Patent Publication Number: US-2007107780-A1

Title: Fluid handling device

Description:
CROSS-REFERENCE TO RELATED PATENT APPLICATIONS  
      The present application is related to U.S. Provisional Patent Application No. 60/734,064 filed Nov. 07, 2005, the contents of which are incorporated by reference herein in their entirety. 
    
    
     FIELD OF THE INVENTION  
      This disclosure relates generally to the handling of an assay and more particularly to a multi-directional device for handling an assay.  
     BACKGROUND OF THE INVENTION  
      One of the main challenges for pharmaceutical companies in developing cures and treatments for illnesses involves controlling the costs required to develop and process the biological materials, such as proteins, enzymes and cell based assays, needed to create the desired drugs and medicines. Unfortunately however, many of the compounds included in drug screening assays are archival and only available in very limited quantities or they are the products of combinatorial synthesis procedures and thus are only produced in microgram to milligram quantities. As such, a significant effort has been put forth by the pharmaceutical industry to develop methods and devices that would promote conservation of these valuable compounds by increasing assay efficiency to minimize costs. One such method, assay miniaturization, is an immediate and viable route to this objective.  
      In response to this trend toward assay miniaturization, several types of devices have been developed to process these assays in small quantities. Referring to  FIG. 1 , one such device is a fluid handling device  100  which was developed to automatically dispense precisely controlled quantities of fluids, such as buffers, reagents and solvents for plate preparation and assay development into assay vials and/or assay plates. Typically, the fluid handling device  100  of  FIG. 1 , includes a flow controller device  102  connected to a fluid container  104  via a flow tube  106 , wherein the fluid container  104  includes a fluid and is further connected to a dispensing device  108  via a dispensing tube  110  for dispensing the fluid into a receiving device, such as an assay vial and/or an assay plate. Referring to  FIG. 2 , the fluid handling device  100  is typically configurable for use with a plurality of reagents and/or fluid containers  104 .  
      Unfortunately however, current fluid handling devices, such as the fluid handling device  100 , include several disadvantages which involve limitations in its fluid handling capabilities. For example, one disadvantage involves the dispensing of a fluid containing suspended matter. When dispensing a fluid containing suspended matter, current fluid handling devices are unable to evenly and consistently dispense the fluid. This is because during periods of inactive dispensing and between periods of active dispensing when the fluid is not flowing through the flow tube(s), a small portion of the fluid is stationary within the flow tube(s). During this stationary period, the suspended matter contained within the fluid tends to ‘settle’ out of the fluid into ‘clumps’ and may actually adhere to the inner walls of the tubing. As such, when active dispensing is again initiated and the fluid begins to flow through the flow tube, the settled matter may cause stratification of the flow or the settled matter may be dispensed as ‘clumps’ as opposed to being dispensed in a controlled and consistent manner. As a result, the matter contained within the fluid tends to be dispensed in groups or “hot spots’ of material. This lack of distribution control is undesirable because the uneven distribution of cells and/or beads can cause results from future processing to be skewed and inaccurate.  
      Another disadvantage involves the inability of current fluid handling devices to accurately and controllably dispense small volumes of fluids (and hence suspended matter) in several different formats. As a result, approximately only 40% of assays are currently capable of being miniaturized on automated platforms. This lack of miniaturization capability is undesirable because it requires that a majority of assays be processed by hand thus imposing a limitation on the number of assays that are capable of being processed in this manner using automation.  
     SUMMARY OF THE INVENTION  
      A fluid handling device is provided and includes a pressure control device configurable to generate at least one of a positive pressure and a negative pressure and a flow control device having a flow control device output, wherein the flow control device is configurably associated with the pressure control device such that at least one of the positive pressure and the negative pressure is in flow communication with the flow control device output.  
      A fluid handling device is provided and includes a vacuum generation device, a pressure generation device, a fluid container having a container cavity and a flow controller device, wherein the flow controller device is in flow communication with the pressure generation device, the vacuum generation device and the fluid container and wherein the flow controller device is configurable between a first configuration and a second configuration. When the flow controller device is configured into the first configuration, the pressure generation device is in flow communication with the fluid container and wherein when the flow controller device is configured in the second configuration, the vacuum generation device is in flow communication with the fluid container.  
      A method for implementing a fluid handling device is provided, wherein the fluid handling device includes a pressure control device configurable to generate at least one of a positive pressure and a negative pressure and a flow control device having a flow control device output, wherein the flow control device is configurably associated with the pressure control device such that at least one of the positive pressure and the negative pressure is in flow communication with the flow control device output. The method includes operating the pressure control device to generate at least one of the positive pressure and the negative pressure and configuring the flow control device such that at least one of the positive pressure and the negative pressure is present at the flow control device output.  
