text:
|Publication number
|Publication type
|Application number
|Publication date
|Apr 4, 2000
|Filing date
|Aug 13, 1997
|Priority date
|Dec 20, 1994
|Fee status
|Also published as
|Publication number
|Sanford L. Cook, Joseph N. Villa, Katherine T. Cansfield, David J. Kenyon
|Original Assignee
|Tcp/Reliable Inc., Johnson & Johnson
|Export Citation
|BiBTeX, EndNote, RefMan
|Patent Citations (10), Referenced by (95), Classifications (20), Legal Events (3)
|External Links: USPTO, USPTO Assignment, Espacenet
This is a continuation-in-part of application Ser. No. 08/359,802 filed Dec. 20, 1994 which is now abandoned.
The present invention relates generally to shipping and storing thermally sensitive materials such as biologically active proteins and medicaments, and more particularly to containers for maintaining such materials at an essentially constant temperature during transport and storage.
With the recent development of recombinant DNA technologies, increasing numbers of biologically active materials such as peptides, proteins and glyco-proteins have become available for research and therapeutic use. These products have a significant potency and are frequently supplied as dilute aqueous solutions of the active ingredient combined with small quantities of pharmaceutically acceptable adjuvant and carrier substances such as serum albumin. It is believed that if the solution freezes, it can generate physicochemical alterations which are not spontaneously reversible upon thawing, such as formation of both lower and higher molecular weight species of the proteins. These changes could potentially affect the biological potency of the products which have been subjected to freezing. A common problem encountered with transporting and storing pharmaceuticals is to maintain the pharmaceutical preparation within a constant temperature range.
The prior art is rife with various container designs fashioned from polymer materials, alone or in combination with cardboard or particle-board boxes. Shipping boxes with insulated interiors run the gamut from ubiquitous "food-coolers" to esoteric single vessel transport units. For example, a cardboard box filled with foam peanuts surrounding a second cardboard box holding the medicament is but one common embodiment. Other examples are plastic containers which are filled with open cell or closed cell foam and contain a cutout adapted to receive a second box, the second box contains the medication. Still another commonly employed container is an inner vessel surrounded by a space which has been evacuated of air and surrounded by a second or outer wall (i.e. the Thermos� bottle).
Persons seeking to transport highly labile samples, which must be maintained in a frozen state, have used ice and dry-ice for maintaining temperatures sufficient to keep the samples in a frozen condition. Unfortunately, the use of dry-ice preparations are of limited utility due to rapid evaporation, and as well may be dangerous due to the release of carbon dioxide. The use of ice and dry-ice creates the untoward risk of introducing a toxic contaminant, or a pathogen.
Still, other transportable containers rely on refrigeration units to maintain sub-ambient conditions. With these systems a power failure, which might proceed undetected, could prove fatal to the efficacy of the preparation.
While most people are familiar with spoilage due to exposure to heat, or to sub-freezing temperatures, maintaining a constant temperature within ambient values is a highly desirable objective. There is a vast array of pharmaceutical preparations that must be maintained within an ambient temperature range. The preferred range is generally from about 40� to 80� Fahrenheit. Therefore, the container must prevent extreme changes in outside temperatures which are often encountered in shipping from affecting the preparation contained therein. A shipment of pharmaceuticals which is stored on the tarmac prior to loading on an aircraft must endure elevated temperatures for extended periods of time. On the other hand, once loaded in the aircraft the medicaments are often exposed to sub-freezing temperatures during flight.
The emphasis of prior art containers teaches the construction of containers for maintaining a payload at sub-ambient temperatures.
Schea, III et al. U.S. Pat. No. 5,181,394 issued Jan. 26, 1993 discloses a previous attempt to provide a shipping and storage container adapted to maintain vials of liquid in a refrigerated, but not frozen state. The container comprises an outer side wall having the shape of a rectangular open tray and an inner side wall having a number of wells to accommodate a number of vials. The inner and outer side walls are dimensioned and shaped to nest the inner side wall component within the outer side wall component. A phase change material comprising a freshly prepared mixture of water and 2% by weight self-gelling carboxymethylcellulose is provided between the inner and outer side walls. A freeze indicator is positioned within the container and exhibits a color change upon being subjected to temperatures below a predetermined level. The carboxymethylcellulose gel exhibits relatively poor insulating properties, and conducts heat from the vials.
U.S. Pat. No. 5,355,684 issued to Guice discloses a shipping container for the cryogenic shipping or storage of biologic materials. Further, this invention utilizes a plurality of "heat sinks" disposed within an insulated container. The heat sink material is preferably composed of a phase change material that is first frozen and as it thaws, absorbs free heat to keep the sample inside the vessel in a frozen condition.
U.S. Pat. No. 5,058,397 issued to MacDonald discloses a storage container where microcentrifuge tubes are embedded into a coolant matrix of gel. Overlying the embedded tubes is a gel contained in an envelope within a lid means which is comprised of an envelope of gel.
