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At least 991 records · Page 55Linked to original sources
PubMed2005

Physiologically precise simulation of multiple lung gas exchange during anaesthesia by simultaneous gas infusion and extraction.

UNLABELLED: A lung gas exchange simulator was tested which produces simultaneous uptake and/or elimination of multiple gases by an artificial test lung with physiologically realistic gas expired and exhaust gas flows, using a combination of infusion of diluting/enriching gases into the lung with lung gas extraction. A deterministic algorithm is incorporated which calculates required gas infusion and extraction flow rates for any set of possible target gas exchange values with any given set of fresh gas flows and concentrations. Six different scenarios were simulated, comprising a range of gas exchange values for each gas species which lie within a physiologically realistic range for anaesthetized patients. For each of these experiments the system was tested for 15 consecutive measurements over 25 min by measurement of gas exchange in the system using the Haldane transformation. RESULTS: the mean bias and standard error of the mean bias (SE, in parentheses) relative to the target value was: +0.001 (0.002) l min(-1) for O(2) uptake, -0.002 (0.005) l min(-1) for CO(2) production, -0.001 (0.002) l min(-1) for uptake of nitrous oxide and +0.3 (0.1) ml min(-1) for uptake of a volatile anaesthetic agent (isoflurane). The confidence limits of the mean bias were within 5% of the target value for all gases and scenarios with the exception of those where a low uptake of anaesthetic gas was specified. The confidence limits of the mean bias for the lower uptakes of isoflurane were within 10% of the target value for these scenarios and within 15% for the low uptake of N(2)O. Good accuracy and precision of this approach to lung gas exchange simulation were demonstrated, resulting in a versatile simulator.

Algorithms↗
PubMed2005

A configurable three-dimensional microenvironment in a microfluidic channel for primary hepatocyte culture.

We have developed a technique for the in situ three-dimensional (3D) immobilization of primary rat hepatocytes within a localized matrix in a microfluidic channel that provides a 3D microenvironment incorporating both a configurable 3D matrix and fluid perfusion. This is based on the laminar flow complex coacervation of a pair of oppositely charged polyelectrolytes, i.e., methylated collagen and a terpolymer of HEMA-MMA-MAA. 3D collagen matrices were formed with minimal gelation times (<8 min), were able to entrap cells under aqueous noncytotoxic conditions, and permitted culture media to be perfused in the microchannel by virtue of the spatial confinement of the 3D matrix on one side of the channel. The architecture and stability of the collagen matrix could be configured by the use of different material combinations and changes in the polyelectrolyte flow rates and retention time. Primary rat hepatocytes cultured for 24 h in the 3D matrix within the microchannel showed comparable or enhanced cytochrome P450 7-ethoxyresorufin-O-deethylation activity with static controls. The configurable 3D microenvironment in the microfluidic channel may be a potential 3D culture model of primary hepatocytes for drug testing applications.

Animals↗
PubMed2005

Piezo- and solenoid valve-based liquid dispensing for miniaturized assays.

Miniaturization of biological assays requires dispensing liquids in the submicroliter range of volumes. Accuracy and reproducibility of dispensing this range depend on both the dispenser and the receptacle in which the assay is constructed. Miniaturization technologies developed by Aurora Discovery, Inc. (San Diego, CA) include high-density multiwell plates for assay samples and reagent storage, as well as piezo-based and solenoid valve-based liquid dispensers. Some basic principles of small-volume dispensing by jetting are described to provide context for dispenser design and function. Performance of the latest instruments incorporating these dispensing devices is presented.

Biological Assay↗
PubMed2005

Precise nanoliter fluid handling system with integrated high-speed flow sensor.

A system for accurate low-volume delivery of liquids in the micro- to nanoliter range makes use of an integrated miniature flow sensor as part of an intelligent feedback control loop driving a micro-solenoid valve. The flow sensor is hydraulically connected with the pressurized system liquid in the dispensing channel and located downstream from the pressure source, above the solenoid valve. The sensor operates in a differential mode and responds in real-time to the internal flow-pulse resulting from the brief opening interval of the solenoid valve leading to a rapid ejection of a fluid droplet. The integral of the flow-pulse delivered by the sensor is directly proportional to the volume of the ejected droplet from the nozzle. The quantitative information is utilized to provide active control of the effectively dispensed or aspirated volume by adjusting the solenoid valve accordingly. This process significantly enhances the precision of the fluid delivery. The system furthermore compensates automatically for any changes in the viscosity of the dispensed liquid. The data delivered by the flow sensor can be saved and backtracked in order to confirm and validate the aspiration and dispensing process in its entirety. The collected dispense information can be used for quality control assessments and automatically be made part of an electronic record.

