Patent Grant
10898869
A portion of the disclosure of this patent document contains material which is subject to copyright protection. The copyright owner has no objection to the photocopy reproduction of the patent document or the patent disclosure in exactly the form it appears in the Patent and Trademark Office patent file or records, but otherwise reserves all copyright rights whatsoever.
For certain pharmaceutical applications, manufacturers need to process and mix expensive liquid drugs for testing and production using the lowest possible volume of fluid to save money. Current mixing devices operate by pumping the fluid to be mixed under high pressure through an assembly that includes two mixing chamber elements secured within a housing. The fluid mixes between the two mixing chamber elements under high pressure, resulting in high energy dissipation. The two mixing chamber elements must be held secure enough to withstand the high pressures and energy resulting from this mixing. In current mixing chambers, the two mixing chamber elements are secured with a tube held under high tension such that the tube stretches slightly, and the necking down effect holds the mixing chamber elements secure. To hold the mixing chamber elements in this way, the tube must be relatively long, and current devices are large and require many component parts. The relatively large and complex construction of current mixing devices also implies a large holdup volume of the fluid being mixed, which results in excess waste of expensive mixing product.
The present disclosure is generally directed to a compact interaction chamber that secures mixing chamber elements using internal forces of the components of the assembly rather than applied torque to put the assembly in tension and cause a necking down effect. The compact interaction chamber results in the requirement of fewer components and a smaller size. By decreasing the size and complexity of compact interaction chamber, the flow paths are also shortened, thereby decreasing the holdup volume and saving the manufacturer using the system valuable resources without sacrificing quality and consistency of the mixing.
Specifically, the compact interaction chamber of the present disclosure includes, among other components: a first housing; a second housing; an inlet retaining member; an outlet retaining member; an inlet mixing chamber element; and an outlet mixing chamber element. When assembled, the inlet retaining member and the outlet retaining member are situated facing one another within a first opening of the first housing. The inlet and outlet mixing chamber elements reside adjacent one another and between the inlet and outlet retaining members within the first opening. The second housing is fastened to the first housing such that a male protrusion on the second housing is inserted into the first opening making contact with the second retaining member. When the first and second housings are fastened together, the first retaining member and second retaining member are forced toward one another, thereby compressing the inlet and outlet retaining members and properly aligning the inlet and outlet mixing chamber elements together. The mixing chamber elements are further secured for high pressure mixing by the hoop stress exerted on the inlet and outlet mixing chamber elements by the inner wall of the first opening, as will be explained in further detail below.
Referring now to
The inlet flow coupler 220 is arranged within the inlet cap 202, and the outlet flow coupler 222 is arranged within the outlet flow cap 204. When assembled, the tube 221 stays aligned with both the inlet flow coupler 220 and the outlet flow coupler 222 with the use of a plurality of pins 229. The inlet retainer 224 and the outlet retainer 226 are arranged within the tube 221, and serve to align and retain the inlet mixing chamber element 228 and the outlet mixing chamber element 230. The inlet and outlet retainers 224 and 226 make contact with the inlet flow coupler 220 and the outlet flow coupler 222 respectively.
When the device is fully assembled, a flow path is formed between the inlet flow coupler 220, the inlet retainer 224, the inlet mixing chamber element 228, the outlet mixing chamber element 230, the outlet retainer 226 and the outlet flow coupler 222. The unmixed fluid enters the inlet flow coupler 220 and travels through the inlet retainer 224 and to the inlet mixing chamber element 228. Under high pressure and as a result of the high energy reaction, the unmixed fluid is mixed between the inlet mixing chamber element 228 and the outlet mixing chamber element 230. The mixed fluid then travels through the outlet retainer 226 and the outlet flow coupler 222.
