Abstract:
An apparatus ( 10 ) for performing microfluidic processes comprising a base ( 50 ), a plurality of fluidic modules ( 20 ) releasably attached to the base ( 50 ), each fluidic module ( 20 ) comprising a fluid port ( 25 ) and a microfluidic manifold module ( 40 ) comprising a plurality of ports ( 45 ). A frame ( 70 ) is attached to the base ( 50 ) for releasably retaining the microfluidic manifold module ( 40 ), the frame ( 70 ) being moveable relatively to the base ( 50 ) to move the microfluidic manifold module ( 40 ) into contact with the fluidic modules ( 20 ) such that each fluid port ( 25 ) of the fluidic modules ( 20 ) aligns and seals with a respective port ( 45 ) on the microfluidic manifold module ( 40 ) thus completing a microfluidic circuit. A method for constructing and testing the apparatus ( 10 ) is also disclosed.

Description:
CROSS REFERENCE TO RELATED APPLICATIONS  
       [0001]     The present application claims priority to Great Britain Application No. 0427464.3, filed Dec. 15, 2004, which application is incorporated herein fully by this reference.  
       BACKGROUND OF THE INVENTION  
     Field of the Invention  
       [0002]     The present invention relates to a modular apparatus for performing microfluidic processes.  
         [0003]     The concept of integrating a series of processes onto a single microfluidic device or chip has been well documented. Processes typically include pumping, mixing, heating, sensing and separating. Such systems are known as ‘Lab-on-a-chip’ (LOC) systems and also cover ‘Micro Total Analysis Systems’ (μTAS). In such systems a chemical reagent, biological sample or a cell goes through a series of processes on a chip. The aim might be to analyse a sample/cell or to synthesise a new compound.  
         [0004]     Miniaturisation of laboratory processes is considered to be of key importance in the future of biological and chemistry science. Chemical and biological reactions happen faster at micro scale as a result of lower diffusion distances and efficient heat transfer. Less material is used in reactions resulting in cheaper and more environmentally friendly operation.  
         [0005]     Microfluidic devices have other potential benefits above conventional systems including simple integration of devices, access to information about reaction kinetics and easy scale up.  
         [0006]     A microfluidic chip is well known in the art and is typically a planar layered device fabricated using processes pioneered in the microelectronics industry. This normally involves using substrate materials such as silicon or glass wafers and processes such as photolithography, etching, metal deposition and anodic/thermal bonding.  
         [0007]     Microfabrication techniques have evolved so that devices can also be manufactured from polymer layers, using hot embossing techniques to create features and welding or adhesives to create bonds between layers.  
         [0008]     The term “microfluidic device”, is believed to be a term which is clearly understood in the art. The term is best understood functionally as relating to a device which is sufficiently small that diffusional mixing predominates and efficient heat transfer occurs, resulting in optimal reaction conditions in the microchannel. The dimensions of the microchannel should be sufficiently small that the flow results in a low Reynold&#39;s number (&lt;10 3 ) and a predominantly laminar flow regime.  
         [0009]     Generally at its narrowest point, the microchannel should have, in cross-section, a maximum internal dimension of 5-1000 μm, and preferably 5-500 μm. However, it is possible to envisage a channel which has a long thin cross-section having a dimension greater than 1000 μm, but which still operates as a microchannel as it is small in other dimensions.  
         [0010]     Therefore, it might be more appropriate to define a microfluidic device as having a channel with a cross-section in a plane perpendicular to the direction of flow which, at its narrowest part, is sized so that the largest circle which can be drawn in the cross-section has a diameter of &lt;1000 μm (and preferably &lt;5001 μm). In other words, if the cross-section is such that a circle of &gt;10001 μm can be drawn within the cross-section, it will not operate as a microchannel.  
         [0011]     With an increasing range of fabrication techniques and also increasing on-chip functions, it is often the case that a single microfluidic chip with a single fabrication process, cannot deliver the functionality required for a whole system. The concept of having a microfluidic system that integrates multiple microfluidic chips has therefore become popular.  
         [0012]     There are also several cost benefits of going to a “multiple chip” system. The cost of integrating all the required functions onto a single chip can be very high as the fabrication process required to do this will be very complex. By using multiple chips the lowest cost fabrication process can be chosen for each chip, reducing the overall system cost. The second benefit is related to chip failure either during fabrication or during operation. If all the functions are integrated onto one chip then the whole device needs to be replaced if one thing fails. If multiple chips are used then typically only one chip needs to be replaced. The cost of a failure is therefore reduced significantly.  
