text:
|Publication number
|Publication type
|Application number
|Publication date
|Jun 24, 2008
|Filing date
|Sep 29, 2005
|Priority date
|Sep 29, 2004
|Fee status
|Also published as
|Publication number
|Mark C. Tondra, John M. Anderson, David J. Brownell, Anthony D. Popple
|Original Assignee
|Nve Corporation
|Export Citation
|BiBTeX, EndNote, RefMan
|Patent Citations (32), Non-Patent Citations (10), Referenced by (25), Classifications (14), Legal Events (3)
|External Links: USPTO, USPTO Assignment, Espacenet
This application claims the benefit of Provisional Application No. 60/614,279 filed on Sep. 29, 2004 for "MAGNETIC PARTICLE FLOW DETECTOR".
The present invention relates to small magnetic material particles, or magnetizable beads, in fluid flows and, more particularly, to detection of such particles or beads in such flows.
Among the biomolecular detection methods used to detect selected molecules in the presence of other kinds of molecules mixed therewith are binding assays which are based on use of certain binding molecules to capture through specific chemical bondings the molecules selected for detection. Such specific bondings include polynucleic acid bondings or hybridizations involving DNA and RNA, antibody to antigen bondings, and various ligand to various receptor bondings. The detection of the selected molecules may be of primary interest in its own right, but may instead be of primary interest in indicating the presence of some other analyte molecule, species or organism.
An assay to measure the presence and concentration of such is begun by applying a sample solution containing various kinds of molecules, possibly including the molecules selected for detection, to the sensor along with label molecules attached to label magnetizable beads (or magnetic material particles) also present in the sample solution or in a supplemental solution concurrently also applied. The binding molecules through specific bondings, or recognition events, capture the selected molecules or the label molecules attached to label beads, or both, and thereafter hold them at the corresponding capture sites, i.e. the sites of the binding molecules undergoing such a bonding.
Label molecules on label beads are needed so that the occurrence of a recognition event leads to some measurable signal to indicate that a selected molecule was found present. One kind of label bead for doing this is a paramagnetic material bead having magnetizations that depend on externally applied magnetic fields. Application of such an externally applied field forcefully draws away any unbound label beads leaving the bound label beads at the capture sites while also magnetizing those bound label beads. Magnetic field detectors at the capture sites must sense the anomalies introduced into the externally applied field by the presence of bound label beads to produce the desired signals indicating the number of, and possibly the location of, such bound label beads. From this information the number of selected molecules, and kinds thereof, in the sample solution can be determined.
Such label beads can range in magnetic material composition from pure ferromagnetic material (e.g. permalloy) to small percentages of paramagnetic material encapsulated in plastic or ceramic spheres. As indicated above, such label beads are typically coated with a chemical or biological species that selectively binds to the selected molecules in an analyte of interest including DNA, RNA, viruses, bacteria, microorganisms, proteins, etc. to define the assay function, or the kind of recognition events, to be associated with that bead.
However, the label beads must typically be very small, that is, on the order of a few to tens of nanometers (nm) up to may be a hundred or so or even up to a few microns in some instances. As a result the anomalies in an externally applied field will be very small. The capability for detection of such very small magnetic material particles in a microfluidic flow system has many uses. The presence and the motion of a particle in a flowing liquid relates to the velocity of the flow stream, to the transport of a particular species that may be connected to the particle, and to the results of any biochemical binding events occurring in connection with such flows, including with the species in such particle flows.
Detecting individual magnetic material particles in microfluidic flow streams is difficult in many such situations. Several magnetoresistive devices have been previously fabricated for this purpose. There has been some success with these devices, particularly in detecting relatively large (13�18�85 μm) segments of ferrofluids in such flows. These segments filled an entire microfluidic channel in the detection device, and were directed so as to pass over some "giant magnetoresistive" effect (GMR) magnetic fields detectors formed from two ferromagnetic layers, such as permalloy material layers, being separated by a sufficiently thin conductive layer such as copper.
A significant difficulty in extending such detection technology to the detection of individual ones of the magnetic material particles in such flows is that a single particle is not necessarily confined to a specific location in the cross section of a microfluidic channel during such flow of the ferrofluids. Thus, a 1.0 μm diameter particle may stray up to 17 μm from the bottom of an 18 μm deep channel, or it may hug the bottom, the left side, or the right side of that channel. This lack of certainty in position in the flow channel leads to drastically different magnetic field disruptions or anomalies (magnetic intensity vs. time) due to those otherwise substantially identical particles passing by the magnetic field detector. These differences in field disruption characteristics result in a smaller probability of the magnetic fields detectors being able to distinguish disruption signals due to magnetic material particles passing the detector from background magnetic fluctuation noise, and so both in making quantitative calculations of particle magnetic properties and in counting each particle separately in flows of multiple magnetic material particles. Thus, there is desired a magnetic particle detector arrangement that provides for better detection of passing magnetic particles in a liquid flow entraining to an extent such particles.
The present invention provides a ferromagnetic thin-film based magnetic field detection system having a substrate with a magnetic field sensor supported on at least a portion thereof at a sensor location. A channel base material is supported directly on at least a portion of the substrate but without being across the magnetic field sensor from the substrate so as to form sides of an extending opening at the sensor location that extends past the magnetic field sensor in at least two directions to thereby form an extended channel gap in the channel base material across from at least a portion of the sensor location. A first electrical conductor is supported on the substrate positioned at least in part along the channel gap and in direct contact with at least some surface of the magnetic field sensor. A second electrical conductor is supported on the substrate positioned at least in part along the channel gap in a region thereof adjacent to, but separated from, the magnetic field sensor.
Detection of individual magnetic material particles in a liquid flow entraining them to some extent is not so difficult for many larger size magnetic material particles (Dynal 2.8 mm diameter particles, for instance) because the intrinsic signal to noise ratio is very large. As such particles get smaller, however, the detection problem becomes more difficult.
Confining small magnetic material particles entrained to an extent in a liquid flow to specific parts of the cross section of the flow channel so as to pass a particle detector, however, greatly enhances the detectability of single ones of multiple particles in such flows. Furthermore, confining particles to that part of the cross section of the flow channel that is nearest to the magnetic field detector increases the magnitude at that detector of the magnetic field disruptions that result from the passage thereby of single ones of the multiple particles in the flow.
Controlling both the flow speed and the location of particles in the channel cross sectional planes, at least in the vicinity of the detector, is needed so that the magnetic field disruption due to a passing particle is predictable. Combining a magnetic field sensing based magnetic material particle flow detector with a magnetic material particle path director results in the particle path director applying magnetic field based forces to passing magnetic material particles in a liquid flow such that those particles are confined to a small fraction of the total cross section of the operating flow channel near the magnetic field disruption detector. Thus, this magnetic field disruption detector is situated near the flow channel, and on that side or bottom of the channel to which the particle director is confining the particles entrained in those flows.
In a dilute aqueous suspension, the magnetic force Fmag acting on a superparamagnetic particle in a magnetic field of free-air inductance B in free air is given in SI units as
where V is the particle volume, χ is the magnetic susceptibility of the particle, and μ0 is the magnetic permeability value in a vacuum. Since the current density J within the microchannel equals zero, Amp�re's law (∇�B=μ0J) indicates that the curl of vector B vanishes within the volume element defined by the microfluidic channel. We can therefore use the vector identity ∇(B.B)=2B�(∇�B) +2(B.∇)B to transform the previous force equation into
The magnetic force acting on the particle can now be calculated using this last equation. Because of the flow channel geometry (long and narrow), and because of the use of current straps entrenched along the bottom of the channel form the particle director, the analysis can be reduced to being based on two dimensions rather than on three dimensions. Thus, the magnetic field present at any point in the area of a cross section of the channel can be calculated based on the external field present thereabout, including the sum of an applied field from a source thereof external to the immediate channel vicinity and the particle director current-induced field contributions as determined from the Biot-Savart law.
For the director to work effectively, the width and the position of the channel must be designed relative to the current straps in such a way that particles experience only the field above those current strap conductors extending along the channel length, conductors that are also used to interconnect to external operating circuitry the detector in that channel through being in contact with it either at the bottom or top surfaces thereof depending on the structure chosen for the current straps. That is, the direction of the magnetic field based force on particles due to the downward field gradient must be relatively uniform.