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
      The foregoing and other features and advantages of the present invention will be more fully understood from the following detailed description of illustrative embodiments, taken in conjunction with the accompanying drawings in which like elements are numbered alike:  
       FIG. 1  is a schematic block diagram illustrating a fluid handling device, in accordance with the prior art;  
       FIG. 2  is a schematic block diagram illustrating a plurality of prior art fluid handling devices in  FIG. 1 ;  
       FIG. 3  is a schematic block diagram illustrating one embodiment of a fluid handling device, in accordance with the present invention;  
       FIG. 4  is a schematic block diagram illustrating one embodiment of a plurality of the fluid handling devices in  FIG. 3 ;  
       FIG. 5A  is a schematic block diagram illustrating the fluid handling device in  FIG. 3 ;  
       FIG. 5B  is a schematic block diagram illustrating the fluid handling device in  FIG. 3 ;  
       FIG. 6  is a schematic block diagram illustrating an alternative embodiment of a fluid handling device, in accordance with the present invention;  
       FIG. 7  is a schematic block diagram illustrating the fluid handling device of  FIG. 6 , in accordance with the present invention;  
       FIG. 8  is a schematic block diagram illustrating the fluid handling device of  FIG. 6 , in accordance with the present invention;  
       FIG. 9  is a schematic block diagram illustrating the fluid handling device of  FIG. 6 , in accordance with the present invention; and  
       FIG. 10  is a schematic block diagram illustrating one embodiment of a method for implementing the fluid handling device of  FIG. 3 . 
    
    
     DETAILED DESCRIPTION  
      Referring to  FIG. 3 , a schematic block diagram illustrating one embodiment of a fluid handling device  200  in accordance with the present invention is shown and includes a pressure controller device  202 , a primer/deprimer device or flow control device  204 , a fluid container  206 , a fluid transfer device  208  and a vacuum device  210  (which may be integrated with pressure controller device  202 ), wherein the pressure controller device  202  is in flow communication with the fluid container  206  via the flow control device  204 . The at least one pressure controller device  202  is configured to be in flow communication with a valve  212  via a pressure tube  214  and a pressure monitoring device, such as transducer tube  216 , wherein the valve  212  is in further flow communication with the flow control device  204  via a valve tube  218 . The flow control device  204  is further communicated with the vacuum device  210  and the fluid container  206  via a vacuum tube  222  and a container flow tube  224 , respectively. The fluid container  206  is further in flow communication with the fluid transfer device  208  via a dispensing tube  226  for dispension into at least one assay vial and/or at least one assay plate. Referring to  FIG. 4 , it should be appreciated that the fluid handling device  200  of  FIG. 3  may be configurable to operate with a single fluid container  206  or a plurality of fluid containers  206 . Additionally, it should be appreciated that the flow control device  204  may be configurable between a first configuration to allow fluid to flow in one direction and a second configuration to allow fluid to flow in another direction.  
      Referring to  FIG. 5A , a schematic block diagram  500  illustrating one embodiment of an operational flow for the fluid handling device  200  of  FIG. 3  and/or  FIG. 4  is shown and includes a pressure controller device  202  that may be operated to generate a pressure within the pressure tube  214  such that the pressure flows through the valve  212 , through the valve tube  218 , through the flow control device  204 , through the container flow tube  224  and into the fluid container  206 . This causes the pressure within the fluid container  206  to increase thereby causing the fluid contained within the fluid container  206  to flow into the dispensing tube  226  and into the fluid transfer device  208  for distribution to at least one holding device, such as an assay vial and/or an assay plate. The pressure flowing through the fluid handling device  200  may be monitored and communicated back to the pressure controller device  202  via the transducer  216  which allows the pressure controller device  202  to continuously adjust the pressure to maintain a constant pressure throughout the fluid handling device  200 . Additionally, the volume of the fluid being dispensed by the fluid dispenser  208  may be monitored and the pressure controller device  202  may be continuously adjusted to maintain a constant fluid volume out of the fluid transfer device  208 .  
      Referring to  FIG. 5B , when the dispensing of the fluid is paused, the flow control device  204  may be configured such that the pressure flow into the flow control device  204  is isolated and the vacuum tube  222  is communicated with the container flow tube  224 . The vacuum device  210  may then be operated to cause a vacuum within the vacuum tube  222  thereby generating a vacuum within the container flow tube  224  and thus within the fluid container  206 . This vacuum within the fluid container  206  causes any fluid within the dispensing tube  226  to flow out of the dispensing tube  226  and back into the fluid container  206 . It should be appreciated that the vacuum within the container flow tube  224  and/or the fluid container  206  may be monitored and adjusted to ensure that the magnitude of the vacuum within the container flow tube  224  and/or the fluid container  206  is not so great that it causes the fluid within the fluid container  206  to flow into the container flow tube  224 .  
