Abstract:
A device and method of addressing a microfluidic cartridge to interface with external fluid supplies and external activation of internal control devices. The fluid interface couples the microfluidics of the cartridge to the macrofluidics of the external system with little or no dead volume.

Description:
CROSS REFERENCE TO RELATED APPLICATIONS  
       [0001]    This application claims benefit from U.S. Provisional patent application Ser. No. 60/206,878, filed May 24, 2000, which application is incorporated herein by reference. 
     
    
     
       BACKGROUND OF THE INVENTION  
         [0002]    1. Field of the Invention  
           [0003]    This invention relates generally to microfluidic devices for performing analytic testing, and, in particular, to a device and method for interfacing a microfluidic cartridge with external fluid supplies and valve controls.  
           [0004]    2. Description of the Related Art  
           [0005]    Microfluidic devices have recently become popular for performing analytical testing. Using tools developed by the semiconductor industry to miniaturize electronics, it has become possible to fabricate intricate fluid systems which can be inexpensively mass produced. Systems have been developed to perform a variety of analytical techniques for the acquisition of information for the medical field.  
           [0006]    Valves and valve activating devices are well known in the art. U.S. Pat. No. 4,499,756, which issued on Feb. 19, 1985, is directed to a test controller for closure of ganged, cam operated main control valves in a steam turbine. The controller incrementally controls one set of main control valves in the closing direction while controlling the other set of main control valves in the opposite direction. U.S. Pat. No. 4, 696,195, which issued on Sep. 29,1987, is directed to a valve having a plurality of orifices with a resilient closure membrane adjacent thereto which is positioned to yield in response to a pressure differential so as to permit flow between respective ports. U.S. Pat. No. 4,858,885, which issued Aug. 22, 1989, is directed to a valve having a flexible valve sheet member which is flexed to open and close fluid passageways. U.S. Pat. No. 5,743,960, which issued Apr. 28, 1998, is directed to a reagent dispensing apparatus which includes a positive displacement syringe pump in series with a solenoid valve dispenser which is opened and closed at a predetermined frequency and duty cycle to dispense droplets of reagent onto a target substrate at a metered flow rate. U.S. Pat. No. 5,755,942, which issued May 26, 1998, is directed to a system for processing a plurality of syntheses by using an array of microelectronic and fluidic transfer devices for carrying out various processes.  
           [0007]    A sample microfluidic analysis instrument for performing analytical testing which uses a disposable fluidic analysis cartridge is disclosed in U.S. patent application Ser. No. 09/080,691, which was filed on May 18, 1998, the disclosure of which is incorporated herein by reference in its entirety. This instrument includes a cartridge holder, a low cytometric measuring apparatus positioned for optical coupling with a flow cytometric measuring region on the cartridge, and a second measuring apparatus positioned to be coupled with a second analysis region on the cartridge. The cartridge holder includes alignment markings to mate with cartridge alignment markings. It also includes pump mechanisms to couple with pump interfaces on the cartridges and valve mechanisms to couple with valve interfaces on the cartridge.  
           [0008]    In this type of system, valve and pump mechanisms are external to the cartridge, while the cartridge includes the valve and pump interfaces. Upon loading the cartridge into the apparatus, the valve and pump mechanisms engage the valve and pump interfaces. Thus, it is critical that the interfaces provide an efficient and precise coupling between the cartridge of the external mechanisms. In addition, it is imperative that these external devices provide for a smooth flow of the fluids into and out of the cartridge to ensure accurate measurements within a microfluidic analysis system.  
           [0009]    Therefore, it is desirable to provide a device and method for efficiently interfacing a microfluidic cartridge with external macrofluidic supplies, as well as for addressing the microfluidic circuitry internal to the cartridge.  
         SUMMARY OF THE INVENTION  
         [0010]    It is therefore an object of the present invention to provide a device which allows a microfluidic cartridge to be coupled to a plurality of external devices which supply the fluids which are essential for the cartridge in performing analyses.  
           [0011]    It is also an object of the present invention to provide a device which accurately connects a microfluidic cartridge to a plurality of external devices which serve to provide external forces for operating different features of the cartridge.  
           [0012]    It is a further object of the present invention to provide a method by which a microfluidic device may be accurately coupled to external sources to enable the cartridge to perform a desired analysis.  
           [0013]    These and other objects of the present invention will be more readily apparent from the description and drawings which follow. 
       
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
       [0014]    [0014]FIG. 1 is a fragmentary plan view of a microfluidic analysis cartridge for use with the present invention;  
         [0015]    [0015]FIG. 2 is a perspective view of a system which includes the present invention;  
         [0016]    [0016]FIG. 3 is another view of the system shown in FIG. 2; and  
         [0017]    [0017]FIG. 4 is another view of the system shown in FIG. 2. 
     
