13C+magnetic+resonance+imaging+and+spectroscopy.">Detecting tumor response to treatment using hyperpolarized 13C magnetic resonance imaging and spectroscopy.</a> Nature medicine. 13, 1382-1387 (2007).</li><li>Keshari, K. R., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Hyperpolarized+13C+dehydroascorbate+as+an+endogenous+redox+sensor+for+in+vivo+metabolic+imaging.">Hyperpolarized 13C dehydroascorbate as an endogenous redox sensor for in vivo metabolic imaging.</a> Proceedings of the National Academy of Sciences of the United States of America. 108, 18606-18611 (2011).</li><li>Gallagher, F. A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Magnetic+resonance+imaging+of+pH+in+vivo+using+hyperpolarized+13C-labelled+bicarbonate.">Magnetic resonance imaging of pH in vivo using hyperpolarized 13C-labelled bicarbonate.</a> Nature. 453, 940-943 (2008).</li><li>Larson, P. E., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Investigation+of+tumor+hyperpolarized+[1-13C]-pyruvate+dynamics+using+time-resolved+multiband+RF+excitation+echo-planar+MRSI.">Investigation of tumor hyperpolarized [1-13C]-pyruvate dynamics using time-resolved multiband RF excitation echo-planar MRSI.</a> Magnetic resonance in medicine : official journal of the Society of Magnetic Resonance in Medicine / Society of Magnetic Resonance in Medicine. 63, 582-591 (2010).</li><li>Cunningham, C. 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Publication of this video-article is supported by Bruker corporation.

Real time imaging of hyperpolarized metabolites has many unique challenges for sequence design, validation, and quality control. The ability to resolve spatiotemporal and spectral heterogeneity offers substantial clinical potential but precludes QA and validation methods associated with conventional MRI. Complex imaging sequences or reconstruction algorithms can have subtle dependencies that render them difficult to characterize or validate outside of the imaging experiment. Biological heterogeneity and other practical c...

The clinical impact of hyperpolarized magnetic resonance imaging (MRI) of 13C-labeled compounds is critically dependent on its ability to measure chemical conversion rates through real time magnetic resonance spectroscopy and spectroscopic imaging1-5. During sequence development and verification, dynamic chemical conversion is generally achieved through in vivo or in vitro models6-9 that offer limited control and reproducibility. For robust testing and quality assurance, a more controlled system that preserves the chemical conversion endemic to this measurement would be preferred. We outline a method to achieve this conversion in a reproducible manner using a dynamic single enzyme phantom.
Most studies with hyperpolarized 13C agents focus on imaging hyperpolarized substrates in a functioning biological environment. This is the obvious choice if the goal is to study biological processes or determine potential for impact on clinical care. However, if characterization of some measurement system or data processing algorithm is desired, biological models have numerous drawbacks such as inherent spatial and temporal variability10. However, conventional static phantoms lack the chemical conversion that drives the primary clinical interest in MRI of hyperpolarized substrates, and cannot be used to characterize detection of conversion rates or other dynamic parameters11. Using a single enzyme system we can provide controllable and reproducible chemical conversion, enabling rigorous examination of dynamic imaging strategies.
This system is directed to investigators who are developing imaging strategies for hyperpolarized substrates and wish to characterize performance for comparison against alternate approaches. If static measurements are the desired endpoint then static 13C-labled metabolite phantoms will suffice11. On the other end if more complex biological characterization is critical to the method (delivery, cellular density, etc.) then actual biological models will be needed12-14. This system is ideal for assessment of imaging strategies that aim to provide a quantitative measure of apparent chemical conversion rates.