To ensure that the mixing chamber elements are held with sufficient security to withstand the high pressure and high energy of the mixing, the inlet cap 202 threadingly engages the outlet cap 204. As torque is increased on the inlet cap 202 and outlet cap 204, the inlet flow coupler 220 and outlet flow coupler 222 are forced toward one another, and the tube 221 is put under tension. As the tension increases, the tube stretches slightly, undergoing a necking down effect, and thereby reducing in diameter. The fluid being mixed between the inlet mixing chamber element 228 and the outlet mixing chamber element 230 is under very high pressure, and therefore the inlet cap 202 and outlet cap 204 must be capable of imparting high amounts of force on the flow couplers, retainers and mixing chamber elements. Additionally, the inlet cap 202 and the outlet cap 204 must be capable of forcing the tube 221 to stretch and thereby slightly decrease in diameter to clamp down radially on the inlet mixing chamber element 228 and the outlet mixing chamber element 230. As the force increases, the inlet flow coupler 220 pushes on the inlet retainer 224 and the outlet flow coupler 222 pushes on the outlet retainer 226, which in turn sealingly compresses the inlet mixing chamber element 228 and the outlet mixing chamber element 230. To achieve the levels of torque required to ensure a fluid tight seal at high pressure, and to stretch the tube 221 with sufficient tensile force to hold the inlet mixing chamber element 228 and the outlet mixing chamber element 230, the tube must be relatively long, and therefore flow couplers, the inlet cap and outlet cap must accordingly be large enough to accommodate the longer tube. As a result of the longer tube, and larger flow couplers and caps, the flow path from the inlet flow coupler to the outlet flow coupler is longer than necessary, and therefore the holdup volume and amount of wasted fluid is higher than in smaller devices that provide comparable mixing results.
As discussed below, in the compact interaction chamber of the present disclosure, the mixing chamber elements are secured using both compression from the torque of fastening two housings together as well as hoop stress of the inner walls of the first housing directed radially inwardly on the mixing chamber elements. However, rather than using a tube member that would need to be stretched to hold the mixing chamber elements radially, the first housing is heated prior to insertion of the mixing chamber elements, and allowed to cool and contract once the mixing chamber elements are inserted and aligned. By securing the mixing chamber elements with the hoop stress of the first housing applied as a result of thermal expansion and contraction, the torque required to compress the mixing chamber elements together is significantly reduced. Therefore, the compact interaction chamber can be reduced in size, number of components, and complexity that results in a significant reduction in holdup volume.
Referring now to
As seen in
Between the first housing 102 and the second housing 104 resides an inlet retainer 108, an outlet retainer 110, an inlet mixing chamber element 112 and outlet mixing chamber element 114. The inlet retainer 108 is arranged adjacent to the inlet mixing chamber element 112. The inlet mixing chamber element 112 is arranged adjacent to the outlet mixing chamber element 114, which is arranged adjacent to the outlet retainer 110. When the compact interaction chamber 100 is assembled, bolts 106 clamp the first housing 102 to the second housing 104, thereby compressing the inlet mixing chamber element 112 and outlet mixing chamber element 114 between the inlet retainer 108 and the outlet retainer 110.
After assembly, an unmixed fluid flow is directed into inlet 116 of the first housing 102, and through an opening in inlet retainer 108. As discussed in more detail below, the unmixed fluid flow is then directed though a plurality of small pathways in the inlet mixing chamber element 102 in the direction of the fluid path. The fluid then flows in a direction parallel to the face of the inlet mixing chamber element 112 and the face of the adjacent outlet mixing chamber element 114 through a plurality of micro channels formed between the inlet mixing chamber element 102 and the outlet mixing chamber element 104. The fluid is mixed when the plurality of micro channels converge. The mixed fluid is directed through a plurality of small pathways in the outlet mixing chamber element 104, through an opening 120 in outlet retainer 110, and through outlet 122 of the second housing 104.
It should be appreciated that the plurality of bolts 106 used to fasten the first housing 102 to the second housing 104 provide a clamping force sufficient to compress the inlet mixing chamber element 112 and the outlet mixing chamber element 114 so that the microchannels formed between the two faces are fluid tight. However, due to the high pressure and the high energy dissipation resulting from the mixing taking place between the inlet mixing chamber element 112 and the outlet mixing chamber element 114, the compression force applied by the torqued bolts 106 alone may not be sufficient to hold the mixing chamber elements static within the first opening of the first housing 102 during mixing. Thus, in addition to the compressive force applied by the bolts 106, the mixing chamber elements 112, 114 are held circumferentially by the inner wall 117 of the first opening 115 of the first housing 102, which applies a large amount of hoop stress directed radially inwardly on the mixing chamber elements, as will be further discussed below. This secondary point of retention and security reduces the required amount of compressive force to hold the mixing chamber elements in place during high pressure and high energy mixing.
