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A flexible package and interconnects for microfluidic systems

Description: A slide-together compression package and microfluidic interconnects for microfabricated devices requiring fluidic and electrical connections is presented. The package assembles without tools, is reusable, and requires no epoxy, wirebonds, or solder, making chip replacement fast and easy. The microfluidic interconnects use standard HPLC PEEK tubing, with the tip machined to accept either an o-ring or custom molded ring which serves the dual function of forming the seal and providing mechanical retention strength. One design uses a screw to compress the o-ring, while others are simply plugged into a cartridge retained in the package. The connectors are helium leak-tight, can withstand hundreds of psi, are easy to connect and disconnect, are low dead volume, have a small footprint, and are adaptable to a broad range of microfabricated devices.
Date: January 1, 1999
Creator: Benett, W & Krulevitch, P
Partner: UNT Libraries Government Documents Department

Inductively Heated Shape Memory Polymer for the Magnetic Actuation of Medical Devices

Description: Presently there is interest in making medical devices such as expandable stents and intravascular microactuators from shape memory polymer (SMP). One of the key challenges in realizing SMP medical devices is the implementation of a safe and effective method of thermally actuating various device geometries in vivo. A novel scheme of actuation by Curie-thermoregulated inductive heating is presented. Prototype medical devices made from SMP loaded with Nickel Zinc ferrite ferromagnetic particles were actuated in air by applying an alternating magnetic field to induce heating. Dynamic mechanical thermal analysis was performed on both the particle-loaded and neat SMP materials to assess the impact of the ferrite particles on the mechanical properties of the samples. Calorimetry was used to quantify the rate of heat generation as a function of particle size and volumetric loading of ferrite particles in the SMP. These tests demonstrated the feasibility of SMP actuation by inductive heating. Rapid and uniform heating was achieved in complex device geometries and particle loading up to 10% volume content did not interfere with the shape recovery of the SMP.
Date: September 6, 2005
Creator: Buckley, P; Mckinley, G; Wilson, T; Small, W; Benett, W; Bearinger, J et al.
Partner: UNT Libraries Government Documents Department

Multiplexed gas spectroscopy using tunable VCSELs

Description: Detection and identification of gas species using tunable laser diode laser absorption spectroscopy has been performed using vertical cavity surface emitting lasers (VCSEL). Two detection methods are compared: direct absorbance and wavelength modulation spectroscopy (WMS). In the first, the output of a DC-based laser is directly monitored to detect for any quench at the targeted specie wavelength. In the latter, the emission wavelength of the laser is modulated by applying a sinusoidal component on the drive current of frequency {omega}, and measuring the harmonics component (2{omega}) of the photo-detected current. This method shows a better sensitivity measured as signal to noise ratio, and is less susceptible to interference effects such as scattering or fouling. Gas detection was initially performed at room temperature and atmospheric conditions using VCSELs of emission wavelength 763 nm for oxygen and 1392 nm for water, scanning over a range of approximately 10 nm, sufficient to cover 5-10 gas specific absorption lines that enable identification and quantization of gas composition. The amplitude and frequency modulation parameters were optimized for each detected gas species, by performing two dimensional sweeps for both tuning current and either amplitude or frequency, respectively. We found that the highest detected signal is observed for a wavelength modulation amplitude equal to the width of the gas absorbance lines, in good agreement with theoretical calculations, and for modulation frequencies below the time response of the lasers (<50KHz). In conclusion, we will discuss limit of detection studies and further implementation and packaging of VCSELs in diode arrays for continuous and simultaneous monitoring of multiple species in gaseous mixtures.
Date: April 10, 2012
Creator: Bond, T; Bond, S; McCarrick, J; Zumstein, J; Chang, A; Moran, B et al.
Partner: UNT Libraries Government Documents Department

Shape Memory Polymer Therapeutic Devices for Stroke

Description: Shape memory polymers (SMPs) are attracting a great deal of interest in the scientific community for their use in applications ranging from light weight structures in space to micro-actuators in MEMS devices. These relatively new materials can be formed into a primary shape, reformed into a stable secondary shape, and then controllably actuated to recover their primary shape. The first part of this presentation will be a brief review of the types of polymeric structures which give rise to shape memory behavior in the context of new shape memory polymers with highly regular network structures recently developed at LLNL for biomedical devices. These new urethane SMPs have improved optical and physical properties relative to commercial SMPs, including improved clarity, high actuation force, and sharper actuation transition. In the second part of the presentation we discuss the development of SMP based devices for mechanically removing neurovascular occlusions which result in ischemic stroke. These devices are delivered to the site of the occlusion in compressed form, are pushed through the occlusion, actuated (usually optically) to take on an expanded conformation, and then used to dislodge and grip the thrombus while it is withdrawn through the catheter.
Date: October 11, 2005
Creator: Wilson, T S; Small IV, W; Benett, W J; Bearinger, J P & Maitland, D J
Partner: UNT Libraries Government Documents Department

