Patent Document

CROSS REFERENCE OF RELATED APPLICATION 
       [0001]    This application is a divisional application under 35 U.S.C. §121 claiming the benefit under 35 U.S.C. §120 of the filing date of non-provisional patent application Ser. No. 14/206,903 filed Mar. 12, 2014, which claims the benefit under 35 U.S.C. §119(e) of the filing date of provisional patent application Ser. No. 61/798,091 filed Mar. 15, 2013, the disclosure of which is incorporated herein by reference. 
     
    
     FIELD OF THE INVENTION 
       [0002]    Aspects of the invention relate to systems, methods, and apparatus for selectively opening deformable fluid vessels. One aspect of the invention relates to generating compressive forces for compressing deformable fluid vessels to displace fluid therefrom in a low profile instrument. Other aspects of the invention relate to opening the deformable fluid vessel in a manner that reduces the amount of compressive force required to displace fluid from the vessel. Other aspects of the invention relate to an apparatus for protecting the deformable fluid vessel from inadvertent exposure to external forces and for interfacing with the vessel to permit intentional application of external compressive force without removing the vessel-protective features. 
       BACKGROUND OF INVENTION 
       [0003]    The present invention relates to systems, methods, and apparatus for manipulating deformable fluid vessels. An exemplary device having such deformable fluid vessels is shown in  FIGS. 1A and 1B . A liquid reagent module  10  includes a substrate  12  on which a plurality of deformable fluid vessels, or blisters, are attached. Devices such as the liquid reagent module  10  are often referred to as cartridges or cards. In an embodiment, the liquid reagent module  10  includes an input port  16 , which may comprise a one-way valve, for dispensing a sample fluid into the module  10 . A fluid channel  18  carries fluid from the input port  16 . A sample vent  14  vents excess pressure from the module  10 . A labeled panel  20  may be provided for an identifying label, such as a barcode or other human and/or machine-readable information. 
         [0004]    Liquid reagent module  10  further includes a plurality of deformable (collapsible) vessels (blisters), including, in the illustrated embodiment, an elution reagent blister  22 , a wash buffer blister  24 , a water blister  26 , a lysis reagent blister  28 , an air blister  30 , a binding agent blister  32 , and an oil blister  34 . Note that the number and types of blisters shown are merely exemplary. Each of the blisters may be interconnected with one or more other blisters and/or the fluid channel  18  by one or more fluid channels formed in or on the substrate  12 . 
         [0005]    The liquid reagent module  10  may be processed by selectively compressing one or more of the blisters to completely or partially collapse the blister to displace the fluid therefrom. Instruments adapted to process the liquid reagent module  10 , or other devices with deformable fluid vessels, include mechanical actuators, e.g., typically pneumatically or electromechanically actuated, constructed and arranged to apply collapsing pressure to the blister(s). Typically, such actuator(s) is(are) disposed and are moved transversely to the plane of the module  10 —for example, if module  10  were oriented horizontally within an instrument, actuators may be provided vertically above and/or below the module  10  and would be actuated to move vertically, in a direction generally normal to the plane of the module. The liquid reagent module  10  may be processed in an instrument in which the module  10  is placed into a slot or other low profile chamber for processing. In such a slot, or low profile chamber, providing actuators or other devices that are oriented vertically above and/or below the module  10  and/or move in a vertical direction may not be practical. The pneumatic and/or electromechanical devices for effecting movement of such actuators require space above and/or below the module&#39;s substrate, space that may not be available in a slotted or other low profile instrument. 
         [0006]    Accordingly, a need exists for methods, systems, and/or apparatus for effecting movement of an actuator for collapsing a vessel within a low profile component space of an instrument. 
       SUMMARY OF THE INVENTION 
       [0007]    Aspects of the invention are embodied in an apparatus for processing a fluid module including a collapsible vessel supported on a planar substrate by applying a force compressing the vessel against the substrate. The apparatus comprises a first actuator component configured to be movable in a first direction that is generally parallel to the plane of the substrate, a second actuator component configured to be movable in a second direction having a component that is generally normal to the plane of the substrate, and a motion conversion mechanism coupling the first actuator component with the second actuator component and constructed and arranged to convert movement of the first actuator component in the first direction into movement of the second actuator component in the second direction. 
         [0008]    According to further aspects of the invention, the first actuator component comprises an actuator plate configured to be movable in the first direction and including a cam follower element, the second actuator component comprises a platen configured to be movable in the second direction, and the motion conversion mechanism comprises a cam body having a cam surface. The cam body is coupled to the platen and is configured such that the cam follower element of the actuator plate engages the cam surface of the cam body as the actuator plate moves in the first direction thereby causing movement of the cam body that results in movement of the platen in the second direction. 
         [0009]    According to further aspects of the invention, the cam follower element of the actuator plate comprises a roller configured to rotate about an axis of rotation that is parallel to the actuator plate and normal to the first direction, the motion conversion mechanism further comprises a chassis, and the cam body is pivotally attached at one portion thereof to the chassis and at another portion thereof to the platen. 
