Abstract:
It is an object of the present invention to ensure quite high-speed and highly efficient production using the microreactors and facilitate transition from laboratory-basis synthesis to industrial production. 
     A microreactor system collecting a mixture solution obtained by mixing up material solutions in a microreactor includes a plurality of microreactors arranged in parallel; a flowmeter disposed on a downstream side; a detector detecting a composition of the mixture solution; and a processing device calculating both a reaction time from when the material solutions are mixed up until the detector detects the composition of the mixture solution and an yield of the target product. The processing device includes means for changing the amount of each of the material solutions supplied by the pump in each of the microreactors; means for calculating and storing the reaction time and the yield of the target product for every change in the supply amount; and means for deciding which of the plurality of microreactors is selected on the basis of the reaction time and the yield of the target product.

Description:
BACKGROUND OF THE INVENTION 
       [0001]    1. Field of the Invention 
         [0002]    The present invention relates to a microreactor system for producing a chemical reaction among at least two solutions in a microchannel of about several tens to several hundreds of micrometers. The present invention is particularly suitable for obtaining optimum conditions and increasing production. 
         [0003]    2. Description of the Related Art 
         [0004]    During transition time from synthesis in a laboratory to industrial production, it is essential to build and evaluate a pilot plant for scale-up purposes, which however takes lots of time and labor. 
         [0005]    It is known that a microreactor can precisely control temperature and reaction time and can cause chemical reaction with high efficiency. Furthermore, it is known that to appropriately adjust various conditions relevant to a chemical reaction of interest in a microchannel of a microchannel chip, e.g., a temperature condition of a reaction region and a concentration, a flow rate and the like of a test reagent, the microreactor samples and analyzes a product obtained from the microchannel, and controls the reaction conditions in the microchannel chip based on the sampling and analysis result. The conventional microreactor is disclosed in, for example, Japanese Patent Application Laid-Open No. 2006-145516. 
         [0006]    When a next treatment solution is to be obtained by changing a type and a mixture ratio of solutions, the micro-fluid chip is replaced by another chip for every treatment in order to prevent remaining solutions of a previous treatment from getting mixed. It is known that a clamp is provided to fixedly brace a micro-fluid chip together by its opposing sides so that different types of solutions are supplied to the micro-fluid chip. This technique is disclosed in, for example, Japanese Patent Application Laid-Open No. 2006-102650. 
         [0007]    Furthermore, it is known that a predetermined number of microchips are integrally stacked so as to enable synthesis of a large quantity of compounds using the microchips and achieve the high efficiency in chemical reaction. The technique is disclosed in, for example, Japanese Patent Application Laid-Open No. 2002-292275. 
         [0008]    According to the technique disclosed in the Japanese Patent Application Laid-Open No. 2006-145516, the chemical reaction is produced by the single microreactor. Due to this, it is disadvantageously difficult to secure productivity necessary for practical production by the production volume of matters obtained by the microreactor that can provide only a small reaction situation. 
         [0009]    Furthermore, according to the technique disclosed in the Japanese Patent Application Laid-Open No. 2006-102650, it is disadvantageously necessary to replace one micro-fluid chip by another chip whenever a treatment is carried out. For working mass-production, it takes a large number of man-hours, resulting in cost increase. 
         [0010]    Moreover, the technique disclosed in the Japanese Patent Application Laid-Open No. 2002-292275 is intended simply to increase production, and is inappropriate to optimize a channel structure of the microreactor itself, and to change reaction conditions such as reaction temperature with respect to each microreactor. 
       SUMMARY OF THE INVENTION 
       [0011]    It is an object of the present invention to provide a microreactor system capable of solving the conventional problems, facilitating transition from laboratory-basis synthesis to industrial production, and ensuring quite high-speed and highly efficient production using the microreactors. 
         [0012]    According to one aspect of the present invention, there is provided a microreactor system including a microreactor having a microchannel for mixing up two solutions as material solutions to obtain a target product; a material tank for storing each of the material solutions introduced into the microreactor; a pump for supplying each of the material solutions to the microreactor; a temperature control device for setting a temperature of the microreactor; and a mixture solution tank for collecting a mixture solution obtained by the microreactor, the microreactor system including: a plurality of the microreactors arranged in parallel; a flowmeter disposed on a downstream side of each of the microreactors; a detector for detecting a composition of the mixture solution obtained by each of the microreactors as a detection intensity; and a processing device for controlling an amount of each of the material solutions supplied by the pump, for receiving both a value indicating a flow rate measured by the flowmeter and a value indicating the detection intensity detected by the detector, and for calculating both a reaction time from when the material solutions are mixed up until the detector detects the composition of the mixture solution and an yield of the target product, wherein the processing device includes means for changing the amount of each of the material solutions supplied by the pump, in each of the microreactors; means for calculating and storing the reaction time and the yield of the target product for every change in the supply amount; and means for deciding which of the plurality of microreactors is selected on the basis of the reaction time and the yield of the target product stored. 