         [0013]     A number of modular systems which integrate multiple microfluidic chips are known in the art. Examples of such modular systems are given in WO 2004/022233, WO 0230560, U.S. Pat. No. 5,580,523 and U.S. Pat. No. 6,488,895. In these systems, the microfluidic chips are integrated by fixing the individual chip modules to one another, or to a manifold. Generally, fasteners such as screws, pins or clips are used to hold the individual modules together. The fluidic paths between the microfluidic chips are generally sealed by means of o-rings or other similar sealing devices.  
         [0014]     One of the problems with the known modular systems is ensuring that the fluidic paths between the modules are sealed correctly. Poor sealing of the fluidic paths can arise if the sealing members do not receive sufficient compressive force to completely seal the fluidic path. This can be due to the fasteners being incorrectly installed, incompletely engaged or missing. In addition, it is often not possible to determine whether the fluidic paths have been sealed correctly before the microfluidic system is put into operation.  
         [0015]     If one or more of the fluidic paths are incorrectly sealed the system will not function properly. Incorrect sealing may lead to expensive or dangerous chemical reagents being lost and valuable lab time being wasted. Additionally, if a fluidic path is inactive due to incorrect sealing, a reaction or experiment may be run to completion without the fault being detected.  
       SUMMARY OF THE INVENTION  
       [0016]     The present invention provides an apparatus for performing microfluidic processes comprising, a base, a plurality of fluidic modules releasably attached to the base, each fluidic module comprising a fluid port, a microfluidic manifold module comprising a plurality of ports, a frame attached to the base for releasably retaining the microfluidic manifold module, the frame being moveable relatively to the base to move the microfluidic manifold module into contact with the fluidic modules such that each fluid port of the fluidic modules aligns and seals with a respective port on the microfluidic manifold module thus completing a microfluidic circuit.  
         [0017]     Engaging the individual modules by means of relative motion between the base and the frame has a number of benefits. The sealing of the fluidic paths between the individual modules can be controlled by controlling the movement of the frame. Sufficient motive force can be applied to the frame to ensure complete sealing of the fluidic paths, and the speed of approach can be optimised to further ensure correct sealing of the fluidic paths. The apparatus of the present invention has the further advantage that the location and fixing of the individual modules is divorced from the sealing of the fluidic paths. This reduces greatly the possibility of damage to the seals as the apparatus is assembled.  
         [0018]     In a preferred example the ports of the microfluidic manifold module comprise a plurality of inlet ports and at least one outlet port. However, in an alternative example the ports of the microfluidic manifold module may comprise a plurality of outlet ports and at least one inlet port.  
         [0019]     The frame preferably comprises a sensor to detect the presence of the microfluidic manifold module. This provides a safeguard against the apparatus being operated without the microfluidic manifold module in place.  
         [0020]     The relative motion between the base and the frame may be any relative motion which allows the individual modules to be brought into fluidic communication with one another, for example the frame may be connected to the base by a hinged connector. In a preferred example, the relative motion between the base and the frame is linear. The use of linear motion has the advantage that a uniform sealing force may be applied.  
         [0021]     The fluidic modules which are releasably attached to the base may in certain circumstances be non-microfluidic, for example, a non-microfluidic pump module may be used. However, in a preferred example all of the fluidic modules are microfluidic.  
         [0022]     Preferably, each fluidic module, and the microfluidic manifold module, have a housing surrounding an inner body to provide a support and location structure.  
         [0023]     Each interface between a fluid port of the fluidic module and the corresponding inlet port of the microfluidic manifold module is preferably sealed by means of a resiliently deformable sealing member. In a preferred example the sealing member is an o-ring. More preferably, the sealing member is an o-ring of generally annular shape with flat ends.  
         [0024]     In a further preferred example, each sealing member is retained in a recess formed in the housing of a fluidic module. Alternatively or additionally, the sealing member may be retained in a recess formed in the housing of the microfluidic manifold module.  
         [0025]     The sealing members may be compressed by the force exerted upon them by the relative movement between the frame and the base, thus improving the integrity of the seals. The compression of the sealing members has the further advantage that any seal tolerances may be taken up. For example, if a batch of sealing members are at the lower end of their manufacturing tolerance, sufficient compressive force may be applied to ensure that the sealing members are compressed sufficiently to seal the fluidic paths.  