         [0010]    According to further aspects of the invention, the cam surface of the cam body comprises an initial flat portion and a convexly-curved portion, and movement of the roller from the initial flat portion to the convexly-curved portion causes the movement of the cam body that results in movement of the platen in the second direction. 
         [0011]    According to further aspects of the invention, the first actuator component comprises a cam rail configured to be movable in the first direction, the second actuator component comprises a platen configured to be movable in the second direction, and the motion conversion mechanism comprises a cam surface and a cam follower coupling the cam rail to the platen and configured to convert motion of the cam rail in the first direction into movement of the platen in the second direction. 
         [0012]    According to further aspects of the invention, the cam surface comprises a cam profile slot formed in the cam rail, and the cam follower comprises a follower element coupling the platen to the cam profile slot such that movement of the cam rail in the first direction causes movement of the cam follower within the cam profile slot that results in the movement of the platen in the second direction. 
         [0013]    Further aspects of the invention are embodied in an apparatus for displacing fluid from a fluid container. The fluid container includes a first vessel and a second vessel connected or connectable to the first vessel and including a sealing partition preventing fluid flow from the second vessel, and the fluid container further includes an opening device configured to be contacted with the sealing partition to open the sealing partition and permit fluid flow from the second vessel. The apparatus comprises a first actuator configured to be movable with respect to the first vessel to compress the first vessel and displace fluid contents thereof and a second actuator movable with respect to the opening device and configured to contact the opening device and cause the opening device to open the sealing partition, The second actuator is releasably coupled to the first actuator such that the second actuator moves with the first actuator until the second actuator contacts the opening device and causes the opening device to open the sealing partition, after which the second actuator is released from the first actuator and the first actuator moves independently of the second actuator to displace fluid from the first vessel. 
         [0014]    Further aspects of the invention are embodied in a fluid container comprising a first vessel, a second vessel connected or connectable to the first vessel, a sealing partition preventing fluid flow from the second vessel, and a spherical opening element initially supported within the second vessel by the sealing partition and configured to be contacted with the sealing partition to open the sealing partition and permit fluid flow from the second vessel. 
         [0015]    Further aspects of the invention are embodied in a fluid container comprising a first vessel, a second vessel connected or connectable to the first vessel, a sealing partition preventing fluid flow from the second vessel, and a cantilevered lance having a piercing point and disposed with the piercing point adjacent to the sealing partition and configured to be deflected until the piercing point pierces the sealing partition to permit fluid flow from the second vessel through the pierced sealing partition. 
         [0016]    Further aspects of the invention are embodied in a fluid container comprising a first vessel, a second vessel connected or connectable to the first vessel, a sealing partition preventing fluid flow from the second vessel, and a cantilevered lance having a piercing point and being fixed at an end thereof opposite the piercing point, the cantilevered lance being disposed with the piercing point adjacent to the sealing partition and configured to be deflected until the piercing point pierces the sealing partition to permit fluid flow from the second vessel through the pierced sealing partition. 
         [0017]    According to further aspects of the invention, the fluid container further comprises a substrate on which the first and second vessels are supported and which includes a chamber formed therein adjacent the sealing partition wherein an end of the cantilevered lance is secured to the substrate and the piercing point of the lance is disposed within the chamber. 
         [0018]    Further aspects of the invention are embodied in a fluid container comprising a first vessel, a second vessel connected or connectable to the first vessel, a sealing partition preventing fluid flow from the second vessel, and a lancing pin having a piercing point and disposed with the piercing point adjacent to the sealing partition and configured to be moved with respect to the sealing partition until the piercing point pierces the sealing partition to permit fluid flow from the second vessel through the pierced sealing partition. 
         [0019]    According to further aspects of the invention, the lancing pin has a fluid port formed therethrough to permit fluid to flow through the lancing pin after the sealing partition is pierced by the piercing point. 
         [0020]    According to further aspects of the invention, the fluid container further comprises a substrate on which the first and second vessels are supported and which includes a chamber formed therein adjacent the sealing partition within which the lancing pin is disposed. 
         [0021]    According to further aspects of the invention, the chamber in which the lancing pin is disposed comprises a segmented bore defining a hard stop within the chamber and the lancing pin includes a shoulder that contacts the hard stop to prevent further movement of the lancing pin after the piercing point pierces the sealing partition. 
         [0022]    According to further aspects of the invention, the fluid container further comprises a fluid channel extending between the first and second vessels. 
         [0023]    According to further aspects of the invention, the fluid container of further comprises a seal within the fluid channel, the seal being configured to be breakable upon application of sufficient force to the seal to thereby connect the first and second vessels via the fluid channel. 