A particle trajectory in the plane of corresponding ones of channel cross section areas can be derived from the equation of motion involving viscous-drag forces in the liquid flow and channel region magnetic field based forces, or
where m is the mass of a particle, v is the particle velocity down through the flow stream in the plane, α is the particle diameter, and η is the dynamic viscosity of the carrier fluid which typically is 0.890 mPa at room temperature. The basic behavior of a magnetic material particle near a current carrying conductor at the bottom of a channel transporting a fluid entraining such a particle can be understood by considering the simple situation of no other magnetic fields present other than that due to such a current. The vector direction of the magnetic force is then always pointed at the conductor, and the magnitude of the force grows as the particle approaches the conductor. The lowest magnitude of force, then, is experienced by the particle at the furthest possible distance from the conductor. Solving the last equation is complicated if the changing magnetic force versus time is taken into account. But the maximum time required to draw the particle towards the conductor can be calculated by using the lowest value of the magnetic force on the particle (i.e. the force on the particle at its largest distance from the condutor). Assume that Fmag is a constant perpendicular to the z-axis. The particle will then accelerate along the direction of the force, and the velocity dependence on time is obtained from integrating the last preceding equation to yield
The basic result is that the magnetic material particle is attracted towards the conductor, and reaches some terminal velocity toward the conductor with a magnitude that is determined by the parameters of viscosity, particle mass, and particle diameter. Of course, the velocity towards the conductor goes to zero once the particle hits the conductor. There may be some "bouncing" although this is generally damped out by the fluid friction.
The time required for the particle to be "captured" by the conductor is calculated by integrating this last equation versus dt to find y(t). This is the maximum time for capture as the lowest possible value for the magnitude of the magnetic force generated on the particle was used. Once the particle is captured, the magnetic force continues to hold it near the conductor until other forces are applied to disrupt it. Further description of these trajectories of particles through the fluid will be provided following the description of some specific structures that take advantage of this effect.
An arrangement representing an implementation of the structures described in the foregoing is shown in
A silicon nitride layer, 11, is provided over the substrate to support a GMR magnetic field sensor, 12, having tapered or triangular shaped ends, and to further support the flow channel side walls, 13, so as together form a basic structural channel. Side walls 13 in turn support a channel cover, 13′ as indicated in
The fragmentary cross section view of this channel in
The coordinate system to be used in connection with describing matters in connection with channel cross sections is shown in more detail in
Turning again to describing the forces on, and trajectories of, magnetic material particles entrained in a flowing fluid system, the net magnetic force on a linearly magnetizable particle can be calculated using the second equation given in the description above. Qualitatively, this equation indicates that the particle will be attracted to the point where the B field magnitude is largest. In contrast to the description above of particles being attracted to current carrying conductors, where the current carrying conductor was assumed to be the only source of magnetic fields, the addition of other field sources can result in generating stronger and more locally controllable magnetic forces on magnetic material particles. An effective addition is the presence of a large and uniform externally applied magnetic field, as shown in
The magnitude of the magnetic field B due to electrical current in the special case of an infinitely long wire is given by |B|(Tesla)=μo I/(2πA) where μo =4 π�10−7 Henries/meter, A is the vector distance away from the wire, and I is the magnitude of the electrical current in the wire in Amps. The orientation of B due to this current in the wire is always perpendicular to the wire and to the vector distance and has an algebraic sign according to the right hand rule. This infinite wire approximation is appropriate when the distance from the point to the wire is much larger than the wire diameter, but much smaller than the length of the wire. These conditions are true in the outer and upper regions of the microfluidic channel.
Because of the radially symmetrical nature of the magnetic field due to the conductor just beneath the channel, the field is simpler to describe in terms of A, θ, and z (cylindrical coordinates). Take the y axis as θ=0, the −x axis as θ =−90, and the +x axis as θ=+90. Also, nA is the unit vector in the direction of A, nθ is the unit vector in the direction of θ, nz is the unit vector in the direction of z, nx is the unit vector in the direction of x, and ny is the unit vector in the direction of y. A, θ, x, y and z are the scalar values of the vectors A, θ, x, y and z, respectively, and carry both magnitude and algebraic sign thereof.
Far away from the conductor, the conductor can be considered to be at the origin of the coordinates. Then the field in the channel can be rewritten as:
B x=[μo I/(2πA)cos θ]+B applied−x and B y=[μo I/(2πA)sin θ]+B applied−y.
The force magnitude for two situations where the magnetic material particle is far away from the wire can be calculated. Assume that Bapplied is uniform and along the x-axis, so
In the top center of the channel, θ=0. So the forces simplify to:
F mag A =[Vχ/2Aμ o ]{−2(B applied x)[μo I/(2πA)]−2[μo I/2πA)]2} and
Fmag θ=0.
In the bottom left corner of the channel, θ=−90. So the forces simplify to:
F mag A=−2[Vχ/2Aμ o][μo I/(2πA)]2 and
F mag θ=+2 [Vχ/2Aμ o][μo I(2πA)](B applied x).
In the top center channel (θ=0) situation, only the A component is nonzero, meaning the force and trajectory are directly down toward the conductor along the A vector. In the channel corners, there are both A and θ components of the magnetic force. The A component is, again, directly towards the conductor. The θ component, however, is perpendicular to the A component, and directed away from the channel bottom. One way to understand this is to see that, at a fixed distance from the conductor, the field magnitude is always largest at θ=0 because there Happlied and the wire field are exactly parallel. As indicated above, the tendency of the particle is to move toward the region of largest field magnitude. The trajectory of a particle in the bottom corner is a combination of upward and toward the conductor motions. As the particle gets further from the channel floor, θ gets closer to zero, and the θ force component decreases. At the same time, the A force component increases as the distance from the conductor decreases. In any event, while the detailed trajectory of a particle attracted from the corner to the conductor is more complicated than that of one attracted from the center top, the net result is that the particle is always in motion toward the conductor until it hits that conductor.
The equation used above to approximate B in the channel in the vicinity of a conductor is only appropriate at values of A much larger than the conductor dimensions. The equation goes toward infinity at small values for A which is clearly non-physical. For close-in calculations, B can be reasonably calculated using Ampere's circuital theorem:
Thus, a conductor beneath the channel with a length that is largely along the channel extent is useful for directing magnetizable particles moving with a flowing fluid in the channel. This conductor attracts them and holds them near so long as the particles are in the director region. The design of this region must be such that the time for a magnetic material particle to be directed to the immediate vicinity of the conductor is less than the time for that particle in the fluid flow through the channel to traverse the entire region of the channel containing that director.
As the basis for a specific example, consider the properties of commercially available magnetic material particles and liquids:
The magnitude of the terminal velocity toward the director from the fourth equation in the description above is found from setting t=∞ which yields
The characteristic time in the exponent in that equation is the reciprocal of the factor multiplying time in that exponent or
So, the particle in being first attracted towards the channel bottom, reaches an initial speed of about 1100 microns/second, and it reaches that speed in less than 1 microsecond (during which time it travels about 1 nm towards the attracting conductor). In this example, the characteristic time is orders of magnitude less than the time to travel to the wire. The longest time for this particle to reach the wire from the top of the channel is 35 μm/(1100 μm/second)=32�10−3 seconds. The actual time is less because the attractive force grows as the particle approaches the conductor rather than staying constant.
The design of a director region must be such that the desired particle route resulting from the directing of the particle takes place in within the time available for performing such directing. Assuming a lateral flow speed of 1�10−3 meters/second. The director region would have to be at least 32�10−6 meters=32 μm long to capture magnetic material particles in the fluid flow at the top of the channel. This is approximately the same as the channel depth. The directing force at a corner of the channel is considerably smaller, and so the resulting time required for the particle being directed from there to complete the desired route is longer. A more conservative design for the above example would have the director region extend along the channel for about 300 μm of channel length.
The plots shown in the graphs of
Assuming that the dimensions of the detector surface facing the flow are 1.4 by 2.8 μm (2 squares), its electrical resistance would be about 20 Ω. Using 1 mA of excitation current through the detector, the total voltage across the detector would then be 20 mV. Assuming a 5% resistance change over 100 Oe, or 5%/100 Oe=0.05%/Oe, the detector output signal voltage is 20 mV�0.0005/Oe=10 μV/Oe.
The Johnson noise developed in a 20 Ω resistor is about 0.5 nV/√{square root over (Hz)}. Supposing 10 times this quantity of Johnson noise at the measurement frequency (approximately 1000 Hz), the noise density including 1/f noise would be 5 nV/√{square root over (Hz)}. Making an amplifier with a Q of 10 (frequency of measurement/bandwidth) is not too difficult allowing the assumption of a bandwidth of 100 Hz. Then the root-mean-square (rms) noise in the measurement band is (5 nV/√{square root over (Hz)})�(√{square root over (100 Hz)})=50 nV. Thus, the effective field noise is 50 nV/10 μV/Oe=5 mOe rms. Considering
Although there are many geometrical and circuit arrangements for GMR detector 12,
A more complete showing of the bridge circuit is shown in
The output voltage signal from the bridge is substantially zero in value in the absence of a magnetic particle proximate detector 12 because of the balanced electrical currents in the two sides of the bridge circuit between the conductors merger locations in these circumstances. As a particle 16 passes over the region of magnetoresistor 12′ in being entrained in liquid flowing in the operating channel, this output voltage signal will become negative, and will then become positive as it subsequently passes over the region of magnetoresistor 12″. If output voltage interconnection 17 between these two magnetoresistors in the detector channel bridge legs is relatively narrow compared to the particle size and those the lengths of bridge circuit legs in the channel, the output signal voltage waveform in connection with single magnetic particle passing over the detector will, to a degree, approximate a full sine wave.
