Abstract:
A microfluidic chip interface for providing fluid communication with external fluid sources and external fluid waste containers, and for providing electrical contact with voltage sources and voltage and current measuring devices, is described. The microchip is first placed into electrical communication with at least one electrical source and at least one electronic measurement device, and reversibly secured in place. Chosen fluids are provided into the microchip and directed through the chip using a fluid manifold having dispensing tubes and fluid aspiration tubes, which is brought into the vicinity of the secured microchip. The distance between the fluid manifold and the microchip is chosen such that the injection tubes are located within wells in the microchip connected to microfluidic channels, and the aspiration tubes are located near the surface of the microchip in the vicinity of the wells such that fluid spillage onto the surface of the microchip during fluid transfer is avoided. The fluid manifold is removed from fluid communication with the microchip during electrical measurements.

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
       [0001]    The present application claims the benefit of U.S. Provisional Patent Application No. 61/559,497 for “Fluidic And Electrical Interface For Microfluidic Chips” which was filed on Nov. 14, 2011, the entire contents of which is hereby specifically incorporated by reference herein for all that it discloses and teaches. 
     
    
     FIELD OF THE INVENTION 
       [0002]    The present invention relates generally microfluidic chips suitable for capillary electrophoresis as an example and, more particularly, to a fluidic and electrical interface effective for transferring fluids from external fluid sources through a microfluidic chip to external waste containers, and for providing electrical contact to the microfluidic chip to enable measurements to be made on the fluids. 
       BACKGROUND OF THE INVENTION 
       [0003]    Microfluidic chips find use in many areas such as fluid mixing for chemical reactions, cell sorting, and electrophoresis, as examples, and often have both electrical terminals and microfluidic channels in which electrokinetic phenomena, which include electro-osmotic flow and electrophoresis, are generated. 
         [0004]    Microfluidic chips suitable for capillary electrophoresis typically provide a carrier channel in which substances within a sample are separated by electrophoresis and detected, and a sample channel in fluid communication with the carrier channel for introducing samples into the carrier channel. Generally, samples and carrier fluids are manually introduced into the microchip by dropper, syringe, and the like, and these fluids flow through a network of channels by capillary action, external pressure or electro-osmotic flow. Voltages between a few hundred volts and greater than one thousand volts may be applied to the channels using electrical probes, for inducing electrophoretic and/or electro-osmotic flow useful for introducing small amounts of the sample fluid into the carrier channel at an intersection of the two channels. As stated, charged substances in the sample will separate in the carrier channel as a consequence of differences in electrophoretic mobility. At chosen locations, the fluid in the carrier channel may be optically or electrically interrogated yielding component analysis information for the sample. 
         [0005]    Although certain substances within a sample fluid may be efficiently separated for analysis using conventional microfluidic chips for capillary electrophoresis, the handling, timing and delivery of very small fluid volumes to flow paths in the chip, along with the manual transfer of fluids to corresponding reservoirs, renders automated capillary electrophoresis for sample analysis difficult. 
       SUMMARY OF THE INVENTION 
       [0006]    Embodiments of the present invention overcome the disadvantages and limitations of the prior art by providing a microfluidic interface which cooperates with a microfluidic chip to provide fluid from one or more external fluid sources to flow paths within the chip without spilling or leaving fluid on the surface of the chip. 
         [0007]    Another object of embodiments of the invention is to provide an interface between a voltage source, generally a high voltage source, and electrical measurement apparatus and a microfluidic chip. 
         [0008]    Yet another object of embodiments of the invention is to provide an interface between a voltage source and a microfluidic chip effective for separating components in a sample by capillary electrophoresis. 
         [0009]    Still another object of embodiments of the invention is to provide an interface between a current measuring device and a microfluidic chip for analysis of the separated components. 
         [0010]    Another object of embodiments of the invention is to provide an interface for permitting a variety of sample handling and sample analyses within a microfluidic chip. 
         [0011]    Additional objects, advantages and novel features of the invention will be set forth in part in the description which follows, and in part will become apparent to those skilled in the art upon examination of the following or may be learned by practice of the invention. The objects and advantages of the invention may be realized and attained by means of the instrumentalities and combinations particularly pointed out in the appended claims. 
