Abstract:
An apparatus that is capable of performing at least some of the physical operations that are used in conjunction with growing cells in cell-cultivation flasks. The operations performed include one or more of the following: receiving a plurality of cell-cultivation flasks, re-orienting the flasks; agitating liquid within the flasks, and knocking the cell-cultivation flasks to loosen cellular material within the flasks. In accordance with the illustrative embodiment, re-positioning is implemented using a movable platform that cooperates with guides, and a drive that moves the movable platform. In some embodiments, the guides are implemented as slots in a frame. In some embodiments, a single drive is used to conduct all operations.

Description:
STATEMENT OF RELATED CASES  
       [0001]    This case claims priority of U.S. Provisional Patent Application Serial No. 60/430,255, filed Dec. 2, 2002. 
     
    
     
       FIELD OF THE INVENTION  
         [0002]    The present invention relates to an apparatus for performing operations that are required or otherwise desirable in conjunction with growing cells within a cell-cultivating flask.  
         BACKGROUND OF THE INVENTION  
         [0003]    Developments in cellular biology and related fields have led to increased demands for devices capable of producing cells. The cells are often used, for example, to produce biologically-active compounds.  
           [0004]    For growing static cell cultures, flat, flask-like containers (“cell-cultivating flasks”) are typically used. The flasks usually incorporate a neck and an opening that is closed using a screw cap. Some flasks in the prior art incorporate internal structures for cultivating the cells, while others do not.  
           [0005]    After adding a cultivating medium and cells to the flask, it is sometimes necessary to conduct certain physical operations. These operations include, for example, changing the orientation of the flask (e.g., from a horizontal position to a vertical position, or visa-versa, etc.) and agitating the flask. Furthermore, on the completion of cell growth, and prior to emptying the cell-cultivating flasks, it is sometimes necessary to “knock” or shake the flask to loosen cellular material that otherwise adheres to the internal walls of the flask.  
           [0006]    Traditionally, these physical operations have been performed manually. Such manual operations limit production and increase production expenses. As a consequence, the art would benefit from an apparatus that can automatically perform these operations.  
         SUMMARY  
         [0007]    The illustrative embodiment of the present invention is an apparatus that is capable of performing at least some of the physical operations that are used in conjunction with growing cells in cell-cultivation flasks. The physical operations performed by an apparatus in accordance with the illustrative embodiment include one or more of the following functions, in addition to any others:  
           [0008]    Receiving, in a stack, a plurality of cell-cultivation flasks, wherein the flasks can be fed manually or by a robotic system to the apparatus.  
           [0009]    Re-orienting the flasks from a horizontal position to a vertical position or visa versa.  
           [0010]    Agitating liquid within the flasks, advantageously creating a circular flow of liquid.  
           [0011]    “Knocking” the cell-cultivation flasks to loosen cellular material within the flasks.  
           [0012]    In accordance with the illustrative embodiment, horizontal-to-vertical re-positioning is implemented using a movable platform that cooperates with guides. In use, cell-cultivating flasks are stacked on the movable platform.  
           [0013]    In the illustrative embodiment, the guides are implemented as slots in a frame. More particularly, in some embodiments, the frame includes two, spaced plates, each of which has a generally horizontal base and a generally vertical riser, wherein the riser depends from one end of the base. A slot is defined in both the base portion and the riser portion of each plate.  
           [0014]    The slot in the base is horizontal, while the slot in the riser takes the form of a vertical arc. In the illustrative embodiment, two sets of rollers depend from the platform; one set (proximal to a first end of the platform) engages the slot in the base and the other set (distal to the first end of the platform) engages the slot in the riser. Moving the platform towards the riser causes the set of rollers that cooperate with the slot in the riser to ride upwards in a vertical arc. This causes the second end of the platform to move upward. Since the first end of the platform does not move in the vertical direction due to its engagement with the horizontal slot, the platform rotates about the first end toward a vertical orientation. The motion of the platform is actually a combination of sliding and rotating, since the platform moves horizontally toward the riser while the second end rises. With continued movement toward the riser, the platform attains full vertical orientation, having rotated ninety degrees from its horizontal orientation. Cell-cultivating flasks that are stacked on the platform are, of course, rotated along with the platform.  
           [0015]    The use of the slotted frame and cooperating movable platform, in accordance with the illustrative embodiment, enables the apparatus to maintain the same bottom reference plane. That is, at least part of the movable platform is always engaged to horizontal slot in the base, which defines a bottom reference plane. This is in contrast to a classic mechanism for rotating an object, which utilizes a “twisting” action. The classic mechanism typically does not maintain the bottom reference plane, and, in fact, has to be lifted to enable an object to be rotated (assuming that the object is resting upon a surface).  
           [0016]    In accordance with the illustrative embodiment, the slot in the riser of one of plates and a slot in the base of the other of the two plates include a deviated portion. The deviated portion causes a local change in the height of slots. Moving the movable platform back-and-forth such that it successively passes the deviated portions in the two slots causes a wobbling motion in the platform—and in any cell-cultivating flasks that are disposed on the platform. This wobbling motion places liquid within the flasks in orbital (i.e., circular) motion.  
           [0017]    The slots in the frame are, therefore, dual functional, in the sense that they enable both the re-positioning and agitation functions. And as a consequence of this dual functionality, a single actuator can be used to drive both the re-positioning and agitating operations.  
           [0018]    In some embodiments, the apparatus also incorporates a spring-loaded “hammer” mechanism that generates an adjustable and repeatable force (a “knocking”) that is directed against the side of the cell-cultivating flasks. In some embodiments, the spring-loaded hammer is implemented as a passive device, wherein the energy that loads the spring is imparted by the actuator that drives the re-positioning (and agitating) operation. An embodiment of the spring-loaded “hammer” mechanism is described in applicant&#39;s co-pending patent application entitled “Passive Force-Imparting Mechanism” (Attorney Docket No. 153-035, filed 02 Dec. 2003), incorporated by reference herein. 
       