         [0013]    According to the present invention, the chemical reaction apparatus in which a plurality of microreactors is arranged in parallel can simultaneously produce a plurality of reactions different in reaction condition, can calculate reaction results as yields of products, and can automatically compare the yields among channels. It is possible to ensure considerably high-speed and highly efficient production using the microreactors, and to facilitate transition from laboratory-basis synthesis to industrial production. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0014]      FIG. 1  is a block diagram showing a microreactor system according to an embodiment of the present invention; 
           [0015]      FIGS. 2A ,  2 B and  2 C are graphs showing yield versus reaction time according to an embodiment of the present invention; 
           [0016]      FIG. 3  is a block diagram showing that the microreactor system shown in  FIG. 1  is adapted to mass production; 
           [0017]      FIG. 4  is a flowchart of a processing performed during a parameter survey according to an embodiment of the present invention; 
           [0018]      FIG. 5  is a flowchart of operation using the microreactor system shown in  FIG. 3 ; and 
           [0019]      FIG. 6  is a block diagram showing the parameter survey using a channel inside diameter as a parameter according to an embodiment of the present invention. 
       
    
    
     DESCRIPTION OF THE PREFERRED EMBODIMENTS 
       [0020]    An embodiment of the present invention will be described hereinafter in detail with reference to  FIGS. 1 to 6 . 
         [0021]      FIG. 1  shows a configuration of a microreactor system in which microreactors are arranged in parallel. Namely, three microreactors  101  are arranged in parallel. The microreactors  101  are connected to their respective channels in front and rear thereof by joints or the like (not shown), thereby making them detachable and replaceable. A solution in each of material tanks  103  is supplied to the microreactors  101  arranged in parallel by corresponding pumps  102 . The microreactors  101   a,    101   b,  and  101   c  differ in channel structure. 
         [0022]    To mix up three or more solutions, the material tanks  103  and the pumps  102  are prepared for the number corresponding to that of types of the mixed solutions. By providing microreactors  101  having channel structures to mix up three or more solutions, the microreactor system can be configured in a similar fashion to that for mixture of two solutions. 
         [0023]    A flowmeter  104  and a detector  105  are provided in a rear channel of each of the microreactors  101 . The detector  105  detects a solute composition of a mixture solution mixed up in each microreactor  101  and is preferably a detector based on absorption spectrometry, a detector based on photothermal conversion spectroscopy, or the like. The flowmeter  104  and the detector  105  are electrically connected to a processing device  108  and a detection value is supplied to the processing device  108 . 
         [0024]    The processing device  108  calculates reaction time from both a flow rate measured by the flowmeter  104  and a channel volume from the microreactor  101  to the detector  105 , calculates a reaction ratio of a material in a mixture solution from a solution composition of both materials and a product detected by the detector  105 , and calculates yields of the product and a byproduct, and stores therein calculated values as data. 
         [0025]    The processing device  108  includes a flow control function for the pumps  102  and a temperature control function for temperature control devices  107 . 
         [0026]    Each of the temperature control devices  107  functions to keep a temperature of each of the microreactors  101  constant, and is preferably a temperature-controlled bath, a Peltier, or the like. It is also preferable to use a light irradiation device (not shown) such as an optical fiber, a microwave irradiation device (not shown) or the like together with or independently of the temperature control device  107  so as to control or promote a reaction in the microreactor  101 . 
         [0027]    A reaction efficiency evaluation with respect to each of the microreactors  101  using the microreactor system shown in  FIG. 1  will be described in detail. 
         [0028]    Suppose that the flow rate detected by the flowmeter  104  is Q and the channel volume from the microreactor  101  to the detector  105  is V. A reaction time t R  from mixture of solutions until detection is represented by t R =V/Q. 
         [0029]    As shown in  FIG. 2A , when the flow rate of each of the solutions supplied by the respective pumps  102  during from operation time t 11  to t 12  is changed from Q 11  to Q 12 , a flow rate detected by the flowmeter  104  is changed from Q 13  to Q 14 , and the reaction time t R  decreases from t R11  to t R12  in inverse proportion to the flow rate. 