U.S. Pat. No. 4,250,998 issued to Taylor discloses a container for transporting insulin and syringes wherein there is an insulated container with a plurality of cavities. The inner cavities are to be filled with water for freezing, while the outer cavities are designed to house the syringes.
A container according to the present invention provides for storage and shipping of vessels containing a liquid composition susceptible to physicochemical alteration upon freezing or upon exposure to elevated temperatures. It comprises an enclosure created by an upstanding means. It is best illustrated by a plurality of upstanding walls where there are at least two pairs of opposing walls of essentially equal dimensions thereby defining an inner space. The base portion of the enclosure contains a first heat sink, comprising a thermal energy absorbing phase change material. A vial holder is disposed within the chamber and thereby divides the container into a bottom chamber and top chamber. The vial holder is adapted to hold one or more of the vials suspended within the bottom chamber and above the first heat sink. The vial holder possesses a like number of apertures therethrough so that the resulting array of apertures is essentially in an equidistant relation to one another. A central aperture is disposed in an equidistant relationship relative to the other apertures. Within the central aperture there is a temperature indicator means disposed within a housing of a similar size and shape of the proposed sample containers which are to be disposed within the apertures to signal exposure to contraindicated temperatures. An insulating gas is contained in the inner space.
A lid may be introduced to seal the top chamber and provide closure to the container. The lid is removably retained and provides access for removal of the vessels held in the planar holder. Additionally, the lid houses a second heat sink which incorporates the same phase change material as in the first sink.
The vial holder is a thin planar panel, resides above the first heat sink and possesses at least one or more apertures for receiving the vials. The vial holder divides the container into top and bottom chambers. When in a closed condition, the vial holder retains the vials within the bottom chamber while a gas, namely air surrounds the vials.
Further features, objects and advantages will become evident from the following detailed description of the preferred embodiments of the present invention taken in conjunction with the accompanying drawings, in which;
FIG. 1 is an exploded view of a storage container according to the invention;
FIG. 2 is a plan view of the container of FIG. 1 with a lid of the container partially cut away to reveal an inner vial holder;
FIG. 3 is an elevational view in cross section taken along line 3--3 of FIG. 2;
FIG. 4 is an elevational view as a partial cut-away thereof;
FIG. 5 is a top plan view of the container in an opened condition;
FIG. 6A is an alternate top plan view thereof;
FIG. 6B is an alternate top plan view thereof;
FIG. 7 is an elevational view of the vial holder;
FIG. 8. is an elevational view in cut-away of the container in a closed condition;
FIG. 9 is a cross-sectional view of the container of the capillary tube and bulb;
FIG. 10 is a bottom plan view depicting the reinforcing ribs; and
FIG. 11 is a perspective view of the container.
Turning now to the drawings wherein like numerals refer to like parts throughout, FIG. 1 depicts a container for transporting and storing temperature-sensitive materials, said container being generally identified by the numeral 10. Although, container 10 can be of a triangular, rectangular, circular or other construction, for purposes of the present invention, the preferred container shape for description will be essentially rectilinear.
In accordance with the present invention and FIG. 1, walls 12, 14, 16, and 18 are integral and in communication with each other and base 20. The resulting preferred assemblage is essentially box-shaped, being closed on the bottom end by base 20 and open on the opposing end.
Turning to FIG. 2, base 20 is of a reduced dimension there-around, in relation to upstanding walls 12, 14, 16, 18, and at its meeting point provides shoulder 44. Panel 22 is in communication with base 20 at shoulder 44 and may be hermetically affixed thereon. The cell created by the aforesaid union provides a receptacle for a first heat sink 24.
The tops of each wall 12, 14, 16 and 18 terminates in an outwardly projecting flange area 38. Pursuant to FIGS. 1&2, lid 26 is adapted to close container 10 by nesting within the open end of said container 10 and by reversible interlocking engagement between flanges 36 and 38. Lid 26 is further comprised of panel 28 which is in integral communication as by being hermetically affixed to upper lid surface 30 and provides a cavity 32 for second heat sink 34. Second heat sink 34 projects downward and thereby furnishes an indented area of approximately the same dimensions as the opening formed by upstanding walls 12, 14, 16, 18 of container 10 to effect closure by nesting and interlocking engagement thereto.
For purposes of the present invention, differences in outside temperature will act upon a container by virtue of the phenomena of heat transfer. Heat is energy that flows, by virtue of a temperature differential, from regions of higher temperature to lower temperature. The various modes of heat transfer are by conduction, radiation and convection. In the instant regard, the greatest change in sample temperature occurs as a result of conduction.