<table border="0" cellpadding="0" cellspacing="0" width="1045">
	<tbody>
		<tr height="21">
			<td height="21" style="height:21px;width:259px;">BioSpect 7T</td>
			<td style="width:147px;">Bruker</td>
			<td style="width:195px;">BioSpec 70/30 USR</td>
			<td style="width:445px;">7 Tesla Pre-Clinical MRI Scanner</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:259px;">HyperSense</td>
			<td style="width:147px;">Oxford Instruments</td>
			<td style="width:195px;">Hypersense DNP Polarizer</td>
			<td>Dynamic Nuclear Polarizer for MRI agents</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:259px;">1-13C-Pyrvic Acid</td>
			<td style="width:147px;">Sigma Aldrich</td>
			<td style="width:195px;">677175</td>
			<td>Carbon 13 labled neat pyruvic acid</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:259px;">Trityl Radical</td>
			<td style="width:147px;">GE Healthcare</td>
			<td style="width:195px;">OX063</td>
			<td>Free radical used in Dynamic Nuclear Polarization</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:259px;">NaOH</td>
			<td style="width:147px;">Sigma Aldrich</td>
			<td style="width:195px;">S8045</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:259px;">EDTA</td>
			<td style="width:147px;">Sigma Aldrich</td>
			<td style="width:195px;">E6758</td>
			<td style="width:445px;">Ethylenediaminetetraacetic acid</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:259px;">LDH</td>
			<td style="width:147px;">Worthingthon</td>
			<td style="width:195px;">LS002755</td>
			<td>Lactate Dehydrogenase from rabbit muscle</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:259px;">NADH</td>
			<td style="width:147px;">Sigma Aldrich</td>
			<td style="width:195px;">N4505</td>
			<td>&#946;-Nicotinamide adenine dinucleotide, reduced dipotassium salt</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:259px;">Trizma</td>
			<td style="width:147px;">Sigma Aldrich</td>
			<td style="width:195px;">T7943</td>
			<td>Trizma&#174;&#160;Pre-set crystals</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:259px;">NaCl</td>
			<td style="width:147px;">Sigma Aldrich</td>
			<td style="width:195px;">S7653</td>
			<td></td>
		</tr>
	</tbody>
</table>

use of a multi-compartment dynamic single enzyme phantom for studies of hyperpolarized magnetic resonance agents

Imaging of hyperpolarized substrates by magnetic resonance shows great clinical promise for assessment of critical biochemical processes in real time. Due to fundamental constraints imposed by the hyperpolarized state, exotic imaging and reconstruction techniques are commonly used. A practical system for characterization of dynamic, multi-spectral imaging methods is critically needed. Such a system must reproducibly recapitulate the relevant chemical dynamics of normal and pathological tissues. The most widely utilized substrate to date is hyperpolarized [1-13C]-pyruvate for assessment of cancer metabolism. We describe an enzyme-based phantom system that mediates the conversion of pyruvate to lactate. The reaction is initiated by injection of the hyperpolarized agent into multiple chambers within the phantom, each of which contains varying concentrations of reagents that control the reaction rate. Multiple compartments are necessary to ensure that imaging sequences faithfully capture the spatial and metabolic heterogeneity of tissue. This system will aid the development and validation of advanced imaging strategies by providing chemical dynamics that are not available from conventional phantoms, as well as control and reproducibility that is not possible in vivo.

Slice-selective 2D images were acquired using a snapshot radEPSI sequence. Metabolite images were reconstructed using filtered back projection. The metabolite images were well aligned with proton images, as seen in Figure 2. In this system hyperpolarized lactate signal can only be generated from the enzymatic conversion of hyperpolarized pyruvate. In Figure 4, the bottom chamber, with higher LDH concentration, has a stronger lactate and weaker pyruvate si...

Watch this Scientific Journal Video about Use of a Multi-compartment Dynamic Single Enzyme Phantom for Studies of Hyperpolarized Magnetic Resonance Agents at JoVE.com

Use of a Multi-compartment Dynamic Single Enzyme Phantom for Studies of Hyperpolarized Magnetic Resonance Agents

A multi-compartment dynamic phantom is used to simulate some biology of interest for metabolic studies using hyperpolarized magnet resonance agents.

Imaging of hyperpolarized substrates by magnetic resonance shows great clinical promise for assessment of critical biochemical processes in real time. Due ...

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6.8K Views.  University of Texas M.D. Anderson Cancer Center. A multi-compartment dynamic phantom is used to simulate some biology of interest for metabolic studies using hyperpolarized magnet resonance agents.