For example, due to the hoop stress applied to the mixing chamber elements, each of six bolts 106 in one embodiment need only a torque force of 100 inch-pounds to hold the mixing chamber elements together to create a seal. Prior art devices that use primarily compression to secure the mixing chamber elements as discussed above, however, tend to require significantly higher amounts of torque force to hold the mixing chamber elements together to create a seal (about 130 foot-pounds of torque). Because the prior art devices use a tube member that must be stretched to decrease its diameter and clamp down on the mixing chamber elements, the prior art devices require larger housings, more components and therefore, a higher hold-up volume of approximately 0.5 ml. In one embodiment of the present disclosure, the mixing chamber elements are secured within the first opening of the first housing and achieve the high hoop stress imparted from the inner wall of the first housing onto the outer circumference of the mixing chamber elements, the present disclosure takes advantage of precision fit components and the properties of thermal expansion. The hold-up volume of the compact interaction chamber of the present disclosure is around 0.05 ml.
An example procedure for assembling one embodiment of the compact interaction chamber of the present disclosure are now described with reference to the assembled compact interaction chamber in
First, the inlet retaining member 108, as shown in
Second, the first housing 102 may be heated to at least a predetermined temperature, at which point the first opening 115 expands from a first opening diameter to at least a first opening expanded diameter. In some example embodiments, the first housing is made of stainless steel, and the first housing is heated using a hot plate or any other suitable method of heating stainless steel. In one such embodiment, the predetermined temperature at which the first housing is heated is between 100° C. and 130° C. It should be appreciated that, when the first opening 115 is at the first diameter, the mixing chamber elements 112, 114 are unable to fit within the first opening 115. However, the mixing chamber components 112, 114 are manufactured and toleranced such that, after the first housing 102 is heated and the first diameter expands to the first expanded diameter, the mixing chamber elements 112, 114 are able to fit within the first opening 115. In one embodiment, the first expanded diameter is between 0.0001 and 0.0002 inches larger than the first diameter.
Third, the inlet mixing chamber element 112 is inserted into the first opening 115 of the heated first housing 102. The top surface 304 of the inlet mixing chamber element 112 is configured to be in contact with the bottom surface 132 of inlet retaining member 108. Because the inlet retaining member 108 is self-aligned with the chamfered mating surfaces of 119 and 130, the inlet mixing chamber element 112 is also properly aligned when surface 304 makes complete contact with surface 132 of inlet retaining member 108.
Fourth, the outlet mixing chamber element 114 is inserted into the first opening 115 of the heated first housing 102. The top surface 310 of the outlet mixing chamber element 114 is configured to be in contact with the bottom surface 306 of the inlet mixing chamber element 112. It should be appreciated that in some embodiments, the surface 306 and surface 310 include complimentary features that ensure the inlet mixing chamber element 112 is properly oriented and aligned with the outlet mixing chamber element 114. For example, in one embodiment, the inlet mixing chamber element 112 includes one or more protrusions that fit one or more complimentary recesses in the outlet mixing chamber element 114 so as to ensure proper rotational alignment of the two mixing chamber elements.
Fifth, once the mixing chamber elements 112, 114 are arranged within the first opening 115 of the heated first housing 102, the outlet retaining member 110 may be inserted into the first opening 115. The outlet retaining member 110 is substantially similar in structure to the inlet retaining member 108. Similar to the inlet retaining member 108, surface 132 of the outlet retaining member 110 is configured to make contact with surface 312 of the outlet mixing chamber element 114.
