Patent Publication Number: US-9901921-B2

Title: Disposable invitro diagnostic cartridge and method of performing an invitro diagnostic test

Description:
CROSS-REFERENCE TO RELATED APPLICATION 
     This application claims the benefit of U.S. Provisional Application Ser. No. 62/167,481, filed May 28, 2015, which is incorporated herein by reference in its entirety. 
    
    
     BACKGROUND 
     1. Technical Field 
     This invention relates generally to invitro diagnostics, and more particularly to disposable invitro diagnostic cartridges and methods of performing invitro diagnostic tests. 
     2. Related Art 
     Diagnostic tests are increasingly being used to determine the state or condition of a biological environment, such as in human healthcare, agriculture, live stock management, municipal systems management, and national defense, by way of example and without limitation. A new market is emerging wherein diagnostic tests are being performed at the point-of-care. The diagnostic test can be complex, requiring multiple fluids and multiple steps to execute an assay. An assay is a sequence of steps or procedures used measure the presence or absence of a substance in a sample, the amount of a substance in a sample, or the characteristics of a sample. An example of a common and relative simple point-of-care assay, which can be readily conducted by a layperson, is a blood glucose test. In this test, generally speaking, the blood is mixed with glucose oxidase, which reacts with the glucose in the sample, creating gluconic acid, wherein the gluconic acid reacts with a chemical, typically ferricyanide, producing ferrocyanide. Current is passed through the ferrocyanide and the impedance reflects the amount of glucose present. 
     Although the aforementioned blood glucose assay is relative common and simple, many assays are far more complex, in that they require specific fluids, often of differing types and quantities, to be stored for future use on the diagnostic device. These fluids may be, but are not limited to, a buffer solution for dilution, fluids containing antibodies and antigens, microspheres coated with binding agents, cell lysing agents, and other fluids required to manipulate the sample being tested. Diagnostic tests that utilize millifluidic and microfluidic volumes of the fluids are intended to provide an incredibly high degree of specificity, sensitivity, and a precise volume and rate of fluid delivery to achieve as accurate a test result as possible. Nearly all microfluidic tests require the introduction of fluids throughout the assay sequence to manipulate the sample being tested and to produce an accurate diagnosis. 
     Typically, consumable diagnostic devices, meaning the diagnostic device is disposable upon being used, require a companion durable hardware device that interfaces with the consumable diagnostic device to execute the test. The durable hardware performs many functions, one of which is to facilitate dispensing a reagent in a reservoir or reagents from separate reservoirs on the consumable diagnostic into a specimen containing reaction chamber via microfluidic or millifluidic channels formed within the consumable diagnostic device. The introduction of the reagent into the reaction chamber requires precision; including flow rate, volume and timing, so as to best replicate the protocols of a laboratory where precession pipettes are employed. Upon the reagent being introduced into the reaction chamber, the reagent and specimen are generally kept in the reaction chamber for a minimum specified amount of time to allow the sample to mix as best possible with the reagent. Further, it is known to incorporate a mixing apparatus within the reaction chamber to further mix the specimen and the reagent prior to performing the analysis. The incorporation of a mixing member within the reaction chamber adds complexity, which can lead to error in test results, and further adds cost to the construction of the diagnostic device. Further yet, the mixing member can result in the specimen being over diluted, thereby resulting in volumetric loss of the specimen, and thus, resulting in a less than optimal, or failed test result. 
     SUMMARY OF THE INVENTION 
     In accordance with one aspect of the invention, a disposable, point-of-care diagnostic cartridge is provided. The cartridge includes a rigid base having opposite upper and lower surfaces. A mixing chamber is formed on the base. The mixing chamber has at least one mixing chamber inlet and a mixing chamber outlet. A detection chamber is formed on the base downstream from the mixing chamber. A fluidic channel extends in fluid communication between and with the mixing chamber and the detection chamber via the mixing chamber outlet and a detection chamber inlet. The mixing chamber includes mixing reservoir bounded at least in part by a flexible upper member operably fixed to the upper surface of the base. The flexible upper member is expandable to increase the volume of the mixing reservoir and collapsible to decrease the volume of the mixing reservoir. Each mixing chamber inlet has an inlet valve member that provides one way flow of fluid into the mixing reservoir and prevents fluid from flowing in a reverse direction outwardly from the mixing reservoir. The mixing chamber outlet has an outlet valve member that provides one way flow of fluid outwardly from the mixing reservoir to the detection chamber and prevents fluid from flowing in a reverse direction into the mixing reservoir. The inlet valve member opens while a liquid is selectively injected through the mixing chamber inlet, thereby causing the flexible upper member to expand and form a raised blister, whereupon the inlet valve member automatically closes upon the fluid being injected into the mixing reservoir. The fluid is contained in the mixing reservoir and mixed with a specimen for a desired amount of time to form a mixture until the blister is selectively collapsed under an externally applied force, at which time the outlet valve member opens to allow the mixture to flow to the detection chamber for analysis. 