         [0012]    To achieve the foregoing and other objects and, in accordance with the purposes of the present invention as embodied and broadly described herein, the apparatus for establishing a fluidic and electrical interface to a microfluidic chip having a top surface and at least two wells opening to the top surface, hereof, includes: a microchip tray for receiving and holding the microfluidic chip; an electrical bus adapted for electrical communication with at least one voltage source and at least one electronic measurement device; a microchip tray slide adapted for receiving the microchip tray and placing the microchip into electrical communication with the electrical bus and for reversibly securing the microchip tray and the microchip in electrical communication therewith; a fluid manifold assembly for providing chosen fluids to the microchip and for aspirating the chosen fluids from the wells of the microchip, the fluid manifold assembly including: an electrolyte pump; a sample pump; a vacuum pump; and a fluid manifold including: at least two liquid dispensing tubes for establishing fluid communication with either the electrolyte pump or the sample pump and the at least two wells, one of the dispensing tubes in fluid communication with one of the at least two wells; and at least two liquid aspiration tubes for establishing fluid communication with said vacuum pump, one of the aspiration tubes in fluid communication with one of the at least two wells; a fluid manifold mounting plate for holding the fluid manifold; a pushrod having a first end and a second end, the first end of said pushrod affixed to the fluid manifold mounting plate; a pivoted rocker arm for driving the pushrod toward or away from the microchip; a cam for causing the rocker arm to pivot; a motor for rotating the cam; and at least one spring for causing the pushrod to follow the rocker arm and the rocker arm to follow the cam; whereby the fluid manifold is disposed a chosen distance from the microchip for establishing fluid communication between the at least two liquid dispensing tubes and the at least two liquid aspiration tubes and the at least two wells, and at greater than the chosen distance for electrical measurements. 
         [0013]    In another aspect of the invention and, in accordance with its objects and purposes, the apparatus for establishing a fluidic and electrical interface to a microfluidic chip having a top surface and at least two wells opening to the top surface, hereof, includes: a microchip tray for receiving and holding the microfluidic chip; an electrical bus adapted for electrical communication with at least one voltage source and at least one electronic measurement device; means for placing the microchip into electrical communication with the electrical bus and for reversibly securing the microchip tray and the microchip in electrical communication therewith; a fluid manifold assembly for providing chosen fluids to the microchip and for aspirating the chosen fluids from the wells of the microchip, said fluid manifold assembly including: an electrolyte pump; a sample pump; a vacuum pump; and a fluid manifold including: at least two liquid dispensing tubes for establishing fluid communication with either the electrolyte pump or the sample pump, and the at least two wells, one of the dispensing tubes in fluid communication with one of the at least two wells; and at least two liquid aspiration tubes for establishing fluid communication with the vacuum pump, one of the aspiration tubes in fluid communication with one of the at least two wells; means for moving the fluid manifold to a chosen distance from the microchip for establishing fluid communication between the at least two liquid dispensing tubes and the at least two liquid aspiration tubes and the at least two wells, and to a greater than the chosen distance for electrical measurements. 
         [0014]    In yet another aspect of the invention and, in accordance with its objects and purposes, the method for providing a fluidic and an electrical interface for a microfluidic chip having a top surface at least two wells opening to the top surface, hereof includes: placing the microchip into electrical communication with an electrical bus capable of electrical communication with at least one voltage source and at least one electronic measurement device; reversibly securing the microchip in electrical contact with the bus; providing chosen fluids to the wells of the microchip using a fluid manifold having one injection tube and one aspiration tube for each well; moving the fluid manifold to a chosen distance from the secured microchip, whereby each injection tube is disposed in its corresponding well, and each aspiration tube is disposed near the surface of the microchip in the vicinity of a well, such that fluid does not spread over the top surface of the microchip during said step of providing chosen fluids to the wells, and to a greater than the chosen distance for electrical measurements. 