The detector configuration can be varied and enhanced. An advantage can be obtained in some circumstances by electrically separating the magnetic detector and director. This arrangement is shown in
One advantage in separating magnetic flow detector 12 v and magnetic flow director 18 is that the electrical current magnitude requirements may be different for the two devices in view of their different purposes. For example, the GMR resistor may be able to handle only 2 mA without generating significant internal heat. The director wires are much thicker than the GMR resistors, and the magnitude of force applied by them is proportional to the electrical current, and hence currents of magnitudes around 50 mA may be desired in some situations for director 18.
Another advantage in separating magnetic flow detector 12 v and magnetic flow director 18 is the ability to operate them independently. One example is choosing to switch the algebraic sign of the applied magnetic force in a director through switching the direction of electrical current therethrough without concurrently changing the operation of the detector. Another advantage is that director 18 may be a composite of more than one wire, and so be too complicated to conveniently be attached to detector 12 v.
Flow channel sidewalls 13 can be spaced from 5 μm to hundreds or even thousands of microns apart (50 μm being typical) with the channel depth being from a few microns to hundreds of microns (35 μm being typical). The GMR magnetoresistors are typically 2 μm wide and the interconnections are typically 1 μm wide. The bridge is positioned so that one of the four GMR magnetoresistors, 22′″, is underneath the path that directed magnetic particles are most likely to take as a result of the influence of the director. This path is shown in the figure to have been chosen to be in the center of the channel though this is not a requirement.
The modified GMR sensors are electrically connected to one another and to external circuitry by overlapping the structures of GMR magnetoresistor 22′, 22″, 22′″ and 22 iv directly over entrenched Cu interconnection conductors 24 but with the upper surfaces thereof exposed except as covered by such magnetoresistors or by layer 15 provided to form the operating bottom surface of the operating flow channel set in the basic structural channel. The starting point for the fabrication process leading to these structures is a silicon wafer, 10′, as part of substrate 10 which wafer may have monolithic integrated circuits therein providing capabilities for operating the directors and detectors, and for amplifying and processing detector signals. The silicon wafer so formed is coated with a layer of a positive photoresist polymer material, 10″, the material being B-staged bisbenzocyclobutene (BCB), to a thickness of approximately 2 μm to complete substrate 10. Recesses of the shape and depth that conductors 24 and 27 are intended to take are etched into the BCB using standard photolithography techniques and reactive ion etching (RIE) to form substrate 10. The recesses are about 1 μm deep.
A silicon nitride layer, 11′, about 40 nm thick is deposited over all of the recessed layer of BCB and so into the recesses. A thin adhesion layer, 20, of about 4 nm of Ta is deposited over the entire nitride layer 11′ and so into the recesses. The material for magnetoresistor interconnection conductors 24 and external connection conductors 27 is electroplated Cu, which is plated on in a thick blanket (˜2 microns) over all of adhesion layer 20 and so again into the recesses. A chemical mechanical polishing (CMP) tool is used to remove unwanted Cu and Ta from the wafer, leaving Cu and Ta only in the recesses to form conductors 24 and 27 in this damascene process, and leaving also the exposed portions of silicon nitride layer 11′ on the top of BCB layer 10″ where not recessed.
The GMR magnetoresistor structures films are deposited and patterned in a well known manner to leave film structures that are about 30 μm long and 2 μm wide that serve to provide the desired GMR magnetoresistors 22′, 22″, 22′″ and 22 iv resulting over the gaps between magnetoresistor interconnection conductors 24. Remaining portions of these film structures are on the corresponding portions of conductors 24 to thus be electrically shorted by these conductor portions so that the magnetoresistors indeed occur just over the gaps between the various interconnection conductors 24. The film structures width versus length aspect ratio is a component of their magnetic design, which affects the performance of the sensors in terms of hysteresis and sensitivity (mV per unit applied magnetic field). Passivating film 15 is formed by depositing silicon nitride in a vacuum sputtering system to a thickness of about 10 nm. Other dielectrics such as silicon dioxide can instead be substituted therefor.
These layer diagrams in
There are several advantages to using the above described fabrication process. The topological profile of the GMR sensor in the flow channel is very small, about 10 nm. And the profile of the associated interconnections and director conductors is essentially zero nm. This means that there is little disturbance of the flow as it passes over the GMR sensor region. Very small magnetic particles can come extremely close to the detector and director without getting snagged or trapped by the bumps there. Another advantage is the great freedom of device design. Because the Cu conductors are beneath the channel surface, the channels can be of arbitrary width and orientation with respect to the detectors, directors, and associated circuitry. The SU-8 UV-curable epoxy is also very versatile for channel formation. It can be spun on and exposed in thicknesses ranging from <2 microns to 1000 microns. The aspect ratios can be much greater than 1, and the sidewalls of this material are rather sharp. Furthermore, the SU-8 cured epoxy is fairly impervious to water, biological buffers, and organic solvents. This is a great improvement over other means of forming channels such as PDMS, which absorbs water and gas. The wafer-to-wafer SU-8 bonding procedure for forming lids also leads to the ability to have multi-layer wafer-scale fluidic structures on the sensor chip.
In situations in which an applied external field Hext, as indicated in
The interconnections conductors 27 for connecting director 18′ to external circuitry, provided at the opposite ends of director 18′ under the channel, are designed to form a current path away from the field concentration region that minimizes forces acting on the magnetic particles in the channel due to the fields generated by the corresponding currents in those interconnections. For example, the conductor forming director 18′ splits two ways taking right-angle turns because current in wires along these directions will not generate appreciable magnetic forces as indicated above. The conductor is divided into six parallel conductors in order to further minimize the stray fields from the conductor end structure, and to minimize the electrical resistance. As indicated above, wider conductors are formed this way rather than by making a solid wider conductor because the CMP tool for Cu removal in the fabrication process following the blanket Cu plating operates best when all the conductors are the same width.
The channel shown in
A further alternative embodiment for director 18 for directing the routes of magnetic particles in the channel is represented in the top view shown in
A wide variety of uses exist for devices that can differentiate between individual particles, on the one hand, and pairs of particles on the other that are bound together through specially designed biochemical action based binding. Particles are commonly provided with coatings that allow them to bind to DNA, proteins, or other molecules of biochemical interest, or some combination thereof. One common way to use these particles is to capture an analyte of interest on some convenient surface, and then capture the coated label particles on the "other end" of the analyte. The analyte is thus "sandwiched" between the surface and the particle label. The number of particles per unit area in this sandwich can be used as a quantitative measurement of the supply of analyte in the fluid being assayed for same.
The flow based magnetic material particle detection system described above replaces the surface indicated above (typically a flat surface, a glass slide, for instance) with another coated label magnetic material particle. Thus, two specifically prepared label magnetic material particles, bound together "sandwiching" an analyte of interest between them for which the concentration thereof in the assay fluid is to be measured, represent a countable entity whose quantity is related to that analyte concentration. A cross section view diagrammatic representation is shown in
This capability can result in a general purpose biochemical assay tool where the chemistry is performed on a particle rather than on a more or less flat surface. Such assays can be performed in real time in a continuous channel flow arrangement, and the labeling particles can be recycled assuming appropriate analyte-release and label particle-recovery steps are performed.
Many desired investigations material samples of interest based on using magnetic material particles with such samples involve performing multiple operations on the particles with such samples through magnetic field manipulations of those magnetic material particles. For example, first concentrate the magnetic material particles bound in some way in some sample, and then count the number of particles in a flow of that sample. In addition, a sort of various types of magnetic particle based objects (e.g. magnetic labels in connection with biological cells having the magnetic labels on them) may be desired followed by performing a subsequent counting of the sort categories. Magnetic manipulation based devices offering multiple operations on objects based on magnetic material particles require self-consistent magnetic devices designs where sorting, concentrating, directing, and detecting functions are all to be provided on the same monolithic integrated circuit chip that is fabricated in a single manufacturing process common to all. The external field that is applied to operate the directors must also, to the extent needed, operate the GMR sensors, the sorters and the concentrators, etc., or at least not prevent such operation where not needed for the operation.
This need for self-consistency in the chip structures used and their fabrication forces choosing magnetic field biasing and manufacturing processes in advance of performing chip designs. Some of these choices can seem needlessly limiting in the context of a single particle manipulation or sensing device, but are essential for chip structures with more kinds devices contained therein. For example, the externally applied magnetic field has only been described above being directed across the primary channel extent direction in the flow direction parallel to the channel bottom and perpendicular to the direction of primary channel extent and the direction of fluid flow. This does not, however, indicate that other orientations or modes of magnetic field biasing are impossible. Rather, changing the direction of the external biasing field to be across the channel in direction perpendicular to the channel bottom (along the y-axis) for example, requires redesigning the sensors, sorters, and directors. Some advantages of external magnetic field biasing shown in connection with the devices described above are that it generally allows better optical access to the chip, and simpler mechanical design of the field generation structures. Biasing field excitation along the y-axis, on the other hand, could allow larger field magnitudes with the same power, and may allow much greater field magnitudes without saturating the magnetic detector response (the detectors are typically not very sensitive to fields directed across the film stack forming the detectors).