     In accordance with another aspect of the invention, the mixing chamber can contain a reactive substance prior to the injection of the fluid. 
     In accordance with another aspect of the invention, the specimen and fluid mixture can be injected into the mixing chamber through the mixing chamber inlet valve member. 
     In accordance with another aspect of the invention, a single mixing chamber can include a plurality of inlets and inlet valve members. 
     In accordance with another aspect of the invention, the at least one inlet of the mixing chamber can be in fluid communication with an upstream source of fluid via a fluidic channel, wherein the upstream source of fluid can be sealed within a flexible fluid dispensing member. 
     In accordance with another aspect of the invention, a specimen chamber can be disposed between the mixing chamber and the flexible fluid dispensing member and in fluid communication with the mixing chamber and the fluid dispensing member. 
     In accordance with another aspect of the invention, the specimen chamber can have a cover movable between an open state and a closed state to allow a specimen to be disposed and sealed within the specimen chamber. 
     In accordance with another aspect of the invention, a method of performing a diagnostic test is provided. The method includes disposing the specimen in a specimen chamber; injection fluid and/or air through the specimen chamber and causing a mixture including the specimen to flow into a mixing chamber through a one way inlet valve member and simultaneously causing a flexible upper member of the mixing chamber to expand to accommodate the increased volume of matter within the mixing chamber. Then, imparting an external force on the flexible upper member and causing the mixture to flow out of the mixing chamber through a one way outlet valve member to a detection chamber. Then, analyzing the specimen within a detection apparatus. 
     In accordance with another aspect of the invention, the method can further include disposing a reactive substance with the mixing chamber prior to the injection of the fluid through said at least one inlet. 
     In accordance with another aspect of the invention, the method can further include providing the mixing chamber with a plurality of the inlets. 
     In accordance with another aspect of the invention, the method can further include configuring the at least one inlet of the mixing chamber in fluid communication with an upstream source of fluid via a fluidic channel. 
     In accordance with another aspect of the invention, the method can further include providing the upstream source of fluid as a fluid sealed within a flexible fluid dispensing member on the base. 
     In accordance with another aspect of the invention, the method can further include configuring a specimen chamber in fluid communication with the mixing chamber and the flexible fluid dispensing member. 
     In accordance with another aspect of the invention, the method can further include arranging the specimen chamber between the mixing chamber and the fluid dispensing member. 
     In accordance with another aspect of the invention, the method can further include providing the specimen chamber with a cover movable between an open state and a closed state to allow a specimen to be disposed and sealed within the specimen chamber. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       These and other aspects, features and advantages of the invention will become more readily appreciated when considered in connection with the following detailed description of presently preferred embodiments and best mode, appended claims and accompanying drawings, in which: 
         FIG. 1  is a perspective view of a disposable invitro diagnostic cartridge constructed in accordance with one aspect of the invention shown in a pre-actuated state; 
         FIG. 2  is a cross-sectional view of the disposable invitro diagnostic cartridge of  FIG. 1  shown in a pre-actuated state; 
         FIG. 3  is a view similar to  FIG. 1  showing the disposable invitro diagnostic cartridge in a fully actuated state; 
         FIG. 4  is an enlarged cross-sectional view of a mixing chamber of the disposable invitro diagnostic cartridge of  FIG. 1 , with a flexible upper member enclosing the mixing chamber shown in a collapsed state; 
         FIG. 4A  is an enlarged cross-sectional view of the mixing chamber of the disposable invitro diagnostic cartridge of  FIG. 1 , with the flexible upper member enclosing the mixing chamber shown in a partially expanded state while receiving a sample and reagent mixture through an inlet valve member; 
         FIG. 4B  is a view similar to  FIG. 4A  showing the flexible upper member being collapsed to dispense the mixture therein through an outlet valve member; 
         FIG. 5  is a perspective view of a disposable invitro diagnostic cartridge constructed in accordance with another aspect of the invention shown in a pre-actuated state; 
         FIG. 6  is an enlarged cross-sectional view of a mixing chamber of the disposable invitro diagnostic cartridge of  FIG. 5 , with a flexible upper member enclosing the mixing chamber shown in a partially collapsed, pre-mixing state; 
         FIG. 7  is a view similar to  FIG. 6  showing the flexible upper member being expanded while receiving a sample and reagent mixture through an inlet valve member; and 
         FIGS. 8A-8E  illustrate sequential steps used to perform a test using a disposable invitro diagnostic cartridge constructed in accordance with yet another aspect of the invention. 