Biological Assay↗
PubMed2005

Nanoliter dispensing for uHTS using pin tools.

Miniaturization of assays is an important objective in Ultra-HTS. One of the major obstacles has been to find fluid handling systems capable of reliably and accurately delivering between 2 and 200 nl of test compound to assay plates. New methods of forming pins, placing slots in the pins, and hydrophobic coatings bonded onto the pins solve many of the problems encountered by early pin tools. Unlike other low-volume liquid handlers, these new pin tools provide the ability to transfer approximately 2 nl-5 microl of compounds. These pin tools can also use low-volume source plates (2-10 microl) and achieve an accuracy of better than 5%. This, coupled with the ability to transfer small volumes directly from the compound library to assay plates without an intervening dilution plate, saves reagents, throughput time, and consumables and is, therefore, very cost effective. Pin tool compound transfers in the 2-100 nl range provide a simple method to dilute away from the toxic effect that dimethyl sulfoxide has on some assay target cells. The factors that affect liquid transfers by pin tools are discussed in detail as well as the advantages and limitations of pin tools.

Biological Assay↗
PubMedDate not supplied

Bioreactor design for successive culture of anchorage-dependent cells operated in an automated manner.

A novel bioreactor system was designed to perform a series of batchwise cultures of anchorage-dependent cells by means of automated operations of medium change and passage for cell transfer. The experimental data on contamination frequency ensured the biological cleanliness in the bioreactor system, which facilitated the operations in a closed environment, as compared with that in flask culture system with manual handlings. In addition, the tools for growth prediction (based on growth kinetics) and real-time growth monitoring by measurement of medium components (based on small-volume analyzing machinery) were installed into the bioreactor system to schedule the operations of medium change and passage and to confirm that culture proceeds as scheduled, respectively. The successive culture of anchorage-dependent cells was conducted with the bioreactor running in an automated way. The automated bioreactor gave a successful culture performance with fair accordance to preset scheduling based on the information in the latest subculture, realizing 79- fold cell expansion for 169 h. In addition, the correlation factor between experimental data and scheduled values through the bioreactor performance was 0.998. It was concluded that the proposed bioreactor with the integration of the prediction and monitoring tools could offer a feasible system for the manufacturing process of cultured tissue products.

Algorithms↗
PubMed1985

Microcolumn high pressure liquid chromatography with a glass-frit nebulizer interface for plasma emission detection.

Microcolumn high pressure liquid chromatography (micro-HPLC) is rapidly gaining recognition as a practical separation tool for organometallic compounds. The use of the inductively coupled plasma (ICP) as a detector for micro-HPLC is studied. Several miniaturized glass-frit nebulizers are investigated as interfaces between the output of the microbore column and the ICP torch. Their performance with aqueous and methanolic solutions is evaluated by direct nebulization and flow injection analysis. The most efficient of these nebulizers is used in the micro-HPLC/ICP study of some Cd, Pb, and Zn organometallic compounds. Detection limits of 1.92 ng of Pb for tetramethyllead and 5.01 ng of Pb for tetraethyllead are obtained and compared with regular HPLC/ICP of these same compounds. Approximately equivalent detection limits were obtained when using a microwave induced plasma as an alternate plasma source.

Chromatography, High Pressure Liquid↗
PubMedDate not supplied

Tissue distribution of different mercurial compounds analyzed by the improved FI-CVAAS.