Conduction takes place on the molecular level and involves the transfer of energy from more energetic molecules to molecules possessing less energy. Hence, the closer the molecules are to one another, the greater the incidence of collision and transfer of energy. Conduction would be greater where molecules touch each other and significantly less as the density of molecular space increases. Heat flux, or the rate of heat flow from greater temperature to lower temperature, is therefore proportionate when taken in view of the thermal conductivity of the material.
In addition, there are yet other phenomena that exist when one speaks in terms of heat transfer. Where there are different species of chemically distinct molecules there exists a concentration gradient. The term mass transfer describes the relative motion of species in a mixture due to the presence of concentration gradients. Heat will move across the gradient from areas of greater concentration to lesser concentration.
Radiation, or more appropriately in terms of the instant case, thermal radiation is electromagnetic radiation emitted by a body by virtue of its temperature and at the expense of its internal energy. Unlike conduction, radiation does not require a material medium.
Finally, the container when exposed to the vagaries of shipping will be exposed to convection. Although the sample itself will be almost immune from the direct effect of the outside convective force, the environment inside will not. Convection, as a transfer mode relates to the transfer of heat from a bounding surface to a fluid in motion or to the heat transfer across a flow plane within the interior of the flowing fluid. Mainly, the phenomenon requires the flow of a fluid or gas over a surface. When the container is exposed to the elements, as during shipping or upon exposure to ambient conditions, air currents outside the container will act upon the container encouraging changes in temperature within the container. Inside the container, the vibratory motion encountered during transportation will encourage heat transfer and temperature change, as will natural convection currents produced by the inherent temperature differential within the container.
In the preferred embodiment as shown in FIG.2, there are two heat sinks 24 and 34. Heat sinks 24 and 34 cooperate to provide a media to absorb increases or decreases in temperature within bottom chamber 42 and top chamber 40. For purposes of the present invention, the preferred heat sink material is a phase change material. As a class, phase change materials can absorb a tremendous amount of heat energy in their transition between phases. When maintained in a frozen state, the product of net specific heat and density would represent an inverse logarithmic relationship. For example, once the material which has been in a frozen condition reaches the point of freeze/thaw, the temperature remains substantially constant until complete melting occurs. Maintaining a temperature plateau allows for great amounts of heat to be absorbed at a constant rate, and encourages maintenance of a constant ambient interior container temperature. Therefore, heat sinks 24 and 34 are preferably constructed from a phase change material such as carboxymethylcellulose gel, having a freezing temperature of approximately -1� C. It should be noted that most phase change materials like carboxymethlycellulose are relatively poor insulating materials. Other materials for constructing heat sinks are phenols, salts, water, glycols, starches and alcohols.
Heat sinks 24 and 34 preferably exhibit a phase change at a temperature slightly above the freezing temperature of the liquid contained within vials 100. Thus, when container 10 is exposed to a temperature below the freezing temperature of the liquid in vials 100, a large quantity of heat energy relative to the mass of the phase change material within heat sink 24 and 34 must be dissipated to the external environment before the temperature of the heat sinks 24 and 34 will fall below the freezing temperature of the liquid in the vials 100. Heat sinks 24 and 34 thus provide a thermal damping effect against temperature changes in the environment of the container 10. In accordance with the present invention, using a total weight of carboxymethylcellulose of 6.5 ounces, container 10 should resist 8 hours of exposure to a -20-degree Celsius external temperature.
As described hereinabove, the heat sink material may be chosen from a variety of materials, based on their freezing point and the desired temperature at which the sample is to be maintained. For example, many alcohols or glycols are particularly suited for maintaining sub-ambient interior temperatures. Alcohols, glycols or any compound that has an extremely low freezing point, once frozen, requires a great amount of heat to raise their temperature above its freezing point and the freezing point of a biologic sample.
Returning to the preferred embodiment of FIGS. 1 and 2 base 12 is substantially equilateral and square in overall shape, having walls 12, 14, 16, and 18 integrally connected thereto by hermetically sealed or thermo-formed. Panel 22 is in communication with the aforesaid walls and is joined at a lower portion 24. At their lower extent, the walls 12, 14, 16, 18, extend inwardly to form support lip 44 which supports panel 22. A well formed within the boundaries of panel 22 and base 20 contains a first heat sink 24.
First and second heat sinks 24 and 34 may be retained within a well or envelope formed by hermetically sealing panels or sides to each other. Various other embodiments or materials could be operatively substituted. For example, solids like dry-ice or frozen aqueous solutions which remain solid through their "phase change" would obviate the need for encapsulating a gel material. An indented base 20 lends a distinctive appearance to container 10 as well as providing greater stability. The material contained within base 20 provides sufficient weight to encourage maintenance in an upright position.
