Diverter Valve Research Articles

The effect of β-cyclodextrin on liquid chromatography/electrospray-mass spectrometry analysis of hydrophobic drug molecules

Cyclodextrins (CDs) are widely used in the pharmaceutical industry for their capability of improving bioavailability, solubility, or stability of drugs via the formation of soluble inclusion complexes. CDs have also been widely used in various chemical analysis methods. In this work, liquid chromatography/electrospray mass spectrometry (LC/ESI-MS) analysis for four different drugs (imipramine, desipramine, propranolol, and naproxen) that form inclusion complexes with CDs was performed in the presence and absence of β-CD. These drugs are subject to nonspecific adsorption when brought into contact with plastics, such as HPLC tubing, sample collection and preparation apparatus, etc. Inclusion of the CD in the samples reduces this nonspecific adsorption due to competitive complex formation between the CD and the analyte. ESI-MS ion intensities increased when β-CD was included in the sample with concentrations up to 1% (w:v), with a diverter valve installed post LC column. The degree of increased ion signal correlated with the β-cyclodextrin:analyte binding constant. β-CD appeared to elute within the void volume time and was observed in a full spectrum scan among the different analyte samples with up to 0.01% β-CD injected directly to the LC/MS system with the diverter valve switched inline with the mass spectrometer. The use of the diverter valve allowed for direct injection of samples containing up to 1% β-CD to the LC/MS without any deterioration of analyte ion signal.

Simultaneous LC–MS–MS determination of cyclosporine A, tacrolimus, and sirolimus in whole blood as well as mycophenolic acid in plasma using common pretreatment procedure

The purpose of the study was to develop rapid and simple procedure for simultaneous determination of cyclosporine A (CsA), tacrolimus (TCR), and sirolimus (SIR) in whole blood and mycophenolic acid (MPA) in plasma. Ascomycin (ASCO), cyclosporine D (CsD), and desmethoxysirolimus (DMSIR) were used as internal standards (IS) for TCR, CsA and MPA, and SIR, respectively. In the method development, six-level blood calibrators were used for CsA (range 47–1725 ng/ml), TCR (range 2.1–38.8 ng/ml), and SIR (range 2.4–39.6 ng/ml). Four-level calibrators were used for MPA (range 0.15–5.48 μg/ml). Four levels of quality control (QC) standards were used for blood samples, together with two levels of QC standards in plasma. All QC standards and calibrators were obtained from commercial sources. Sample preparation based on precipitation of 50 μl of sample in zinc sulfate–methanol–acetonitrile mixture containing IS, followed by centrifugation. HPLC was performed on ChromSpher π column, 30 mm × 3 mm, in ballistic gradient of ammonium formate buffer–methanol at 0.8 ml flow rate. Following gradient elution profile was applied: 0–1.2 min at 30% methanol (divert valve to waste), 1.21–3.1 min 97% methanol (divert valve to detector), 3.11–3.7 min 30% methanol (divert valve to waste). ESI–MS–MS (MRM) was done on TSQ Quantum instrument with ESI source in positive ion mode. Ammoniated adducts of protonated molecules were used as precursor ions for all analytes but MPA. For this compound sodium adduct was used. Following transitions were monitored: for CsA m/z 1220–1203; for CsD 1234–1217; for SIR 931.6–864.5 and 882.6; for DMSIR 902–834.5; for TCR 821.5–768.5 and 785.5; for ASCO 809.5–756; for MPA 343–211.6; for MPA-glucuronide 514–306 and 211.6. The limits of quantitation were: 1 ng/ml for TCR and SIR, 20 ng/ml for CsA, and 0.1 μg/ml for MPA. Post-column infusion experiments showed that no positive or negative peaks appeared after injection of matrix in the elution range of target compounds. General signal suppression caused by matrix ranged from 20–40%, and was caused mainly by zinc sulfate present in deproteinizing solution. Extracted samples were stable for 2 days at 4 °C and for at least 20 days at −20 °C. MPA was fully separated from its glucuronide, which was eluted at around 0.7–0.8 min and directed to the waste. Some mutual cross-contribution of CsD and CsA was observed (below 1%), other IS did not contribute to target compounds and vice versa. Observations of chromatograms from patients taken single therapy demonstrated that possible metabolites of CsA, TCR, or SIR did not interfere with target compounds or IS.