Mercury contents in biological samples can be measured by cold vapor atomic absorption spectroscopy combined with the flow-injection analysis system. However, water vapor in the absorption cell attenuated and distorted the signals. This study described the strategy to overcome this problem by adding an additional gas-liquid separator after the mixing/separator assembly. This modification can efficiently minimize the moisture in the transfer line and in the absorption cell. This improved technique was adopted to study the differential tissue distribution of methylmercury and HgS after oral administration to mice for five consecutive days. The present study suggests that the insoluble HgS (the main constituent of a Chinese mineral drug, cinnabar, used as a sedative) can still be absorbed from gastrointestinal tract and distributed to various tissues including the brain. As compared with methylmercury, the total amount of HgS accumulated in the tissues ranging about one five-thousandth of methylmercury, which is well correlated with the biological activity of HgS reported previously.

Administration, Oral↗
PubMed2004

Simultaneous determination of eight underivatized amphetamines in hair by high-performance liquid chromatography-atmospheric pressure chemical ionization mass spectrometry (HPLC-APCI-MS).

The aim of this study was to develop, optimize, and validate an analytical procedure to determine a group of eight amphetamines, amphetamine (AMP), ephedrine (EP), methcathinone (MTC), paramethoxyamphetamine (PMA), methamphetamine (MA), methylenedioxyamphetamine (MDA), methylenedioxymethamphetamine (MDMA), and methylenedioxyethylamphetamine (MDEA), in hair. The target substances were extracted with 1-chlorobutane after alkaline (1M NaOH) digestion and analyzed underivatized with high-performance liquid chromatography-atmospheric pressure chemical ionization mass spectrometry (LC-APCI-MS). APCI-MS parameters such as fragmentor and capillary voltage, corona current, drying gas temperature and flow rate, vaporizer temperature, and nebulizer gas pressure were optimized with the application of flow injection analysis. Quantitation was performed using selected ion monitoring of protonated molecular ions of the studied drugs, and their deuterated analogues were used as internal standards. The limits of detection were 0.05 ng/mg for MA, MDA, MDMA, and MDEA; 0.10 ng/mg for EP and AMP; and 0.20 ng/mg for MTC and PMA. A linear response was observed for all drugs from 0 to 20 ng/mg. The method was applied to the determination of amphetamines in 93 authentic hair samples obtained from detoxification and methadone treatment patients, revealing the following concentrations: 0.17-17.28 ng/mg (EP), 0.52-2.08 ng/mg (MTC), 0.15-62.52 ng/mg (AMP), 0.10-16.52 ng/mg (MA), 0.10-0.88 ng/mg (MDMA), and 0.10-0.16 ng/mg (MDEA). MDA and PMA were never detected.

Amphetamines↗
PubMed2006

Mixing in a square and a rectangular duct regarding selection of locations for extractive sampling of gaseous contaminants.

Tests were conducted to characterize the uniformity of velocity and tracer gas profiles in a square and a rectangular duct with respect to defining the suitability of locations for single point sampling of gaseous contaminants. Several configurations, such as a straight duct with unidirectional flow at the entrance section and straight ducts preceded by mixing elements (a 90 degrees mitered bend and double 90 degrees bends in S- and U-type configurations) were tested. Results are compared with those from circular ducts. For a straight duct of square cross section, which is not preceded by a mixing element, the coefficients of variation (COV) of tracer gas concentration at 19 duct diameters downstream of the gas release location is 143% (center release of tracer gas). COVs of velocity and tracer gas concentration in a straight square duct 9.5 duct diameters downstream of a 90 degrees mitered bend are 6% and 24.3% (top inside release), respectively, which does not meet the ANSI N13.1 limit of 20% for the tracer gas COV. In case of the rectangular duct with a 3:1 (width to height) aspect ratio, COVs of velocity and tracer gas concentration at 9 duct diameters downstream of a 90 degrees mitered bend are 29% and 62% (bottom inside release), respectively. A mixing element in a square duct comprised of two 90 degrees mitered bends in a U-configuration produces results similar to those obtained with a single 90 degrees bend. However, COVs of velocity and tracer gas concentration in a square duct 6 duct diameters downstream of an S-type double bend are 10.6% and 8.3% (top inside release), respectively, which comply with the ANSI tracer gas and velocity criteria for single point representative sampling. When mixing elements were employed in square ducts, the COV results were comparable with those of other researchers for circular ducts.

Air Pollutants, Radioactive↗
PubMed2007

A generic-tee-plenum mixing system for application to single point aerosol sampling in stacks and ducts.