Video: Use of a Multi-compartment Dynamic Single Enzyme Phantom for Studies of Hyperpolarized Magnetic Resonance Agents

Hyperpolarized Xenon for NMR and MRI Applications

Nuclear magnetic resonance (NMR) spectroscopy and imaging (MRI) suffer from intrinsic low sensitivity because even strong external magnetic fields of ~10 T generate only a small detectable net-magnetization of the sample at room temperature 1. Hence, most NMR and MRI applications rely on the detection of molecules at relative high concentration (e.g., water for imaging of biological tissue) or require excessive acquisition times. This limits our ability to exploit the very useful molecular specificity of NMR signals for many biochemical and medical applications. However, novel approaches have emerged in the past few years: Manipulation of the detected spin species prior to detection inside the NMR/MRI magnet can dramatically increase the magnetization and therefore allows detection of molecules at much lower concentration 2.
Here, we present a method for polarization of a xenon gas mixture (2-5% Xe, 10% N2, He balance) in a compact setup with a ca. 16000-fold signal enhancement. Modern line-narrowed diode lasers allow efficient polarization 7 and immediate use of gas mixture even if the noble gas is not separated from the other components. The SEOP apparatus is explained and determination of the achieved spin polarization is demonstrated for performance control of the method.
The hyperpolarized gas can be used for void space imaging, including gas flow imaging or diffusion studies at the interfaces with other materials 8,9. Moreover, the Xe NMR signal is extremely sensitive to its molecular environment 6. This enables the option to use it as an NMR/MRI contrast agent when dissolved in aqueous solution with functionalized molecular hosts that temporarily trap the gas 10,11. Direct detection and high-sensitivity indirect detection of such constructs is demonstrated in both spectroscopic and imaging mode.

The production of hyperpolarized xenon by means of spin exchange optical pumping (SEOP) is described. This method yields a ~10000-fold enhancement of the nuclear spin polarization of Xe-129 and has applications in nuclear magnetic resonance spectroscopy and imaging. Examples of gas phase and solution state experiments are given.

Nuclear magnetic resonance (NMR) spectroscopy and imaging (MRI) suffer from intrinsic low sensitivity because even strong external magnetic fields of ~10 ...

Analysis of Contact Interfaces for Single GaN Nanowire Devices

Single GaN nanowire (NW) devices fabricated on SiO2 can exhibit a strong degradation after annealing due to the occurrence of void formation at the contact/SiO2 interface. This void formation can cause cracking and delamination of the metal film, which can increase the resistance or lead to a complete failure of the NW device. In order to address issues associated with void formation, a technique was developed that removes Ni/Au contact metal films from the substrates to allow for the examination and characterization of the contact/substrate and contact/NW interfaces of single GaN NW devices. This procedure determines the degree of adhesion of the contact films to the substrate and NWs and allows for the characterization of the morphology and composition of the contact interface with the substrate and nanowires. This technique is also useful for assessing the amount of residual contamination that remains from the NW suspension and from photolithographic processes on the NW-SiO2 surface prior to metal deposition. The detailed steps of this procedure are presented for the removal of annealed Ni/Au contacts to Mg-doped GaN NWs on a SiO2 substrate.

A technique was developed that removes Ni/Au contact metal films from their substrate to allow for the examination and characterization of the contact/substrate and contact/NW interfaces of single GaN nanowire devices.

Single GaN nanowire (NW) devices fabricated on SiO2 can exhibit  a strong degradation after annealing due to the  occurrence of void formation at the ...

Scalable Nanohelices for Predictive Studies and Enhanced 3D Visualization

Spring-like materials are ubiquitous in nature and of interest in nanotechnology for energy harvesting, hydrogen storage, and biological sensing applications.&#160; For predictive simulations, it has become increasingly important to be able to model the structure of nanohelices accurately.&#160; To study the effect of local structure on the properties of these complex geometries one must develop realistic models.&#160; To date, software packages are rather limited in creating atomistic helical models.&#160; This work focuses on producing atomistic models of silica glass (SiO2) nanoribbons and nanosprings for molecular dynamics (MD) simulations. Using an MD model of &#8220;bulk&#8221; silica glass, two computational procedures to precisely create the shape of nanoribbons and nanosprings are presented.&#160; The first method employs the AWK programming language and open-source software to effectively carve various shapes of silica nanoribbons from the initial bulk model, using desired dimensions and parametric equations to define a helix.&#160; With this method, accurate atomistic silica nanoribbons can be generated for a range of pitch values and dimensions.&#160; The second method involves a more robust code which allows flexibility in modeling nanohelical structures.&#160; This approach utilizes a C++ code particularly written to implement pre-screening methods as well as the mathematical equations for a helix, resulting in greater precision and efficiency when creating nanospring models.&#160; Using these codes, well-defined and scalable nanoribbons and nanosprings suited for atomistic simulations can be effectively created.&#160; An added value in both open-source codes is that they can be adapted to reproduce different helical structures, independent of material.&#160; In addition, a MATLAB graphical user interface (GUI) is used to enhance learning through visualization and interaction for a general user with the atomistic helical structures.&#160; One application of these methods is the recent study of nanohelices via MD simulations for mechanical energy harvesting purposes.