A self-consistent design arrangement for magnetic structures and the fabrication process therefor can be described by the use of distinct "operational locations" where the various magnetic manipulation and sensing operations are being performed. For a biological cell counter, the operational locations would be those for 1) a gatherer, 2) a sorter), and 3) a detector, with the possible addition of 4) a splitter (channel splits to split flows). Each operational location is designed for a certain fluid flow rate to have the length thereof be long enough to assure that the corresponding operation is performed within the time that the magnetic objects are within the location extent. The device in each operational location is designed to have minimal magnetic influence on the devices in other operational locations in the system. The various operational locations in a chip are connected to each other through the flow channel, and in the appropriate sequence.
In microfluidic systems such as the those being described herein, the flows may be characterized as being "laminar." This means that there is very little turbulence, little random action, and the fluid is carried in a very orderly fashion downstream (z-direction) without significant mixing in the x- or y-direction. Such flows mean that magnetic objects entrained therein that are within a certain region of the channel cross section on leaving one operational location in the overall flow system can be expected to stay in that region as they flow downstream to the next operational location. For example, when magnetic particles have passed through a director operation location, and they have been drawn down to the sub-region of the channel cross section at the middle and bottom before leaving that location; they can be expected to remain in the middle and bottom sub-region of the channel cross section as they are transported in the flow to pass into a detector operational location downstream. There are some important exceptions to this general rule having to do with the nature of particle interactions with channel side walls 13, and the tendency for the middle portions of a flow in a channel to have a higher flow rate than the portions near the channel walls, bottom and lid.
Distinguishing magnetic material particle pairs, or bead pairs, from single particles, or beads, requires forces to be generated in the channel that pull the label particles, or label beads, apart from each other. Typically, this is not achievable with macroscopic magnets because the influence of the magnet pulls both analyte joined beads in the same direction. Also, the applied magnetic field generates a magnetization, M, in both of the beads having the same orientation in each which tends to cause them to attract each other. Thus, a manipulation structure is needed where magnetic fields and field gradients are formed on a length scale on the order of the dimensions of the magnetic material beads. Such an arrangement will allow the directions of forces on the pair of beads to be opposite one another toward opposite sides of the operating flow channel.
In doing so, the pairs of joined magnetic material beads have to be oriented with the binding between them directed across the channel so as to each be in the channel cross section plane as shown in
In these circumstances, the currents into the plane of the cross section view in the outer two conductors beneath the channel representation in
Another arrangement for generating a mutually repulsive force between beads 16 and 16′ applies a field out of the plane of the bottom of the channel directed upward, while keeping the beads oriented across that plane, as shown for two further beads, 16″ and 16′″, in
One solution for these problems is to simply stop applying the externally applied field and establish electrical currents in conductors positioned on the channel sides as shown by rectangular shaped conductors in such positions in
Part of the solution to the problem has to do with the relative size and magnetic content of the beads. If the beads have a magnetic core whose radius is significantly less than the total bead radius as shown for beads 16″ and 16′″ in
A director, 18′″, for directing paired magnetic objects in the channel between side walls 13 is shown in the top view of
The pair of conductors is shown with a typical center-to-center separation of approximately 2.8 μm, which is ideal for guiding the motion of pairs of 2.8 μm diameter beads through this director location. Particle pairs, after being subjected to the guiding forces of the magnetic fields generated by the currents in these two conductors, travel out of the paired device director location along the fine dashed lines shown. The size and separation of the wires can be scaled to appropriately match the size of paired magnetic objects chosen to be directed by this device. The channel width is shown with a typical value of 50 μm. The length of the pair director wires is not shown to scale, and is again typically a few hundred microns to be whatever is required by flow velocities and magnetic object properties.
Electrical currents, in use of the device, are established as indicated by the fine arrows in the conductors through the conductor pairs in director 18″″ that are located immediately beneath the channel. These conductors are typically 1 μm wide, and the channel is typically about 50 μm wide. The length along the channel of this device, as with previous devices, is much greater relative to the channel width than represented in the diagram, and is typically about 400 μm for a 50 μm by 50 μm cross section for the channel.
As particle pairs flow downstream into the pair gatherer location, they are attracted towards the inner member of the two pairs of conductors but repelled by the outer members because of the currents in the outer members of the two pairs being in a direction opposite to the direction of current in the corresponding inner members thereof. This repulsion keeps the pair from traveling outside of the two pairs of conductors of the device. When the paired particles reach the downstream end of the gatherer 18″″, they naturally are attracted by both of the inner members of the two pairs of conductors, and so line up with one particle over the inner member of one, and the other particle over the inner member of the other. Paired particles travel out of the pair director location along the fine dashed lines shown.
There can be advantages in some situations to attracting and directing magnetic objects along more than one or two sub-regions about a corresponding conductor in the cross section of a flow channel.
Paired particles enter first an upstream particle pair splitter device in the channel bottom regions along the two dashed lines shown. Section A has three parallel conductor branch portions to form this device with the outer two portions carrying electrical current in the fluid flow direction and the conductor branch portion between them carrying current in the reverse direction to thereby generate splitting forces on the pairs as described previously to result in splitting apart the more loosely bound pairs. Section B has three conductor branch portions that diverge away from one another to varying degrees along the fluid flow direction with the outer two portions carrying current in the fluid flow direction to attract single particles in the flow toward the sides of the channel, and the portion between them carrying current in the reverse direction which has an insignificant effect on still bound paired particles leaving such bound pairs moving along the bottom center.
These still bound pairs move to the centrally located parallel split conductors in section C which gathers these pairs to keep them moving along the channel center and bottom following the centered, nearby one another, dashed lines. The unbound individual particles move out of the device along the widely separated dashed line paths near the channel side walls, and along the channel bottom. Thus, GMR magnetoresistor detectors can be positioned downstream aligned with these dashed lines to detect both individual and paired particles. In some instances, the microfluidic channel may be split into two or more channels just downstream from such pair splitter and sorter location.
The purpose of the sorter is to physically separate large and small magnetic material objects. An example, depicted in
The repulsive conductor repels because the electrical current therein is flowing opposite to that in the attractive conductors. This current direction is indicated by the thin arrows in the three conductors. Because the three directors in this location are connected to separate external current sources, they can carry completely different magnitudes of electrical current, which allows for fine-tuning the magnetic force being applied to the magnetic objects being sorted. It also allows for using time varying signals such as a very large but short in time current burst in the second attractive conductor. The balance that must be found for a given set of objects is to make the attraction of the large objects to the second attractive conductor much greater than to the first, while maintaining a sufficient repulsive barrier to small objects following the repulsive conductor. These conductors are typically 1 μm wide, and the channel is again typically about 50 μm wide. The length along the channel of this device, as with previous devices, is much greater relative to the channel width than represented in the diagram, and may be several hundred microns long.
A further arrangement to create a force that tends to pull particle pairs apart is to use electrostatic forces in addition to magnetic forces. Particles with drastically different electrical polarization, or even excess electrical charge could be used. The sorting environment can be set up so that the force from electric fields and magnetic fields are opposite in direction and roughly equal in magnitude on the two particles. Then single electric and magnetic beads would be taken one way or the other, and paired ones would go straight (if using the 3-way sorter of
The detector array is another way of distinguishing between single particles and pairs. It can also increase throughput, and allow for distinguishing one magnetic particle size or type from another.
A non-ellipsoidal particle (say it is a rectangular solid with dimensions 1 micron�1 micron�500 nm for the sake of this discussion) can be made with a permanent (high coercivity) magnetic layer just beneath the surface. In the absence of an externally applied magnetic field, this permanent magnet generates stray fields will attract linearly magnetizable particles.
If a large external field is applied (larger than the magnitude of the stray field at the block's surface) the block will rotate in the fluid so that its magnetization is parallel to the external field. This assumes that the moment of the block is larger than the soft magnetic particle. Then, the magnetization of the magnetically soft particle will rotate to be parallel to the large applied field. This generates a repulsive magnetostatic interaction between the block and sphere. This can be used to cause non-specifically bound particles to separate.
In practice, there are several forces and energy scales involved. At length scales below 100 nm, the thermal energy of the fluid (Brownian motion) will be competitive with the magnetostatic attractive energies. Also, there are other fluidic forces in the flowstream that might act to pull particles apart (e.g. non-uniform flow velocities and differential viscous drag).
Although the present invention has been described with reference to preferred embodiments, workers skilled in the art will recognize that changes may be made in form and detail without departing from the spirit and scope of the invention.
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|U.S. Classification
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|International Classification
|Cooperative Classification
|European Classification
|Dec 20, 2005
Owner name: NVE CORPORATION, MINNESOTA
Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:TONDRA, MARK C.;ANDERSON, JOHN M.;BROWNELL, DAVID J.;ANDOTHERS;REEL/FRAME:017387/0174
Effective date: 20051219
|Sep 23, 2011
|Fee payment
Year of fee payment: 4
|Nov 24, 2015
|Fee payment
Year of fee payment: 8


text:
Quality Marine Hardware, Equipment and Boating Supplies.