         [0026]     In a preferred example the frame is arranged to stop moving relatively to the base when a predetermined reaction force is reached. This is advantageous since the elasticity of the seals may vary over time as a result of exposure to heat and solvents.  
         [0027]     In an alternative preferred example, the frame is arranged to stop moving when a predetermined position is reached.  
         [0028]     In a second aspect, the present invention provides a method for constructing and testing a modular apparatus for carrying out microfluidic processes, the method comprising, assembling a plurality of fluidic modules and a microfluidic manifold module to complete a microfluidic circuit, and testing the integrity of the microfluidic circuit by supplying pressurised gas to the circuit, sealing the circuit and measuring the gas pressure within the circuit after a predetermined time.  
         [0029]     This second aspect of the present invention provides the advantage that it is possible to determine whether interfaces between the individual modules have been sealed correctly before the apparatus is operated.  
         [0030]     In a preferred example the apparatus for carrying out microfluidic processes is assembled by releasably attaching a plurality of fluidic modules to a base, releasably attaching a microfluidic manifold module to a frame attached to the base, moving the frame relatively to the base such that ports in the fluidic modules align and seal with respective ports in the microfluidic manifold module such that the fluidic circuit is completed.  
         [0031]     In a preferred example the gas is an inert gas. This has the advantage that the gas will not react with reagents contained within the microfluidic circuit.  
         [0032]     The pressure within the microfluidic circuit may be measured by one or more pressure sensors located in the microfluidic circuit. A single sensor may be used to detect the pressure. This has the advantage of reducing the cost of the apparatus.  
         [0033]     The pressure sensor may be located in one of the fluidic modules. In a preferred example, the or each pressure sensor is located in a fluidic pump module downstream of a pump. This has the advantage that the pressure of the fluid being pumped may be measured. Alternatively, the pressure sensor may be located in a gas supply line. 
     
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
       [0034]     Examples of the present invention will now be described with reference to the accompanying drawings, in which:  
         [0035]      FIG. 1  is a schematic plan view of an apparatus according to the present invention that is used to carry out microreactions.  
         [0036]      FIG. 2  is a partial schematic sectional side view of the apparatus of  FIG. 1  depicting the fluidic connection between the pump modules and the reaction chip module.  
         [0037]      FIG. 3  is a partial schematic sectional side view of the apparatus of  FIG. 1  depicting the fluidic connection between the sensor module and the reaction chip module.  
         [0038]      FIG. 4  is a schematic plan view of the frame for releasably retaining the reaction chip module.  
         [0039]      FIGS. 5   a  to  5   c  are a series of schematic side views of the apparatus of  FIG. 1  depicting how the apparatus is assembled.  
         [0040]      FIG. 6  is a partial schematic sectional side view of the apparatus of  FIG. 1  depicting an alternative pump module to that shown in  FIG. 2 .  
         [0041]      FIG. 7  is a schematic representation of the alternative pump of  FIG. 6 .  
         [0042]      FIG. 8  is a schematic plan view of the apparatus of  FIG. 1  further comprising a test apparatus to verify the integrity of the fluidic circuit.  
         [0043]      FIG. 9  is a partial schematic sectional side view of the apparatus of  FIG. 1  depicting the connection of a gas supply.  
         [0044]      FIG. 10  is a schematic plan view of a further embodiment of the present invention. 
     
    
       [0045]      FIG. 1  depicts a modular microfluidic apparatus  10  comprising a base  50 . Three pump modules  20   a ,  20   b ,  20   c  and a sensor module  30  are releasably attached to the base  50  as described below. A heater plate  80  is also fixed to the base  50 . A reaction chip module  40  is also shown, the attachment of which will be described below.  
       DESCRIPTION OF THE PREFERRED EMBODIMENTS  
       [0046]     Referring to  FIGS. 1, 2  and  9 , each pump module  20   a ,  20   b .  20   c  comprises a reservoir  21  for supplying a reagent A or B, or a solvent S, to the reaction chip module  40 . The reservoir  21  comprises an exterior portion  2  and an interior portion  3 . The exterior portion  2  has an opening  5  at its upper end and a threaded section  4  at its lower end. The inner portion  3  has an opening  7  at its upper end and a threaded section  6  at its lower end. A rubber cap  1  closes the opening  5 . The rubber cap  1  allows extra reagent to be added to the reservoir by syringe if required.  
