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Rhinehart R.R.,Oklahoma State University | Darby M.L.,Principal CMiD Solutions | Wade H.L.,CT Associates Inc.
ISA Transactions | Year: 2011

The editorial section of ISA Transactions deals with the selection of advanced regulatory control (ARC). The editorial deals with a comparison of feedback control strategies, and includes nonlinear and adaptive algorithms along with model predictive control (MPC) in the definition of APC. Adaptive controllers have models or internal learning ability that adapts to the dynamic process data, tracks changes in process dynamics and gain, and uses the models for control action. MPC is the most often considered component of APC and MPC packages include some features, such as SISO or MISO constraint-handling control, linear MIMO Control, and nonlinear MIMO Control. Some of the significant benefits of advanced control include throughput increase, process stability improvement, energy consumption reduction, and increased yield of more valuable products.

Jeon S.,University of Minnesota | Oberreit D.R.,Kanomax FMT | Van Schooneveld G.,CT Associates Inc. | Hogan C.J.,University of Minnesota
Analytical Chemistry | Year: 2016

Despite the importance of examining the formation of nanoparticle-protein conjugates, there is a dearth of routine techniques for nanoparticle-protein conjugate characterization. The most prominent change to a nanoparticle population upon conjugate formation is a shift in the nanoparticle size distribution function. However, commonly employed dynamic light scattering based approaches for size distribution characterization are ineffective for nonmonodisperse samples, and further they are relatively insensitive to size shifts of only several nanometers, which are common during conjugate formation. Conversely, gas phase ion mobility spectrometry (IMS) techniques can be used to reliably examine polydisperse samples, and are sensitive to ∼1 nm size distribution function shifts; the challenge with IMS is to convert nanoparticle-protein conjugates to aerosol particles without bringing about nonspecific aggregation or conjugate formation. Except in limited circumstances, electrospray based aerosolization has proven difficult to apply for this purpose. Here we show that via liquid nebulization (LN) with online, high-flow-rate dilution (with dilution factors up to 10 000) it is possible to aerosolize nanoparticle-protein conjugates, enabling IMS measurements of their conjugate size distribution functions. We specifically employ the LN-IMS system to examine bovine serum albumin binding to gold nanoparticles. Inferred maximum protein surface coverages (∼0.025 nm-2) from measurements are shown to be in excellent agreement with reported values for gold from quartz crystal microbalance measurements. It is also shown that LN-IMS measurements can be used to detect size distribution function shifts on the order of 1 nm, even in circumstances where the size distribution function itself has a standard deviation of ∼5 nm. In total, the reported measurements suggest that LN-IMS is a potentially simple and robust technique for nanoparticle-protein conjugate characterization. © 2016 American Chemical Society.

Jeon S.,University of Minnesota | Oberreit D.R.,Kanomax FMT | Van Schooneveld G.,CT Associates Inc. | Hogan C.J.,University of Minnesota
Analyst | Year: 2016

We apply liquid nebulization (LN) in series with ion mobility spectrometry (IMS, using a differential mobility analyzer coupled to a condensation particle counter) to measure the size distribution functions (the number concentration per unit log diameter) of gold nanospheres in the 5-30 nm range, 70 nm × 11.7 nm gold nanorods, and albumin proteins originally in aqueous suspensions. In prior studies, IMS measurements have only been carried out for colloidal nanoparticles in this size range using electrosprays for aerosolization, as traditional nebulizers produce supermicrometer droplets which leave residue particles from non-volatile species. Residue particles mask the size distribution of the particles of interest. Uniquely, the LN employed in this study uses both online dilution (with dilution factors of up to 104) with ultra-high purity water and a ball-impactor to remove droplets larger than 500 nm in diameter. This combination enables hydrosol-to-aerosol conversion preserving the size and morphology of particles, and also enables higher non-volatile residue tolerance than electrospray based aerosolization. Through LN-IMS measurements we show that the size distribution functions of narrowly distributed but similarly sized particles can be distinguished from one another, which is not possible with Nanoparticle Tracking Analysis in the sub-30 nm size range. Through comparison to electron microscopy measurements, we find that the size distribution functions inferred via LN-IMS measurements correspond to the particle sizes coated by surfactants, i.e. as they persist in colloidal suspensions. Finally, we show that the gas phase particle concentrations inferred from IMS size distribution functions are functions of only of the liquid phase particle concentration, and are independent of particle size, shape, and chemical composition. Therefore LN-IMS enables characterization of the size, yield, and polydispersity of sub-30 nm particles. © The Royal Society of Chemistry 2016.