Feasibility of “intermittent” active control of combustion instabilities in liquid fueled combustors using a “smart” fuel injector

This paper describes an experimental investigation of the feasibility of an “intermittent” active control approach for suppressing combustion instabilities in liquid fueled combustors. The developed controller employs a “smart” fuel injector that can modify the spray properties in response to changes in combustor operating conditions. This action weakens or breaks up the coupling between the combustion process and combustor acoustic modes oscillations, thus preventing the excitation of large amplitude instabilities. This approach differs significantly from previously proposed active control methods, both in concept and implementation, as it requires only “intermittent” modification of the combustion process by a single control action as opposed to the continuous action required by most other active control methods. The “smart” fuel injector used in this study consisted of a double-staged, air-assisted atomizer in which counter swirling, primary (inner stage) and secondary (outer stage) air streams were supplied to the injector through separate sets of tangentially oriented orifices. Control of the ratio of air mass flow rates supplied to these two stages, by use of a diverter valve, resulted in significant changes in the spray shape and its axial, tangential, and radial velocity components. This variation in spray properties of the “smart” injector was characterized for different values of the inner to outer air flow rate ratio in cold flow tests with a PDPA system. These results were then correlated with the characteristics of the “intermittently” controlled combustor. Measured quantities included the instability amplitudes, axial dependence of the mean and oscillatory heat release amplitudes, and the characteristics of the recirculation zones, which were all shown to depend on the fuel spray properties. The results of this study demonstrate the feasibility of using “smart” fuel injectors with capabilities for varying the combustion process characteristics to reduce the amplitudes of detrimental combustion instabilities in real engines to acceptable levels.

Molecular Mechanisms of Vascular Calcification

Vascular calcification increasingly afflicts our aging and dysmetabolic population. Once considered a passive process, it has emerged as an actively regulated form of calcified tissue metabolism, resembling the mineralization of endochondral and membranous bone. Executive cell types familiar to bone biologists, osteoblasts, chondrocytes, and osteoclasts, are seen in calcifying macrovascular specimens. Lipidaceous matrix vesicles, with biochemical and ultrastructural "signatures" of skeletal matrix vesicles, nucleate vascular mineralization in diabetes, dyslipidemia, and uremia. Skeletal morphogens (bone morphogenetic protein-2 (BMP) and BMP4 and Wnts) divert aortic mesoangioblasts, mural pericytes (calcifying vascular cells), or valve myofibroblasts to osteogenic fates. Paracrine signals provided by these molecules mimic the epithelial-mesenchymal interactions that induce skeletal development. Vascular expression of pro-osteogenic morphogens is entrained to physiological stimuli that promote calcification. Inflammation, shear, oxidative stress, hyperphosphatemia, and elastinolysis provide stimuli that: (1) promote vascular BMP2/4 signaling and matrix remodeling; and (2) compromise vascular defenses that limit calcium deposition, inhibit osteo/chondrogenic trans-differentiation, and enhance matrix vesicle clearance. In this review, we discuss the biology of vascular calcification. We highlight how aortic fibrofatty tissue expansion (adventitia, valve interstitium), the adventitial-medial vasa, vascular matrix, and matrix vesicle metabolism contribute to the regulation of aortic calcium deposition, with greatest emphasis placed on diabetic vascular disease.