Walls 12, 14, 16, 18, base 20 and panel 22 are preferably formed from a thermoplastic polymer component like polyvinyl chloride, PETG or a similar thermoplastic polymer. When constructed as by injection molding or by another thermo-forming method said walls 12, 14, 16, 18 and base 20 are integral. Panel 22 is preferably hermetically affixed to outstanding lips 44 so that first heat sink 24 may be disposed therein. Lid 26 is fashioned from the same polymer as panel 28, and upper lid panel 30 communicate to form downward depending well 32. Lid 26 provides downwardly depending sides 46, 48, 50, and 52 and flange 36 which reversibly communicates with flange 38 of wall 12, 14, 16, and 18 thereby encouraging closure of container 10 as seen in FIGS. 8 and 2.
Downward depending well 32 corresponds to the inside dimension of open container 10 as defined by inner wall surfaces of vial holder 56 and nests therein to accomplish closure while discouraging lateral movement. To effect closure of container 10, lid 26 reversibly nests within the space defined by upstanding walls 12-18, and upward disposed flange 38, in accordance with FIG. 2, extends outwardly radially from the upper extent of the sidewalls. A downwardly disposed flange 36 extends downwardly from outer edges 54 of upper panel 28 of the lid 26. Upper flange 36 and downward flange 38 engage each other to hold the lid 26 in a reversibly interlocked condition. A detente or interlocking members (not shown) may be provided on either the downward flange 36 or upper flange 38 to more securely attach the lid 26. Preferably, upper panel 28 and the downward flange 36 are formed as a single thermo-formed plastic part.
Walls 12, 14, 16, 18 and lid 26 are the first barrier to prevent temperature changes within the container. The thermoplastic polymer is non-porous, insulating and retards heat transfer. Therefore, depending on the thickness of the polymer there will be an insulating or "R" factor, while the material itself will by definition facilitate or retard heat transfer by virtue of its "K" factor. Not only does the non-porous material prevent radiation but also the inherent insulation rating of the material itself heat transfer through conduction. Finally, heat loss from convection caused by air passing over the non-porous outer skin of the container greatly reduces heat transfer within the container.
Vial holder 56 possesses a step-shaped appearance and contains peripheral ledge 58 which creates a horizontal surface to abuttingly retain insulating insert 68, said ledge approximates the width dimensions of the upper surface of insulating insert 68, and is secured thereon. Surfaces 58, 60, 62,64 depend substantially inward and downward from an outer edge flange 104 of vial holder 56 and terminates in an outwardly extending flange 38. Vial holder 56 and outer edge flange 104 rests atop insulating insert panel 68, and walls 12, 14, 16, 18. Preferably, vial holder 56 is formed from a single piece of plastic in a thermo-forming operation and communicates with sidewalls 12-18, insulating insert 68 and flange 38 being hermetically affixed thereon. Further, vial holder 56 divides container 10 into a top chamber 40 and bottom chamber 42.
As shown by FIGS. 1 and 2 depict placement of insulating insert 68 which is immovably retained adjacent to the inner surface of walls 12, 14, 16 and 18 by vial holder 56. As best seen in FIG. 2, surfaces 62 and 64 extend over and abut insulated insert 68. Surface 62 and surface 64 conform dimensionally to insulated insert 68 and immovably retain said insulated insert in position around the inside of walls 12, 14, 16, and 18. Overall both insert members 70 and 72 and surfaces 62 and 64 are angled sufficient to constitute mating as seen in FIGS, 2 and 8. Insulated insert 68 is preferably comprised of two L-shaped members 70 and 72 which abut one another. Insulated insert 68 is thus held securely between the lower panel 22, sidewalls 12, 14, 16, 18 and vial holder 56, and is preferably hermetically affixed or sonically welded within. Other means of affixing by the use of adhesives or by thermo-forming procedures may be substituted.
Insulating insert 68 contributes a shock absorbing component to the assemblage. Insulating insert 68 when derived from the preferred material, a closed cell foam like polyvinyl chloride, urethane or PETG, or other closed cell polymer insulator, absorbs shock waves by the inherent memory of the polymer. Not only is mechanical damage to the vials prevented, but also convection within the chamber is discouraged. Vial holder 56 is preferably formed of a single piece of plastic in a thermo-forming operation.
In accordance with FIG. 7 a series of buttresses or support struts 98 are disposed on the bottom of base 20. Struts 98 prevent deformation of the container caused by expansion of the gel of heat sink 24. Therefore, struts 98 prevent a bowing outward from the bottom of container 10, while providing overall rigidity to retard outward expansion of base 20. While the preferred embodiment is X-shaped, struts which encourage container support and structural integrity may be operatively substituted.
The preferred representation of vial holder 56, as illustrated by FIGS. 5 and 6, is further comprised of a series of descending surfaces. Hence horizontal peripheral ledge 58 descends via vertical wall 60 to slanted surface 62 which in turn and in a step-wise relation descends via wall 64 to planar surface 102. Planar surface 64 resides above the panel 22. Said planar surface 102 contains a plurality of apertures 66a-f adapted to receive a like number of vials therethrough. A central aperture 88 furnishes said plurality of apertures 66a-f a point for their arrangement in equidistant relation thereto. In accordance with FIGS. 5, 6A and 6B the overall disposition of apertures is in a circular pattern around central aperture 88. Therefore, notwithstanding the geometric figure which results, an infinite number of points which are equidistant to a central point or in circular arrangement may be operatively substituted. A further advantage inherent to the equidistant arrangement is that the vials will undergo equal cooling.