         [0047]     Each pump module  20   a ,  20   b ,  20   c  further comprises a housing  22  and a pump chip  23 . The housing  22  has threaded sections  19  and  59  and a fluid port  25 . An o-ring  18  is located within the threaded section  19 . Two location pins  29  extend through the housing  22  and the chip  23  and protrude from the lower side of the pump module  20 . The fluid port  25  has an o-ring  60  retained therein. The o-ring  60  has a substantially annular shape with flat ends.  
         [0048]     The outer portion  2  and the inner portion  3  of the reservoir  21  are releasably attached to the housing  22  via the threaded sections  19  and  59 . The o-ring  18  provides a gas tight seal between the interior of the reservoir  21  and the atmosphere.  
         [0049]     Each pump chip  23  is of a planar layered construction. For example, a layered glass/polymer/glass construction. Each pump chip  23  comprises a microchannel  24  connecting the reservoir  21  to the fluid port  25  in the pump module housing.  
         [0050]     Referring to  FIGS. 1 and 3 , the sensor module  30  has substantially the same construction as described above for the pump modules  20   a ,  20   b ,  20   c . The sensor module  30  comprises a reagent reservoir  31  with the same construction as described above for the pump module reservoir  21 .  
         [0051]     The sensor module  30  further comprises a housing  32  and a sensor chip  33 . The housing  32  has threaded sections  36  and  58  and a fluid port  35 . An o-ring  37  is located within the threaded section  36 . Two location pins  39  extend through the housing  32  and the chip  33  and protrude from the lower side of the sensor module  30 . The port  35  has a sealing member  60  retained therein.  
         [0052]     The outer portion  2  and the inner portion  3  of the reservoir  31  are releasably attached to the housing  32  via the threaded sections  36  and  58 , the o-ring  37  provides a gas tight seal. The housing  32  of the sensor module further comprises an electrical connector  38  located on the lower surface of the sensor module  30 .  
         [0053]     The sensor chip  33  has a microchannel  34  which connects the port  35  to the reagent reservoir  31 . The reaction sensor chip  33  is of a planar layered construction. For example, a layered glass/platinum/glass diffusion bonded construction. The electrical connector  38  is in electrical connection with the sensor chip  33 .  
         [0054]     Referring to  FIGS. 1, 2 , and  4 , The reaction chip module  40  comprises a housing  41  and a reaction chip  47 . The housing  41  has two semi-spherical indents  48  located on the outer surface. The reaction chip  47  comprises three inlet ports  45   a ,  45   b ,  45   c  and an outlet port  46 . Three inlet microchannels  42   a ,  42   b ,  42   c  connect the inlet ports  45   a ,  45   b ,  45   c  to a reaction microchannel  44  via a microchannel junction  43 . The reaction channel  44  connects the microchannel junction  43  to the outlet port  46 . The reaction chip  47  is of a planar layer construction. For example, a layered glass/glass diffusion bonded construction. The reaction chip module  40  further comprises two location pins  49  which pass through the housing  41  and chip  47  and which protrude from the lower side of the reaction chip module  40 .  
         [0055]     The base  50  has eight receiving holes  51  for receiving the location pins  29  and  39  of the pump modules  20   a ,  20   b ,  20   c  and the sensor module  30  respectively. The base  50  further comprises five sprung latches  13  for holding the pump modules and the sensor module in place on the base  50 . The spaces between the sprung latches  13  define four docking stations  52 ,  53 ,  54 ,  55  for the three pump modules  20   a ,  20   b ,  20   c  and sensor module  30  respectively. The sprung latches  13  comprise a knob  14  located at the upper end of a shaft  16 , and a stopper plate  17  located at the lower end of the shaft  16 . The shaft  16  passes through the base  50 . A spring  15  is located between the stopper plate  17  and the base  50 .  
         [0056]     An electrical connector  11  is located on the upper surface of the base  50  at the docking station  55  of the sensor module  30 . The electrical connector  11  has an electrical power supply  12 .  
         [0057]     Referring to  FIGS. 4 and 5   a , the apparatus  10  further comprises a frame  70  moveably attached to the base  50 . The frame  70  has four legs  71  retained within receiving hols in the base  50  (not shown). The legs  71  are constrained to move linearly by linear bearings located in the receiving holes. The frame  70  further comprises two ball spring plungers  72  and a microswitch  73 . The microswitch  73  is connected to a system controller  110 .  