Sixth, the second housing 104 is aligned with the first housing 102 and the assembled first and second housings are operatively fastened together. As seen in
Seventh, the first housing may be operatively fastened to the second housing so that the inlet retainer, the inlet mixing chamber element, the outlet mixing chamber element, the outlet retainer, and the male member of the second housing are in compression. In the illustrated embodiment, six bolts 106 may be used to fasten the first housing 102 to the second housing 104. To ensure equal clamping force between the first housing 102 and the second housing 104, the bolts 106 are spaced sixty degrees apart and equidistant from central axis A. As discussed above, the fastening of six bolts 106 provides sufficient clamping force to seal surface 306 of the inlet mixing chamber element with surface 310 of the outlet mixing chamber element. It will be appreciated that any appropriate fastening arrangement or numbers of bolts may be used.
Eighth, the first housing is allowed to cool down from its heated state. In various embodiments, the first housing is cooled down by allowing it to return to room temperature or actively causing it to cool with an appropriate cooling agent. When the first housing is cooled, the material of the first housing contracts back, and the first housing expanded diameter is urged to contract back to the first housing diameter. Because the mixing chamber elements are already arranged and aligned inside of the first opening of the first housing, the contracting diameter of the first opening exerts a high amount of force directed radially inwardly on the mixing chamber elements. This force, in combination with the compressive force applied from the six bolts 106, is sufficient to hold the mixing chamber elements in place for the high pressure mixing. It should be appreciated that the mixing chamber elements can be made of any suitable material to withstand the radially inward stress of 30,000 pounds per square inch applied when the first opening diameter contracts. In one embodiment, the mixing chamber elements are constructed with 99.8% alumina. In another embodiment, the mixing chamber elements are constructed with polycrystalline diamond.
Referring now more specifically to
In
In operation, when the inlet mixing chamber element 112 and the outlet mixing chamber element 114 are secured and held in the first housing between the inlet and outlet retaining members, surface 306 makes a fluid-tight seal with surface 310. The unmixed fluid is pumped through flow path 116 of the first housing 102, and through inlet retainer 108 to inlet mixing chamber element 112. At inlet mixing chamber element 112, the fluid is pumped at high pressure into ports 300 and 302, and then into the plurality of microchannels 308. Due to the decrease in fluid port size from flow path 116 to ports 300, 302 to microchannels 308, the pressure and shear forces on the unmixed fluid becomes very high by the time it reaches the microchannels 308. As discussed above, and because of the secure holding between the inlet and outlet mixing chamber elements, microchannels 308 and 318 combine to form micro flow paths, through which the unmixed fluid travels. When the micro flow paths converge on one another, the high pressure fluid experiences a powerful reaction, and the constituent parts of the fluid are mixed as a result. After the fluid has mixed in the micro flow paths, the mixed fluid travels through outlet ports 314, 316 of outlet mixing chamber element 114.
It will be understood that the compact interaction chamber assembly of the present disclosure succeeds in reducing the number and size of the components making the mixing assembly, resulting in cheaper manufacture and lower holdup volumes leading to less waste. In addition to saving cost and resources, the present disclosure performs consistently and reliably, and can advantageously be configured to operate with current machines needing no modification.
In one example embodiment of the present disclosure, the compact interaction chamber assembly includes a first housing with a first central axis, a second housing with a second central axis, a first mixing chamber element, a second mixing chamber element, and at least one retaining member.
The first housing has a first opening at a bottom face of the first housing, the first opening having a generally cylindrical shape with a first opening diameter and sharing the first central axis. The first housing also includes a first inlet protrusion extending from a top face of the first housing. The first inlet protrusion includes a first flow path that extends from the first opening through the first inlet protrusion and shares the first central axis.
The second housing includes a second outlet opening at a bottom face of the second housing, the second outlet opening sharing the second central axis. The second housing also includes a second protrusion of a second diameter extending from a top face of the second hosing. The second protrusion includes a second flow path that extends from the second outlet opening through the second protrusion and shares the second central axis. The second housing is configured to be fastened to the first housing so that the second central axis is collinear with the first central axis and the second protrusion is configured to extend into the first opening when the first and second housings are fastened to one another.