         [0030]    Using the value detected by the detector  105 , a reaction ratio of each material or yields of a target product and a byproduct based on a difference in detection intensity between the materials and the product can be calculated. If the pump flow rate is changed similarly to  FIG. 2A , the yields are changed as shown in  FIG. 2B . 
         [0031]      FIG. 2C  is a graph showing the relationship between reaction time and the yield of the target product in the case of the microreactor system shown in  FIG. 1  in which three microreactors  101  having the different channel structures are arranged in parallel. In  FIG. 2C , Y a , Y b , and Y c  indicate yields in the microreactors  101   a,    101   b,  and  101   c,  respectively. 
         [0032]    A reaction produced by the microreactor  101  is influenced by the channel structure and a channel width of the microreactor  101 . Thus, since the reaction ratio of the materials or the yields of the target product and byproduct in the different microreactors can be calculated as shown in  FIG. 2C , reaction efficiencies among the different microreactors can be compared. In the example shown in  FIG. 2C , the reaction efficiency is high when the microreactor  101   b  is used and the reaction time is set to t R13  or more. Furthermore, if a plurality of microreactors  101  are used and reaction conditions, e.g., temperature condition are changed with respect to each channel, it is possible to decide efficient reaction conditions. 
         [0033]      FIG. 3  shows a configuration of a microreactor system according to another embodiment of the present invention. The microreactor system shown in  FIG. 3  is configured, as compared with the microreactor system shown in  FIG. 1 , such that rear channels of the microreactors  101  are joined together and a three-way solenoid valve is used for channel switching. 
         [0034]    Each of the microreactors  101  is detachable and replaceable, a three-way solenoid valve  301  is disposed in rear of each of the detectors  105 , and rear channels of the three-way solenoid valves  301  are joined together, and a produced solution tank  302  is arranged at a downstream end of the joined channels. The three-way solenoid valves  301  are switched by the processing device  108 . 
         [0035]    As for an introduction part from a channel branching portion in rear of each pump  102  to each microreactor  101  and a piping from the rear channel of the microreactor  101  to a channel joint portion of the three-way solenoid valve  301  corresponding to the microreactor  101 , when the microreactors  101  identical in channel structure are arranged, it is preferable to set their piping equal to each other in length and diameter among the microreactors  101  so as to make flow rates of the microreactors  101  equal to each other. A needle valve  303  is installed in each piping, and a channel sensor  304  detecting a flow rate or a pressure is disposed in a front channel of the needle valve  303 . The needle valves  303  regulate the flow rates based on detection values of their channel sensors  304 , thereby making it possible to uniformly supply solutions to their respective channels. 
         [0036]    A parameter survey using the microreactor system shown in  FIG. 1  or  FIG. 3  and an example of a processing flow of the processing device  108  will be described with reference to  FIGS. 2A to 2C ,  FIG. 3 , and a flowchart of  FIG. 4 . 
         [0037]    First, a parameter survey using the yield of the target product as an evaluation criterion will be described. Examples of parameters or conditions changed with respect to each channel include a channel width, a channel structure, and a reaction temperature of each microreactor  101 . At least one parameter differs among the channels. 
         [0038]    An overall flow rate is decided (step  401 ) and each pump  102  is started. Thereafter, the number of trials n is counted (step  402 ), and for each of branch channels, reaction time is calculated from both the value of its flowmeter  104  and the channel volume from its microreactor  101  to its detector  105  (step  403 ). 
         [0039]    For each of the branch channels including their respective microreactors  101 , an yield Y of its microreactor  101  is calculated based on an input value to its detector  105  (step  404 ). The yield is recorded only if the number of trials n is 1, and the processing returns to the step  401  of deciding the overall flow rate. 
         [0040]    The overall flow rate at the second and following trials is made to always increase or decrease with respect to the previous flow rate. At the second and following trials, the processing device  108  compares the yield Y n-1  at the previous trial with the yield Y n , for each of the branch channels including their respective microreactors  101  (step  406 ). If the yield Y n  is almost equal to or higher than the yield Y n-1  for at least one of the branch channels as a result of comparison, the processing is returned to the step  401  of deciding the overall flow rate and the next trial is carried out. 