     
    
    
     DETAILED DESCRIPTION OF PRESENTLY PREFERRED EMBODIMENTS 
     Referring in more to the drawings,  FIGS. 1-3  show a disposable invitro diagnostic cartridge constructed in accordance with one aspect of the invention, referred to hereafter as diagnostic cartridge  10 , and sometimes referred to in the diagnostic industry as blister card, as well as point-of-care invitro diagnostic device (IVD). The diagnostic cartridge  10  is sized to be hand held and is intended to be disposable after use. The diagnostic cartridge  10  has a rigid or substantially rigid base  11 , which can be constructed as a monolithic piece of material or a plurality of material layers bonded to one another, with a mixing chamber  12  formed thereon. The mixing chamber  12  includes at least one mixing chamber inlet  14  and a mixing chamber outlet  16 . A detection chamber  18  is formed on the base  11  downstream from the mixing chamber  12 , wherein a fluidic channel  20  extends in fluid communication between the mixing chamber  12  and the detection chamber  18  via the mixing chamber outlet  16  and a detection chamber inlet  22 . A waste chamber  19  can be provided downstream from the detection chamber  18 , if desired, with a further fluidic channel  21  extending in fluid communication therebetween. The mixing chamber  12  includes mixing reservoir  28  bounded at least in part by a flexible upper member  24  operably fixed to the upper surface of the base  11 . The flexible upper member  24  is expandable, without being plastically deformed, to increase the volume of the mixing reservoir  28  to a predetermined volume and collapsible to decrease the volume of the mixing reservoir  28 . Each mixing chamber inlet  14  has an inlet valve member  30  that provides one way flow of fluid into the mixing reservoir  28  and prevents or substantially prevents fluid from flowing in a reverse direction outwardly from the mixing reservoir  28 . The mixing chamber outlet  16  has an outlet valve member  32  that provides one way flow of fluid outwardly from the mixing reservoir  28  to the detection chamber  18  and prevents fluid from flowing in a reverse direction into the mixing reservoir  28 . The inlet valve member  30  opens while a supply of fluid F is selectively injected through the mixing chamber inlet  14 , thereby causing the flexible upper member  24  to expand from a collapsed state ( FIG. 4 ) and form a raised blister  34  ( FIG. 4A ), thereby increasing the volume of the mixing reservoir  28 , whereupon the inlet valve member  30  automatically closes upon the fluid F being injected into the mixing chamber  12 . The fluid F is contained in the mixing reservoir  28  and mixed with a specimen S to form a homogeneous or substantially homogeneous mixture M within the mixing reservoir  28  until the blister  34  is selectively collapsed under an externally applied force via an actuator apparatus  35  ( FIG. 4B ), at which time the outlet valve member  32  opens to allow the mixture M to flow to the detection chamber  18  for analysis, such as via a diagnostic camera (not shown), through a viewing window  36 . 