Central aperture 88 is adapted to receive temperature indicator 74. Central aperture 88 is of a reduced diameter and is adapted to receive capillary tube 86 of stem 82 and prevents bulbous portion 84 from falling therethrough. Temperature indicator 74 is assembled as a unit with dome 78 interlocking with retention ring 80 thereby preventing stem 82 and bulbous portion 84 from ejecting upward and outward therefrom.
In the preferred embodiment, panel 102 possesses an aperture centered on said panel and a plurality of apertures 66a-f which is adapted to receive a like number vials 100 of medicaments, as seen in FIGS. 5, 6A and 6B. Said vials 100 are retained within said apertures 66a-f.
FIGS. 2 and 8 show container 10 in an assembled condition, vial holder 56 and vials 100 are so situated within chambers 40 and 42 and above panel 22 and below panel 28 or above first heat sink 24 and below second heat sink 34, so that vials 100 placed in apertures 66a-f are held suspended within bottom chamber 42. Vials 100, thus positioned, are substantially spaced from the sidewalls 22 and are positioned above the first heat sink 14.
Entrapped gases which, by definition, possess a random molecular configuration, are excellent insulators. Lid 26 and base 20 defining the uppermost boundaries of top and bottom chambers 40 and 42 may contain an insulating gas, in this case air, to insulate vials 100 from the vagaries of the exterior environment. Heat sinks 24 and 34 and the carboxymethylcellulose contained therein conducts heat from the vials faster than air. Thus, by not directly embedding the vials within the gel, heat loss from the vials is reduced.
Turning to FIGS. 1 and 4, temperature indicator 74 resides within central aperture 88. Temperature indicator 74 comprises a casing 76 of approximately the same dimensions as vials 100a-f to be retained within apertures 66a-f and having an outwardly extending outer edge flange 104 at its upper extent. Flange 104 attaches to or is integral with panel 102 of vial holder 56 and surrounds a central aperture of reduced circumference 88. Casing 76 thus depends beneath the panel 102.
A clear dome cover 78 fits over casing 76. It has an outwardly extending radial flange 106 which attaches to panel 102 of vial holder 56 and adjacent the cylindrical casing flange 104. An upper surface 108 of dome cover 78 is preferably planar and imprinted with a warning regarding the color change of the indicator and including a toll-free number which a user may call for information regarding proper use of container 10 (see also FIG. 2).
Disk-shaped divider 80 fits between casing 76 and dome cover 90. A central aperture of reduced diameter 110 in divider 80 receives elongated ampule 82. Bulbous portion 84 of ampule 82 at an upper end of ampule 82 is larger than the divider aperture 110 whereby the ampule 82 is supported upon divider 80 and held secure by dome cover 78. Ampule 82, casing 76 and dome cover 78 are dimensionally similar so that when assembled, ampule 82 cannot move up and out of divider 80 through aperture 88, even if the container 10 is completely inverted. Also, temperature indicator 74 is preferably permanently attached to the vial holder 56 so that vials 100 cannot be shipped or stored without said indicator 74.
Turning to FIG. 4, bulbous portion 84 of temperature indicator 74 contains a clear fluid 90 which contracts upon freezing, preferably, a mixture of 75% octyl caprate and 25% hexyl laurate. Temperature indicator 74 further comprises a capillary stem 100 and the clear fluid 90 extends partially into the stem 86. Stem 86 contains a liquid barrier chemical 92, preferably ethylene glycol AR grade and green food dye, adjacent the clear fluid 90. A violet liquid 94, preferably a mixture of 98% iso-amyl laurate and 2% waxoline violet BA dye, is contained within the stem 86 on an opposite side of the barrier chemical 92.
Barrier chemical 92 tends not to mix with either the clear fluid 90 or the violet liquid 94 and thus keeps the violet liquid 94 out of the bulbous portion 84. The capillary nature of the stem 86 also prevents the layers 90, 92 and 94 from mixing. However, when the clear liquid 90 freezes, it contracts and pulls the violet liquid 94 into the bulbous portion where it irreversibly mixes with the clear liquid 90 to produce a noticeable color change therein. The divider 96 is preferably white or another light and contrasting color so that the color change is easily visible.
Alternatively, a temperature indicator can be provided which contains a frangible ampule (not shown, but as is well known in the art) which breaks upon the freezing and expansion of a liquid contained within the ampule. Preferably, an indicator sensitive to the liquid is provided to show a color or other change indicating that the ampule has broken. To improve the accuracy of such an indicator, the liquid may comprise a placebo preparation of the liquid contained within vials 100.