      It should be appreciated that the pressure generated from the pressure controller device  202  may be sensed via the transducer tube  216  which may be communicated with the pressure tube  214  via the valve  212 . This allows the pressure controller device  202  to make adjustments to the pressure as needed to control the flow of fluid out of the fluid container  206 . It should be further appreciated that the fluid handling device  200  of  FIG. 3  and  FIG. 4 , allows for the controllable and precise distribution of a small volume fluid sample from the fluid container  206  into an assay vial and/or an assay plate. It should be further appreciated that the flow control device  204  allows the fluid handling device  200  to pause the dispension of fluids and to configure the dispensing tube  226  such that fluid within the dispensing tube  226  is returned into the fluid container  206  leaving no fluid remaining within the dispensing tube  226 . As such, this allows for the controllable and precise distribution of a fluid sample from the fluid container  206  into a holding device, such as an assay vial and/or an assay plate such that any suspended matter within the fluid sample remains suspended within the fluid in a controllable and predictable population distribution.  
      Additionally, although the fluid handling device  200  is shown as including several devices including a pressure controller device  202 , a flow control device  204 , a fluid container  206 , a fluid transfer device  208  and a vacuum device  210 , it is contemplated that any greater and/or lesser number of devices may be used to achieve the same or similar results. Furthermore, it is contemplated that the present invention may be configured to directly and/or indirectly interface and/or integrate with existing fluid handling devices via an in-line configuration and/or an add-on configuration. This would allow existing technologies to be ‘up-graded’ to better control the flow of a fluid, thus allowing for more accurate and better fluid dispension and retention.  
      It should also be appreciated that other configurations are also contemplated and are considered to be within the scope of the present invention. For example, referring to  FIG. 6 , an alternative embodiment of the fluid handling device  200  is shown and includes a pressure control device  202  associated or integrated with the flow control device  204  which is shown as being in flow communication with an assay container/plate  300  via fluid transfer device  208  and an assay tube  302 . In this configuration, the fluid flow between the fluid container  206  and the flow control device  204  could be initiated and controlled by selectively and controllably generating a positive pressure and/or a vacuum, or negative pressure, within the dispensing tube  226  and/or the assay tube  302 .  
      Consider the situation where a fluid transfer process has been terminated/paused and a fluid still remains within the dispensing tube  226  and the assay tube  302 . To recover the fluid contained in the dispensing tube  226 , the pressure control device  202  may generate a positive pressure within the dispensing tube  226  causing the fluid contained therein to flow out of the dispensing tube  226  and into the fluid cavity of the fluid container  206 . In a similar fashion, the pressure control device  202  may generate a positive pressure within the assay tube  302  causing the fluid contained therein to flow out of the assay tube  302  and into an assay disposal device. Alternatively, the fluid remaining in the assay tube  302  may be recovered by directing the fluid to flow through the assay tube  302  and into the dispensing tube  226 , wherein the fluid may then be dispensed back into the fluid cavity of the fluid container  206  for future use.  
      One way to accomplish this would be to have a flow control device  204  that is configured to selectively and controllably isolate the dispensing tube  226  from the assay tube  302 . This would allow the flow within the dispensing tube  226  to be controlled independently from the flow within the assay tube  302 . For example, if transfer of fluid was interrupted/paused and fluid remained in both the dispensing tube  226  and the assay tube  302 , the dispensing tube  226  could be isolated from the assay tube  302 . The pressure control device  202  could then be operated to generate a positive pressure within the dispensing tube  226 , thereby causing the fluid within the dispensing tube  226  to flow away from the flow control device  204  and back into the fluid container  206 , as shown by the arrowed lines in  FIG. 7 . The pressure control device  202  may be operated to generate a negative pressure within the assay tube  302 , thereby causing the fluid within the assay tube  302  to flow through the assay tube  302  toward the flow control device  204 , wherein the recovered fluid could then be contained within an isolated cavity  304  that may be disposed external or internal to the flow control device  204 , as shown by the arrowed lines in  FIG. 8 . When the assay tube  302  is evacuated of fluid, the pressure control device  202  may then be operated to generate a positive pressure causing the recovered fluid to flow out of the isolated cavity  304 , through the dispensing tube  226  and back into the fluid container  206 , as shown by the arrowed lines in  FIG. 9 .  
      It should be appreciated that although the fluid handling device  200  described herein includes a pressure control device  202  for controlling the flow fluid, any fluid flow control device and/or method suitable to the desired end purpose, such as electric and gas flow devices, may be used. Additionally, although the pressure control device  202  is shown as having a vacuum generation device and a pressure generation device, any atmosphere generation device suitable to the desired end purpose, such as a positive pressure/vacuum/negative pressure generation device, may be used. Furthermore, it is contemplated that the pressure within each of the components (i.e. container cavity, dispensing tube  226 , assay tube  302  . . . ) throughout the fluid handling device may be monitored, collectively or individually, wherein each of the components (i.e. pressure control device  202  and/or flow control device  204 ) the fluid handling device  200  may be operated, collectively or individually, responsive to obtained pressure levels.  