Southern Seas Marine is Australian authorized distributor for
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subset: commoncrawl


text:
comparing values p_rgh and p
Hey there,
I have a problem at the moment that I unluckily can't solve using the search function of this board.
I need to compare values of total pressure (sum of dynamic, hydraulic and static pressure as in the Bernoulli equation) between two different cases, that use the same geometry but different solver and (now it becomes tricky) also a different OpenFoam version.
My case is new (OF 2.1.0, SIMPLE) and pressure is defined in p-file as [m^2/s^2].
To obtain total pressure from this, I think I have to multiply p*rho (=static pressure) and add rho/2*mag(U)^2 (=dynamic pressure). The hydraulic pressure should be neglectable (gas with a height difference of 10cm........).
The old case that I have to compare with, was set up in OF 2.0 (I believe, interFoam), but pressure is defined as p_rgh [kg/ (m*s^2)].
I found out that p_rgh=p-rho*g*h, but
1) is p in the equation above the same as static pressure in the Bernoulli equation? Would (static pressure in the Bernoulli equation) than be p.stat=p_rgh+rho*g*h ?
2) what steps should i perform to obtain a comparable total pressure from this?
Pressure differs from 1800 to 270, so I tried all kinds of conversions but end up with wrong numbers.
I am not sure if the flaw is within my case setup or caused by my misunderstanding of p_rgh.
Thanks for everyone taking time to answer my stupid questions.
Best regards,
Hello Simon,
I hope you have found an answer since your post but i prefer to post this answer to help you if you are waiting for this response facing your computer, with a very long hair.
p_rgh is a dynamic pressure, the exact definition is :
p_rgh = p - rho*g*h.
So you are right when you say :
p (the static one) = p_rgh + rho*g*h.
Have a good day.
|All times are GMT -4. The time now is 15:10.


text:
|1,100 sq. ft.
|Property type
|Minimum Stay
|2 nights
An authentic log cabin overlooking the Central Crossings Bridge on Table Rock Lake. Perched on a high bluff overlooking the White River, this cabin was built in 1934. Prior to the formation of Table Rock Lake, the logs were floated down the River and brought up the bluff. The fireplace rock came from the banks of the White River. I am proud to own this little part of Shell Knob history, and share it with my guests.
The Cabin has two newly remodeled bedrooms, one with a queen size bed and one with a full size bed; plus a queen size bed on a sleeping porch facing the lake. Full kitchen with dishes, cookware, small appliances and utensils. Coffee supplies provided, as well as linens and paper products.
This property offers direct access to the beautiful and clear waters of Table Rock Lake. There is a private boat dock available for our guests pleasure that features a boat lift and also has a large swim deck attached for hours of fun in the sun. Pet Friendly. Free WiFi. Open Year Round.
Thank You for taking time to check out my property. My name is Sharon Caddell; the proud owner of the Green Cocoon Lakefront Cabins located on Table Rock Lake in Shell Knob, Missouri. A native of Kansas City, I grew up coming to Table Rock Lake for family vacations and fell in love with the Ozarks. After 25+ years as Business Manager for a large architectural firm, I chose the quiet lifestyle of living, working and playing on Table Rock Lake. The best part of offering my cabins to guests, is sharing this special place with others.
Sharon Caddell purchased this cabin in 1987
Come fall in love with the rustic log cabin where history abounds. Our quaint neighborhood of High Dive was platted and established in the early 1930's as a cabin fishing retreat. Over the years, all the other log cabins burnt down. A little bit of history combined with access to Table Rock Lake makes this a fun spot to spend time ... rest, relax, and renew at the Green Cocoon.
The logs, the rocks, the bluffs, the outdoor shower, the stone fireplace, the private boat dock, the screened-in porch with views of Table Rock Lake ... what's not to love about this place.
This place was great. Loved the setting in the woods and having our own private dock. Love the character of the cabin. It's very old but well maintained and clean. The only challenge was that 2 kids had to sleep on the screened in porch (which they LOVED to start) but we got big storms at night and we had to squeeze them inside and it was tight. And, it didn't affect us because it was still cool in the eves, but there isn't AC on the porch so if it's July, heads up to future renters if they r counting on that bed. Could be pretty hot out there but it is the best room in the place! Would totally go back. Quiet, clean, yet rustic. The perfect getaway from the stress of life!
I have been to the Green Coccon many times over the years and have never been disappointed by the beauty of this cabin. It's gives me so much peace from the hectic and stressful job I have. They view from the porch is truly breathtaking. Our host Sharon is the best. The Mark Twain National Forest is very close by and the fishing is fabulous. From a romantic weekend t "peace seeking" for your mind, this is the place you want to be!
This place is ideal for a romantic get away. I will return here in a heartbeat. The cabin is truly rustic, in that the shower is outdoors. This turned me off at first, until I took my first shower - AMAZING. It is in an enclosed area, with a crazy view of the lake/mountains. Breath taking is the only way to describe it. The lack of TVs in the bedroom was also a VERY refreshing change of pace. The enclosed patio sleeping/dining/siting area was so much fun. I cannot say enough good things about this place. Plenty of room for 2 people, very romantic, perfectly rustic. The owner was excellent at communicating with us and was available all week by text to give me suggestions on places to go, things to do, and areas to stay out of ( we are runners and were trying to find places to run, but it was hunting season so luckily the owner warned us where to avoid!) She also was able to give us great recommendations on where to buy souvenirs for our family back home - and through that I found my favorite little store.
My only recommendation for here would be to take your own cooking supplies if you plan on cooking much. While the kitchen is stocked with pots & pans, the baking items (9x13 dish, anything like that) weren't available. Having said that, the owner was nice enough to put her crock pot in the cabin for us.
I cannot wait to return to the cabin. The location was AMAZING, literally steps (maybe 15) from the lake. The entire area was great, we took our dog and taking her for her daily walks was so fun in that area. This is truly a fantastic place to stay. We will be back!
Nice, clean cabin on the lake. Lakefront with good views and access to a dock just below the cabin. Quiet area. Comfortable beds and large living area. Some little quirks, small tub (showers around back), small tv but has dish. Also has a nice bed and seating area on the screened in back porch looking out at lake. So, in warm weather, it's a 3 bedroom. I would recommend to friends.
our experience at this lovely cabin exceeded our expectations. Mrs. Cadell's 100 year old cabin has amenities like central heat and air but hasn't lost it's rustic charm. The cabin is built in a rectangle with a spacious living room combined with a kitchen and dining room. The bathroom is off the main area as are the two small bedrooms. Of course, the walls are exposed logs and the old fireplace is stone. There is a comfy couch and oversized chair in the living room. There is a TV with cable and a DVD player. The Internet is spotty. The bathroom has a tub with a hand held shower. The second shower requires a short trip outside across the side deck. Don't let this dissuade you. It's almost "spa like". It is a small room built beneath the cabin. The owner has thought out and provided everything we needed in the kitchen - full sized fridge, oven, microwave, cooking and eating utensils.
The view from the back screened porch feels like you are in a tree house since it's elevated and gives you peeks of the lake below and the bridge beyond. We enjoyed sipping wine in the rocking chair and wicker love seat and relaxing away our time. There's also a small wooden table where we enjoyed breakfasts. The porch runs the full length of the cabin with a sleeping area at one end. The weather was unusually cool and a fan is provided so one member of our crew took full advantage of the sleeping porch every night of our stay.
The private dock is accessible for the sure footed down a path to the water. We fished without much luck but boaters in the area faired better. Some were even scuba diving under the bridge.
You will need to travel beyond the community of Shell Knob for most restaurants and activities but they are all just a short drive away. We sailed on Table Rock in a catamaran, tram toured Dogwood Canyon and dined aboard a vintage train in Eureka Springs.
The cabin owner, Sharon Cadell, is quite helpful and knowledgable about the area. She has appointed the cabin with what you'll need and want during your stay (also, she has a two person cabin next to this one). It is a good value for vacationers and we will recommend it to anyone wanting a good relaxing and fun stay in the Table Rock area.
Table Rock Lake offers boating, water sports, fishing, and endless hours of fun and relaxation. Roaring River State Park, Mark Twain National Forest, Piney Creek Wilderness, Silver Dollar City, Bass Pro, Dogwood Canyon Nature Park all close by. One hour to Springfield, Branson, Rogers & Eureka Springs.
|Rate Period
|Weekend Night
My Standard Rate
2 night minimum stay
|Notes: Rates are based on 4 guests; add $25 per night, per additional guest
|Pet Fee
|$25 + Tax
|Tax Rate
Rates are subject to change until reservation is confirmed. For guests that are bringing a boat with them, please be aware that there are special arrangements for boat launching and trailer parking due to steep driveway.


text:
Server is running SQL Server 2005.
This is my first trek into getting SQL Server to create output files of data.