The first and second mixing chamber elements are configured to reside within the first opening of the first housing. As a result of the first and second housings being fastened to one another, a bottom face of the first mixing chamber element makes a fluid tight contact with a top face of the second mixing chamber element. After the first and second mixing chamber elements are arranged within the first opening, an outer edge of each of the first and second mixing chamber elements contacts the inner surface of the first opening such that the first and second mixing chamber elements are stressed radially inwardly to cause a fluid tight seal between the outer edge of each of the first and second mixing chamber elements and the inner surface of the first opening. The at least one retaining member is configured to reside within the first opening of the first housing and contacts the mixing chamber elements. When fully assembled, the hold-up volume of the compact interaction chamber is 0.05 ml, compared to the hold-up volumes of prior art devices that are on the order of about 0.5 ml.
It should be understood that various changes and modifications to the presently preferred embodiments described herein will be apparent to those skilled in the art. Such changes and modifications can be made without departing from the spirit and scope of the present invention and without diminishing its intended advantages. It is therefore intended that such changes and modifications be covered by the appended claims.
The present application is a continuation application of U.S. patent application Ser. No. 12/986,477 filed on Jan. 7, 2011, the entire disclosure of which is incorporated by reference herein in its entirety for all purposes.
| Number | Name | Date | Kind |
|---|---|---|---|
| 4533254 | Cook et al. | Aug 1985 | A |
| 4634134 | Entrikin | Jan 1987 | A |
| 4684072 | Nelson et al. | Aug 1987 | A |
| 4746069 | Entrikin et al. | May 1988 | A |
| 4908154 | Cook et al. | Mar 1990 | A |
| 5314506 | Midler, Jr. et al. | May 1994 | A |
| 5417956 | Moser | May 1995 | A |
| 5466646 | Moser | Nov 1995 | A |
| 5533254 | Gallo et al. | Jul 1996 | A |
| 5570955 | Swartwout et al. | Nov 1996 | A |
| 5578279 | Dauer et al. | Nov 1996 | A |
| 5615949 | Morano et al. | Apr 1997 | A |
| 5620147 | Newton | Apr 1997 | A |
| 5664938 | Yang | Sep 1997 | A |
| 5984519 | Onodera et al. | Nov 1999 | A |
| 6159442 | Thumm et al. | Dec 2000 | A |
| 6221332 | Thumm et al. | Apr 2001 | B1 |
| 6558435 | Am Ende et al. | May 2003 | B2 |
| 6607784 | Kipp et al. | Aug 2003 | B2 |
| 6869617 | Kipp et al. | Mar 2005 | B2 |
| 6932914 | LeClair | Aug 2005 | B2 |
| 6960307 | LeClair | Nov 2005 | B2 |
| 6977085 | Werling et al. | Dec 2005 | B2 |
| 7297288 | LeClair | Nov 2007 | B1 |
| 7326054 | Todd et al. | Feb 2008 | B2 |
| 20020071870 | Sharma | Jun 2002 | A1 |
| 20020196701 | Mastbrook | Dec 2002 | A1 |
| 20030206959 | Kipp et al. | Nov 2003 | A9 |
| 20040266890 | Kipp et al. | Dec 2004 | A1 |
| 20050089993 | Boccazzi | Apr 2005 | A1 |
| 20050191359 | Goldshtein et al. | Sep 2005 | A1 |
| 20060151899 | Kato et al. | Jul 2006 | A1 |
| 20070291581 | Ehrfeld et al. | Dec 2007 | A1 |
| 20080038333 | Magadassi et al. | Feb 2008 | A1 |
| 20090269250 | Panagiotou et al. | Oct 2009 | A1 |
| 20090297565 | Muller et al. | Dec 2009 | A1 |