     As shown in  FIGS. 1-3 , in addition to the mixing chamber  12  being in fluid communication with the downstream detection chamber  18 , the mixing chamber  12  is also in fluid communication with at least one upstream specimen chamber, shown as a single specimen chamber  40 , by way of example and without limitation, and at least one upstream fluid dispensing member, shown as a single fluid dispensing member  42 , by way of example and without limitation, with the specimen chamber  40  shown as being between and in fluid communication with the fluid dispensing member  42  via an inlet  44  and fluidic channel  45  and with the mixing chamber  12  via an outlet  46  and a fluidic channel  47 . It is to be recognized that the mixing chamber  12  can be in fluid communication with a plurality of specimen chambers and fluid dispensing chambers, such as in a spoke configuration, like spokes on a hub, wherein the hub represents the mixing chamber  12 . The specimen chamber  40  is shown as extending into an upper surface  36  of the base  11 , by way of example and without limitation. A lid, also referred to as cover  48 , is configured to seal off the specimen chamber  40 , wherein the cover  48  can be moved from a closed and sealed position ( FIG. 3 ) to an open position ( FIGS. 1 and 2 ). As such, the specimen S, when desired, can be readily disposed into the specimen chamber  40  and sealed therein for testing. The cover  48  can be provided as an impervious flexible film, including a living hinge, or otherwise, such as a relatively rigid impervious member having a mechanical or living hinge, by way of example and without limitation. As such, the cover  48  allows the sample S to be disposed within the specimen chamber  40  and then sealed therein for testing. One possessing ordinary skill in the art will recognize the function of the cover  48  is to allow the specimen S to be disposed into the specimen chamber  40  and sealed therein, and could readily devise other covers than shown, with those covers being contemplated herein. 
     The fluid dispensing member  42  is shown as having a flexible upper member  50  forming a flexible, raised blister  52  bounding dispensing reservoir  54  of a predetermined volume. The dispensing reservoir  54  contains a predetermined volume of sealed fluid F therein, or it could be air, depending on the nature of the test to be performed, wherein the volume of the dispensing reservoir  54  plus the volume of the specimen chamber  40  is equal or less than the maximum volume of the downstream mixing chamber  12 . The fluid F contained in dispensing reservoir  54  can be of any desired type of fluid, again depending on the nature of the test to be performed, including an inactive, non-reactive fluid, such as water, for example, or an active, reactive fluid, such as a reagent capable of lysing a cell. The fluid dispensing member  42  has an outlet valve member  56  that provides one way flow of the fluid F, or air, out of the dispensing reservoir  54  through the fluidic channel  45  to the specimen chamber  40  and through the fluidic channel  47  into the mixing reservoir  28 . The outlet valve member  56  prevents or substantially prevents the fluid F, or air, from flowing in a reverse direction back into the dispensing reservoir  54 . 
     The mixing chamber  12  and fluid dispensing member  42  can be constructed separately from the rigid or substantially rigid base  11  and then subsequently attached thereto, or they can be formed on the rigid base  11  in a series of laminations, as will be understood by one ordinarily skilled in the art upon viewing the disclosure herein. For example, the mixing chamber  12  can include a lamination of the upper flexible member  24 , a rigid or substantially rigid substrate  58  having a plurality of through openings  57 ,  59  configured to align with the inlet and outlet valve members  30 ,  32 , respectively, and flexible film materials forming the inlet and outlet valve member  30 ,  32 . The inlet and outlet valve members  30 ,  32  can be constructed as reed-type valve members, thereby being biased toward their closed positions in the absence of a suitable force causing the valve members  30 ,  32  to be moved to their open positions. In one example, the inlet valve member  30  can be formed from a piece of impervious, flexible film material having an outer periphery  62  bonded to an upper surface  64  of the rigid substrate  58  and the outlet valve member  32  can be formed from a piece of impervious, flexible film material having an outer periphery  66  bonded to a lower surface  68  of the rigid substrate  58 . It should be recognized that if the inlet and outlet valve members  30 ,  32  are formed from sheets of material having outer peripheries similar in size as the outer periphery of the flexible upper member  24 , then the sheet providing the inlet valve member  30  has a through opening configured to register with the through opening  59  in the substrate  58  and the outlet valve member  32  and the sheet providing the outlet valve member  32  has a through opening configured to register with the through opening  57  in the substrate  58  and the inlet valve member  30 . Further, if provided as a single sheets of material, the inlet and outlet valve members  30 ,  32  are preformed therein, such as via a weakened region, such as via die-cut or a stamped, thinned region, sometimes referred to as “kiss-cut”, and/or perforated region, for example, wherein each inlet and outlet valve member  30 ,  32  has a respective living hinge  70 ,  72 . 