         [0015]    Benefits and advantages of the present invention include, but are not limited to, providing a microfluidic chip interface for reliably and reproducibly flushing fluids from external sources through the wells of the microchip to external waste containers, in a manner that prevents fluid films from spreading across the top surface of the microchip that can divert the driving current from the capillary elements in the microchip. Another benefit is the establishment of electrical contact with the microfluidic chip for delivering chosen voltages and enabling current and voltage measurements to be made on the fluid components. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0016]    The accompanying drawings, which are incorporated in and form a part of the specification, illustrate embodiments of the present invention which, together with the description, serve to explain the principles of the invention. In the drawings: 
           [0017]      FIG. 1A  is a schematic representation of an embodiment of the manifold assembly of the present invention effective for filling and flushing (dispensing) various fluid wells of a microchip with sample solutions and/or standard solutions, or with background electrolyte, and for aspirating these wells, while  FIG. 1B  is a schematic representation of the disposition of a dispensing tube and an aspiration tube in a fluid well of the microchip shown in  FIG. 1A  hereof. 
           [0018]      FIG. 2  is a schematic representation of a front perspective view of an embodiment of the microchip interface of the present invention without the microchip and microchip tray in place, showing the microchip tray slide portion, the fluid manifold assembly for providing fluids to the microchip and receiving fluids therefrom disposed in its partially withdrawn position, and the spring-loaded electrical pins adapted for providing voltages to the microchip and for receiving voltages and currents therefrom for measurement. 
           [0019]      FIG. 3  is a schematic representation of a top perspective view of an embodiment of the microchip tray adapted for insertion into the microchip interface illustrated in  FIG. 2 , hereof, showing a microchip in place and the microchip clamps in their open position. 
           [0020]      FIG. 4  is a schematic representation of a top perspective view of the microchip tray shown in  FIG. 3  hereof, illustrated in its locked-down position in the tray slide portion of the microchip interface shown in  FIG. 2  hereof, and with the microchip clamps in their locked position securing a microchip. 
           [0021]      FIG. 5  is a schematic representation of a front perspective view of the embodiment of the microchip interface shown in  FIG. 2  hereof, with the microchip and microchip tray shown in  FIG. 3  hereof in place, and showing the microchip tray slide portion shown in  FIG. 4  hereof, the fluid manifold assembly being disposed in a partially extended position. 
           [0022]      FIG. 6A  is a schematic representation of a front perspective view of the fluid manifold assembly illustrated in  FIG. 2  hereof, showing the mounting block for the spring-loaded, rocker arm, the pushrod-actuated manifold mounting plate and the guide rods therefor, while  FIG. 6B  is a schematic representation of a rear perspective view of the fluid manifold assembly illustrated in  FIG. 6A  hereof, showing the cam and the motor for rotating the cam which drives the rocker arm and pushrod. 
           [0023]      FIG. 7A  is a schematic representation of a front perspective view of the fluid manifold mounting plate, with the manifold disposed slightly above a microchip, illustrating the injection and aspirate tubes in proximity to their insertion locations in wells in the microchip, while  FIG. 7B  is a schematic representation of a bottom view of the manifold in proximity to a microchip, and illustrates the injection and aspiration tubes extending into the microchip wells. 
       
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
       [0024]    Briefly, embodiments of the present invention include a fluidic and electrical interface effective for transferring fluids from external fluid sources through microfluidic channels in a microfluidic chip to external waste containers, and for providing electrical contact to the chip for enabling measurements to be made on the fluid components. As used herein, the terms chip and microchip are intended to mean a microfluidic chip. 
         [0025]    Reference will now be made in detail to the present embodiments of the invention, examples of which are illustrated in the accompanying drawings. In what follows, similar or identical structure will be identified using identical reference characters. Turning now to  FIG. 1A , a schematic representation of an embodiment of a fluid manifold assembly including fluid manifold,  16 , of the present invention effective for filling and flushing (dispensing fluid to) fluid well,  47   a,  of microchip,  18 , with sample solution from source,  110 , and with an internal standard solution from source,  112 , if desired, through mixer,  114 , using pumps,  116 , and,  118 , respectively, for filling and flushing fluid wells,  47   b - 47   d , with background electrolyte from source,  120 , using pump,  122 , and for aspirating the wells  47   a - 47   d  using aspiration pump,  124 , which pumps fluid to waste receptacle  126 .  FIG. 1B  is a schematic representation of narrow-bore (0.5 mm) dispensing tubes,  94 - 97  ( FIG. 6B ), and narrow-bore (0.5 mm) aspiration tubes,  98   a - 98   d  ( FIG. 6B ), which may be cut at an angle, in relationship to fluid well  47   a - 47   d  of microchip  18  shown in  FIG. 1A  hereof. 