    
     DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT  
       [0018]    Referring now to FIG. 1, there is shown a section of a liquid analysis cartridge or card, generally designated at  10 . Cartridge  10  is described in detail in U.S. patent application No. 09/080,091, which was filed May 18, 1998, and is herein incorporated by reference in its entirety. A series of circular apertures  12  are formed within cartridge  10  to allow fluid to flow from outside cartridge  10  to the interior of the card to be used in the analysis process. A series of fluid seals  14  are located within cartridge  10  contacting the inside surface of apertures  12 . Seals  14  also contact a series of ports  16  within cartridge  10  which lead to the interior of cartridge  10 . Ports  16  allow desired fluids which are necessary for conducting various tests to be pumped into and out of cartridge  10  from analysis channels.  
         [0019]    Cartridge  10  also contains a series of slots  20  in which a series of actuators  22  are located. At one end of each of actuators  22  is a port  24 . In operation, actuators  22  are selectively operated through slots  20  from the exterior of cartridge  10  to open and close ports  16  as desired to perform various analyses within channels of cartridge  10 .  
         [0020]    FIGS. 2 - 5  show an apparatus for carrying out a preferred embodiment of the present invention. Referring now to FIG. 2, an interfacing device, generally indicated at  50 , contains a frame  52  having a cartridge engaging manifold  54  slidably mounted thereupon. Manifold  54  consists of a fluid interface section  56  and a valve actuator section  58 . A cartridge holding unit  60  is fixedly mounted on frame  52  in perpendicular relationship to manifold  54 . Unit  60  contains a groove  62  such that a cartridge such as cartridge  10  can be inserted into unit  60  and locked into place such that it solidly captured within unit  60 . A tip cleaning station  64  is affixed to frame  52  on the side of unit  60  opposite manifold  54  in parallel relationship to groove  62  within unit  60 .  
         [0021]    A linear drive motor  66  is rotatably coupled to manifold  54 , which is slidably mounted on frame  52 . In operation, motor  66  rotates in response to a command to move manifold  54  into and out of an operating position adjacent cartridge  10  mounted within groove  62  of unit  60 .  
         [0022]    A series of tubes  70  are connected to section  56 , while a series of corresponding tubing tips  72  extend from the opposite end of section  56 . Tubes  70 , which are preferably constructed from a sturdy material such as Teflon, carry the fluids necessary for cartridge  10  to perform the desired analysis. A series of cables  74  are connected to section  58 , while a series of a valve actuator arms  76  extend from the opposite end of section  78  upon receipt of a command via cables  74 . Actuator arms  76  act to selectively operate valves within cartridge  10 .  
         [0023]    Also located on interface section  56  is a pair of locating pins  80 . Pins  80  are used to insure correct orientation between manifold  54  and cartridge  10 . Pins  80  may have locating holes in either the cartridge or in cartridge holding unit  60 . When pins  80  are securely located within the proper receptacles, tips  72  are assured of proper alignment with apertures  12 , such that fluids will be accurately delivered to cartridge  10  for analysis purposes. In addition, pins  80  also act to align actuator arms  76  with actuators  22  in cartridge  10 .  
         [0024]    Tubes  70  extend from the end of fluid interface section  56  to a control unit  90  (FIG. 2). Unit  90  serves to operate interfacing device  50 . Unit  90  provides the proper fluids to cartridge at the proper times and intervals. Control unit  90  also provides the necessary signals to operate valve actuator arms  76  at the proper times. Control unit  90  is also responsible for operating motor  66  to adjust manifold  54  into position.  
         [0025]    Tip cleaning station  64  is provided with a series of apertures  94 . Apertures  95  which align with tips  72  on section  56 , are filled with an absorbing material, such as filter paper, cellulose, or any other material which can wipe a droplet from the tip. It may also be constructed from silicon rubber or plexiglass.  
         [0026]    In operation, interfacing device  50  is loaded with cartridge  10  by sliding the cartridge into groove  62  where it is tightly held in position and it cannot shift. A locking mechanism may be added to insure that cartridge  10  does not move during operation. After cartridge  10  has been positioned on cartridge holding unit  60 , manifold  54  may be advanced until locating pins  80  enter the locating holes on either cartridge  10  or unit  60 . At this time, unit  50  is properly aligned for use.  
         [0027]    Tube tips  72  may be individually advanced by control unit  90  to enter into apertures  12  and are sealed tightly with fluid seals  14  with little or no dead volume. In addition, valve actuator  76 arms may be advanced using control unit  90  to contact valve actuators  22  as is necessary.  
         [0028]    After the desired analysis has been performed by cartridge  10 , manifold  54  is retracted away from unit  60  so that cartridge  10  may be removed. Tips  72  can be cleaned at this time.  
         [0029]    Manifold  54  is advanced toward unit  60  until it is adjacent unit  60  and tip cleaning station  64 . Tips  72  may then be advanced under command from control unit  90  such that tips  72  extend into apertures  94 , where tips  76  contact the absorbing material such that any excess droplets or material can be removed. This procedure may also be performed before cartridge  10  is mounted within groove  62  in unit  60 .  
         [0030]    While the present invention has been shown and described in terms of several embodiments thereof, it will be understood that this invention is not limited to these particular embodiments and that many changes and modifications may be made without departing from the true spirit and scope of the invention as defined in the appended claims.