         [0041]    If the yield Y n  is obviously lower than the yield Y n-1  for all of the branch channels including their respective microreactors  101  as a result of the comparison, comparisons are made among maximum yields Y max  each of which has been obtained through the trials carried out so far for its individual branch channel including its microreactor  101  (step  407 ). The channel for which the maximum yield has been obtained, and the flow rate and reaction time (if calculated at the step  403  of calculating the reaction time) at the trial at which the maximum yield has been obtained are displayed as optimum conditions (step  408 ). The flow rate, the reaction time, and the yields are recorded as data (step  409 ), thus finishing the processing. 
         [0042]    If a parameter survey using the magnitude of reaction ratio of each material or the magnitude of yield of the byproduct as an evaluation criterion is to carried out, judgments and processings at and after the step  406  of comparing the yield Y n-1  at the previous trial with the yield Y n  are performed as follows differently from the parameter survey using the magnitude of the yield of the target product. 
         [0043]    At the step  406 , if the yield Y n  is nearly equal to or lower than the yield Y n-1  for at least one of the branch channels as a result of the comparison, the processing is returned to the step  401  of deciding the overall flow rate and the next trial is carried out. If the yield Y n  is obviously higher than the yield Y n-1  for all of the branch channels including the respective microreactors  101  as a result of the comparison, comparisons are made among minimum yields Y min  each of which has been obtained through the trials carried out so far for its individual branch channel including its microreactor  101 . The channel for which the minimum reaction ratio or yield has been obtained, and the flow rate and the reaction time (if calculated at the step  403  of calculating the reaction time) at the trial at which the minimum reaction ratio or yield has been obtained are displayed as optimum conditions (step  408 ). The flow rates, the reaction time, and the yields are recorded as data (step  409 ), thus finishing the processing. 
         [0044]    The microreactor system shown in  FIG. 1  or  FIG. 3  and the use of the system based on the process flow of  FIG. 4  facilitate simultaneously changing channel widths, channel shapes, reaction temperatures, and reaction time which serve as parameters necessary to consider in the proving tests for the microreactors  101 . Moreover, if the optimum conditions are obtained by the proving tests, then the microreactors  101  included in the microreactor system shown in  FIG. 3  are detached and replaced such that a plurality of microreactors  101  identical in channel structure to the microreactor  101  connected to the branch channel for which the optimum conditions have been obtained, are arranged in parallel, thereby increasing production and carrying out continuous operation. 
         [0045]    An operation flow for continuous production using the identical microreactors  101  will next be described with reference to  FIGS. 3 and 5 . 
         [0046]    The processing device  108  controls the pumps  102  and the temperature control devices  107  to operate at preset flow rates and temperatures, respectively. Thereafter, it is checked whether the solutions are equally supplied to their respective channels, on the basis of the values detected or measured by the channel sensors  304  and the flowmeters  104  (step  501 ). If it is determined that the solutions are not uniformly supplied to their respective channels, that is, the values of the channel sensors  304  or the flowmeters  104  differ among the channels, the needle valves  303  are operated to regulate the flow rates (step  506 ). 
         [0047]    If it is determined that the flow rates are uniform among the channels, it is determined whether detection values for the solute compositions from the detectors  105  are uniform among the channels (step  502 ). If the input values are not uniform, that is, the channels have irregular reaction efficiencies, there is a probability of some abnormality in the channels. Therefore, the processing device  108  displays an alarm (step  504 ). If it is determined that the pumps  102  are to be stopped (step  503 ) and the processing device  108  receives an instruction to stop the pumps  102 , the flow rates, the reaction time, and the yields at the trials are recorded (step  505 ), thus finishing the processing. 
         [0048]    If the input values are uniform, operation is continued. If it is determined that the pumps  102  are not to be stopped (step  503 ) and the processing device  108  is not given the instruction to stop the pumps  102 , the processing is returned again to the step  502  of determining whether detection values for the solute compositions from the detectors  105  are uniform among the channels, thereby repeatedly monitoring the channels and continuously operating the pumps  102 . If the instruction to stop the pumps  102  is received as a result of the step  503  of determining whether to stop the pumps  102 , the flow rates, the reaction time, and the yields at the trials are recorded (step  505 ), thus finishing the processing. 
         [0049]    Moreover, if it is determined at the step  502  that the detection values for the solute compositions from the detectors  105  are not uniform among the channels, the processing device  108  switches the three-way solenoid valves  301  in rear of their respective detectors  105  from the produced solution tank  302  side to the mixture solution tank  106  side. Conversely, if it is determined at the step  502  that the detection values for the solute compositions from the detectors  105  are uniform among the channels, the processing device  108  switches the three-way solenoid valves  301  in rear of their respective detectors  105  from the mixture solution tank  106  side to the produced solution tank  302  side. These operations make it possible to keep qualities of products constant in the production using a plurality of microreactors  101 . 