I wanted to design a stored procedure that would take a single parameter, grab results from another stored procedure using that parameter + other hard-coded ones, build a temp table, and then output only the columns that are needed into a tab-separated file on a network drive that would then be accessible by the user. The procedure would by fired by a user from within the ERP system.
I have gotten started enough to learn about osql, sqlcmd, xp_cmdshell. Xp_cmdshell is disabled by default and I will not enable it without fully understanding the repercusions. I am to the point of having several questions and wondering if anyone out here has attempted something similar. Will the shell even be able to extract results from a temp table? Is there another, perhaps better way? If xp_cmdshell must be used what are the best practices are for enabling it? [Change service account to account with limited OS privileges, etc.]
6 Replies
Jun 1, 2011 at 4:46 UTC
See if MS TechNet is helpful http:/
Jun 2, 2011 at 8:12 UTC
The package would have to be capable of doing a couple of things I can think of right off the top:
1) create a unique filename
2) accept a parameter and pass it to the view / query
Remember, this is dynamic data that is governed by the parameter. Also the resulting filename has to be unique enough so that existing files are not overwritten. From what I see so far, the wizard does not support this in building the export package, at least in 2005.
Jun 2, 2011 at 8:38 UTC
I have successfully used code similar to this link:
http://www.sqlteam.com/forums/topic.asp?TOPIC_ID=49926%C2%A0; (number 5 is most likely the best route). Sometimes this business is best handled inside an internal web page where its all server sided and is driven through the web asp page and results are displayed on the page. If you need a physical file then this wouldn't fly.
The challenge becomes permissions and whether the user can launch the proc on the server side. If client side, then exposing the connection string becomes problematic. If the user group is not huge (a dozen or so) setting up ODBC connections ahead of time can eliminate that concern, but it becomes a maintenance issue if you change SA passwords often.
Jun 2, 2011 at 9:40 UTC
Ah, that reminds me that I was going to look into OPENROWSET as a possibility.
The security is setup within the ERP system so I do not anticipate any issues there as far as getting the stored proc to run. The problem security area is where xp_cmdshell is involved because it must be enabled, and since the ERP system is hitting the proc with a sysadmin account, that will run under the context of the SQL Server service account. So one thing that seems to be suggested is to make sure that account does not have local admin rights. How it runs without local admin rights I cannot imagine, but will see I guess.
The bigger question I think I have with using xp_cmdshell is whether the data can be read from the temp table of results I am creating in the sp. If it cannot, then I have to create a hard table with a little more smarts to manage the output and cleanup afterwards.
At the moment I might just try and bring the data back into the ERP system and do a vb.net script to output to a file from there.
Jun 2, 2011 at 10:24 UTC
Isn't this what SSIS (SQL Server Integration Services) is all about? I had plenty of experience with DTS (Data Transformation Services), it's previous incarnation, and we did stuff like this all the time in our data warehouse.
Jun 2, 2011 at 12:42 UTC
If you can pass in a user supplied parameter, execute on demand, then sure. I am not talking about reading data from existing tables. Problem is, it cannot be 'like' this - it either is this or it isn't. And that is my question.
Maybe I could think along the lines of the user operation dumping in the data, and then using a package that is scheduled to run in a short time frame to manage and control the creation of the file. However, I have to be able to manipulate the name of the file for the reasons stated.
I know from the wizard these things are not possible, but maybe there is more on the backend. I will keep SSIS / DTS in mind and dig into it in more detail.
This discussion has been inactive for over a year.
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Pandora Media shares are up 3.6%
Pandora Media shares are up 3.6%
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Pandora Media shares are up 3.6%
Shares of Pandora Media are up more than 2% in premarket
Pandora Media shares are up 5%
Shares of Pandora Media Inc. fell nearly 2% after the market opened on Tuesday following news that Founder and Chief Executive Tim Westergren is officially stepping down. Westergren will also no longer sit on the company's board. Reports over the weekend had said Westergren was expected to exit the company. The internet radio company said the board of directors will begin the search for a new CEO immediately. Chief Financial Officer Naveen Chopra will serve as CEO in the interim. Pandora said it will fill Westergren's seat on the board with Jason Hirschhorn. "Tim stepped in to be CEO at a critical time for the company and was quickly able to reset relations with the major labels, launch our on-demand service, reconstitute the management team and refortify our balance sheet by securing an investment from Sirius XM," said board member Tim Leiweke. Pandora recently secured a $480 million investment from Liberty Media Corp.-owned satellite radio company Sirius XM Holdings Inc. , while also selling its Ticketfly business to Eventbrite for $200 million. Pandora has been struggling to compete with other on-demand music streaming services, like Apple Inc.'s Apple Music and Spotify. Its recent moves give it the cash necessary to move forward with its new subscription-based on demand service, but some analysts believe that might not be best opportunity for Pandora. Shares of Pandora are down more than 36% in the year to date, while the S&P 500 index is up nearly 9%.
Pandora names CFO Naveen Chopra as interim CEO
Pandora says Jason Hirschhorn is joining board
Pandora says board will begin a search for a new CEO immediately
Pandora says Westergren will also leave board
Pandora says CEO Tim Westergren is stepping down
Pandora Media Inc. shares were halted in premarket trade Tuesday. The company recently secured a $480 million investment from Liberty Media Corp.-owned satellite radio company Sirius XM Holdings Inc. and has been the subject of speculation it is a takeover target. On Monday, the stock rallied on a report that Co-founder and Chief Executive Tim Westergren planned to step down. The stock has fallen 35% in 2017, while the S&P 500 has gained 9%.
Pandora's stock was inactive premarket prior to halt
Pandora shares halted premarket
Shares of Pandora Media Inc. rallied 3% in morning trade Monday, putting them on track for a fifth-straight gain, after a report that Co-founder and Chief Executive Tim Westergren planned to step down. Since Westergren became CEO on March 28, 2016 through Friday, the stock had declined 11% while the S&P 500 has soared 20%. Separately, Pandora was upgraded to sector weight from underweight, as reduced expectations of a merger and the likelihood of increased focus on stabilizing cash flow reduces downside risk. The stock's current win streak, which would be the longest since the six-day streak ending Sept. 23, 2016, started after it closed at a record low of $6.91 on June 19. A week before that low, the music streaming service said it secured a $480 million investment from Sirius HX Holdings Inc. , which suggested a buyout was less likely.
Shares of Pandora Media are up 3%
Pandora Media upgraded to sector weight from underweight at Pacific Crest
Plus, reports on Kinder Morgan, Interactive Brokers Group, and Pandora Media
An array of challenges—from increasing impatience on Wall Street and in boardrooms to a corporate landscape rapidly transformed by new technologies and rival upstarts—has made the top job tougher and more precarious than just a few years ago, top executives say.
The Barron's Next 50 was up 7.6% in the first six months of the year, compared to 8.3% rise for the S&P 500. Retail stocks weighed on the Next 50.
Saavn, which operates a niche music service focused on Indian music, says is on track to turn a quarterly profit by the end of next year.
Pandora Media's co-founder and chief executive, Tim Westergren, is resigning from the company as the internet radio service contends with the rise of subscription music platforms.
A new survey found that listeners still prefer more old-school music options.
CEO Tim Westergren is out, as are the company's president and chief marketing officer.
The firm will still struggle, but Sirius-appointed board members will push for a moderated cash burn rate.
Among the companies with shares expected to trade actively in Monday's session are Facebook Inc. and other big-name tech stocks, Arconic Inc., semiconductor companies led by Micron Technology Inc. and Advanced Micro Devices Inc., Pandora Media Inc. and Store Capital Corp.
Pandora is trading at a low valuation pro forma for the Sirius investment compared with Internet peers.
Music-streaming provider Spotify AB saw explosive paid user growth last year but also doubled the size of its net loss, according to filings released Thursday.
Now that SiriusXM has taken a stake in Pandora, what's next for the struggling firm?
By making a strategic investment rather than a complete buyout, Sirius avoids diluting key metrics.
Pandora will get $480 million from SiriusXM and sell its Ticketfly business for $200 million.
Sirius XM will get a foothold in advertising-supported streaming music and help Pandora Media shore up its balance sheet by buying a $480 million stake in the streaming-music company.
Among the companies with shares expected to trade actively in Friday's session are Pandora, VeriFone, Nvidia and Cloudera.
Pandora and SiriusXM race to come to a new deal.
Investors are tired of waiting for a sale.
The music-streaming service is being sued by PayPal, which claims Pandora's new logo is "unlawfully similar" to its own.
If Sirius were to make any offer, it would unlikely be at any huge premium.
Verizon lost 289,000 postpaid customers in 1Q17, and AT&T shed 191,000 postpaid subscribers in the same quarter.
Verizon (VZ) is contemplating making an investment of $100.0 million in Pandora (P), the New York Post reported earlier this month.
What To Look For From Sirius Next Week
Pandora: So Many Questions
Don't Get Too Excited About Tesla Inc's (TSLA) New Streaming Service
The moves in the most shorted stocks traded on the New York Stock Exchange were mostly upward again, demonstrating confidence in the short sellers with the markets near all-time highs after a more than eight-year bull run.