Yet another aspect of the present invention is clear from FIG. 2 which illustrates that the temperature indicator itself can be retained in a vial-shaped holder having substantially the same structure and properties as the vials holding the active contents. By providing apertures to retain vials in a substantially equidistant relationship, and a fluid or gas between the vial-shaped holder and the temperature indicator, so that theh temperature indicator suffers a similar temperature differential as the vials carrying the active contents. Unlike the prior art which teaches in-line disposition of its contents, the instant invention will provide a true reading of temperature ranges which may affect the vials.
Should vials 100 stored in container 10 be exposed to ambient temperature conditions sufficient to overcome the insulating and thermal moderating effect of the container 10, clear liquid 90 will freeze and trigger the color change within temperature indicator 74. By simply opening lid 26 of container 10, a user will thus be alerted to the possibility that the contents in vials 100 have been exposed to temperatures below their freezing point or above the temperature necessary to maintain stability. Preferably, the temperature which triggers the visual indicia of temperature indicator 74 should be slightly above the freezing point of the liquid or slightly below the temperature necessary to maintain stability of the substance in vials 100. Moreover, the choice of a phase change material for heat sinks 24 and 34 can be chosen from the groups listed hereinabove to suit the temperature range of temperature indicator 74.
While the invention has been particularly described in connection with specific embodiments thereof, it is to be understood that this is by way of illustration and not of limitation, and that the scope of the appended claims should be construed as broadly as the prior art will permit.
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|Jan 12, 2005
|Sep 1, 2005
|Wallace Mark W.
|Passive, portable blood storage system
|Feb 22, 2005
|Sep 1, 2005
|Aragon Daniel M.
|Temperature controlled container
|Apr 21, 2004
|Oct 27, 2005
|Colasso Francisco J
|Automatic monitoring system for thermal energy storage plants
|Jul 6, 2005
|Nov 3, 2005
|Laminate structure with polycarbonate sheets and method of making
|Jun 29, 2004
|Dec 29, 2005
|Harl Kara L
|Dec 27, 2004
|Jan 26, 2006
|Donna Roth
|Food storage system
|Oct 7, 2005
|Apr 13, 2006
|Straumann Holding Ag
|Package system for a powdery, granular, paste-like or liquid sterile product
|Dec 7, 2005
|Sep 7, 2006
|Crumlin Ethan J
|Environmentally adaptable transport device
|Feb 16, 2006
|Aug 16, 2007
|Michael Goncharko
|Passively temperature-regulated shipping container suitable for biological, pharmaceutical materials or food products
|Aug 24, 2007
|Mar 6, 2008
|Tcp Reliable, Inc., A New Jersey Corporation
|Thermal packaging system
|Mar 12, 2008
|Jul 24, 2008
|Donna Roth
|Food storage system
|Jan 25, 2007
|Jul 31, 2008
|Fuat Koro
|Infant feeding system
|Feb 14, 2007
|Aug 28, 2008
|Mark Tauer
|Surgical fluid basin
|May 9, 2008
|Feb 5, 2009
|Donna Roth
|Food Storage System
|Sep 10, 2008
|Mar 19, 2009
|O'brien Diane
|Sep 2, 2008
|Mar 26, 2009
|Neritan Mustafa
|Insulated shipping container and method of making the same
|Sep 29, 2008
|Apr 23, 2009
|Kewl Innovations, Llc
|Portable medicine cooler having an electronic cooling controller and medicine efficacy indication circuitry and method of operation thereof
|Jul 16, 2009
|Demirjian George C
|Food serving system
|Dec 9, 2008
|Aug 6, 2009
|Gregory Hamlin
|Insulating Apparatus with Removable Thermal Adjustment Units
|Jan 31, 2008
|Aug 6, 2009
|Gregory Hamlin
|Insulating Apparatus With Removable Thermal Adjustment Units
|May 8, 2008
|Aug 6, 2009
|3Form, Inc.
|Multivariate color system with texture application
|Apr 1, 2009
|Oct 1, 2009
|Sandra Lynn Solmon
|Food product packaging having stabilizing insert
|Oct 29, 2009
|Cole Joseph W
|Beverage container permitting multiple configurations
|Jul 20, 2009
|Nov 12, 2009
|Straumann Holding Ag
|Package system for a powdery, granular, paste-like or liquid sterile product
|May 13, 2009
|Nov 19, 2009
|Hemminger Orin L
|Thermodynamic container
|Jan 14, 2010
|Donna Roth
|Thermal Energy Storage Container
|May 10, 2010
|Nov 11, 2010
|Larry Wendall Leonard
|Mobile Insulin Storage Cooler (MISC)
|Mar 26, 2009
|Mar 24, 2011
|Hubert Eric Walter
|System for providing portioned and tempered beverages for mobile use
|Sep 22, 2011
|3Form, Inc.