         [0050]    Referring next to  FIG. 6 , an example of a parameter survey using an inside diameter of each of the channels corresponding to their respective microreactors  101  as a parameter will be described. As for each of the microreactors  101 , a channel cross section of a mixing portion where solutions mix together is a circular tube shape. If it is defined that channel inside diameters for the microreactors  101   a,    101   b,  and  101   c  are d a , d b , and d c  and channel lengths therefor are l a , l b , and l c , the microreactors  101  for which the relationships of d a =nd b =md c  and l a =nl b =ml c  are satisfied simultaneously, i.e., for each combination of the two taken from the microreactors  101 , its ratio between their channel inside diameters are equal to that between their channel lengths, are connected to the system. 
         [0051]    The material solutions supplied by their respective pumps  102  are distributed from their channel branching portions of the channels in front of microreactors  101  to their branch channels. At this time, the solutions supplied to their respective branch channels are distributed such that the flow rates satisfy ΔP a =ΔP b =ΔP c , where ΔP indicates a pressure loss of each branch channel. This pressure loss ΔP is defined as ΔP=32 ρlv/d 2 , where ρ is a viscosity of each solution, l is a channel length, v is a flow velocity, and d is a channel inside diameter. Accordingly, the relationship of v a =nv b =mv c  is deduced from the equation of ΔP=32 ρlv/d 2  for the flow velocity v in the mixture channel of each microreactor  101 . 
         [0052]    Meanwhile, the reaction time t R  for the mixture channel of each microreactor  101  is expressed by t R =l/v. Therefore, if the relationships of d a =nd b =md c  and l a =nl b =ml c  are simultaneously satisfied for the channel inside diameters and the channel lengths of microreactors  101 , respectively, the relationship of t Ra =t Rb =t Rc  is satisfied for the reaction times t Ra , t Rb , and t Rc  for their respective microreactors  101   a,    101   b,  and  101   c.  In other words, when, for each combination of the two taken from the microreactors  101   a,    101   b,  and  101   c,  its ratio between their channel inside diameters d is set equal to that between their channel lengths l, it is possible to make the reaction times for their respective microreactors  101   a,    101   b,  and  101   c  equal to each other. 
         [0053]    Therefore, by arranging the microreactors  101   a,    101   b,  and  101   c,  for each combination of the two taken from which its ratio between their channel inside diameters is equal to that between their channel lengths, into the microreactor system shown in  FIG. 6 , and by arranging their respective detectors  105  in the rear channels of the microreactors  101 , reaction efficiencies can be simultaneously measured while making their reaction times equal to each other in spite of the differences in reaction efficiency among the microreactors  101  having different channel widths, and can be displayed on a monitor  109 . 
         [0054]    To improve measurement reliability, it is preferable to make efforts to make the piping as short as possible and to make inside diameters of the piping as large as possible so that the pressure loss of the introduction part from the channel branching portion in rear of each pump  102  to each microreactor  101  and that of the piping from the rear channel of the microreactor  101  to the channel joint portion of the three-way solenoid valve  301  corresponding to the microreactor  101  are sufficiently lower than the pressure loss of the mixing portion of each microreactor  101 . 
         [0055]    While the flowmeters  104 , the needle valves  303 , and the channel sensors  304  shown in  FIG. 3  are not always necessary, it is preferable to arrange them so as to monitor states of the channels and to improve the reliability of the microreactor system. 
         [0056]    A processing flow of the processing device  108  when a parameter survey for which the channel inside diameters are changed is carried out for the microreactor system shown in  FIG. 6  is executed according to the flowchart of  FIG. 4  similarly to the microreactor systems shown in  FIGS. 1 and 3 . If the flowmeter is not arranged in the channel including each microreactor  101  in the microreactor system shown in  FIG. 6 , the reaction time is calculated at the step  402  by dividing a sum Vsum of volumes of the respective microreactors  101  by the overall flow rate Q of the microreactor system shown in  FIG. 6 . 
         [0057]    Moreover, since the microreactors  101  are connected to the channels in front and rear of the respective microreactors  101  by joints or the like (not shown), the microreactors  101  and the front and rear channels are made detachable and replaceable. Besides, by arranging the three-way solenoid valves  301 , the produced solution tank  302 , the needle valves  303 , and the channel sensors  304  similarly to the microreactor system shown in  FIG. 3 , the continuous production can be performed similarly to the operation flow of  FIG. 5 .