Leakeas C.L.,Air Force Institute of Technology | Bartell R.J.,Air Force Institute of Technology | Krizo M.J.,Air Force Institute of Technology | Fiorino S.T.,Air Force Institute of Technology | And 2 more authors.
Proceedings of SPIE - The International Society for Optical Engineering | Year: 2010

Laser weapon systems comprise of tiled subapertures are rapidly emerging in the directed energy community. The Air Force Institute of Technology Center for Directed Energy (AFIT/CDE), under sponsorship of the HEL Joint Technology Office has developed performance models of such laser weapon system configurations consisting of tiled arrays of both slab and fiber subapertures. These performance models are based on results of detailed waveoptics analyses conducted using WaveTrain. Previous performance model versions developed in this effort represent system characteristics such as subaperture shape, aperture fill factor, subaperture intensity profile, subaperture placement in the primary aperture, subaperture mutual coherence (piston), subaperture differential jitter (tilt), and beam quality wave-front error associated with each subaperture. The current work is a prerequisite for the development of robust performance models for turbulence and thermal blooming effects for tiled systems. Emphasis is placed on low altitude tactical scenarios. The enhanced performance model developed will be added to AFIT/CDE's HELEEOS parametric one-on-one engagement level model via the Scaling for High Energy Laser and Relay Engagement (SHaRE) toolbox. © 2010 Copyright SPIE - The International Society for Optical Engineering..

Vila L.J.,CT Associates Inc. | Vila L.J.,University of Connecticut | Malla R.B.,University of Connecticut
Journal of Engineering Mechanics | Year: 2016

A series of special percussive drilling devices has been designed by the NASA Jet Propulsion Laboratory and Honeybee Robotics Spacecraft Mechanisms Corporation for exploration of planetary bodies (e.g., Mars). The percussive mechanism of these special drilling devices consists of three main components: ultrasonic horn, free mass, and drill bit/rod. This paper presents the analysis of the interaction between the free mass/striker and the drill rod including the coupled effects of structural vibration; plastic deformation of the rod; repeated impacts; and the support condition of the rod on the contact force, contact duration, and coefficient of restitution. The impact between the free mass and the drill rod is analyzed by means of a modified Hertz force-indentation relation coupled with the structural vibration obtained using the mode superposition method. The material of the striker is considered elastic, while the rod is considered as an elastic perfectly plastic material. A numerical integration scheme, with equilibrium iterations, is implemented to solve the system's equations. It is observed that for both support conditions considered, i.e., fixed and elastic support, the first impact yields the largest plastic deformation, which then decreases as the number of impacts increases. The maximum contact force and the coefficient of restitution are observed to increase with the number of impacts while the duration of contact decreases. Additionally, the effect of the support condition of the rod on the contact force decreases as the number of impacts increases. © 2016 American Society of Civil Engineers.

Viswanathan C.T.,CT Associates Inc.
Bioanalysis | Year: 2012

The concept of microsampling and particularly the dried blood spot methodology has been widely known to the scientific community for considerable time. Yet, there is no formal standard approach available to date for the pharmaceutical community to benefit from, in its regulatory interactions. This article discusses the various aspects of these issues and provides a framework within which a standard set of procedures can be adopted. © 2012 Future Science Ltd.

Albrecht M.,Augustine Biomedical and Design | Gauthier R.L.,Anesthesia Specialty Services | Belani K.,University of Minnesota | Litchy M.,CT Associates Inc. | Leaper D.,University of Cardiff
American Journal of Infection Control | Year: 2011