|Multivariate color system with texture application
|Dec 21, 2011
|Oct 10, 2013
|Carolina Sundberg
|Method, device, and system for preserving of nutritional value at food materials in a course
|Mar 23, 2012
|Jan 9, 2014
|Biocision, Llc
|Phase change thermal-sink apparatus
|Mar 25, 2011
|Feb 27, 2014
|Hyung Keun Hwang
|Ice chest
|Aug 3, 2010
|3Form, Inc.
|Architectural panel with thatch reed design
|Sep 5, 2012
|Oct 8, 2013
|3Form, Inc.
|Panel with cut and aligned thatch interlayer
|Sep 16, 2011
|Mar 14, 2012
|Controllable-temperature passive sample conveying tank
|Feb 29, 2012
|Jul 11, 2012
|Temperature control beverage bottle
|Apr 15, 2015
|Jul 1, 2015
|Unmanned machine for conveying traditional Chinese medicine decoction
|Nov 22, 2001
|May 30, 2002
|Cyclo-Lab Ltd.
|Transportation of biological specimens
|Nov 22, 2001
|Nov 15, 2007
|Cyclo Lab Ltd
|Transportation of biological specimens
|Feb 15, 2002
|Aug 22, 2002
|Creative Packaging Services Pty Ltd
|Temperature retaining container
|Aug 4, 2004
|Feb 24, 2005
|Tcp Reliable, Inc.
|Thermal packaging system
|Dec 15, 2005
|Jun 29, 2006
|Entropy Solutions, Inc.
|Thermally stable containment device and methods
|Dec 15, 2005
|May 5, 2011
|Entropy Solutions, Inc.
|Thermally stable containment device and methods
|May 30, 2007
|Dec 6, 2007
|Advanced Technology Materials, Inc.
|Storage and transport container for materials susceptible to physical state change under variable ambient temperature conditions
|U.S. Classification
|62/130, 62/457.2
|International Classification
|Cooperative Classification
|European Classification
|Oct 22, 2003
|Maintenance fee reminder mailed
|Apr 5, 2004
|Lapse for failure to pay maintenance fees
|Jun 1, 2004
|Expired due to failure to pay maintenance fee
Effective date: 20040404


text:
At the risk of sounding like Floyd Mayweather Jr., the money in the NBA has gone from crazy to stark-raving-needs-a-lobotomy insane.
As a capitalist, I'm all for Timofey Mozgov getting paid whatever the market dictates he's worth. As a basketball fan, I see $64 million and consider it the eighth sign of the apocalypse.
Some NFL fans actually thought the seventh sign came when the Colts signed Andrew Luck to a six-year contract extension worth $139.1 million last week. I have two words for that:
Nicolas Batum.
The Hornets just gave him a five-year $120 million deal, AND NOBODY WAS...
Jul 26, 2013; Foxborough, MA, USA; New England Patriots cornerback Alfonzo Dennard (37) stretches during training camp at the practice fields of Gillette Stadium. Mandatory Credit: Stew Milne-USA TODAY Sports ORG XMIT: USATSI-139126

subset: commoncrawl


text:
I attended an ASP.NET Users Group meeting and saw a presentation given by Demetrie Gerodimos. He is an Architect at Dell and was giving a presentation on Test Driven Development. An interesting point of his presentation for me was when he explained how they execute their tests. A discussion with him after the meeting revealed that they were automating Internet Explorer to test their ASPX pages.
After spending some time researching how easily you can automate Internet Explorer in C# (with the help of some URLs given to me by Demetrie), I began writing my own version of IEDriver. The URLs I looked at had a basic example of how to instruct IE to perform various actions. Over the course of the last year, I have enhanced my IEDriver class to handle other types of interactions with IE that I have required. While this is by no means a complete automation class, I believe it performs many of the common functions needed when writing automated tests.
The basic idea here is that we will use Interop services to invoke methods on the COM interfaces built into Internet Explorer. I have written this article because the documentation available on these interfaces is scarce at best. I have spent a lot of time researching on the web and doing trial and error experimentation with these interfaces to produce much of this IEDriver class.
The gist of it is a class called IEDriver. This class' constructor will create a new IEXPLORE.EXE process and attach to it. From then on, the methods on the IEDriver class can be used to simulate a user using his browser. While I have not implemented every type of interaction you could have with your browser, I have implemented most of the routines that I have needed to write automated tests for my product.
I have tried to hide the inner workings of the driver from the user of the class. You will notice that there are ClickXXX methods and GetXXX values that will deal with all the COM interfaces to perform the actions necessary or return the value you are interested in.