         [0026]    As will be described in more detail hereinbelow, manifold  16  including dispensing and aspiration tubes is raised and lowered relative to chip  18 . As seen in  FIGS. 1A and 1B , narrow-bore tubes  94 - 97  extend from the bottom of manifold  16  and enter wells  47   a - 47   d  of microchip  18  to a position near the bottom,  128 , thereof. Typical distances from the bottom of the wells may be from about 0 mm to about 3 mm, shorter distances generating beneficial fluid mixing in the wells. Shorter tubes  98   a - 98   d  are positioned at or just above (from about 0 to about 3 mm) top surface,  130 , of microchip  18 . In use, electrolyte, sample or an internal standard is pumped through tubes  94 - 97  to near the bottom of wells  47   a - 47   d , while vacuum pump  124  pulls liquid from near the top of the well, thereby both flushing the well and providing a reproducible fill,  132 , therefor. Without the use of aspiration to remove liquids, it has been found that a film forms on at least a portion of surface  130 , which may disrupt electrical measurements. Fluid manifold  16  is retracted from the surface of the microchip during analysis in order to avoid high-voltage leakage through the pumps during electrophoretic measurements. 
         [0027]      FIG. 2 , is a schematic representation of a front perspective view of an embodiment of microchip interface,  10 , of the present invention, showing microchip tray slide portion,  12 , for receiving microchip tray,  14 , not shown in  FIG. 2 , and fluid manifold assembly,  16 , for providing fluids to microchip,  18 , also not shown in  FIG. 2 , and receiving fluids therefrom disposed in its partially withdrawn position. At least two spring-loaded electrical connections,  20   a , and,  20   b , mounted in insulating electric bus,  22 , provide voltages to microchip  18  from at least one voltage source, not shown in  FIG. 2 , and/or at least two spring-loaded electrical connections,  24   a , and,  24   b , also mounted in bus  22  for receiving voltages and currents from microchip  18  for measuring characteristics of the fluids flowing in microchip  18  using measuring apparatus known in the art (not shown in  FIG. 2 ). The locations and functions of pins  20  and  24  depend on the intended application for microchip  18 . Insulating block  22 , is mounted on base,  26 , which supports walls,  28   a , and,  28   b , to which fluid manifold assembly  16  is mounted. 
         [0028]    As will be described in more detail hereinbelow, microchip tray spring stop,  30 , stops,  32   a , and,  32   b , mounted on base  26 , rotatable microchip tray wheels,  34   a , and,  34   b , and,  36   a , and,  36   b , not shown in  FIG. 2 , cooperating with channels,  38   a , and,  38   b , formed in rails,  40   a , and,  40   b , mounted to walls  28   a  and  28   b , respectively, reversibly hold microchip tray  14  in interface  10 . Spring stop  30  may be made from polyurethane, and stops  32   a  and  32   b  may be made from a metal, such as steel. 
         [0029]      FIG. 3  is a schematic representation of a top perspective view of an embodiment of microchip tray  14  adapted for insertion into microchip interface  10  illustrated in  FIG. 2  hereof. Microchip clamps,  42   a , and,  42   b , shown in their open position in  FIG. 3 , are pivotably connected to tray  14  at locations,  44   a , and,  44   b . Rotatable wheels,  34   a , and,  34   b , and  36   a , and  36   b , are adapted for rolling in channels  38   a  and  38   b , respectively. Handle,  46 , is used to direct microchip tray  14  into and out of interface  10 . Wells,  47   a - 47   d , in microchip  18  for accessing microfluidic channels therein are also illustrated. 