Pandora (P) recently announced the exit of its CEO and co-founder, Tim Westergren, who will also be vacating his position on the board of directors.
Investors Lack Belief In The Current Bull Market - Cramer's Mad Money (7/10/17)
This year, Amazon.com (AMZN) is offering four months of unlimited music for 99 cents as part of its annual Amazon Prime Day, a deal which competes heavily with Apple's (AAPL) music streaming service.
Launched in 2008 by entrepreneurs Daniel Ek and Martin Lorentzon, Spotify is one of the most popular music streaming services on the market today. Will it carry out an initial public offering this year? Or choose to go public in a different way?
The top news stories from last week are about Google's (GOOGL) shopping service, and Toshiba's ongoing struggle with Western Digital (WDC) as it struggles to sell its interest in the chip making JV between them.
Needham: Now in Sirius' hands, Pandora will drop subscription push
Can Pandora Media Inc (P) Stock Become More Than a Speculative Play?
No Morgan Stanley, Pandora Is Still Not A Buy
Daily Technical Summary Reports on Radio Broadcasters Stocks -- Sirius XM, Pandora Media, Cumulus Media, and Liberty SiriusXM
Pandora's Artist Marketing Platform Hits a Billion Audio Message Impressions, Adds New Features
Advanced Microgrid Solutions Raises $34 Million in Series B, Energy Leaders See DER Optimization as Major Growth Market
Pandora Sounds Like You: Summer - Exclusive Concert Featuring Big Sean, Machine Gun Kelly, Noah Cyrus & Starley
Watch BizWireTV: Kiva.org Reaches Billion Dollar Mark in Crowd-Funding Loans and Nat Geo Releases Coal Documentary on Free Streaming Platforms
Today's Research Reports on Stocks to Watch: Under Armour and Pandora
Pandora Announces Senior Leadership Transition and Appoints New Board Member
Pandora To Host Sounds Like You: NYC Featuring Nas, Young M.A and Dave East
Pandora Celebrates National Pride Month with "Sounds Like Pride"
Watch BizWireTV: JetBlue and Utrip Bring AI to Trip Planning and Pandora Gets a Huge Boost from SiriusXM
Featured Company News - Sirius Set to Enter the Online Radio Business; Announced $480 Million Strategic Investment in Pandora
Pandora Strengthens Balance Sheet and Sharpens Focus on Core Priorities
Pandora Strengthens Balance Sheet and Sharpens Focus on Core Priorities
SiriusXM to Make $480 Million Strategic Investment in Pandora
Statement From Pandora Regarding KKR Agreement
Today's Research Reports on Stocks to Watch: Celldex Therapeutics and Pandora Media
How These Services Stocks are Faring? -- Sirius XM, Pandora Media, Liberty Broadband, and News
Post Earnings Coverage as Subscription and Ticketing Revenues Boosts Pandora's Q1 Top-line Growth
Today's Research Reports on Stocks to Watch: Pandora and Sirius
Pandora Potential Suitors, Target Price, KKR and Cohen Investments
Pandora Media, Inc. provides an internet radio service in the United States, Australia and New Zealand. It offers a personalized experience for listeners to listen radio on smartphones, tablets, computers, car audio systems, and Internet-connected devices. It operates through Internet Radio Service and Ticketing Service. The Internet Radio Service segment offers personalized ad-supported service or as a subscription service called Pandora Plus. The Ticketing Service segment operates through Ticketfly, a live events technology company that provides ticketing and marketing software services for clients. The company was founded by Timothy Westergren and Jon Kraft in January 2000 and is headquartered in Oakland, CA. (See Full Profile)
|Chg %
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|Newfoundland Capital Corp. Cl A
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Storyful, a division of News Corp, which owns MarketWatch, is a leading social media services company headquartered in Dublin, Ireland. Storyful combines world class journalism with industry-leading technology to discover, verify and acquire original content and provide the on-the-ground sources news and media organizations need to tell the stories that matter to their audience.


text: Nikolay Davydenko Bigs guns crashes out in second round The sport's top players are dropping like flies at the Dubai Open. Andy Murray, Nikolay Davydenko (picture) and Jo-Wilfried Tsonga all crashed out Wednesday joining Roger… Read more Federer survives Davydenko test to qualify for semi-final Title holder Roger Federer will face either Novak Djokovic or Jo-Wilfried Tsonga in the Australian Open semi-final after a hard fought 2-6, 6-4, 6-0, 7-5 victory over Russia's… Read more Davydenko hammers Nadal in Qatar Open final After an astonishing recovery, Nikolay Davydenko defeated Rafael Nadal (0-6, 7-6, 6-4) in the Qatar Open final on Saturday in Doha. The world number six secured his ninth victory… Read more Davydenko crushes Del Potro to win World Tour Finals Russia's Nikolay Davydenko produced a masterful display to defeat Argentina's Juan Martin Del Potro (6-3, 6-4) in less than two hours and clinch his first World Tour Finals title… Read more Davydenko defeats Federer for the first time to clinch spot in final Russia's Nikolay Davydenko secured his spot in the final of the ATP World Tour Finals in London after defeating Swiss world number one Roger Federer, 6-2, 4-6, 7-5. He will face… Read more Nadal knocked out by dominant Davydenko World number two Rafael Nadal lost 6-1 7-6 to Russian Nikolay Davydenko on Wednesday. The loss forces him out of the ATP World Tour Finals even if he wins against Novak Djokovic… Read more Race for top spot heats up ahead of London Masters Switzerland's Roger Federer and Spain's Rafael Nadal will step into the London O2 Arena with the world number one ranking in their sights. Read more Russia's Davydenko and title holder Tsonga advance to the third round The majority of the favourites in the Paris Masters Open have survived the second round, such as Russia's Nikolay Davydenko (pictured) who defeated German Benjamin Becker and… Read more Inspired Davydenko beats Nadal to win Shanghai Masters Russia's Nikolay Davydenko clinched his fourth title of the year with a 7-6 6-3 win over Spain's Rafael Nadal in the final of the Shanghai Masters. The Spaniard is still short of… Read more


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See Figures 1, 2 and 3
To avoid confusion, remove and tag the spark plug wires one at a time, for replacement.
If a distributor is not keyed for installation with only one orientation, it could have been removed previously and rewired. The resultant wiring would hold the correct firing order, but could change the relative placement of the plug towers in relation to the engine. For this reason it is imperative that you label all wires before disconnecting any of them. Also, before removal, compare the current wiring with the accompanying illustrations. If the current wiring does not match, make notes in your book to reflect how your engine is wired.
The firing order of the Rotary Pick-Up engine is alternate (1-2). The distributor cap terminals should be identified by T 1 , L 1 , T 2 and L 2 (Trailing No. 1 cylinder, Leading No. 1 cylinder, etc.). The top plug of each cylinder is the trailing plug and the bottom is the leading. The rotors are numbered from front to rear.


text:
The midfielder had put Spurs ahead but they ended going down 2-1 to their London rivals, who they now trail by seven points in the Premier League.
Eriksen has found hitting the back of the net difficult this season so was pleased to get on the scoresheet, but disappointed it did not change the result.
"I've been unlucky with the keepers having good days or missing at the last moment," Eriksen told Tottenham's official website.
"I've been in good positions and it's just about taking the chance.
"I was in a good position and I took the chance and profited from it, but it takes away from the glory when we end up losing. It makes it a different, bitter feeling."


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What Can Cause Chills With No Fever?READ MORE
What Can Cause Chills and Headache With No Fever?
Hi Ellen,
I know you asked this a long time ago, and I wonder if you have a diagnosis and treatment you would like to share?
We are not doctors here, but there are several things that can cause chills without a fever, including a bladder infection, anemia, hypothyroidism and hypoglycemia, a spider bite, or it could be a side effect of a medication. Your doctor is the only one who can diagnose one of those, so get it checked out if you can.
I do hope you are well!
Give Your Medicine Chest a Check-Up
FROM OUR COMMUNITYYou should know Answers to your question are meant to provide general health information but should not replace medical advice you receive from a doctor. No answers should be viewed as a diagnosis or recommended treatment for a condition. Content posted by community members does not necessarily reflect the views of Remedy Health Media, which also reserves the right to remove material deemed inappropriate.DISPLAY TEXTLINK URL


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Thursday, February 11, 2016
Sorry, don't let the title fool you: I won't be retiring from the Development Beat anytime soon.
What the title actually refers to is a newly filed site review plan for a retirement community that was, oddly enough, previously filed as a new subdivision plan.
Here's what we had to say about it back it was a subdivision. Not much has changed since that time:
After the property at 5501 Departure was rezoned to RX in October to allow for Congregate Care. The only mention of the facility's size is a note that there will be 9,583 square feet of impervious surface added to the property. As this figure likely includes the parking area along with the building itself, it seems a bit small, but perhaps it will be built up, not out.
While the property has been owned since 2000 by the Bell Partnership, it appears that ONE|ƎIGHTY, a hospitality developer which also specializes in senior housing, will be developing the new facility.