     The fluid dispensing member  42 , like the mixing chamber  12 , can include a lamination of the upper flexible member  50 , a rigid or substantially rigid substrate  74  having a through opening  76  configured to align with the outlet valve member  56  respectively, and flexible film material forming the outlet valve member  56 . In contrast to the mixing chamber, however, the fluid dispensing member  42  only has a valve on one side of the substrate  74 , namely, the outlet valve member  56 . An outer periphery  78  of the upper flexible member  50  is operably bonded via a first adhesive to an upper surface  80  of the substrate  74 , wherein the first adhesive provides a sufficient bond to resist delamination over the useful life of the cartridge  10  and the flexible film layer forming the outlet valve member  56  is operably bonded to a lower surface  82  of the substrate  74  via a second adhesive. The second adhesive can be provided to allow selective delamination of the outlet valve member  56  from the lower surface  82  of the substrate  74  during intended actuation. 
     The material used to form the upper flexible layers  24 ,  50  is provided as flexible, cold-formable, tough and tear-resistant material. For example, the layers  24 ,  50  can be formed as a lamination of an outwardly facing material, including foil, such as aluminum, and an inwardly facing, fluid impervious vapor barrier, including a sheet of plastic, such as an oriented polyamide coating (oPA), with an intermediate adhesive, such as a polyvinyl chloride (PVC) or other suitable heat-activated adhesive, bonding the outer and inner laminated layers together. One such material can be purchased from Amcor Flexibles Shelbyville out of Shelbyville, Ky., USA, under the trademark FORMPACK®, under product code 15288, which is incorporated herein by reference. It should be recognized that the aforementioned materials are not plastically deformed during use. 
     During actuation of the cartridge  10 , upon depressing the blister  52  of the fluid dispensing member  42 , the outlet valve member  56  is caused to rupture or hingedly open prior to any substantial delamination of the flexible upper member  50  from the substrate  74 . Accordingly, the flexible upper member  50  is assured of remaining in a leak-free bond with the substrate  74 . Meanwhile, the outlet valve member  56  is assured of opening, as intended, as a result of the relatively weak bond or rupture strength of the valve member  56 , whether as a result of a relatively weak material rupture strength and/or a relatively weak rupture strength imparted by intentionally weakened regions within the flexible layer forming the outlet valve member  56  in comparison to the relatively strong material strength of the flexible upper member  50 , and also the relatively strong bond strength of the adhesive bonding the flexible upper member  50  operably to the substrate  74 . 
     The fluid F flows through the fluidic channel  45  to the specimen chamber  40 , whereupon it picks up and mixes with the specimen S to form the mixture M, whereupon the mixture M then flows through the fluidic channel  47  and into the mixing chamber  12  through the inlet  14 . Accordingly, the inlet valve member  30  is caused to open temporarily under the pressure of the mixture M, whereupon the flexible upper member  24  is caused to expand from its accordion folded collapsed state to accommodate the presence of the mixture M ( FIG. 4A ). At this time, with the inlet valve member  30  in its closed state, the mixture M is contained in the mixing reservoir  28  of the mixture chamber  12 . When desired, the expanded blister  34  of the mixing chamber  12  is then collapsed under application of an externally applied force, such as via the apparatus  35 , thereby causing the outlet valve member  32  to move to its open position ( FIG. 4B ) to allow the mixture M to flow through the outlet  16  and through the fluidic channel  20  to the detection chamber  18 . Then, once in the detection chamber  18 , the sample within the mixture M can be analyzed ( FIG. 3 ), with any overage being able to flow to the waste chamber  19  via the fluidic channel  21 . 
       FIGS. 5-7  illustrate an embodiment of the cartridge  10 ′ similar to the cartridge  10  described above, wherein the same reference numerals, shown primed, are used to identify like features as described above; however, the manner in which a flexible upper member  24 ′ is initially collapsed is different. Rather than being folded in accordion fashion, a central region CR of the flexible upper member  24 ′ is depressed or dimpled inwardly and bonded lightly to an underlying surface ( FIGS. 5 and 6 ). Then, upon the mixture M′ entering the mixing reservoir  28 ′ through the inlet valve member  30 ′, the bond is broken and the flexible upper member  24 ′ is free to expand to accommodate the increased volume of matter ( FIG. 7 ). Otherwise, the cartridge is the same as discussed above for the cartridge  10 . 