         [0024]    Further aspects of the invention are embodied in a fluid container comprising a first vessel, a second vessel disposed within the first vessel, a substrate on which the first and second vessels are supported and having a cavity formed therein adjacent the second vessel, a fixed spike formed within the cavity, and a fluid exit port extending from the cavity, wherein the first and second vessels are configured such that external pressure applied to the first vessel will collapse the second vessel and cause the second vessel to contact and be pierced by the fixed spike, thereby allowing fluid to flow from the first vessel through the pierced second vessel, the cavity, and the fluid exit port. 
         [0025]    Further aspects of the invention are embodied in a fluid container comprising a collapsible vessel configured to be collapsed upon application of sufficient external pressure to displace fluid from the vessel, a housing surrounding at least a portion of the collapsible vessel, and a floating compression plate movably disposed within the housing. The housing includes an opening configured to permit an external actuator to contact the floating compression plate within the housing and press the compression plate into the collapsible vessel to collapse the vessel and displace the fluid contents therefrom. 
         [0026]    Other features and characteristics of the present invention, as well as the methods of operation, functions of related elements of structure and the combination of parts, and economies of manufacture, will become more apparent upon consideration of the following description and the appended claims with reference to the accompanying drawings, all of which form a part of this specification, wherein like reference numerals designate corresponding parts in the various figures. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0027]    The accompanying drawings, which are incorporated herein and form part of the specification, illustrate various, non-limiting embodiments of the present invention. In the drawings, common reference numbers indicate identical or functionally similar elements. 
           [0028]      FIG. 1A  is a top plan view of a liquid reagent module. 
           [0029]      FIG. 1B  is a side view of the liquid reagent module. 
           [0030]      FIG. 2  is a perspective view of a blister compressing actuator mechanism embodying aspects of the present invention. 
           [0031]      FIG. 3A  is a partial, cross-sectional perspective view of the articulated blister actuator platen assembly in an initial, unactuated state. 
           [0032]      FIG. 3B  is a partial, cross-sectional side view of the articulated blister actuator platen assembly in the initial unactuated state. 
           [0033]      FIG. 4A  is a partial, cross-sectional perspective view of the articulated blister actuator platen assembly as the platen is about to be actuated. 
           [0034]      FIG. 4B  is a partial, cross-sectional side view of the articulated blister actuator platen assembly as the platen is about to be actuated. 
           [0035]      FIG. 5A  is a partial, cross-sectional perspective view of the articulated blister actuator platen assembly with the platen in a fully actuated state. 
           [0036]      FIG. 5B  is a partial, cross-sectional side view of the articulated blister actuator platen assembly with the platen in a fully actuated state. 
           [0037]      FIG. 6A  is a partial, cross-sectional perspective view of the articulated blister actuator platen assembly with the platen returned to the unactuated state. 
           [0038]      FIG. 6B  is a partial, cross-sectional side view of the articulated blister actuator platen assembly with the platen returned to the unactuated state. 
           [0039]      FIG. 7A  is a perspective view of an alternative embodiment of a blister compressing actuator mechanism in an unactuated state. 
           [0040]      FIG. 7B  is a perspective view of the blister compressing actuator mechanism of  FIG. 7A  in the fully actuated state. 
           [0041]      FIG. 8A  is a partial, cross-sectional side view of a collapsible fluid vessel configured to facilitate opening of the vessel. 
           [0042]      FIG. 8B  is an enlarged partial, cross-sectional side view of a vessel opening feature of the collapsible fluid vessel. 
           [0043]      FIGS. 9A-9D  are side views showing an apparatus for opening a collapsible vessel configured to facilitate opening of the vessel in various states. 
           [0044]      FIG. 10  is a side view of an alternative embodiment of an apparatus for opening a collapsible vessel configured to facilitate opening of the vessel. 
           [0045]      FIG. 11  is a bar graph showing exemplary burst forces for fluid-containing blisters of varying volumes. 
           [0046]      FIG. 12  is a load versus time plot of the compression load versus time during a blister compression. 
           [0047]      FIG. 13A  is a partial, cross-sectional side view of an alternative apparatus for opening a collapsible vessel configured to facilitate opening of the vessel. 
           [0048]      FIG. 13B  is a perspective view of a cantilever lance used in the embodiment of  FIG. 13A . 
           [0049]      FIG. 14  is a partial, cross-sectional side view of an alternative apparatus for opening a collapsible vessel configured to facilitate opening of the vessel. 
           [0050]      FIG. 15A  is a partial, cross-sectional side view of an alternative apparatus for opening a collapsible vessel configured to facilitate opening of the vessel. 
           [0051]      FIG. 15B  is a perspective view of a lancing pin used in the apparatus of  FIG. 15A . 
           [0052]      FIG. 16A  is a partial, cross-sectional side view of an alternative apparatus for opening a collapsible vessel configured to facilitate opening of the vessel. 
           [0053]      FIG. 16B  is a perspective view of a lancing pin used in the apparatus of  FIG. 16A . 