         [0058]      FIGS. 5   a  to  5   c  depict how the microfluidic apparatus  10  is assembled. The pump modules  20   a ,  20   b ,  20   c  and the sensor module  30  are releasably attached to the base  50  by placing the location pins  29  and  39  in the receiving holes  51 . The pump modules  20   a ,  20   b ,  20   c  and the sensor module  30  are then releasably secured by turning the knob  14  through 90° as illustrated in  FIGS. 1 and 2 .  
         [0059]     Positioning and securing the sensor module  30  on the base  50  brings the base electrical connector  38  into contact with the sensor module electrical connector  11 , thus providing an electrical supply to the sensor chip  33 . In this example the sensor chip functions by measuring variations in electrical conductivity. However, any other type of sensor chip known in the art may be used.  
         [0060]     The reaction chip module  40  is releasably attached to the frame  70  by sliding it into the frame via horizontal rails (not shown). The reaction chip module  40  is held in place by the ball spring plungers  72  which locate with the recesses  48  in the housing  41 . The reaction chip module  40  takes its vertical alignment from the rails on the frame  70  and its horizontal alignment from the location pins  49  which locate with holes in the heater plate  80  and base  50  (not shown). Placement of the reaction chip module  40  in the frame  70  depresses the microswitch  73  thus indicating to the system controller  110  that the reaction chip module  40  is in place.  
         [0061]     Once the pump modules  20   a ,  20   b ,  20   c , the sensor module  30  and the reaction chip module  40  are in place, the frame  70  is lowered by a pneumatic drive to bring the reaction chip module  40  into contact with the pump modules  20   a ,  20   b ,  20   c , the sensor module  30 , and the heater plate  80 . The frame  70  may be actuated by any driving means known in the art such as an electric motor or by mechanical levers.  
         [0062]     When the reaction chip module  40  is in the lowered position, the reaction chip inlet ports  45   a ,  45   b ,  45   c  align with the pump module ports  25 . Similarly, the reaction chip outlet port  46  aligns with the sensor module port  35 . Thus, by lowering the reaction chip module  40  a microfluidic circuit is completed and a direct connection is made between the planar chip devices. The base  50  and frame  70  hold the pump modules, sensor module and reaction chip module in correct alignment so that the fluid ports align and the microfluidic circuit is completed. The reaction chip module  40  performs a function similar to a manifold in connecting all the microfluidic modules together.  
         [0063]     The basic function of the apparatus  10  is to pump reagents A and B, and solvent S, from the reservoirs  21  to the microfluidic junction  43  where they mix and flow along a heated reaction channel  44 . The reaction mixture then passes through a reaction sensor chip  33  before being collected in the reservoir  31 .  
         [0064]      FIG. 6  shows a further embodiment of the present invention. For reasons of clarity, in cases where equivalent parts are shown the reference numerals used are the same as those given above. In this alternative embodiment, one or more pump modules  26  are used in place of one or all of the microfluidic pump modules  20   a ,  20   b ,  20   c . The pump module  26  is not a microfluidic device, instead, a more conventional pump  27  is used as described below.  
         [0065]     The pump  27  comprises a rotary valve  61  which is driven by a rotary drive  62 . The pump  27  further comprises two glass syringes  63   a ,  63   b  which are driven by a linear drive  64 . The rotary valve  61  and rotary drive  62  are located within housing  22  of the alternative pump module  26 . The syringes  63   a ,  63   b  project from the lower side of the pump module  26  and into the base  50 . The linear drive  64  is located in the base  50 .  
         [0066]     Referring to  FIGS. 6 and 7 , The rotary valve  61  comprises an outer body  66  and an inner body  67  which is able to rotate within the outer body  66 . The inner body  67  comprises two discrete channels  65   a ,  65   b . The outer body  66  comprises an inlet channel  68   a  and an outlet channel  68   b . The outer body also comprises two syringe channels  90   a ,  90   b.    
         [0067]     The inlet channel  68   a  is connected to a fluid reservoir  21  located on the pump module  26  and the outlet channel  68   b  is connected to a polymer pipe  28  which leads to a port  25  in the housing  22  of the pump module  26 . The syringe channels  90   a ,  90   b  are connected to the syringes  63   a ,  63   b  respectively.  