Techbits: Deepwater Heavy-Oil Challenge Extends to Reliable Completions

Optimized sandface and wellbore production-systems technologies intended to maximize both productivity and hydrocarbon recovery in deepwater developments were the focus of a 3-day Applied Technology Workshop (ATW) held in Brazil. Keynote speaker Ricardo Beltrao of Petrobras set the stage for the meeting by giving an overview of the challenges the energy industry is facing to produce heavy oil in deep water and by offering a glimpse of the challenges ahead. Following an agenda in which the majority of time was designated for problem solving, ATW participants heard presentations and discussion by subject matter experts, identified gaps, and then met in groups to categorize issues of concern in the following subject areas: chemicals, sand control, artificial lift, and reservoir. In the area of chemicals, discussion centered on these existing gaps for producers: - For new developments, mechanical devices are available to minimize the necessity for chemical solutions; however, such solutions are not offered on existing wells. - A process to divert scale inhibitor and remove scale in horizontal wells is needed. - A more permanent reduction of permeability to water is required. - Chemicals to prevent emulsion and organic/inorganic deposition need to be formulated. With regard to sand control, gravel packing long horizontal wells in low-fracture-gradient scenarios remains a major concern. Workshop attendees concluded that not only does the industry need to better understand fines migration in the heavy-oil environment, but it must somehow gather and connect all data from completed wells. Sand control should be approached from the standpoint of the entire operation. Of particular interest was the need to address washouts and to correctly estimate the fracture gradient. While low-density proppant plus beta and diverter valves can be used, the issue of cake removal remains. An accurate method of measuring the filter-media opening must be found to handle the mobile fraction of fines in the formation in addition to a means of measuring fines size and quantity. Is it possible to standardize comparative testing of screens, such as laser vs. sieve? A predictive technique would be extremely useful in measuring the impact of produced solids on surface equipment and filters. In an unconsolidated heavy-oil environment, taking a close look at the impact of injection above fracture pressure in gravel-packed wells is key. Currently, there exists a lack of data for injectors and for determining the appropriate method of sand control. It was emphasized that existing models for light-oil scenarios are inaccurate in predicting the potential deposition of asphaltenes and scale in the heavy-oil environment. Dialogue in the artificial-lift arena included whether electrical submersible pumps could handle gas when marginal heavy-oil fields required injection. Also, possible production of sand in flowlines represents a major problem, particularly in ultradeep water. In addition to discussion on aspects of reservoir modeling, sand prediction, and compaction prediction, water-influx and -coning control were deemed essential. Compartmentalization, in which control can be exercised over each segment, offers a solution, but while packers can isolate each single joint, they cannot eliminate water coning. The use of intelligent control devices for monitoring and control was suggested to achieve maximum efficiency.

Dual Parallel Liquid Chromatography/Dual Mass Spectrometry (LC2/MS2) of Bovine Brain Total Lipid Extract

A commercially available bovine brain total lipid extract containing polar and non‐polar lipid fractions has been separated in one analytical run using two high performance liquid chromatography (HPLC) systems in parallel, coupled to dual mass spectrometers, in parallel. The whole extract of bovine brain was separated on normal phase (NP, LC1) and reversed‐phase (Rp, LC2) columns simultaneously, with detection using an ion trap mass spectrometer (MS1) and a tandem mass spectrometer (MS2) coupled to the two HPLC systems, respectively. A single injection was loaded onto an amine column to perform separation of phospholipid components. Non‐polar components, such as triacylglycerols, were unretained on this polar column. Using the diverter valve on the front of the ion trap mass spectrometry (MS1), the bolus of neutral lipids was redirected to a RP liquid chromatography system (LC2) on which the neutral lipids were separated using a second chromatographic system at the same time that the polar lipids were separated on LC1. Electrospray ionization (ESI)‐mass spectrometry (MS) on an ion trap mass spectrometer (MS1), with ammonium formate added as a sheath liquid, was used for analysis of the phospholipids. Electrospray ionization‐mass spectrometry, with ammonium formate incorporated into the solvent system, was used on a tandem mass spectrometer (MS2) for identification of triacylglycerols (TAGs) and other neutral lipids. This dual liquid chromatography/dual mass spectrometry (LC2/MS2) system represents a unified approach for a total lipid analysis in one experiment using a single sample injection.

Improved procedure for the determination of malonaldehyde by gas-chromatography with electron-capture detection as 2,4,6-trichlorophenylhydrazine derivative

A previously described derivatization method using trichlorophenylhydrazine was developed for the estimation of malonaldehyde measured by gas-chromatography (GC) with electron-capture detection. The precision and reliability of the procedure are improved here by the use of methylmalonaldehyde as internal standard and by the introduction of a diverter valve at the end of the capillary column to protect the electron-capture detector, respectively. The method was applied to determine malonaldehyde content in bovine plasma samples.