      Moreover, it is also contemplated that the present invention can be used for recovery or aspiration of fluids within an external device, such as an assay plate. For example, to recovery fluid disposed in or on an external device, the fluid transfer device  208  may include a pipette (which may be connected to the dispensing tube  226  via the fluid transfer device  208 ) disposed to be in contact with the fluid. The pressure control device  202  and flow control device  204  are configured such that a vacuum or negative pressure is present in the dispensing tube  226  and hence at the pipette. This vacuum causes the fluid to be recovered to flow into the pipette, through the dispensing tube  226  and into the fluid container  206 . It should be appreciated that, regardless of terminology used, it is contemplated that each and every element of the fluid handling device  200  is bi-directional and allows for the controlled transfer of fluids into and/or out of the fluid handling device  200 . Moreover, the present invention may be expanded to accommodate multiple fluid dispension/recovery stations.  
      Referring to  FIG. 10 , a block diagram illustrating one embodiment of a method  600  for implementing the fluid handling device  200  is shown and includes operating the flow control device  204  such that the valve tube  218  is in flow communication with the container flow tube  224 , as shown in operational block  602 . The pressure controller device  202  is configured to generate a predetermined amount of pressure within the valve tube  218 , as shown in operational block  604 , to cause the pressure within the fluid container  206  to increase to a desired pressure level. It should be appreciated that the desired pressure level may be configured responsive to the desired flow rate of the fluid out of the fluid container  206  and through the dispensing tube  226 . During downtimes of the fluid handling device  200  and/or during pauses in fluid flow through the dispensing tube  226 , the flow control device  204  may be configured to communicate the vacuum tube  222  with the container flow tube  224 , as shown in operational block  606 . The vacuum device  210  may then be operated to generate a vacuum within the vacuum tube  222  thereby creating a vacuum within the container flow tube  224  and thus, within the fluid container  206 , as shown in operational block  608 . This causes any fluid contained within the dispensing tube  226  to flow out of the dispensing tube  226  and back into the fluid container  206  preventing any settlement, adherence and/or ‘clumping’ of material suspended in the fluid.  
      In accordance with an exemplary embodiment, processing of the method in  FIG. 10 , in whole or in part, may be implemented through a processing device operating in response to a computer program which may have a Graphical User Interface for user controlled operation or which may be automatic. In order to perform the prescribed functions and desired processing, as well as the computations therefore (e.g., the execution of fourier analysis algorithm(s), the control processes prescribed herein, and the like), the controller may include, but not be limited to, a processor(s), computer(s), memory, storage, register(s), timing, interrupt(s), communication interfaces, and input/output signal interfaces, as well as combinations comprising at least one of the foregoing. For example, the controller may include signal input signal filtering to enable accurate sampling and conversion or acquisitions of such signals from communications interfaces. It is also considered within the scope of the invention that the processing of the method of  FIG. 10 , in whole or in part, may be implemented by a controller located remotely from the processing device.  
      Moreover, in accordance with an exemplary embodiment, the above embodiment(s) can be embodied in the form of computer-implemented processes and apparatuses for practicing those processes. The above can also be embodied in the form of computer program code containing instructions embodied in tangible media, such as floppy diskettes, CD-ROMs, hard drives, or any other computer-readable storage medium, wherein, when the computer program code is loaded into and executed by a computer, the computer becomes an apparatus for practicing the invention. Existing systems having reprogrammable storage (e.g., flash memory) can be updated to implement the invention. The above can also be embodied in the form of computer program code, for example, whether stored in a storage medium, loaded into and/or executed by a computer, or transmitted over some transmission medium, such as over electrical wiring or cabling, through fiber optics, or via electromagnetic radiation, wherein, when the computer program code is loaded into and executed by a computer, the computer becomes an apparatus for practicing the invention. When implemented on a general-purpose microprocessor, the computer program code segments configure the microprocessor to create specific logic circuits.  
      While the invention has been described with reference to an exemplary embodiment, it should be understood by those skilled in the art that various changes may be made and equivalents may be substituted for elements thereof without departing from the scope of the invention. In addition, many modifications may be made to adapt a particular situation or material to the teachings of the invention without departing from the scope thereof. Therefore, it is intended that the invention not be limited to the particular embodiment disclosed as the best mode contemplated for carrying out this invention, but that the invention will include all embodiments falling within the scope of the appended claims. Moreover, unless specifically stated any use of the terms first, second, etc. do not denote any order or importance, but rather the terms first, second, etc. are used to distinguish one element from another.