Accurate modeling of nanohelical structures is important for predictive simulation studies leading to novel nanotechnology applications.&#160; Currently, software packages and codes are limited in creating atomistic helical models.&#160; We present two procedures designed to create atomistic nanohelical models for simulations, and a graphical interface to enhance research through visualization.

Spring-like materials are ubiquitous in nature and of interest in nanotechnology for energy harvesting, hydrogen storage, and biological sensing ...

High-Sensitivity Nuclear Magnetic Resonance at Giga-Pascal Pressures: A New Tool for Probing Electronic and Chemical Properties of Condensed Matter under Extreme Conditions

Nuclear Magnetic Resonance (NMR) is one of the most important techniques for the study of condensed matter systems, their chemical structure, and their electronic properties. The application of high pressure enables one to synthesize new materials, but the response of known materials to high pressure is a very useful tool for studying their electronic structure and developing theories. For example, high-pressure synthesis might be at the origin of life; and understanding the behavior of small molecules under extreme pressure will tell us more about fundamental processes in our universe. It is no wonder that there has always been great interest in having NMR available at high pressures. Unfortunately, the desired pressures are often well into the Giga-Pascal (GPa) range and require special anvil cell devices where only very small, secluded volumes are available. This has restricted the use of NMR almost entirely in the past, and only recently, a new approach to high-sensitivity GPa NMR, which has a resonating micro-coil inside the sample chamber, was put forward. This approach enables us to achieve high sensitivity with experiments that bring the power of NMR to Giga-Pascal pressure condensed matter research. First applications, the detection of a topological electronic transition in ordinary aluminum metal and the closing of the pseudo-gap in high-temperature superconductivity, show the power of such an approach. Meanwhile, the range of achievable pressures was increased tremendously with a new generation of anvil cells (up to 10.1 GPa), that fit standard-bore NMR magnets. This approach might become a new, important tool for the investigation of many condensed matter systems, in chemistry, geochemistry, and in physics, since we can now watch structural changes with the eyes of a very versatile probe.

Nuclear magnetic resonance is one of the most important spectroscopic tools. Here, the development of a new approach under high pressure, currently up to 10.1 GPa, is presented. This opens a new window into condensed matter physics and chemistry, where high-pressure research is of great importance.

Nuclear Magnetic Resonance (NMR) is one of the most important techniques for the study of condensed matter systems, their chemical structure, and their ...

A Method for Studying the Temperature Dependence of Dynamic Fracture and Fragmentation

The dynamic fracture of a body is a late-stage phenomenon typically studied under simplified conditions, in which a sample is deformed under uniform stress and strain rate. This can be produced by evenly loading the inner surface of a cylinder. Due to the axial symmetry, as the cylinder expands the wall is placed into a tensile hoop stress that is uniform around the circumference. While there are various techniques to generate this expansion such as explosives, electromagnetic drive, and existing gas gun techniques they are all limited in the fact that the sample cylinder must be at room temperature. We present a new method using a gas gun that facilitates experiments on cylinders from 150 K to 800 K with a consistent, repeatable loading. These highly diagnosed experiments are used to examine the effect of temperature on the fracture mechanisms responsible for failure, and their resulting influence on fragmentation statistics. The experimental geometry employs a steel ogive located inside the target cylinder, with the tip located about halfway in. A single stage light gas gun is then used to launch a polycarbonate projectile into the cylinder at 1,000 m/sec-1. The projectile impacts and flows around the rigid ogive, driving the sample cylinder from the inside. The use of a non-deforming ogive insert allows us to install temperature control hardware inside the rear of the cylinder. Liquid nitrogen (LN2) is used for cooling and a resistive high current load for heating. Multiple channels of upshifted photon Doppler velocimetry (PDV) track the expansion velocity along the cylinder enabling direct comparison to computer simulations, while High speed imaging is used to measure the strain to failure. The recovered cylinder fragments are also subject to optical and electron microscopy to ascertain the failure mechanism.

Fracture and fragmentation are late stage phenomena in dynamic loading scenarios and are typically studied using explosives. We present a technique for driving expansion using a gas gun which uniquely enables control of both loading rate and sample temperature.