Design and Uncertainty Analysis for a PVTt Gas Flow Standard.

A new pressure, volume, temperature, and, time (PVTt) primary gas flow standard at the National Institute of Standards and Technology has an expanded uncertainty (k = 2) of between 0.02 % and 0.05 %. The standard spans the flow range of 1 L/min to 2000 L/min using two collection tanks and two diverter valve systems. The standard measures flow by collecting gas in a tank of known volume during a measured time interval. We describe the significant and novel features of the standard and analyze its uncertainty. The gas collection tanks have a small diameter and are immersed in a uniform, stable, thermostatted water bath. The collected gas achieves thermal equilibrium rapidly and the uncertainty of the average gas temperature is only 7 mK (22 × 10−6 T). A novel operating method leads to essentially zero mass change in and very low uncertainty contributions from the inventory volume. Gravimetric and volume expansion techniques were used to determine the tank and the inventory volumes. Gravimetric determinations of collection tank volume made with nitrogen and argon agree with a standard deviation of 16 × 10−6 VT. The largest source of uncertainty in the flow measurement is drift of the pressure sensor over time, which contributes relative standard uncertainty of 60 × 10−6 to the determinations of the volumes of the collection tanks and to the flow measurements. Throughout the range 3 L/min to 110 L/min, flows were measured independently using the 34 L and the 677 L collection systems, and the two systems agreed within a relative difference of 150 × 10−6. Double diversions were used to evaluate the 677 L system over a range of 300 L/min to 1600 L/min, and the relative differences between single and double diversions were less than 75 × 10−6.

High-pressure microfluidic control in lab-on-a-chip devices using mobile polymer monoliths.

We have developed a nonstick polymer formulation for creating moving parts inside of microfluidic channels and have applied the technique to create piston-based devices that overcome several microfluidic flow control challenges. The parts were created bycompletely filling the channels of a glass microfluidic chip with the monomer/ solvent/initiator components of a nonstick photopolymer and then selectively exposing the chip to UV light in order to define mobile pistons (or other quasi-two-dimensional shapes) inside the channels. Stops defined in the substrate prevent the part from flushing out of the device but also provide sealing surfaces so that valves and other flow control devices are possible. Sealing against pressures greater than 30 MPa (4,500 psi) and actuation times less than 33 ms are observed. An on-chip check valve, a diverter valve, and a 10-nL pipet are demonstrated. This valving technology, coupled with high-pressure electrokinetic pumps, should make it possible to create a completely integrated HPLC system on a chip.

Microfluidic valves for flow control at low Reynolds numbers

Fluidics is a technology of generating and controlling fluid flows - preferably without the action of mechanical moving components. Microfluidics perform these tasks in small, typically micron-sized structures. Essential part of almost all microfluidic systems are flow control valves. The basic problem is the low Reynolds number Re: inertial effects used in large-scale fluidics are too small relative to viscous dissipation. New approaches, such as pressure or electrokinetic driving are required. In the subdynamic, viscosity dominated flow regime, Re ceases to be of importance and for pressure-driven valves a new characterisation number was to be introduced. An example of a diverter valve, developed by the author, is described and the meaning of the new dimensionless parameter is demonstrated.

Robust H∞ Control for Linear Systems with Uncertain Parameters and Scheduling Parameters

In this paper, we consider a scheduled robust H∞, control problem via state feedback controllers in linear systems with uncertain parameters and scheduling parameters. Controllers are characterized by parameter dependent Linear Matrix Inequalities (LMIs), and a feasible approach to solving parameter dependent LMIs is proposed. A numerical example of fuel diverter and return valve of turbofun engines is discussed.