         [0030]      FIG. 4  is a schematic representation of a top perspective view of microchip tray  14  shown in  FIG. 3  hereof, illustrated in its locked-down position in tray slide portion of microchip interface  10 , and with microchip clamps  42   a  and  42   b  in their locked position securing microchip  18  onto tray  14 . Channel  38   a  is shown to have two perpendicular sections,  48   a , and,  48   b , into which wheels  34   a  and  34   b , respectively, may freely move. Similar, opposing perpendicular sections,  50   a , and,  50   b , not shown in  FIG. 3 , are formed in channel  38   b  for receiving wheels  36   a  and  36   b , respectively. 
         [0031]    In use, microchip tray  14  bearing locked microchip  18  is slid between rails  40   a  and  40   b  in interface  10  such that wheels  34   a  and  34   b  and  36   a  and  36   b  enter channels  38   a  and  38   b . Tray  14  is pushed forward into interface  10  between rails  40   a  and  40   b  until wheels  34   a  and  34   b  encounter perpendicular sections  48   a  and  48   b , respectively, and wheels  36   a  and  36   b  encounter perpendicular sections  48   a  and  48   b , respectively, at which time tray  14  drops downward such that microchip  18  is in electrical communication with electrical connections  20   a  and  20   b , and/or  24   a  and  24   b  on insulated block  22  ( FIG. 2 , hereof). It should be mentioned that in use, chip  18  is oriented approximately horizontally. Stops  32   a  and  32   b  contact slots,  52   a , and,  52   b , in front wall,  54 , of tray  14 , and rear wall,  56 , of tray  14  contacts spring stop  30 , which has sufficient flex to permit tray  14  to reversibly snap into position, such that tray  14  is reversibly secured with electrical contacts in microchip  18 , not shown in  FIG. 4 , in electrical communication with the electrical connections on insulating block  22 . Tray  14  may be removed from microchip tray slide portion  12  of interface  10  by grasping handle  46  attached to rear face  56  of microchip tray  14  and pulling microchip tray  14  upward against the spring action of spring stop  30  against wall  56 , which permits wheels  34   a  and  34   b , and  36   a  and  36   b  to move upwardly in vertical channels  48   a  and  48   b , and  50   a  and  50   b , respectively, and into channels  38   a  and  38   b , respectively, from which tray  14  may be removed from interface  10 . 
         [0032]      FIG. 5  is a schematic representation of a front perspective view of the embodiment of microchip interface  10  shown in  FIG. 2  hereof, with the microchip  18  and microchip tray  14  shown in  FIG. 3  hereof locked in place in microchip tray slide portion  12  shown in  FIG. 4  hereof, and fluid manifold assembly  16  being disposed in a partially extended position. Manifold,  58 , is configured to provide fluid transfer to microchip  18  in accordance with the particular application thereof, and pumps and valves as known in the art, but not shown in  FIG. 5 , suitable for accomplishing this function are provided. Block,  60 , attached to walls  28   a  and  28   b , supports motor,  62 , which pivots rocker arm,  64 , around axle,  66 , by rotating cam,  68 , not shown in  FIG. 4 . Axle  66  is supported by mounts,  69   a , and,  69   b , attached to block  60  and motor  62  is attached to mount  69   a . Rocker arm  64  drives spring-loaded manifold mounting plate,  70 , to which manifold  58  is attached toward microchip  18 , by pushing on pushrod,  72 , which travels through hole,  74 , in block  60 , and is attached to mounting plate  70 . Rocker arm bearing,  76 , which rotates around axle,  78 , in rocker arm  64  facilitates the action of rocker arm  64  on pushrod  72 . Springs,  80   a , and,  80   b , not shown in  FIG. 5 , attached between block  60  and plate  70 , act against the force of pushrod  72  and permit rocker arm  64  to follow cam  68  through the complete rotation thereof. Bearing-mounted guide rods,  82   a - 82   d,  attached to mounting plate  70  slide in holes,  84   a , and,  84   b , and,  84   c  and,  84   d , not shown in  FIG. 5 , in block  60  through bearings,  86   a , and,  86   b - 86   d , not shown in  FIG. 5 . 