The dynamic fracture of a body is a late-stage phenomenon typically studied under simplified conditions, in which a sample is deformed under uniform ...

A Cost-effective and Reliable Method to Predict Mechanical Stress in Single-use and Standard Pumps

Pumps are mainly used when transferring sterile culture broths in biopharmaceutical and biotechnological production processes. However, during the pumping process shear forces occur which can lead to qualitative and/or quantitative product loss. To calculate the mechanical stress with limited experimental expense, an oil-water emulsion system was used, whose suitability was demonstrated for drop size detections in bioreactors1. As drop breakup of the oil-water emulsion system is a function of mechanical stress, drop sizes need to be counted over the experimental time of shear stress investigations. In previous studies, the inline endoscopy has been shown to be an accurate and reliable measurement technique for drop size detections in liquid/liquid dispersions. The aim of this protocol is to show the suitability of the inline endoscopy technique for drop size measurements in pumping processes. In order to express the drop size, the Sauter mean diameter d32 was used as the representative diameter of drops in the oil-water emulsion. The results showed low variation in the Sauter mean diameters, which were quantified by standard deviations of below 15%, indicating the reliability of the measurement technique.

Shear stress investigations on an oil-water emulsion system result in drop breakup over the experimental time. To count drop sizes in pumping processes, the suitability of inline endoscopy was successfully demonstrated in this protocol.

Pumps are mainly used when transferring sterile culture broths in biopharmaceutical and biotechnological production processes. However, during the pumping ...

Design and Use of a Full Flow Sampling System (FFS) for the Quantification of Methane Emissions

The use of natural gas continues to grow with increased discovery and production of unconventional shale resources. At the same time, the natural gas industry faces continued scrutiny for methane emissions from across the supply chain, due to methane&#39;s relatively high global warming potential (25-84x that of carbon dioxide, according to the Energy Information Administration). Currently, a variety of techniques of varied uncertainties exists to measure or estimate methane emissions from components or facilities. Currently, only one commercial system is available for quantification of component level emissions and recent reports have highlighted its weaknesses.
In order to improve accuracy and increase measurement flexibility, we have designed, developed, and implemented a novel full flow sampling system (FFS) for quantification of methane emissions and greenhouse gases based on transportation emissions measurement principles. The FFS is a modular system that consists of an explosive-proof blower(s), mass airflow sensor(s) (MAF), thermocouple, sample probe, constant volume sampling pump, laser based greenhouse gas sensor, data acquisition device, and analysis software. Dependent upon the blower and hose configuration employed, the current FFS is able to achieve a flow rate ranging from 40 to 1,500 standard cubic feet per minute (SCFM). Utilization of laser-based sensors mitigates interference from higher hydrocarbons (C2+). Co-measurement of water vapor allows for humidity correction. The system is portable, with multiple configurations for a variety of applications ranging from being carried by a person to being mounted in a hand drawn cart, on-road vehicle bed, or from the bed of utility terrain vehicles (UTVs). The FFS is able to quantify methane emission rates with a relative uncertainty of &#177; 4.4%. The FFS has proven, real world operation for the quantification of methane emissions occurring in conventional and remote facilities.

Design and Use of a Full Flow Sampling System FFS for the Quantification of Methane Emissions

We have designed, developed, and implemented a novel full flow sampling system (FFS) for quantification of methane emissions and greenhouse gases from across the natural gas supply chain.

The use of natural gas continues to grow with increased discovery and production of unconventional shale resources. At the same time, the natural gas ...

A Modular Microfluidic Technology for Systematic Studies of Colloidal Semiconductor Nanocrystals

Colloidal semiconductor nanocrystals, known as quantum dots (QDs), are a rapidly growing class of materials in commercial electronics, such as light emitting diodes (LEDs) and photovoltaics (PVs). Among this material group, inorganic/organic perovskites have demonstrated significant improvement and potential towards high-efficiency, low-cost PV fabrication due to their high charge carrier mobilities and lifetimes. Despite the opportunities for perovskite QDs in large-scale PV and LED applications, the lack of fundamental and comprehensive understanding of their growth pathways has inhibited their adaptation within continuous nanomanufacturing strategies. Traditional flask-based screening approaches are generally expensive, labor-intensive, and imprecise for effectively characterizing the broad parameter space and synthesis variety relevant to colloidal QD reactions. In this work, a fully autonomous microfluidic platform is developed to systematically study the large parameter space associated with the colloidal synthesis of nanocrystals in a continuous flow format. Through the application of a novel translating three-port flow cell and modular reactor extension units, the system may rapidly collect fluorescence and absorption spectra across reactor lengths ranging 3 - 196 cm. The adjustable reactor length not only decouples the residence time from the velocity-dependent mass transfer, it also substantially improves the sampling rates and chemical consumption due to the characterization of 40 unique spectra within a single equilibrated system. Sample rates may reach up to 30,000 unique spectra per day, and the conditions cover 4 orders of magnitude in residence times ranging 100 ms - 17 min. Further applications of this system would substantially improve the rate and precision of the material discovery and screening in future studies. Detailed within this report are the system materials and assembly protocols with a general description of the automated sampling software and offline data processing.