           [0054]      FIG. 17  is an exploded, cross-sectional, perspective view of an apparatus for protecting and interfacing with a collapsible vessel. 
           [0055]      FIG. 18  is a cross-sectional, side view of the apparatus for protecting and interfacing with a collapsible vessel in an unactuated state. 
           [0056]      FIG. 19  is a cross-sectional, perspective view of the apparatus for protecting and interfacing with a collapsible vessel in fully actuated state. 
       
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
       [0057]    Unless defined otherwise, all terms of art, notations and other scientific terms or terminology used herein have the same meaning as is commonly understood by one of ordinary skill in the art to which this disclosure belongs. Many of the techniques and procedures described or referenced herein are well understood and commonly employed using conventional methodology by those skilled in the art. As appropriate, procedures involving the use of commercially available kits and reagents are generally carried out in accordance with manufacturer defined protocols and/or parameters unless otherwise noted. All patents, applications, published applications and other publications referred to herein are incorporated by reference in their entirety. If a definition set forth in this section is contrary to or otherwise inconsistent with a definition set forth in the patents, applications, published applications, and other publications that are herein incorporated by reference, the definition set forth in this section prevails over the definition that is incorporated herein by reference. 
         [0058]    As used herein, “a” or “an” means “at least one” or “one or more.” 
         [0059]    This description may use relative spatial and/or orientation terms in describing the position and/or orientation of a component, apparatus, location, feature, or a portion thereof. Unless specifically stated, or otherwise dictated by the context of the description, such terms, including, without limitation, top, bottom, above, below, under, on top of, upper, lower, left of, right of, in front of, behind, next to, adjacent, between, horizontal, vertical, diagonal, longitudinal, transverse, etc., are used for convenience in referring to such component, apparatus, location, feature, or a portion thereof in the drawings and are not intended to be limiting. 
         [0060]    An actuator mechanism for compressing deformable fluid vessels—such as blisters on a liquid reagent module—embodying aspects of the present invention is shown at reference number  50  in  FIG. 2 . The actuator mechanism  50  may include an articulated blister actuator platen assembly  52  and a sliding actuator plate  66 . The sliding actuator plate  66  is configured to be movable in a direction that is generally parallel to the plane of the liquid reagent module—horizontally in the illustrated embodiment—and may be driven by a linear actuator, a rack and pinion, a belt drive, or other suitable motive means. Sliding actuator plate  66 , in the illustrated embodiment, has V-shaped edges  76  that are supported in four V-rollers  74  to accommodate movement of the plate  66  in opposite rectilinear directions, while holding the sliding actuator plate  66  at a fixed spacing from the actuator platen assembly  52 . Other features may be provided to guide the actuator plate  66 , such as rails and cooperating grooves. A component  40 —which may comprise liquid reagent module  10  described above—having one or more deformable fluid vessels, such as blisters  36  and  38 , is positioned within the actuator mechanism  50  beneath the articulated blister actuator platen assembly  52 . 
         [0061]    Further details of the configuration of the articulated blister actuator platen assembly  52  and the operation thereof are shown in  FIGS. 3A-6B . 
         [0062]    As shown in  FIGS. 3A and 3B , the actuator platen assembly  52  includes a chassis  54 . A cam body  56  is disposed within a slot  57  of the chassis  54  and is attached to the chassis  54  by a first pivot  58 . A platen  64  is pivotally attached to the cam body  56  by means of a second pivot  60 . The cam body  56  is held in a horizontal, unactuated position within the slot  57  by means of a torsional spring  55  coupled around the first pivot  58 . 
         [0063]    Cam body  56  further includes a cam surface  65  along one edge thereof (top edge in the figure) which, in the exemplary embodiment shown in  FIG. 3B , comprises an initial flat portion  61 , a convexly-curved portion  62 , and a second flat portion  63 . The sliding actuator plate  66  includes a cam follow  68  (a roller in the illustrated embodiment) rotatably mounted within a slot  72  formed in the actuator plate  66 . In an embodiment of the invention, one cam body  56  and associated platen  64  and cam follower  68  are associated with each deformable vessel (e.g. blister  36 ) of the liquid reagent module  40 . 
         [0064]    The actuator platen assembly  52  and the sliding actuator plate  66  are configured to be movable relative to each other. In one embodiment, the actuator platen assembly  52  is fixed, and the actuator plate  66  is configured to move laterally relative to the platen assembly  52 , supported by the V-rollers  74 . Lateral movement of the sliding actuator plate  66 , e.g., in the direction “A”, causes the cam follower  68  to translate along the cam surface  65  of the cam body  56 , thereby actuating the cam body  56  and the platen  64  attached thereto. 
         [0065]    In  FIGS. 3A and 3B , before the sliding actuator plate  66  has begun to move relative to the actuator platen assembly  52 , the cam follower  68  is disposed on the initial flat portion  61  of the cam surface  65  of the cam body  56 . In  FIGS. 4A and 4B , the sliding actuator plate  66  has moved relative to the actuator platen assembly  52  in the direction “A” so that the cam follower  68  has moved across the initial flat portion  61  of the cam surface  65  and has just begun to engage the upwardly curved contour of the convexly-curved portion  62  of the cam surface  65  of the cam body  56 . 