A Shape Memory Polymer Dialysis Needle Adapter for the Reduction of Hemodynamic Stress within Arteriovenous Grafts

Description: A deployable, shape memory polymer adapter is investigated for reducing the hemodynamic stress caused by a dialysis needle flow within an arteriovenous graft. Computational fluid dynamics simulations of dialysis sessions with and without the adapter demonstrate that the adapter provides a significant decrease in the wall shear stress. In vitro flow visualization measurements are made within a graft model following delivery and actuation of a prototype shape memory polymer adapter. Vascular access complications resulting from arteriovenous (AV) graft failures account for over $1 billion per year in the health care costs of dialysis patients in the U.S.[1] The primary mode of failure of arteriovenous fistulas (AVF's) and polytetrafluoroethylene (PTFE) grafts is the development of intimal hyperplasia (IH) and the subsequent formation of stenotic lesions, resulting in a graft flow decline. The hemodynamic stresses arising within AVF's and PTFE grafts play an important role in the pathogenesis of IH. Studies have shown that vascular damage can occur in regions where there is flow separation, oscillation, or extreme values of wall shear stress (WSS).[2] Nevaril et al.[3] show that exposure of red blood cells to WSS's on the order of 1500 dynes/cm2 can result in hemolysis. Hemodynamic stress from dialysis needle flow has recently been investigated for the role it plays in graft failure. Using laser Doppler velocimetry measurements, Unnikrishnan et al.[4] show that turbulence intensities are 5-6 times greater in the AV flow when the needle flow is present and that increased levels of turbulence exist for approximately 7-8cm downstream of the needle. Since the AVF or PTFE graft is exposed to these high levels of hemodynamic stress several hours each week during dialysis sessions, it is quite possible that needle flow is an important contributor to vascular access occlusion.[4] We present a method for reducing the hemodynamic stress in an ...
Date: August 16, 2006
Creator: Ortega, J M; Small, W; Wilson, T S; Benett, W; Loge, J & Maitland, D J
Partner: UNT Libraries Government Documents Department

Fabrication and In Vitro Deployment of a Laser-Activated Shape Memory Polymer Vascular Stent

Description: Vascular stents are small tubular scaffolds used in the treatment of arterial stenosis (narrowing of the vessel). Most vascular stents are metallic and are deployed either by balloon expansion or by self-expansion. A shape memory polymer (SMP) stent may enhance flexibility, compliance, and drug elution compared to its current metallic counterparts. The purpose of this study was to describe the fabrication of a laser-activated SMP stent and demonstrate photothermal expansion of the stent in an in vitro artery model. A novel SMP stent was fabricated from thermoplastic polyurethane. A solid SMP tube formed by dip coating a stainless steel pin was laser-etched to create the mesh pattern of the finished stent. The stent was crimped over a fiber-optic cylindrical light diffuser coupled to an infrared diode laser. Photothermal actuation of the stent was performed in a water-filled mock artery. At a physiological flow rate, the stent did not fully expand at the maximum laser power (8.6 W) due to convective cooling. However, under zero flow, simulating the technique of endovascular flow occlusion, complete laser actuation was achieved in the mock artery at a laser power of {approx}8 W. We have shown the design and fabrication of an SMP stent and a means of light delivery for photothermal actuation. Though further studies are required to optimize the device and assess thermal tissue damage, photothermal actuation of the SMP stent was demonstrated.
Date: April 25, 2007
Creator: Baer, G M; Small IV, W; Wilson, T S; Benett, W J; Matthews, D L; Hartman, J et al.
Partner: UNT Libraries Government Documents Department