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
       [0019]    [0019]FIG. 1 depicts an apparatus  100  in accordance with the illustrative embodiment of the present invention, wherein a plurality of cell-cultivating flasks, which are stacked on the apparatus, are in a horizontal orientation.  
         [0020]    [0020]FIG. 2 depicts the apparatus of FIG. 1, wherein the cell-cultivating flasks are in a vertical orientation.  
         [0021]    [0021]FIG. 3 depicts the apparatus of FIG. 1, but without cell-cultivating flasks present. Furthermore, FIG. 3 depicts drive mechanism  330  of apparatus  100 .  
         [0022]    [0022]FIG. 4 depicts the apparatus of FIG. 3.  
         [0023]    [0023]FIG. 5 depicts a flow of liquid within a cell-cultivating flask during agitation. 
     
    
     DETAILED DESCRIPTION  
       [0024]    [0024]FIG. 1 depicts apparatus  100 , which includes frame  102  and platform  118 , which cooperate as depicted.  
         [0025]    In the illustrative embodiment, frame  102  comprises two, identical plates  104 . Each plate  104  has a generally horizontal base  106  and a generally vertical riser  108 . The riser depends from base  106  near one end thereof. In some embodiments, bases  106  are attached to an underlying platform, which is not depicted. The underlying platform can be used, for example, to support a spring-loaded hammer mechanism to implement a knocking operation.  
         [0026]    Each base  106  includes slot  110 , which has a substantially horizontal orientation. Each riser  108  includes arcuate-shaped slot  114 , which has a substantially vertical orientation. As used herein, the term “substantially horizontal orientation” means a near-horizontal orientation of the slot, such as 0 degrees +/−about 5 degrees. As used herein, the term “substantially vertical orientation” means that, relative to the horizontal (e.g., relative to slot  110 ), slot  114  is angled upwards at an angle of at least about 45 degrees (wherein the angle is defined by two intersecting rays, one of which is coincident with slot  110  and the other of which passes through the end points of slot  114 ).  
         [0027]    Slot  110  in base  106  of one of plates  104  includes deviated portion  112 . Vertically-oriented slot  114  in riser  108  of the other of plates  104  includes deviated portion  116 . (Only deviated portion  112  is visible in FIG. 1; see FIGS. 4 and 5 for deviated portion  116 .)  
         [0028]    In the illustrative embodiment, deviated portion  112  is displaced upward relative to the rest of slot  110  and deviated portion  116  is displaced upward relative to the immediately surrounding portion of slot  114 . In some other embodiments (not depicted), each deviated portion  112 , 116  is displaced downward. As described more fully later in this specification, deviated portions  112  and  116  are used during agitation operations to impart circular motion to a liquid being agitated within cell-cultivating flasks  126 .  
         [0029]    Platform  118  receives cell-cultivating flasks  126 . In the illustrative embodiment, platform  118  includes retainer  120 , which depends from the front end of the platform (i.e., the “right” end as viewed in FIG. 1). As described further below, retainer  120  is used in conjunction with re-positioning operations.  
         [0030]    Platform  118  is movable relative to frame  102  to facilitate re-positioning and agitating operations. In the illustrative embodiment, platform  118  is physically adapted to slide within frame  102 . This capability is provided, in the illustrative embodiment, by two sets of rollers that cooperate with slots  110  and  114 . More particularly, platform  118  includes a set of front rollers  122  and a set of rear rollers  124 . Front rollers  122  engage and are guided by slots  110  in bases  106 . Similarly, rear rollers  124  engage and are guided by slots  114  in risers  108 .  
         [0031]    The cooperating arrangement of rollers  122 ,  124  and slots  110 ,  114  are sufficient to keep plates  104  of frame  102  in spaced, parallel relation to one another. In some variations of the illustrative embodiment (not depicted), individual sections  104  are linked to one another at risers  108  by one or more beams to provide additional rigidity.  