         [0066]    In  FIGS. 5A and 5B , the sliding actuator plate  66  has proceeded in the direction “A” to a point such that the cam follower  68  is at the topmost point of the convexly-curved portion  62  of the cam surface  65 , thereby causing the cam body  56  to rotate about the first pivot  58 . The platen  64  is lowered by the downwardly pivoting cam body  56  and pivots relative to the cam body  56  about the second pivot  60  and thereby compresses the blister  36 . 
         [0067]    In  FIGS. 6A and 6B , sliding actuator plate  66  has moved to a position in the direction “A” relative to the actuator platen assembly  52  such that the cam follower  68  has progressed to the second flat portion  63  of the cam surface  65 . Accordingly, the cam body  56 , urged by the torsion spring  55 , pivots about the first pivot  58  back to the unactuated position, thereby retracting the platen  64 . 
         [0068]    Thus, the articulated blister actuator platen assembly  52  is constructed and arranged to convert the horizontal movement of actuator plate  66  into vertical movement of the platen  64  to compress a blister, and movement of the platen does not require pneumatic, electromechanical, or other components at larger distances above and/or below the liquid module. 
         [0069]    An alternative embodiment of a blister compression actuator mechanism is indicated by reference number  80  in  FIGS. 7A and 7B . Actuator  80  includes a linear actuator  82  that is coupled to a cam rail  84 . Cam rail  84  is supported for longitudinal movement by a first support rod  96  extending transversely through slot  86  and a second support rod  98  extending transversely through a second slot  88  formed in the cam rail  84 . The first support rod  96  and/or the second support rod  98  may include an annular groove within which portions of the cam rail  84  surrounding slot  86  or slot  88  may be supported, or cylindrical spacers may be placed over the first support rod  96  and/or the second support rod  98  on opposite sides of the cam rail  84  to prevent the cam rail  84  from twisting or sliding axially along the first support rail  96  and/or the second support rail  98 . 
         [0070]    Cam rail  84  includes one or more cam profile slots. In the illustrated embodiment, cam rail  84  includes three cam profile slots  90 ,  92 , and  94 . Referring to cam profile slot  90 , in the illustrated embodiment, slot  90  includes, progressing from left to right in the figure, an initial horizontal portion, a downwardly sloped portion, and a second horizontal portion. The shapes of the cam profile slots are exemplary, and other shapes may be effectively implemented. The actuator mechanism  80  also includes a platen associated with each cam profile slot. In the illustrated embodiment, actuator  80  includes three platens  100 ,  102 ,  104  associated with cam profile slots  90 ,  92 ,  94 , respectively. First platen  100  is coupled to the cam profile slot  90  by a cam follower pin  106  extending transversely from the platen  100  into the cam profile slot  90 . Similarly, second platen  102  is coupled to the second cam profile slot  92  by a cam follower pin  108 , and the third platen  104  is coupled to the third cam profile slot  94  by a cam follower pin  110 . Platens  100 ,  102 ,  104  are supported and guided by a guide  112 , which may comprise a panel having openings formed therein conforming to the shape of each of the platens. 
         [0071]    In  FIG. 7A , cam rail  84  is in its furthest right-most position, and the platens  100 ,  102 ,  104  are in their unactuated positions. Each of the cam follower pins  106 ,  108 ,  110  is in the initial upper horizontal portion of the respective cam profile slot  90 ,  92 ,  94 . As the cam rail  84  is moved longitudinally to the left, in the direction “A” shown in  FIG. 7B , by the linear actuator  82 , each cam follower pin  106 ,  108 ,  110  moves within its respective cam profile slot  90 ,  92 ,  94  until the cam follower pin is in the lower, second horizontal portion of the respective cam profile slot. Movement of each of the pins  106 ,  108 ,  110  downwardly within its respective cam profile slot  90 ,  92 ,  94  causes a corresponding downward movement of the associated platen  100 ,  102 ,  104 . This movement of the platens thereby compresses a fluid vessel (or blister) located under each platen. Each platen may compress a vessel directly in contact with the platen or it may contact the vessel through one or more intermediate components located between the vessel and the corresponding platen. 
         [0072]    Thus, the blister compression actuator mechanism  80  is constructed and arranged to convert the horizontal movement cam rail  84 , driven by the linear actuator  82 , into vertical movement of the platens  100 ,  102 ,  104  to compress blisters, and movement of the platens does not require pneumatic, electromechanical, or other components at larger distances above and/or below the liquid module. 