| 20100012114 | Greenwood et al. | Jan 2010 | A1 |
| Number | Date | Country |
|---|---|---|
| 1036588 | Sep 2000 | EP |
| S57-89935 | Jun 1982 | JP |
| H05-170852 | Jul 1993 | JP |
| H8-117578 | May 1996 | JP |
| H08-117585 | May 1996 | JP |
| H9-169026 | Jun 1997 | JP |
| 10-192671 | Jul 1998 | JP |
| H10-180065 | Jul 1998 | JP |
| H10-180066 | Jul 1998 | JP |
| H10-180068 | Jul 1998 | JP |
| 2000-254469 | Sep 2000 | JP |
| 2003-164745 | Jun 2003 | JP |
| 2003-311136 | Nov 2003 | JP |
| 2005-083212 | Mar 2005 | JP |
| 2005-144329 | Jun 2005 | JP |
| 2006-021471 | Jan 2006 | JP |
| 2006-326449 | Dec 2006 | JP |
| 2006-341146 | Dec 2006 | JP |
| 2008-037842 | Feb 2008 | JP |
| 2008-081772 | Apr 2008 | JP |
| H10-118474 | May 2008 | JP |
| 2008-284514 | Nov 2008 | JP |
| 2009-131831 | Jun 2009 | JP |
| 100761033 | Oct 2007 | KR |
| 1999007466 | Feb 1999 | WO |
| 2005018687 | Mar 2005 | WO |
| WO2006132443 | Dec 2006 | WO |
| 2007051520 | May 2007 | WO |
| 2007148237 | Dec 2007 | WO |
| Entry |
|---|
| English Translation of Office action dated Jun. 26, 2018 for Korean Patent Application No. 10-2013-7020790. |
| International Search Report and Written Opinion dated May 3, 2012 issued for International PCT Application No. PCT/US2012/020456. |
| Sonolator Product Literature. High Pressure Ultrasonic Mixing and Homogenizing Systems. undated. |
| Gruverman, Breakthrough Ultraturbulent Reaction Technology Opens Frontier for Developing Life-Saving Nanometer-Scale Suspensions & Dispersions, Ultraturbulent Reaction Technology publication, Jan./Feb. 2003, vol. 3, No. 1 (4 pages). |
| Gruverman, A Drug Delivery Breakthrough—Nanosuspension Formulations for Intravenous, Oral & Transdermal Administration of Active Pharmaceutical Ingredients, Nanosuspension Formulations publication, Sep. 2004, vol. 1, No. 7, pp. 58-59. |
| Gruverman, Nanosuspension Preparation and Formulation, Nanosuspension Formulation publication, Sep. 2005, vol. 5, No. 8, pp. 1-4. |
| Gruverman, Optimizing Drug Delivery—Formulation Development and Scaleable Manufacturing Methodology, Nanoemulsions and Nanosuspensions Prepared by Ultrahigh-Shear Fluid Processing, Presentation at Particles 2006, May 14, 2006. |
| Gruverman et al., Production of Nanostructures Under Ultraturbulent Collision Reaction Conditions—Application to Catalysts, Superconductors, CMP Abrasives, Ceramics and Other Nanoparticles, undated. |
| Panagiotiou, et al., Production of Stable Drug Nanosuspensions Using Microfluidics Reaction Technology, Poster Session, single page, undated. |
| Gruverman, Advances in Continuous Chemical Reactor Technology, Oct. 30, 2006, retrieved online Jun. 2, 2009, URlhttp://aimediaserver4com/chemeng/pdf/feature-oct06.pdf, Figure V, p. 5. |
| PCT International Search Report dated Jun. 15, 2009 (PCT/US2009/041511). |
| Johnson, et al., Chemical Processing and Micromixing in Confined Impinging Jets, AIChE Journal, vol. 49, No. 9, Sep. 2003, pp. 2264-2282. |
| U.S. Appl. No. 13/085,903, filed Apr. 13, 2011, Renqiang, X., Bernard, J. |
| U.S. Appl. No. 13/085,939, filed Apr. 13, 2011, Renqiang, X., Bernard, J. |
| Number | Date | Country | |
|---|---|---|---|
| 20190299171 A1 | Oct 2019 | US |
| Number | Date | Country | |
|---|---|---|---|
| Parent | 12986477 | Jan 2011 | US |
| Child | 16420718 | US |