The ANSI/HPS-N13.1-1999 standard is based on the concept of obtaining a single point representative sample from a location where the velocity and contaminant profiles are relatively uniform. It is difficult to predict the level of mixing in an arbitrary stack or duct without experimental data to meet the ANSI/HPS N13.1-1999 requirements. The goal of this study was to develop experimental data for a range of conditions in "S" (S-shaped configuration) duct systems with different mixing elements and "S" systems having one or two mixing elements. Results were presented in terms of the coefficients of variation (COVs) for velocity, tracer gas, and 10-mum aerodynamic diameter (AD) aerosol particle profiles at different downstream locations for each mixing element. Five mixing elements were tested, including a 90 degrees elbow, a commercial static mixer, a Small-Horizontal Generic-Tee-Plenum (SH-GTP), a Small-Vertical Generic-Tee-Plenum (SV-GTP), and a Large-Horizontal Generic-Tee-Plenum (LH-GTP) system. The COVs for velocity, gas concentration, and aerosol particles for the three GTP systems were all determined to be less than 8%. Tests with two different sizes of GTPs were conducted, and the results showed the performance of the GTPs was relatively unaffected by either size or velocity as reflected by the Reynolds number. The pressure coefficients were 0.59, 0.57, and 0.65, respectively, for the SH-GTP, SV-GTP, and LH-GTP. The pressure drop for the GTPs was approximately twice that of the round elbow, but a factor of 5 less than a Type IV Air Blender. The GTP was developed to provide a sampling location less than 4-duct diameters downstream of a mixing element with low pressure drop condition. The object of the developmental effort was to provide a system that could be employed in new stack; however, the concept of GTPs could also be retrofitted onto existing system applications as well. Results from these tests show that the system performance is well within the ANSI/HPS N13.1-1999 mixing criteria--the COVs for velocity, tracer gas, and 10-microm AD aerosol particles are less than the 20% criteria levels.

Aerosols↗
PubMed2003

Evidence for a lactate pool in the rat brain that is not used as an energy supply under normoglycemic conditions.

Lactate derived from glucose can serve as an energy source in the brain. However, it is not certain how much lactate, directly taken from the blood circulation, may replace glucose as an energy source. This study aimed to estimate the uptake, release, and utilization of lactate entering the brain from the blood circulation. The change in cerebral venous-arterial glucose and lactate differences after lactate infusions in the anesthetized rat were measured. Ultrafiltration probes were placed in the aorta and in the jugular vein, and connected to a flow injection analysis system with biosensors for glucose and lactate. Measurements were taken every minute. Lactate efflux was observed at baseline, whereas an influx of lactate was seen during lactate infusion. Immediately after the infusion there was a net efflux of lactate from the brain. The results suggest that the majority of lactate moving into the brain is not used as an energy substrate, and that lactate does not replace glucose as an energy source. Instead, the authors propose the concept of a lactate pool in the brain that can be filled and emptied in accordance with the blood lactate concentration, but which is not used as an energy supply for cerebral metabolism.

Animals↗
PubMed2004

Modeling cerebral arteriovenous lactate kinetics after intravenous lactate infusion in the rat.

Venous-arterial lactate differences across the brain during lactate infusion in rats were studied, and the fate of lactate was described with a mathematical model that includes both cerebral and extracerebral kinetics. Ultrafiltration was used to sample continuously and simultaneously arterial and venous blood. Subsequent application of flow injection analysis and biosensors allowed the measurement of glucose and lactate concentrations every minute. Because of the high temporal resolution, arteriovenous lactate kinetics could be modeled in individual experiments. The existence of both a cerebral lactate sink and a lactate exchangeable compartment, representing approximately 24% of brain volume, was thus modeled.

Animals↗
PubMed2004

Microfluidic systems for chemical kinetics that rely on chaotic mixing in droplets.

This paper reviews work on a microfluidic system that relies on chaotic advection to rapidly mix multiple reagents isolated in droplets (plugs). Using a combination of turns and straight sections, winding microfluidic channels create unsteady fluid flows that rapidly mix the multiple reagents contained within plugs. The scaling of mixing for a range of channel widths, flow velocities and diffusion coefficients has been investigated. Due to rapid mixing, low sample consumption and transport of reagents with no dispersion, the system is particularly appropriate for chemical kinetics and biochemical assays. The mixing occurs by chaotic advection and is rapid (sub-millisecond), allowing for an accurate description of fast reaction kinetics. In addition, mixing has been characterized and explicitly incorporated into the kinetic model.