         [0073]    When compressing a fluid vessel, or blister, to displace the fluid contents thereof, sufficient compressive force must be applied to the blister to break, or otherwise open, a breakable seal that is holding the fluid within the vessel. The amount of force required to break the seal and displace the fluid contents of a vessel typically increases as the volume of the vessel increases. This is illustrated in the bar graph shown in  FIG. 11 , which shows the minimum, maximum, and average blister burst forces required for blisters having volumes of 100, 200, 400, and 3000 microliters. The average force required to burst a blister of 400 or less microliters is relatively small, ranging from an average of 10.7 lbf to 11.5 lbf. On the other hand, the force required to burst a blister of 3000 microliters is substantially larger, with an average burst force of 43.4 lbf and a maximum required burst force of greater than 65 lbf. Generating such large forces can be difficult, especially in low profile actuator mechanisms, such as those described above, in which horizontal displacement of an actuator is converted into vertical, blister-compressing movement of a platen. 
         [0074]    Accordingly, aspects of the present invention are embodied in methods and apparatus for opening a fluid vessel, or blister, in a manner that reduces the amount of force required to burst the vessel and displace the fluid contents of the vessel. 
         [0075]    Such aspects of the invention are illustrated in  FIGS. 8A and 8B . As shown in  FIG. 8A , a fluid vessel (or blister)  122  is mounted on a substrate  124  and is connected by means of a channel  130  to a sphere blister  128 . In certain embodiments, channel  130  may be initially blocked by a breakable seal. A film layer  129  may be disposed on the bottom of the substrate  124  to cover one or more channels formed in the bottom of the substrate  124  to form fluid conduits. An opening device, comprising a sphere  126  (e.g., a steel ball bearing) is enclosed within the sphere blister  128  and is supported, as shown in  FIG. 8A , within the sphere blister  128  by a foil partition or septum  125 . The foil partition  125  prevents fluid from flowing from the vessel  122  through a recess  127  and fluid exit port  123 . Upon applying downward force to the sphere  126 , however, a large local compressive stress is generated due to the relatively small surface size of the sphere  126 , and the foil partition  125  can be broken with relatively little force to push the sphere  126  through the partition  125  and into the recess  127 , as shown in  FIG. 8B . With the foil partition  125  broken, a relatively small additional force is required to break a seal within channel  130  and force the fluid to flow from the vessel  122  through the fluid exit port  123 . 
         [0076]    In  FIG. 8B , the sphere blister  128  is shown intact. In some embodiments, a force applied to the sphere  126  to push it through the foil partition  125  would also collapse the sphere blister  128 . 
         [0077]    An apparatus for opening a vessel by pushing a sphere  126  through foil partition  125  is indicated by reference number  120  in  FIGS. 9A, 9B, 9C, 9D . In the illustrated embodiment, the apparatus  120  includes a ball actuator  140  extending through an opening formed through a blister plate, or platen,  132 . With the blister plate  132  and an actuator  138  configured for moving the blister plate  132  disposed above the vessel  122 , the ball actuator  140  is secured in a first position, shown in  FIG. 9A , by a detent  136  that engages a detent collar  144  formed in the ball actuator  140 . 
         [0078]    As shown in  FIG. 9B , the blister plate  132  is moved by the actuator  138  down to a position in which a contact end  142  of the ball actuator  140  contacts the top of the of the sphere blister  128 . Actuator  138  may comprise a low profile actuator, such as actuator mechanisms  50  or  80  described above. 
         [0079]    As shown in  FIG. 9C , continued downward movement of the blister plate  132  by the actuator  138  causes the ball actuator  140  to collapse the sphere blister  128 , thereby pushing the opening device, e.g., sphere  126 , through a partition blocking fluid flow from the vessel  122 . In this regard, it will be appreciated that the detent must provide a holding force sufficient to prevent the ball actuator  140  from sliding relative to the blister plate  132  until after the sphere  126  has pierced the partition. Thus, the detent must provide a holding force sufficient to collapse the sphere blister  128  and push the sphere  126  through a partition. 
         [0080]    As shown in  FIG. 9D , continued downward movement of the blister plate  132  by the actuator  138  eventually overcomes the holding force provided by the detent  136 , and the ball actuator  140  is then released to move relative to the blister plate  132 , so that the blister plate can continue to move down and collapse the vessel  122 . 
         [0081]    After the vessel  122  is collapsed, the blister plate  132  can be raised by the actuator  138  to the position shown in  FIG. 9A . As the blister plate  132  is being raised from the position shown in  FIG. 9D  to the position shown in  9 A, a hard stop  146  contacts a top end of the ball actuator  140  to prevent its continued upward movement, thereby sliding the ball actuator  140  relative to the blister plate  132  until the detent  136  contacts the detent collar  144  to reset the ball actuator  140 . 