     In accordance with another aspect of the invention, a method of performing an invitro diagnostic test on a specimen S is provided. The method includes disposing the specimen S in a specimen chamber  40 ; injection fluid F and or air through the specimen chamber  40  and causing a mixture M including the specimen S to flow into a mixing chamber  12  through a one way inlet valve member  30  and simultaneously causing a flexible upper member  24  of the mixing chamber  12  to expand to accommodate the increased volume of matter within the mixing chamber  12 . Then, imparting an external force on the flexible upper member  24  and causing the mixture M to flow out of the mixing chamber  12  through a one way outlet valve member  32  to a detection chamber  18 . Then, analyzing the specimen within the detection chamber  18  through a window  36  via a detection apparatus, such as a detection capable camera, as is known in the art, or other detection device. 
       FIGS. 8A-8E  illustrate another method of performing an invitro diagnostic test on a specimen and diagnostic cartridge  110  therefore, constructed in accordance with aspect of the invention, wherein the same reference numerals as used above, offset by a factor of 100, are used to identify like features. The cartridge  110  has a fluid and/or air dispensing member  142 , constructed similarly as discussed above for the fluid and/or air dispensing member  42 , that can be configured in fluid communication with a plurality of downstream mixing chambers  112 ,  112 ′,  112 ″ with a specimen chamber  140  located between the fluid and/or air dispensing member  142  and the mixing chamber  112 . The mixing chambers  112 ,  112 ′,  112 ″ are constructed similarly as discussed above, each having inlet valve members  130 ,  130 ′,  130 ″ and outlet valve members  132 ,  132 ′,  132 ″, and thus, no further discussion is believed necessary to describe their structure or function. Based on this embodiment, it should be recognized that any number of mixing chambers can be integrated into a diagnostic cartridge in accordance with the invention, with the mixing chambers being configured in serial, sometimes referred to as “daisy chain”, fluid communication with one another. As shown in  FIG. 8A , the specimen is disposed into the specimen chamber  140 , whereupon the dispensing member  142  is depressed via an actuator, wherein the fluid from the specimen chamber  140  flows through the specimen chamber  140 , picking up the specimen, and carrying the specimen to the first mixing chamber  112 . As the fluid and specimen flow through the one-way inlet  130  of the first mixing chamber  112 , as shown in  FIG. 8B , the flexible upper member of the first mixing chamber  112  expands to accommodate the sudden increase in volume, wherein the fluid, specimen and contents of the first mixing chamber mix together. Then, as shown in  FIG. 8C , the flexible upper surface of the first mixing chamber  112  is depressed via an actuator, wherein the mixture flows out of the one-way outlet  132  of the first mixing chamber  112  and through a one-way inlet  130 ′ of a second mixing chamber  112 ′, whereupon the flexible upper member of the second mixing chamber  112 ′ expands to accommodate the sudden increase in volume, wherein the fluid, specimen and contents of the second mixing chamber mix together therein. Then, when desired, as shown in  FIG. 8D , the flexible upper surface of the second mixing chamber  112 ′ is depressed via an actuator, wherein the mixture flows out of a one-way outlet  132 ′ of the second mixing chamber  112 ′ and through a one-way inlet  130 ″ of a third mixing chamber  112 ″, whereupon the flexible upper member of the third mixing chamber  112 ″ expands to accommodate the sudden increase in volume, wherein the fluid, specimen and contents of the third mixing chamber, if any, mix together. It should be recognized that the contents of the mixing chambers  112 ,  112 ′,  112 ″ can contain a mixing medium, fluid or dry substance, or can otherwise remain empty or dry, wherein the mixing medium contained therein is suitably mixed with the fluid that flows through the respective one-way inlets  130 ,  130 ′,  130 ″. If empty or dry, the mixing chamber is thusly functions to further the mixing of the constituents therein. Then, as shown in  FIG. 8E , the flexible upper surface of the third mixing chamber  112 ″ can be depressed, wherein the mixture flows out of a one-way outlet  132 ″ of the third mixing chamber  112 ″ and to a specimen detection chamber  118  for analysis, with excess fluid/gas being able to flow freely through a fluidic channel  121  to a waste chamber  119 , as discussed above. 
     Many modifications and variations of the present invention are possible in light of the above teachings. It is, therefore, to be understood that the invention may be practiced otherwise than as specifically described, and that the scope of the invention is defined by claims allowed.