Here is an example of how easy this class is to use. This example will simply navigate to Google and search for "Automating Internet Explorer":
IEDriver driver = new IEDriver();
driver.SetInputStringValue("q", "Internet Explorer Automation");
In this example, "q" is the name of the input control and "btnG" is the name of the button control on the Google page. Preferably, you will have ID attributes on your HTML elements, but if there is no ID attribute, the driver will find the element with a name attribute.
In order to use this code, you will need to do a couple of things. First of all, you will need to add a couple of references to your project. To do this, right click on References and click Add Reference:
When the Add Reference dialog comes up, first select the .NET tab. Scroll down to the Microsoft.MSHtml object, and click the Select button.
Next, click on the COM tab. Scroll down to the Microsoft Internet Controls object and click the Select button.
Now click on OK. This will add the necessary references to your project that will allow IEDriver class to make the necessary calls to automate IE.
Once you have added the appropriate references to your project, just include the IEDriver in your project. Now, all you have to do is import the IEAutomation namespace into your class and you can begin writing automated tests using IE.
One thing to keep in mind. The documentation on this stuff is not very good so if you need to enhance IEDriver to support a feature that it currently doesn't, your best bet is probably to use your intellisense to invoke a method that you think might do what you want, and assign the variable to some temporary local variable. Then, fire up your debugger and use the watch window to find out all you can about the objects returned.
While writing my own automated tests, I have discovered that it is useful to extend the IEDriver class and add methods that do tasks that I might perform quite often so that I can use the intellisense and the compiler to eliminate the possibility of mistyping control names. For example:
class MyIEDriver : IEDriver {
public void ClickSave() {
This gives you compiler checking for things that may normally only be caught at runtime.
Writing Automated Tests With NUnit and IE.
This article has no explicit license attached to it but may contain usage terms in the article text or the download files themselves. If in doubt please contact the author via the discussion board below.
A list of licenses authors might use can be found here
public IEDriver(uint processID)
mProcess = Process.GetProcessById((int)processID);
HTMLDocument document = ((HTMLDocument)ie.Document);
IHTMLElementCollection i = document.forms;
HTMLFormElementClass myForm = (HTMLFormElementClass)i.item("NameOfForm", 0);
ie.Visibile = false;
public IEDriver() {
Process m_Proc = Process.Start("IExplore.exe");
_IE = null;
ShellWindows m_IEFoundBrowsers = new ShellWindowsClass();
foreach(InternetExplorer Browser in m_IEFoundBrowsers) {
if(Browser.HWND == (int)m_Proc.MainWindowHandle) {
_IE = Browser;
IE.Visible = true;
IE.DocumentComplete += new DWebBrowserEvents2_DocumentCompleteEventHandler(IE_DocumentComplete);
public IEDriver() {
_IE = new InternetExplorerClass();
IE.Visible = true;
IE.DocumentComplete += new DWebBrowserEvents2_DocumentCompleteEventHandler(IE_DocumentComplete);
public bool IsLoaded {
get { return _IE != null; }
public IEDriver(string FindByURL)
_IE = null;
ShellWindows m_IEFoundBrowsers = new ShellWindowsClass();
foreach(InternetExplorer Browser in m_IEFoundBrowsers)
_IE = Browser;
if (_IE != null)
IE.Visible = true;
IE.DocumentComplete += new DWebBrowserEvents2_DocumentCompleteEventHandler(IE_DocumentComplete);
Dim compose As New IEAutomation.IEDriver("http://localhost/public/email/Compose.aspx")
Assert.IsTrue(compose.IsLoaded, "Pop up window not found")
public void Quit()
public void ClickElement(string elementId)
IHTMLElement input = GetElementById(elementId);
isDocumentComplete = false;
General News Suggestion Question Bug Answer Joke Praise Rant Admin
Use Ctrl+Left/Right to switch messages, Ctrl+Up/Down to switch threads, Ctrl+Shift+Left/Right to switch pages.


text:
I encountered a conflict with your plugin when installing on MultiSite. The error says I do not have permission to view the admin panel once the plugin is installed, and I can't do anything until the plugin is removed. The WPMS works again when the plugin files have been deleted via cpanel.
Your plugin is great aside from this glitch :) .. How do I proceed to continue to use it on the WPMS?


text:
First time to order with MisterArt. Needed bulk acrylic, gesso, gel and brushes for 6 large pieces for a church project. Didn't know what to expect but did find the larger quantities I needed. The canvas, gesso, gel and brushes were just what we needed. Can't wait for the show on April 6. Working with young people on this project and they're excited.
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text:
"HTTP Error 500.19 - Internal Server Error:cannot access the RA_webclient URL" while opening the Response Assessment Module (RAM) Web Console.
This issue may occur if the ASP.NET role has not been installed for Microsoft Internet Information Services (IIS)
Follow these steps to install ASP.Net with IIS 7.x
Applies To
Windows server 2008 R2, IIS version 7.5.
RAM product version is CCS 10.5 with PCU 2011-4
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