Detailed herein are the operation and assembly protocols of a modular microfluidic screening platform for the systematic characterization of colloidal semiconductor nanocrystal syntheses. Through fully adjustable system arrangements, highly efficient spectra collection may be carried out across 4 orders of magnitude reaction time scales within a mass transfer-controlled sampling space.

Colloidal semiconductor nanocrystals, known as quantum dots (QDs), are a rapidly growing class of materials in commercial electronics, such as light ...

Fabrication of Magnetic Nanostructures on Silicon Nitride Membranes for Magnetic Vortex Studies Using Transmission Microscopy Techniques

Electron and x-ray magnetic microscopies allow for high-resolution magnetic imaging down to tens of nanometers. However, the samples need to be prepared on transparent membranes which are very fragile and difficult to manipulate. We present processes for the fabrication of samples with magnetic micro- and nanostructures with spin configurations forming magnetic vortices suitable for Lorentz transmission electron microscopy and magnetic transmission x-ray microscopy studies. The samples are prepared on silicon nitride membranes and the fabrication consists of a spin coating, UV and electron-beam lithography, the chemical development of the resist, and the evaporation of the magnetic material followed by a lift-off process forming the final magnetic structures. The samples for the Lorentz transmission electron microscopy consist of magnetic nanodiscs prepared in a single lithography step. The samples for the magnetic x-ray transmission microscopy are used for time-resolved magnetization dynamic experiments, and magnetic nanodiscs are placed on a waveguide which is used for the generation of repeatable magnetic field pulses by passing an electric current through the waveguide. The waveguide is created in an extra lithography step.

A protocol for the fabrication of magnetic micro- and nanostructures with spin configurations forming magnetic vortices suitable for transmission electron microscopy (TEM) and magnetic transmission x-ray microscopy (MTXM) studies is presented.

Electron and x-ray magnetic microscopies allow for high-resolution magnetic imaging down to tens of nanometers. However, the samples need to be prepared ...

A 100 KW Class Applied-field Magnetoplasmadynamic Thruster

Applied-field magnetoplasmadynamic thrusters (AF-MPD thrusters) are hybrid accelerators in which electromagnetic and gas dynamic processes accelerate plasma to high speed; they have considerable potential for future space applications with the significant advantages of high specific impulse and thrust density. In this paper, we present a series of protocols for designing and manufacturing a 100 kW class of AF-MPD thruster with water-cooling structures, a 130 V maximum discharge voltage, a 800 A maximum discharge current, and a 0.25 T maximum strength of magnetic field. A hollow tantalum tungsten cathode acts as the only propellant inlet to inhibit the radial discharge, and it is positioned axially at the rear of the anode in order to relieve anode starvation. A cylindrical divergent copper anode is employed to decrease anode power deposition, where the length has been reduced to decrease the wall-plasma connecting area. Experiments utilized a vacuum system that can achieve a working vacuum of 0.01 Pa for a total propellant mass flow rate lower than 40 mg/s and a target thrust stand. The thruster tests were carried out to measure the effects of the working parameters such as propellant flow rates, the discharge current, and the strength of applied magnetic field on the performance and to allow appropriate analysis. The thruster could be operated continuously for significant periods of time with little erosion on the hollow cathode surface. The maximum power of the thruster is 100 kW, and the performance of this water-cooled configuration is comparable with that of thrusters reported in the literature.

The goal of this protocol is to introduce the design of a 100 kW class applied-field magnetoplasmadynamic thruster and relevant experimental methods.

Applied-field magnetoplasmadynamic thrusters (AF-MPD thrusters) are hybrid accelerators in which electromagnetic and gas dynamic processes accelerate ...