         [0082]    An alternative embodiment of an apparatus for opening a vessel embodying aspects of the present invention is indicated by reference number  150  in  FIG. 10 . Apparatus  150  includes a pivoting ball actuator  152  configured to pivot about a pivot pin  154 . A top surface  156  of the pivoting ball actuator  152  comprises a cam surface, and a cam follower  158 , comprising a roller, moving in the direction “A” along the cam surface  156  pivots the actuator  152  down in the direction “B” to collapse the sphere blister  128  and force the sphere  126  through the foil partition  125 . Pivoting actuator  152  may further include a torsional spring (not shown) or other means for restoring the actuator to an up position disengaged with the sphere blister  128  when the cam follower  158  is withdrawn. 
         [0083]      FIG. 12  is a plot of compressive load versus time showing an exemplary load versus time curve for an apparatus for opening a vessel embodying aspects of the present invention. As the apparatus contacts and begins to compress the sphere blister  128 , the load experiences an initial increase as shown at portion (a) of the graph. A plateau shown at portion (b) of the graph occurs after the sphere  126  penetrates the foil partition  125 . A second increase in the force load occurs when the blister plate  132  makes contact with and begins compressing the vessel  122 . A peak, as shown at part (c) of the plot, is reached as a breakable seal within channel  130  between the vessel  122  and the sphere blister  128  is broken. After the seal has been broken, the pressure drops dramatically, as shown at part (d) of the plot, as the vessel  122  is collapsed and the fluid contained therein is forced through the exit port  123  (See  FIGS. 8A, 8B ) supporting the sphere  126 . 
         [0084]    An alternative apparatus for opening a vessel is indicated by reference number  160  in  FIG. 13A . As shown in  FIG. 13A , a fluid vessel (or blister)  162  is mounted on a substrate  172  and is connected by means of a channel—which may or may not be initially blocked by a breakable seal—to a dimple  161 . A film layer  164  may be disposed on the bottom of the substrate  172  to cover one or more channels formed in the bottom of the substrate  172  to form fluid conduits. An opening device comprising a cantilevered lance  166  is positioned within a lance chamber  170  formed in the substrate  172  where it is anchored at an end thereof by a screw attachment  168 . 
         [0085]    A foil partition or septum  165  seals the interior of the dimple  161  from the lance chamber  170 . An actuator pushes the lance  170  up in the direction “A” into the dimple  161 , thereby piercing the foil partition  165  and permitting fluid to flow from the blister  162  out of the lance chamber  170  and a fluid exit port. The spring force resilience of the lance  166  returns it to its initial position after the upward force is removed. In one embodiment, the lance  166  is made of metal. Alternatively, a plastic lance could be part of a molded plastic substrate on which the blister  162  is formed. Alternatively, a metallic lance could be heat staked onto a male plastic post. A further option is to employ a formed metal wire as a lance. 
         [0086]    A further alternative embodiment of an apparatus for opening a vessel is indicated by reference number  180  in  FIG. 14 . A component having one or more deformable vessels includes at least one blister  182  formed on a substrate  194 . In the arrangement shown in  FIG. 14 , an internal dimple  184  is formed inside the blister  182 . Internal dimple  184  encloses an opening device comprising a fixed spike  186  projecting upwardly from a spike cavity  188  formed in the substrate  194 . A film layer  192  is disposed on an opposite side of the substrate  194 . As an actuator presses down on the blister  182 , internal pressure within the blister  182  causes the internal dimple  184  to collapse and invert. The inverted dimple is punctured by the fixed spike  186 , thereby permitting fluid within the blister  182  to flow through an exit port  190 . 
         [0087]    An alternative apparatus for opening a vessel is indicated by reference number  200  in  FIG. 15A . As shown in  FIG. 15A , a fluid vessel (or blister)  202  is mounted on a substrate  216  and is connected by means of a channel—which may or may not be initially blocked by a breakable seal—to a dimple  204 . An opening device comprising a lancing pin  206  having a fluid port  208  formed through the center thereof (see  FIG. 15B ) is disposed within a segmented bore  220  formed in the substrate  216  beneath the dimple  204 . A partition or septum  205  separates the dimple  204  from the bore  220 , thereby preventing fluid from exiting the blister  202  and dimple  204 . An actuator (not shown) presses on a film layer  212  disposed on a bottom portion of the substrate  216  in the direction “A” forcing the lancing pin  206  up within the segmented bore  220  until a shoulder  210  formed on the lancing pin  206  encounters a hard stop  222  formed in the segmented bore  220 . A lancing point of the pin  206  pierces the partition  205  thereby permitting fluid to flow through the fluid port  208  in the lancing pin  206  and out of a fluid exit channel  214 . 