         [0032]    As indicated above, in use, one or more flasks  126  are loaded onto platform  118 . Flasks  126 , which in the illustrative embodiment are flat flasks, each include a port, which will typically having a protruding “neck” or “throat” for receiving liquid. (Not depicted in FIG. 1, see, FIG. 2: “ports  228 ”.) FIG. 1 depicts six flasks  126  on platform  118 , although a greater number or less number of flasks can be accommodated. The flask loading operation can be conducted either manually or automatically, in conjunction with materials-handling equipment (not depicted).  
         [0033]    1. Re-Positioning Function  
         [0034]    With reference to FIG. 2, re-orientation (vertical positioning) of flasks  126  is achieved by forcing platform  118  towards the rising curve of slots  114  until both rear rollers  124  and front rollers  122  reach their limits of travel. When flasks  126  are in a vertical position, ports  228  are oriented “upwards” to be accessed by a fluid-delivery mechanism. (The fluid-delivery mechanism is not a part of this invention and is not described or depicted herein.) Retainer  120  supports plates  126  when platform  118  is in a vertical position.  
         [0035]    Platform  118  is moved via a drive mechanism, which can be implemented in many different ways. In the illustrative embodiment depicted in FIG. 3, drive mechanism  330  is implemented as a linear actuator. The linear actuator is realized, in the illustrative embodiment, as an air-actuated piston/cylinder.  
         [0036]    Drive mechanism  330  is secured to a surface or platform that underlies bases  106  of frame  102 . Piston  332  of drive mechanism  330  is coupled to front (right) end of platform  118  (i.e., near retainer  120 ). Drive mechanism  330  is appropriately positioned so that as piston  332  is retracted in direction  333  into cylinder  334 , platform  118  moves toward generally vertically-oriented slots  114 . As it does so, rollers  124  ride up slots  114  and rollers  122  travel toward the back of slots  110 . This movement re-positions platform  118  and any flasks  126  that are disposed on it, into the vertical orientation depicted in FIG. 2.  
         [0037]    Thus, in the illustrative embodiment, slots  110  and  114  in respective x and z planes convert the linear and horizontal movement of drive mechanism  330  into rotational movement of platform  118 .  
         [0038]    2. Agitation Function  
         [0039]    Any liquid that is present in flasks  126  can be agitated by moving platform  118  back and forth in a reciprocating motion. Furthermore, by virtue of deviated portions  112  and  116 , such liquid can advantageously be agitated into circular wave motion.  
         [0040]    Referring now to FIGS. 4 and 5, moving platform  118  back and forth along vector  436  using drive mechanism  330  will cause liquid to move back and forth in wave motion within flasks  126 . FIG. 5 depicts path  546  of liquid within a flask  126 .  
         [0041]    As platform  118  begins to move toward the “right” along direction  446  (FIG. 4), liquid flows along path  546  toward the “right” side of flask  126  (FIG. 5). As platform  118  moves further rightward, roller  122  rides up deviated portion  112  of slot  110 . This causes “forward” right corner  438  of platform  118  to rise relative to “rearward” right corner  440 . Consequently, platform  118  is tilted toward corner  440 . As depicted in FIG. 5, this causes liquid within flask  126  to move from relatively-higher corner  538  to relatively-lower corner  540  along path  547 .  
         [0042]    As platform  118  begins to move back toward the left along direction  448  (FIG. 4), liquid flows toward the “left” side of flask  126  along path  548  (FIG. 5). As platform  118  moves further leftward, roller  124  rides up deviated portion  116  of slot  114 . This causes “rearward” left corner  442  to rise relative to “forward” left corner  444 . Consequently, platform  118  is tilted toward corner  444 . As depicted in FIG. 5, this causes liquid within flask  126  to move from relatively-higher corner  542  to relatively-lower corner  544  along path  549 .  
         [0043]    In this fashion, circular wave motion is created in flasks  126 . This agitation pattern can be advantageous as a function of the particular processes that are occurring within flasks  126 .  
         [0044]    It is to be understood that the above-described embodiments are merely illustrative of the present invention and that many variations of the above-described embodiments can be devised by those skilled in the art without departing from the scope of the invention. It is therefore intended that such variations be included within the scope of the following claims and their equivalents.