         [0033]      FIG. 6A  is a schematic representation of a front perspective view of fluid manifold assembly  16  illustrated in  FIG. 2  hereof, showing mounting block  60  for spring-loaded, rocker arm, pushrod-actuated manifold mounting plate  70  and guide rods  82   a - 82   d.    FIG. 6B  is a schematic representation of a rear perspective view of the fluid manifold assembly  16  illustrated in  FIG. 6A  hereof, showing motor  62  for rotating cam  68  which pivots rocker arm  64  and pushrod  72 . Shown also in  FIG. 6B  are projections,  88 , and,  90   a , and,  90   b , attached to bottom surface,  92 , of manifold  58 , for resting on microchip  18  to reproducibly attain the proper spacing between manifold  58  and microchip  18  such that fluid injection tubes,  94 , and,  96 , and fluid aspiration tubes,  98 , are effectively placed in corresponding wells  47   a - 47   d  in microchip  18 . Port,  100 , to which an external source of suction is applied and through which fluids are withdrawn from microchip  18  and directed to suitable waste containers, not shown in  FIG. 6B , is connected to aspiration tubes  98  through the body of manifold  58 . 
         [0034]    In use, fluid manifold assembly,  16 , of interface  10  brings fluid manifold  58  into contact with microchip  18 . Motor  62  rotates cam  68  such that rocker arm  64  is pivoted and pushes down on pushrod  72  through bearing  76 . Pushrod  72  is attached to spring-loaded manifold mounting plate  70  to which manifold  58  is mounted. As stated hereinabove, projections  88 ,  90   a  and  90   b  keep manifold  58  from touching microchip  18  over its entire surface such that injection tubes  94  and  96 , and aspiration tubes  98  are properly seated in wells  47   a - 47   d  of microchip  18 . When measurements are completed, cam  68  is rotated such that the downward pressure on pushrod  72  by rocker arm  64  is reduced. Pushrod  72 , rocker arm  64  and cam  68  are all kept in contact in response to the action of springs  80   a  and  80   b  which lift manifold mounting plate  70  and manifold  58  away from microchip  18 , thereby permitting microchip tray  14  to be removed from interface  10 . Motor  62  is chosen such that the force transmitted to manifold  58  cannot break microchip  18 . 
         [0035]    It should be mentioned that microchip tray  14  bearing microchip  18  is secured in interface  10  before fluid manifold assembly  16  is either lowered to contact microchip  18  or raised away from chip  18 . 
         [0036]      FIG. 7A  is a schematic representation of a front perspective view of fluid manifold mounting plate  70 , with manifold  58  disposed slightly above microchip  18 , illustrating the injection tubes  94  and  97  and aspiration tube  98   c  in proximity to their insertion locations in wells  47   a - 47   d  in microchip  18 . Shown also are inlet ports  102   a  and  102   b  which are connected to injection tubes  94  and  97  through the body of manifold  58 , and which are attached to suitable pumps, valves, and fluid sources, not shown in  FIG. 7A , depending on the intended application for microchip  18 .  FIG. 7B  is a schematic representation of a bottom view of manifold  58  in proximity to microchip  18 , and illustrates injection tubes  94 - 97  and aspiration tubes  98   a - 98   d  extending into microchip wells  47   a - 47   d . Schematic microfluidic channels  104   a  and  104   b  are also illustrated in  FIG. 7B . As stated hereinabove, manifold  58  contacts microchip  18  through projections  88 , and  90   a  and  90   b , and through injection and aspiration tubes  94 - 97 , and  98   a - 98   d , respectively. 
         [0037]    The foregoing description of the invention has been presented for purposes of illustration and description and is not intended to be exhaustive or to limit the invention to the precise form disclosed, and obviously many modifications and variations are possible in light of the above teaching. The embodiments were chosen and described in order to best explain the principles of the invention and its practical application to thereby enable others skilled in the art to best utilize the invention in various embodiments and with various modifications as are suited to the particular use contemplated. It is intended that the scope of the invention be defined by the claims appended hereto.