Changes in protein inhibitor of neuronal nitric oxide synthase mRNA expression following facial nerve transection

A short RNA with the sequence of the antisense strand of Patisiran has been selected as test material for the investigation of its common impurities using three different two-dimensional liquid chromatography (2D-LC) platforms. On the one hand, a quinine (QN) carbamate-based weak anion-exchange (AX) stationary phase (QN-AX) and a classical C18 reversed phase (RP) stationary phase in ion-pair (IP) mode with tripropylammonium acetate, respectively, have been used in the first dimension (1D) to provide the selectivity for impurities formed during the synthesis of the RNA. In the next step, certain peaks of interest from 1D have been transferred by multiple-heart-cutting (MHC) into a 2D in which an ESI-MS-compatible non-ionpairing RP method has been used for desalting via a diverter valve to remove non-volatile phosphate buffer components and ion-pair agents, respectively. Thus, a sensitive electrospray-ionization quadrupole time of flight mass spectrometry (ESI-TOF-MS) analysis of resolved impurity peaks of the siRNA has become possible under MS-friendly conditions. With both 2D-LC setups, peak purity of the ON has been evaluated by selective comprehensive (high resolution) sampling of the main peak. In a third MHC 2D-LC approach, the QN-AX LC mode was online coupled with the IP-RPLC in the 2D using UV detection. It allows the separation of additional impurities which coeluted in the first dimension. The potential of these methods for comprehensive impurity profiling of ON therapeutics is illustrated and discussed.

Robust Control for V2500 FDRV.

FDRV (Fuel Diverter and Return Valve) is one of the hydraulic servo valves used in V 2500 turbofun engines in order to control fuel temperature. FDRV, currently in production, is manufactured to meet its specification which allows appropriate tolerance. Hence, there are some performance variation of FDRV. Also, performance of FDRV may significantly vary with operating conditions. In order to meet engine control objectives, performance of the FDRV control system is also specified, which includes response time, overshoot, offset, and sensor noise. To satisfy the above requirements, a compensator, which is part of FADEC(Full Authority Digital Engine Control) software, is used. Single compensator which can accommodate specified performance variation of FDRV is required since it is not practical to adjust parameters in the compensator for each FDRV.In this paper, we design a compensator based on H∞ control theory and evaluate its performance by experiments on bench test stand. Here, we do not use adaptive compensator. We consider performance variation due to the manufacturing tolerance as uncertainty of nominal model and variation due to the operating condition as distarbance to nominal model. Then, we synthesize a robust compensator that satisfies the system performance specification under existence of the uncertainty and the disturbance.

Dual-Conduit Layflat Tubing for Water Conveyance and Distribution

Layflat tubing, or flexible pipe, is used for both distribution and conveyance of irrigation water and has many of the advantages of rigid surface irrigation pipe. The tubing described in this article is uniquely constructed with an interior membrane so as to form a dual-conduit tube. This permits the tube to be used both for water conveyance and distribution. Manual, semi-automatic, and fully automatic diverter valves were developed to direct water flow either to one side of the membrane for distribution through outlets in the side of the tube, or to the opposite side of the membrane for water conveyance to the next irrigation set(s). In the conveyance mode, the membrane covers the distribution outlets or gates in the side of the tube. To change irrigation sets manually, the irrigator either pulls or pushes a handle on a diverter valve to change the tubes operating mode. This eliminates manually opening individual gates for the next succeeding set and closing all of the gates of the previous set. Valve and coupler fittings were designed to be easily assembled and disassembled. The tubing system was satisfactorily tested and evaluated on three farms. The tubing was also tested for surge irrigation by controlling an automatic diverter valve with a surge controller.

Quantitative selected ion monitoring processing system: Software and hardware for the automated collection and analysis of selected ion monitoring data acquired for use in pharmacokinetic studies

The Quantitative Selected Ion Monitoring Processing System (QSIMPS) is a collection of software and hardware which was designed with the capacity to analyze 30,600 samples per year in support of pharmacokinetic studies. On a per sample basis, QSIMPS was designed to inject a sample into the GC, control the GC divert valve, collect selected ion monitoring data, identify the peaks for the drug and one metabolite and each compound's reference standard, fit the peaks to a relevant chromatographic model, calculate chromatographic features of merit, calculate the peak heights and ratio of the drug and its reference standard and the metabolite and its reference standard, and, using calibration data, convert the ratio to an amount of drug. On a per tray (batch) basis, QSIMPS was designed to fit all the peak height ratios from the calibration standards to either a linear equation, or a generalized nonlinear isotope dilution equation, report a statistical analysis of the fit, and, using aliquot factors, convert the measured amount of drug into concentrations. On a per project basis, QSIMPS prints reports summarizing statistical data on the calibration standards and the quality assurance samples, and prints reports presenting the concentration data as a function of, for examples, subject, drug treatment, time postdose, etc., along with other ancillary data such as subject sex, weight, species, etc. In addition, QSIMPS can fit the concentration data to a number of common pharmacokinetic model‐derived equations, and report the resulting pharmacokinetic parameters along with a statistical comparison of the parameters.