Hybridization and Selective Release of DNA Microarrays

Description: DNA microarrays contain sequence specific probes arrayed in distinct spots numbering from 10,000 to over 1,000,000, depending on the platform. This tremendous degree of multiplexing gives microarrays great potential for environmental background sampling, broad-spectrum clinical monitoring, and continuous biological threat detection. In practice, their use in these applications is not common due to limited information content, long processing times, and high cost. The work focused on characterizing the phenomena of microarray hybridization and selective release that will allow these limitations to be addressed. This will revolutionize the ways that microarrays can be used for LLNL's Global Security missions. The goals of this project were two-fold: automated faster hybridizations and selective release of hybridized features. The first study area involves hybridization kinetics and mass-transfer effects. the standard hybridization protocol uses an overnight incubation to achieve the best possible signal for any sample type, as well as for convenience in manual processing. There is potential to significantly shorten this time based on better understanding and control of the rate-limiting processes and knowledge of the progress of the hybridization. In the hybridization work, a custom microarray flow cell was used to manipulate the chemical and thermal environment of the array and autonomously image the changes over time during hybridization. The second study area is selective release. Microarrays easily generate hybridization patterns and signatures, but there is still an unmet need for methodologies enabling rapid and selective analysis of these patterns and signatures. Detailed analysis of individual spots by subsequent sequencing could potentially yield significant information for rapidly mutating and emerging (or deliberately engineered) pathogens. In the selective release work, optical energy deposition with coherent light quickly provides the thermal energy to single spots to release hybridized DNA. This work leverages LLNL expertise in optics, microfluids, and bioinformatics.
Date: November 29, 2011
Creator: Beer, N R; Baker, B; Piggott, T; Maberry, S; Hara, C M; DeOtte, J et al.
Partner: UNT Libraries Government Documents Department

Autonomous system for pathogen detection and identification

Description: This purpose of this project is to build a prototype instrument that will, running unattended, detect, identify, and quantify BW agents. In order to accomplish this, we have chosen to start with the world´┐Ż s leading, proven, assays for pathogens: surface-molecular recognition assays, such as antibody-based assays, implemented on a high-performance, identification (ID)-capable flow cytometer, and the polymerase chain reaction (PCR) for nucleic-acid based assays. With these assays, we must integrate the capability to: l collect samples from aerosols, water, or surfaces; l perform sample preparation prior to the assays; l incubate the prepared samples, if necessary, for a period of time; l transport the prepared, incubated samples to the assays; l perform the assays; l interpret and report the results of the assays. Issues such as reliability, sensitivity and accuracy, quantity of consumables, maintenance schedule, etc. must be addressed satisfactorily to the end user. The highest possible sensitivity and specificity of the assay must be combined with no false alarms. Today, we have assays that can, in under 30 minutes, detect and identify simulants for BW agents at concentrations of a few hundred colony-forming units per ml of solution. If the bio-aerosol sampler of this system collects 1000 Ymin and concentrates the respirable particles into 1 ml of solution with 70% processing efficiency over a period of 5 minutes, then this translates to a detection/ID capability of under 0.1 agent-containing particle/liter of air.
Date: September 24, 1998
Creator: Belgrader, P; Benett, W; Langlois, R; Long, G; Mariella, R; Milanovich, F et al.
Partner: UNT Libraries Government Documents Department

Final Report for the PolyHANAA

Description: The PolyHanaa is a 24 chamber thermal cycling instrument designed to perform rapid, real-time optical detection of biological agents using the Polymerase Chain Reaction (PCR) process with TaqMan{trademark} reagents. Liquid samples are pipetted into small, disposable polypropylene tubes that are then inserted into the chambers. The 24 duplex chambers are divided into 6 independent groups and run information is presented simultaneously, in real time, for all groups.
Date: April 30, 2001
Creator: Richards, J. B.; Stratton, P. L.; Benett, W. J.; Koopman, R. P. & Milanovich, F. P.
Partner: UNT Libraries Government Documents Department

Improved performance of high average power semiconductor arrays for applications in diode pumped solid state lasers

Description: The average power performance capability of semiconductor diode laser arrays has improved dramatically over the past several years. These performance improvements, combined with cost reductions pursued by LLNL and others in the fabrication and packaging of diode lasers, have continued to reduce the price per average watt of laser diode radiation. Presently, we are at the point where the manufacturers of commercial high average power solid state laser systems used in material processing applications can now seriously consider the replacement of their flashlamp pumps with laser diode pump sources. Additionally, a low cost technique developed and demonstrated at LLNL for optically conditioning the output radiation of diode laser arrays has enabled a new and scalable average power diode-end-pumping architecture that can be simply implemented in diode pumped solid state laser systems (DPSSL`s). This development allows the high average power DPSSL designer to look beyond the Nd ion for the first time. Along with high average power DPSSL`s which are appropriate for material processing applications, low and intermediate average power DPSSL`s are now realizable at low enough costs to be attractive for use in many medical, electronic, and lithographic applications.
Date: January 1, 1994
Creator: Beach, R.; Emanuel, M.; Benett, W.; Freitas, B.; Ciarlo, D.; Carlson, N. et al.
Partner: UNT Libraries Government Documents Department