Complex Mixtures↗
PubMed2004

Microfabricated electrophoresis systems for DNA sequencing and genotyping applications: current technology and future directions.

Many routine genomic-analysis assays rely on gel electrophoresis to perform size-selective fractionation of DNA fragments in the size range below 1 kb in length. Over the past decade, impressive progress has been made towards the development of microfabricated electrophoresis systems to conduct these assays in a microfluidic lab-on-a-chip format. Since these devices are inexpensive, require only nanolitre sample volumes, and do not rely on the availability of a pre-existing laboratory infrastructure, they are readily deployable in remote field locations for use in a variety of medical and biosensing applications. The design and construction of microfabricated electrophoresis devices poses a variety of challenges, including the need to achieve high-resolution separations over distances of a few centimetres or less, and the need to easily interface with additional microfluidic components to produce self-contained integrated DNA-analysis systems. In this paper, we review recent efforts to develop devices to satisfy these requirements and live up to the promise of fulfilling the growing need for inexpensive portable genomic-analysis equipment.

DNA↗
PubMed2005

Bubble dispenser in microfluidic devices.

This Brief Report presents experimental and computational results on bubble formation in microfluidic devices. Bubbles are generated at the right-angle intersection of four identical square microchannels. When the pressure gradient generated by the liquid flow dominates the pressure gradient generated by gas flow, the length of the produced confined bubbles follows a law based on the channel size and fluid volume fraction. This bubble production technique was used to produce monodisperse aqueous foam in two-dimensional and three-dimensional microchannels.

Computer Simulation↗
PubMed2004

A versatile rapid-mixing and flow device for X-ray absorption spectroscopy.

A low-temperature rapid-mixing and flow system has been designed and implemented to monitor catalysis involving metal ions by X-ray absorption spectroscopy at the ID-18 beamline of the Advanced Photon Source, Argonne National Laboratory. The system will allow examination of biological metallo-intermediates at dilute metal ion concentrations by the detection of X-ray fluorescence. The instrument can be cooled to sub-zero temperatures, thus lengthening the life time of a reaction intermediate. A portable UV-visible spectrometer is integrated with the flow system to monitor the sample optically. The system can also be used as a continuous-flow device to minimize radiation-induced sample damage by reducing sample exposure to the X-ray beam. The integration of the stop-flow instrument with the synchrotron beamline and X-ray fluorescence detector systems makes it unique for time-resolved X-ray absorption studies of dilute biological reactions. The results of the initial testing of the system are presented.

Catalysis↗
PubMed2004

Characterization of implantable microfabricated fluid delivery devices.

The formal characterization of the performance of microfluidic delivery devices is crucial for reliable in vivo application. A comprehensive laboratory technique was developed and used to optimize, calibrate and validate microfabricated fluid delivery devices. In vivo experiments were carried out to verify the accuracy and reliability of the pressure driven devices. Acute guinea pig experiments were conducted to measure the response to alpha-amino-3-hydroxy-5-methyl-4-isoxalone propionic acid, an excitatory neurotransmitter, at multiple locations in the inferior colliculus. A nondimensional parameter, Q, was successfully used to classify devices in terms of geometry alone (i.e., independent of fluid properties). Functional devices exhibited long-term linearity and reliability in delivering single phase, Newtonian fluids, in discrete volumes with a resolution of 500 picoliters at less than 0.45 lbf/in2 (30 mbar) pressure drop. Results for non-Newtonian fluids are not presented here. The acute results showed a proportional increase in the firing rate for delivered volumes of 2 nL up to 10 nL (at rates of between 0.1 and 1 nL/s). Flow characteristics are maintained during acute experiments and post-implant. A control experiment conducted with Ringer solution produced negligible effects, suggesting the results to be truly pharmacological. The experimental techniques employed have proven to be reliable and will be used for future calibration and testing of next generation chronic microfluidic delivery devices.

Action Potentials↗