The site plans were drawn up local firm Development Engineering
ONE|ƎIGHTY does four different styles of retirement communities, which we'll get into in a minute. First, let's read this brief descriptor of what sets ONE|ƎIGHTY senior living communities apart from the rest.
You'll notice the difference at our communities the first time you see folks having fun. Starting with the fact that folks are actually having fun. Because, while other companies were making senior living gracious, comfortable, and boring. We were giving it a Twist. We were making it a blast.
Yeah, gracious, comfortable … sounds terrible. Maybe it's just me, but the idea of living someplace where the people running the show are trying to "make it a blast" 24/7 sounds like a nightmare.
Here's the four different flavors of ONE|ƎIGHTY communities.
- Leisure Care: The bare-bones basics. Although this is the lowest-tier community, it still boasts that they "go way beyond the typical ideas of independent living and assisted living. And when we say "way beyond" it is, well, kind of an understatement." And that's not all; they promise to "soup [the experience] up like a teenager with a '57 Chev" Uh. OK. Let's move on to the next one.
- Leisure Care Premiere: Obviously an upgrade on the (not-so, if you believe the marketing) standard Leisure Care facility. Here's the main difference: "our popular enhanced programs are included — PrimeFit Complete, SM BrainFit, SM whole-person wellness, and true restaurant dining." BrainFit. Sweet. That's a better sell than the weird '57 Chevy line, for sure.
- Signature 180: Custom-tailored senior living communities. Not surprisingly, ONE|ƎIGHTY is quite braggadocios when it comes to these developments: "If these communities were any more unique, they'd have to be on Mars." I don't want to make this too long, but I'd be remiss if I left out the opening description: "The Signature 180 brand is for communities that are so unique they require their own branding, their own marketing, their own … everything. Yes indeed, these projects are innovative with a capital "I". And the developers behind them are amazingly innovative, too. (With a capital "A" and a capital "I".)" Gag. With a capital "G." Apparently they do things like turn old breweries into senior living spaces. Hipster retirement communities, basically.
- Treeo: I'll be honest, I had kind of a hard time figuring out what the deal with these ones was. The marketing language is surprisingly subdued (well, by ONE|ƎIGHTY standards at least). Here's their pitch: We put on our Twisted Thinking Caps, combed through the data and discovered [some retirees] wanted three things: A good value, A place that looks and feels hip, fresh and fun, and to engage with their community and town. Well to be honest, that doesn't tell me much. There's some talk of special technology, and a mention of the "connectivity" available, which sounds pretty good. But apparently it's an independent living community, rather than an assisted living facility. Although according to some research (reading online reviews of one of the locations) that I did, only two meals per day are included with the rent. Lunch is extra. Maybe it's part of a whole-person wellness program.
Well that took longer than I intended. But as I mentioned, there's not much on the site plans other than the fact that the empty, wooded lot will eventually be turned into a Congregate Care facility run by the top minds behind ONE|ƎIGHTY.


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Template not found for Layout. Template not found for Layout. EUR 150'000 http://www.grabersportgarage.ch/1959-mga-twin-cam-works-car.html EU Duty paid (or Swiss Papers)
This is the Tubeframe car built for the 1980 DRM Championship by Jan Lundgardh (S), Josef Zierkelbach (D) and Porsche Engineer Eberhard Braun (D). to run in the under 2.0 L Class using one of the only two 1.4 L Turbo engines built by the factory in 1977 (The factory built Baby car won the 1977 Season final at Hockenheim using the other 1.4 L engine). The car then raced in the 1980-1981 German DRM Championship, the World Endurance Championship as well as at the 24H of Le Mans in 1981. A 3L Turbo engine was then installed for the 1982 season and the car was entered in further 4 rounds of the World Endurance Championship until retiring from Racing in 1984. Due to the tubeframe construction the car was very light (It showed only 817 Kg on the weithing balance at the 1981 Le Mans 24H scrutineering) and therefore very competitive. In the current ownership since 2004, the car has been completely frame up restored at no expense spared, altough the car still retains the original K3 Body panels fited in 1980. Restoration files and invoices (€ 600'000) are available. This car is very well known among Porsche Enthusiasts, the History meticulously documented and the chain of ownership absolutel
Model W109 - Chassis 109.056.120.026.92 - Dark blue with ligth brown interior Mercedes 300 SEL with 3.5 Liter engine. The car has been in the same family ownership since delivered new by Mercedes Benz in Switzerland. 117'000 original Kilometers. Sunroof - 3498cc engine with 200 HP New paint in 2008. New leather interior. The car is in excellent and superb condition. Service book - Instruction Manual - Tools Vehicle serviced 03/2016 (CHF 6'000.--) - Fresh Veteran MOT 14.03.2016 http://www.grabersportgarage.ch/1970-mercedes-300-sel-3.5.html
993 GT2 with period Race History in ADAC GT, BPR and FIA GT Championship Chassis W09POT212SDM13002 1995 Built by Mamerow Automobiltechnik in Germany. Raced in 1995 ADAC GT Championship with Oliver Mayer and Mike Hezemans Raced in 1996 BPR with Karl Augustin, Horst Felbemayr, Alfred Gramsel, Ernst Gschwender, Stefan Roitmayer and Johannes Huber Raced in 1997 FIA GT Championship with Karl Augustin, Horst Felbemayr, Stefano Buttiero, Frank Schmickler, Hans-Jörg Hofer and Stefan Roitmayer. Mentionned in the John Starkey Book - The Racing Porsches - from R to GT2 - The car was used for show purposes and track days since 1998. Comprehensively restored in 2002-2003 and updated to the latest GT2 period specs. Engine has only 6 hours since restoration. Dyno tested with 671 HP and 915 Nm of Torque. The car is now fully serviced with new FIA Fuel Tank and ready to drive or race on the button. Equiped with a silencer in order to match the 105 DB noise requirements for most of the tracks today. Swiss Form 13.20 (Swiss Tax paid) EUR 395'000 http://www.grabersportgarage.ch/1995-porsche-993-gt2-evo-race-car.html Swiss Tax paid
24H le Mans in 1999 Chassis C52 #02 was built by Courage for Nissan Motorsport, Japan. The engine used was a Nissan VRH 35Z with 3.5L Twin-Turbo. The body is in Carbon fiber-Kevlar and the chassis is in Carbon fiber/honeycomb from Dassault System Technology. The engine has an output of 700 Bhp at 6800 Rpm and the car was measured at 332 Km/h in Le Mans in 1999. The brakes are from Brembo and the transmission is a Nissan X-Track 6 speed sequential gearbox. The C52's have taken impressive 6th and 8th places at the 24 Hours of Le Mans in 1999. This car, starting No. 21 (Chassis #02) was driven by Didier Cottaz (F), Fredrick Ekblom (S) and Marc Goossens (B) to an excellent 8th place after beeing 16th on the starting grid. The car is completely restored and in race ready "on the button" condition. EUR 345'000 http://www.grabersportgarage.ch/1999-courage-c52.html Swiss Tax paid
This is one of the first series "Suffix A" LHD Range Rover with 3 doors and the front mirrors. Chassis #35801940A - Delivered new to Austria in "Masai Red". The car was fully frame up restored between 2014 and 2016 and is now in "as new" condition. The restoration is very well documented. The car is painted in "Sahara Dust" with light brown fabric textil interior. Imported into Switzerland in 2016 and Swiss Veteran registered EUR 79'500 http://www.grabersportgarage.ch/1972-range-rover-classic-suffix-a.html Swiss VAT paid
Special Edition by Mulliner Park Ward. Swiss Duty paid. Monaco Registration papers. Only 65'000 Km and in absolutely stunning condition EUR 85'000 http://www.grabersportgarage.ch/1997-rolls-royce-silver-spur-ii-limousine.html Swiss Duty paid
This car is in excellent condition and ready to race for the 2016 season. The engine is new and has only Dyno testing hours. Ford 289 engine with 340 HP and 426 Nm torque New 2015 FIA HTP Periode F - Class CT10. This car is ideal for all Touring car races in the Pre-65 grid. The car comes with lots of spares (spare engine, wheels, rear axle, diff, C&P, brake calipers and a lot more) EUR 95'000 http://www.grabersportgarage.ch/1965-ford-mustang-mk-i-289-fia.html Net Export


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text: Social network of New Store Openings and other business related open house listings in the province of New Brunswick. Find upcoming Open Houses for businesses and non-profits anywhere in the New Brunswick area. List new brunswick Open Houses online, view schedules, and confirm attendance via your favorite social media application to open house listings in your area.


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About the Book
The book is an account of a tour by a retired couple of the South Island of New Zealand. The text is a transcript of a journal kept at the time, accompanied by photographs
Features & Details
- Category Biographies & Memoirs
Large Format Landscape, 13×11 in, 33×28 cm
34 Pages
- Publish Date Dec 29, 2013
- Language English
- Tags new zealand, camper, Christchurch, Invercargill, Dunedin
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