Performance improvements in diode laser arrays

Description: The average power performance capability of semiconductor laser diode arrays has improved dramatically over the past several years. Additionally, optical conditioning technologies have been developed that increase the effective radiance of stacked two-dimensional arrays by nearly two orders of magnitude. These performance improvements have been accompanied by cost reductions that now make feasible the replacement of flashlamp pump sources by laser diode arrays in a large variety of military and commercial solid state laser systems.
Date: June 1, 1994
Creator: Beach, R. J.; Emanuel, M. A.; Freitas, B. L.; Benett, W. J.; Skidmore, J. A.; Carlson, N. W. et al.
Partner: UNT Libraries Government Documents Department

Final Report BW Sample Collection& Preparation Device

Description: The objective of this project was to develop the technique needed to prepare a field collected sample for laboratory analysis and build a portable integrated biological detection instrument with new miniaturized and automated sample purification capabilities. The device will prepare bacterial spores, bacterial vegetative cells, and viral particles for PCR amplification.
Date: January 31, 2002
Creator: Koopman, R P; Belgrader, P; Meyer, G; Benett, W J; Richards, J B; Hadley, D R et al.
Partner: UNT Libraries Government Documents Department

Final Report Nucleic Acid System - PCR, Multiplex Assays and Sample Preparation Project

Description: The objective of this project was to reduce to practice the detection and identification of biological warfare pathogens by the nucleic acid recognition technique of PCR (polymerase chain reaction). This entailed not only building operationally functional instrumentation but also developing the chemical assays for detection of priority pathogens. This project had two principal deliverables: (1) design, construct, test and deliver a 24 chamber, multiplex capable suitcase sized PCR instrument, and (2) develop and reduce to practice a multiplex assay for the detection of PCR product by flow cytometry. In addition, significant resources were allocated to test and evaluation of the Hand-held Advanced Nucleic Acid Analyzer (HANAA). This project helps provide the signature and intelligence gathering community the ability to perform, on-site or remote, rapid analysis of environmental or like samples for the presence of a suite of biological warfare pathogens.
Date: April 20, 2001
Creator: Koopman, R.P.; Langlois, R.G.; Nasarabadi, S.; Benett, W.J.; Richards, J.B.; Hadley, D.R. et al.
Partner: UNT Libraries Government Documents Department

Final Report Nucleic Acid System - Hybrid PCR and Multiplex Assay Project Phase 2

Description: This report covers phase 2 (year 2) of the Nucleic Acid System--Hybrid PCR and Multiplex Assay project. The objective of the project is to reduce to practice the detection and identification of biological warfare pathogens by the nucleic acid recognition technique of PCR (polymerase chain reaction) in a multiplex mode using flow cytometry. The Hybrid instrument consists of a flow-through PCR module capable of handling a multiplexed PCR assay, a hybridizing module capable of hybridizing multiplexed PCR amplicons and beads, and a flow cytometer module for bead-based identification, all controlled by a single computer. Multiplex immunoassay using bead-based Luminex flow cytometry is available, allowing rapid screening for many agents. PCR is highly specific and complements and verifies immunoassay. It can also be multiplexed and detection provided using the bead-based Luminex flow cytometer. This approach allows full access to the speed and 100-fold multiplex capability of flow cytometry for rapid screening as well as the accuracy and specificity of PCR. This project has two principal activities: (1) Design, build and test a prototype hybrid PCR/flow cytometer with the basic capabilities for rapid, broad spectrum detection and identification, and (2) Develop and evaluate multiplex flow analysis assay protocols and reagents for the simultaneous detection of PCR products. This project requires not only building operationally functional instrumentation but also developing the chemical assays for detection of priority pathogens. This involves development and evaluation of multiplex flow analysis assay protocols and reagents for the simultaneous detection of PCR products.
Date: April 17, 2002
Creator: Koopman, R P; Langlois, R G; Nasarabadi, S; Benett, W J; Colston, B W; Johnson, D C et al.
Partner: UNT Libraries Government Documents Department