An Automated Single-Pipe Irrigation System

ABSTRACT AN automated single-pipe system was developed for both water conveyance and distribution to the field. The pipe has a flexible tube liner inside and is equipped with automated diverter valves. The valves direct water either through the flexible tube for conveyance to downstream pipeline sections or to the outside of the tube for distribution to the field through the pipe gates. The system is well suited for automating multiple-set gated pipe systems for both conventional and surge flow irrigation. Head loss coefficients were determined for the valves and the pipeline for both the conveyance and distribution modes. Field installation procedures are described. The cost of the single-pipe system is about 60% of that for an automated double pipe system.

Estimating diverter valve corrections

A new method has been developed for estimating the corrections to be made to the measured time interval for diverter valves used in primary liquid flow measurement facilities. The model relates the mass flowrate, m, to the measured mass of liquid collected and the effective collection time. The effective collection time is the sum of the measured time interval and the diverter valve correction, τ, to be estimated. The diverter valve correction is the adjustment made to the collection time to account for the non-instaneous diversion of the flow between the collection vessel and the reservoir of the flow loop. An auxiliary flow measurement device in the flow pipeline is used to estimate m and an iterative process is used in the estimation of τ. This method gives statistical information on the variability of the performance of the system as indicated by the individual estimates of τ. Experimental data for two diverters used in the US National Bureau of Standards Primary Liquid Flow Measurement Facility are used to illustrate the calculation procedure

Waste Heat Recovery On Multiple Low-Speed Reciprocating Engines

With rising fuel costs, energy conservation has taken on added significance. Installation of waste heat recovery units (WHRU's) on gas turbines is one method used in the past to reduce gas plant fuel consumption. More recently, waste heat recovery on multiple reciprocating compressor engines also has been identified as having energy conservation potential. This paper reviews the development and implementation of a WHRU for multiple low-speed engines at the Katy (TX) gas plant. WHRU's for these engines should be differentiated from high-speed engines and gas turbines in that low-speed engines produce low-frequency, high-amplitude pulsating exhaust. The design of a WHRU system must take this potentially destructive pulsation into account. At Katy, the pulsation forces were measured at high-amplitude frequencies and then used to design a pulsation filter and structural stiffness into the various components of the WHRU to minimize vibration and improve system reliability.

An automatic pneumatic conveying and weight-dispensing system for floor-feeding pellets to pigs

Experiments were carried out to provide data on which to base the design of pneumatic conveying and dispensing systems for pig feeding pellets. From these data an experimental system for conveying either 9·5 mm or 12·7 mm diameter pellets at rates of up to 1·5t/h through 54 mm rigid p.v.c. pipes and fittings was developed. It was a medium pressure system with a maximum working pressure of 70 kN/m 2 and the experiments indicated a maximum practical conveying distance of 300 to 400 m. The dispenser developed for use with the conveying system (1 per pen of up to 20 pigs) employed coil tension springs for weighing to an accuracy of ±2% and both conveying and dispensing were controlled automatically from a central control panel. An automatic control system was developed which could feed a number of circuits from a single feed store using one blower and ancillary conveying equipment. Conventional diverter valves were used to switch from circuit to circuit. Up to ten 1000-pig houses could be supplied by this means.

A UHV bakeable diverter valve

A bakeable valve is described, useful for deviating a gas flow from one output port to the other in a continuous way. The valve is intended for operation below 1 Torr. The prototype was constructed by modifying a Varian model 951-5027 angle valve. The performance is briefly discussed.