         [0088]    An alternative embodiment of an apparatus for opening a vessel is indicated by reference number  230  in  FIGS. 16A and 16B . As shown in  FIG. 16A , a fluid vessel (or blister)  232  is mounted on a substrate  244  and is connected by means of a channel—which may or may not be initially blocked by a breakable seal—to a dimple  234 . An opening device comprising a lancing pin  236  is disposed within a segmented board  246  formed in the substrate  244  beneath the dimple  234 . A partition or septum  235  separates the dimple  234  from the segmented bore  246 . The upper surface of the substrate  244  is sealed with a film  240  before the blister  232  and dimple  234  are adhered. An actuator (not shown) pushes up on the lancing pin  236  in the direction “A” until a shoulder  238  formed on the lancing pin  236  encounters hard stop  248  within the bore  246 . The pin  236  thereby pierces the partition  235  and remains in the upper position as fluid flows out along an exit channel  242  formed on an upper surface of the substrate  244 . A fluid tight seal is maintained between the pin  238  and the bore  246  by a slight interference fit. 
         [0089]    As the collapsible fluid vessels of a liquid reagent module are configured to be compressed and collapsed to displace the fluid contents from the vessel(s), such vessels are susceptible to damage or fluid leakage due to inadvertent exposures to contacts that impart a compressing force to the vessel. Accordingly, when storing, handling, or transporting a component having one or more collapsible fluid vessels, it is desirable to protect the fluid vessel and avoid such inadvertent contact. The liquid reagent module could be stored within a rigid casing to protect the collapsible vessel(s) from unintended external forces, but such a casing would inhibit or prevent collapsing of the vessel by application of an external force. Thus, the liquid reagent module would have to be removed from the casing prior to use, thereby leaving the collapsible vessel(s) of the module vulnerable to unintended external forces. 
         [0090]    An apparatus for protecting and interfacing with a collapsible vessel is indicated by reference number  260  in  FIGS. 17, 18, and 19 . A component with one or more collapsible vessels includes a collapsible blister  262  formed on a substrate  264 . A dispensing channel  266  extends from the blister  262  to a frangible seal  268 . It is understood that, in some alternative embodiments, the dispensing channel  266  may be substituted with a breakable seal, providing an additional safeguard against an accidental reagent release. 
         [0091]    Frangible seal  268  may comprise one of the apparatuses for opening a vessel described above and shown in any of  FIGS. 8-16 . 
         [0092]    A rigid or semi-rigid housing is provided over the blister  262  and, optionally, the dispensing channel  266  as well, and comprises a blister housing cover  270  covering the blister  262  and a blister housing extension  280  covering and protecting the dispensing channel  266  and the area of the frangible seal  268 . 
         [0093]    A floating actuator plate  276  is disposed within the blister housing cover  270 . In the illustrated embodiments, both the blister housing cover  270  and the floating actuator plate  276  are circular, but the housing  270  and the actuator plate  276  could be of any shape, preferably generally conforming to the shape of the blister  262 . 
         [0094]    The apparatus  260  further includes a plunger  274  having a plunger point  275  at one end thereof. Plunger  274  is disposed above the blister housing cover  270  generally at a center portion thereof and disposed above an aperture  272  formed in the housing  270 . 
         [0095]    The floating actuator plate  276  includes a plunger receiver recess  278 , which, in an embodiment, generally conforms to the shape of the plunger point  275 . 
         [0096]    The blister  262  is collapsed by actuating the plunger  274  downwardly into the aperture  272 . Plunger  274  may be actuated by any suitable mechanism, including one of the actuator mechanisms  50 ,  80  described above. Plunger  274  passes into the aperture  272  where the plunger point  275  nests within the plunger receiver recess  278  of the floating actuator plate  276 . Continued downward movement by the plunger  274  presses the actuator plate  276  against the blister  262 , thereby collapsing the blister  262  and displacing fluid from the blister  262  through the dispensing channel  266  to a fluid egress. Continued pressure will cause the frangible seal at  268  to break, or an apparatus for opening the vessel as described above may be employed to open the frangible seal. The plunger point  275  nested within the plunger point recess  278  helps to keep the plunger  274  centered with respect to the actuator plate  276  and prevents the actuator plate  276  from sliding laterally relative to the plunger  274 . When the blister is fully collapsed, as shown in  FIG. 19 , a convex side of the plunger receiver recess  278  of the floating actuator plate  276  nests within a plunger recess  282  formed in the substrate  264 . 
         [0097]    Accordingly, the blister housing cover  270  protects the blister  262  from inadvertent damage or collapse, while the floating actuator plate inside the blister housing cover  270  permits and facilitates the collapsing of the blister  262  without having to remove or otherwise alter the blister housing cover  270 . In components having more than one collapsible vessel and dispensing channel, a blister housing cover may be provided for all of the vessels and dispensing channels or for some, but less than all vessels and dispensing channels. 
         [0098]    While the present invention has been described and shown in considerable detail with reference to certain illustrative embodiments, including various combinations and sub-combinations of features, those skilled in the art will readily appreciate other embodiments and variations and modifications thereof as encompassed within the scope of the present invention. Moreover, the descriptions of such embodiments, combinations, and sub-combinations is not intended to convey that the inventions requires features or combinations of features other than those expressly recited in the claims. Accordingly, the present invention is deemed to include all modifications and variations encompassed within the spirit and scope of the following appended claims.

Technology Category: 7