         [0068]      FIG. 7  depicts the operation of the pump  27 . In a first action, syringe  63   a  aspirates fluid from the reservoir  21  via the inlet channel  68   a , the inner body channel  65   a  and the syringe channel  90   a . At the same time, syringe  63   b  dispenses fluid into the polymer pipe  28  via the outlet channel  68   b , the inner body channel  65   b  and the syringe channel  90   b . The rotary drive  62  drives the rotary valve  61  into a second position such that inner channel  65   a  connects syringe channel  90   b  with outlet channel  68   b , and inner channel  65   b  connects syringe channel  90   a  and inlet channel  68   a . The process is then reversed such that syringe  63   a  dispenses its fluid contents to the polymer pipe  28  and syringe  63   b  aspirates fluid from the reservoir  21 . The process repeats continuously to pump fluid from the reservoir  21  to the reaction chip module  40 .  
         [0069]     A sealing member  60  is used to make the fluid connection between the pump module  26  and the reaction chip module  40  as before. However, in this case the polymer pipe  28  is located inside the sealing member  60  to create a seal.  
         [0070]     The method for constructing and testing a modular apparatus for carrying out microfluidic processes will now be described.  
         [0071]     Referring to  FIG. 8 , the apparatus of  FIG. 1  is shown further comprising a system test apparatus  100 . For reasons of clarity, in cases where equivalent parts are shown the reference numerals used are the same as those given above. The system test apparatus  100  comprises a system controller  110  connected to a software user interface  170  and a solenoid valve  140 . The solenoid valve  140  is connected to a pressure regulator  130  which is connected in turn to an inert gas supply  120 . Gas supply lines  150  connect the solenoid valve  140  to the reservoirs  21  and  31  as described below. A pressure sensor  160  is located in pump module  20   b  downstream of the pump and connected to the pump chip  23 .  
         [0072]     Referring to  FIG. 9 , the gas supply lines  150  are connected to the reservoirs  21  and  31  via channels  152  located in the pump module housing  22  and sensor module housing  32  respectively. The gas supply lines  150  pass through the base  50  and align with inlet port  154  on the lower surface of the pump module housing  22  and sensor module housing  32  respectively. Each gas supply interface is sealed by means of an o-ring  151 . The channels  152  have an outlet port  153  which aligns with a space  155  formed by the outer portion  2  and the inner portion  3  of the reservoirs  21  and  31 .  
         [0073]     During the test, the system controller  110  applies gas pressure to the reagent reservoirs  21  and  31  by opening the solenoid valve  140  and letting the gas flow into the fluid circuit via gas supply lines  150 . The system controller  110  then closes the solenoid valve  140  thus trapping a volume of pressurized gas in the circuit. Since the microfluidic circuit is closed, the pressure within the circuit should remain at a fixed level. If a fluidic module is missing or incorrectly sealed, the gas will leak out of the circuit and the pressure will rapidly drop to atmospheric pressure. The system controller  110  detects this drop in pressure and indicates the problem to the user via the software user interface  170 .  
         [0074]     Once the pressure test described above is complete, the system controller  110  will start a reaction by pumping reagents A and B, and solvent S, from each reagent reservoir  21  into the reaction chip  47 . Typically one or more of the pump modules  20   a ,  20   b ,  20   c  will have an integrated pressure sensor  160  downstream of the pump to measure the fluid pressure. A rapid increase in pressure during pumping will indicate either a blockage in the reaction chip  47 , misalignment between one or more of the fluid ports of the microfluidic modules or boiling of reagents in the reaction chip  47 . A drop in pressure will indicate a fluid leak in the system or a pump failure. Positive pressure above the reagents in the reservoirs  21  can be used to aid the microfluidic pumping during operation of the apparatus.  
         [0075]     A further example of a modular microfluidic apparatus  200  for mixing chemical reagents is shown in  FIG. 6 . In this example the apparatus  200  comprises a base  250  and a frame  270  (not shown) moveably attached to the base in the same manner as described above. Six reagent input modules  220   a - 220   f , an output module  230  and two pump modules  205 ,  206  are releasably attached to the base  250 . A manifold module  240  is releasably attached to the frame  270 . The apparatus  200  uses the same engagement method for the microfluidic modules as that described above  
         [0076]     Reagents A-F are stored in reservoirs  221   a - 221   f . The reagent input modules  220   a - 220   f  contain valve chips that open to allow reagent to be drawn into the central manifold chip  240 . The two pump modules  205 ,  206  draw the reagent into the manifold module  240 , normally mixing the reagent with another reagent from another input module. The mixture is then dispensed by the pumps out through the output module  230  to an output reservoir  231 .