Background: Forced-air warming (FAW) is widely used to prevent hypothermia during surgical procedures. The airflow from these blowers is often vented near the operative site and should be free of contaminants to minimize the risk of surgical site infection. Popular FAW blowers contain a 0.2-μm rated intake filter to reduce these risks. However, there is little evidence that the efficiency of the intake filter is adequate to prevent airborne contamination emissions or protect the internal air path from microbial contamination buildup. Methods: Five new intake filters were obtained directly from the manufacturer (Bair Hugger 505, model 200708D; Arizant Healthcare, Eden Prairie, MN), and 5 model 200708C filters currently in hospital use were removed from FAW devices. The retention efficiency of these filters was assessed using a monodisperse sodium chloride aerosol. In the same hospitals, internal air path surface swabs and hose outlet particle counts were performed on 52 forced-air warming devices (all with the model 200708C filter) to assess internal microbial buildup and airborne contamination emissions. Results: Intake filter retention efficiency at 0.2 μm was 93.8% for the 200708C filter and 61.3% at for the 200708D filter. The 200708D filter obtained directly from the manufacturer has a thinner filtration media than the 200708C filter in current hospital use, suggesting that the observed differences in retention efficiency were due to design changes. Fifty-eight percent of the FAW blowers evaluated were internally generating and emitting airborne contaminants, with microorganisms detected on the internal air path surfaces of 92.3% of these blowers. Isolates of Staphylococcus aureus, coagulase-negative Staphylococcus, and methicillin-resistant S aureus were detected in 13.5%, 3.9%, and 1.9% of FAW blowers, respectively. Conclusion: The design of popular FAW devices using the 200708C filter was found to be inadequate for preventing the internal buildup and emission of microbial contaminants into the operating room. Substandard intake filtration allowed airborne contaminants (both viable and nonviable) to penetrate the intake filter and reversibly attach to the internal surfaces within the FAW blowers. The reintroduction of these contaminants into the FAW blower air stream was detected and could contribute to the risk of cross-infection. Given the deficiencies identified with the 200708C intake filter, the introduction of a new filter (model 200708D) with substantially lower retention efficiency is of concern. Copyright © 2011 by the Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

Viswanathan C.T.,CT Associates Inc.
Bioanalysis | Year: 2011

Incurred sample reanalysis (ISR) is accepted as both a fundamental concept and an integral part in the conduct of pharmacokinetic, bioequivalence and preclinical safety studies. Reproducibility demonstrated by ISR reinforces confidence that the method is valid and the results dependable. In this article, the history of the uptake of ISR is discussed and the current practices described. The industry is given credit for its awareness of the importance of, and implementation of, ISR practices in bioanalytical laboratories. Finally, in the context of the recent publication of guidelines for ISR by the EMA, implications for globalization and harmonization of regulations pertaining to ISR are described. © 2011 Future Science Ltd.

CT Associates Inc. | Date: 2013-09-19

A method and apparatus for measuring dissolved residue concentrations and particulate residue particle concentrations and size distribution in liquids, particularly colloidal suspensions. The method involves separating dissolved and particulate residues in liquids for subsequent analysis of the residue species. The method includes the steps of forming an aerosol from the liquid sample to be analyzed, evaporating the droplets in the aerosol to dryness, detecting and sizing the particles, and determining the liquid volumetric inspection rate. An apparatus for separating dissolved and particulate residues in liquids for determination of the concentrations of the two residue species as well as the size distribution of the particulate species is also disclosed. The apparatus includes a droplet former, a dryer communicatively connected to the droplet former, and a detector communicatively connected to the evaporator for detecting and sizing particles.

PubMed | CT Associates Inc. and Kanomax FMT
Type: Journal Article | Journal: ACS applied materials & interfaces | Year: 2016

Protein binding and protein-induced nanoparticle aggregation are known to occur for a variety of nanomaterials, with the extent of binding and aggregation highly dependent on nanoparticle surface properties. However, often lacking are techniques that enable quantification of the extent of protein binding and aggregation, particularly for nanoparticles with polydisperse size distributions. In this study, we adapt ion mobility spectrometry (IMS) to examine the binding of bovine serum albumin to commercially available anionic-surfactant-coated superparamagnetic iron oxide nanoparticles (SPIONs), which are initially 21 nm in mean mobility diameter and have a polydisperse size distribution function (geometric standard deviation near 1.4). IMS, carried out with a hydrosol-to-aerosol converting nebulizer, a differential mobility analyzer, and a condensation particle counter, enables measurements of SPION size distribution functions for varying BSA/SPION number concentration ratios. IMS measurements suggest that initially (at BSA concentrations below 50 nM) BSA binds reversibly to SPION surfaces with a binding site density in the 0.05-0.08 nm(-2) range. However, at higher BSA concentrations, BSA induces SPION-SPION aggregation, evidenced by larger shifts in SPION size distribution functions (mean diameters beyond 40 nm for BSA concentrations near 100 nM) and geometric standard deviations (near 1.3) consistent with self-preserving aggregation theories. The onset of BSA aggregation is correlated with a modest but statistically significant decrease in the specific absorption rate (SAR) of SPIONs placed within an alternating magnetic field. The coating of SPIONs with mesoporous silica (MS-SPIONs) as well as PEGylation (MS-SPIONs-PEG) is found to completely mitigate BSA binding and BSA-induced aggregation; IMS-inferred size distribution functions are insensitive to BSA concentration for MS-SPIONs and MS-SPIONs-PEG. The SARs of MS-SPIONs are additionally insensitive to BSA concentration, confirming the SAR decrease is linked to BSA-induced aggregation.

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