Patent Publication Number: US-8534909-B2

Title: Multiple flow path microreactor design

Description:
PRIORITY 
     This application claims priority to European Patent Application Number 08305711.7, filed Oct. 22, 2008 and European Patent Application Number 08305610.1 filed Sep. 29, 2008, titled “Multiple Flow Path Microreactor Design”. 
     BACKGROUND OF THE INVENTION 
     Microfluidic devices, as understood herein, include fluidic devices over a scale ranging from microns to a few millimeters, that is, devices with fluid channels the smallest dimension of which is in the range of microns to a few millimeters, and preferably in the range of from about 10&#39;s of microns to about 2 millimeters. Partly because of their characteristically low total process fluid volumes and characteristically high surface to volume ratios, microfluidic devices, particularly microreactors, can be useful to perform difficult, dangerous, or even otherwise impossible chemical reactions and processes in a safe, efficient, and environmentally-friendly way. Such improved chemical processing is often described as “process intensification.” 
     Process intensification is a paradigm in chemical engineering which has the potential to transform traditional chemical processing, leading to smaller, safer, and more energy-efficient and environmentally friendly processes. The principal goal of process intensification is to produce highly efficient reaction and processing systems using configurations that simultaneously significantly reduce reactor sizes and maximize mass- and heat-transfer efficiencies. Shortening the development time from laboratory to commercial production through the use of methods that permit the researcher to obtain better conversion and/or selectivity is also one of the priorities of process intensification studies. Process intensification may be particularly advantageous for the fine chemicals and pharmaceutical industries, where production amounts are often smaller than a few metric tons per year, and where lab results in an intensified process may be relatively easily scaled-out in a parallel fashion. 
     Process intensification consists of the development of novel apparatuses and techniques that, relative to those commonly used today are expected to bring very important improvements in manufacturing and processing, substantially decreasing equipment-size to production-capacity ratio, energy consumption and/or waste production, and ultimately resulting in cheaper, sustainable technologies. Or, to put this in a shorter form: any chemical engineering development that leads to a substantially smaller, cleaner, and more energy efficient technology is process intensification. 
     The methods and/or devices disclosed herein are generally useful in performing any process that involves mixing, separation, extraction, crystallization, precipitation, or otherwise processing fluids or mixtures of fluids, including multiphase mixtures of fluids—and including fluids or mixtures of fluids including multiphase mixtures of fluids that also contain solids—within a microstructure. The processing may include a physical process, a chemical reaction defined as a process that results in the interconversion of organic, inorganic, or both organic and inorganic species, a biochemical process, or any other form of processing. The following non-limiting list of reactions may be performed with the disclosed methods and/or devices: oxidation; reduction; substitution; elimination; addition; ligand exchange; metal exchange; and ion exchange. More specifically, reactions of any of the following non-limiting list may be performed with the disclosed methods and/or devices: polymerisation; alkylation; dealkylation; nitration; peroxidation; sulfoxidation; epoxidation; ammoxidation; hydrogenation; dehydrogenation; organometallic reactions; precious metal chemistry/homogeneous catalyst reactions; carbonylation; thiocarbonylation; alkoxylation; halogenation; dehydrohalogenation; dehalogenation; hydroformylation; carboxylation; decarboxylation; amination; arylation; peptide coupling; aldol condensation; cyclocondensation; dehydrocyclization; esterification; amidation; heterocyclic synthesis; dehydration; alcoholysis; hydrolysis; ammonolysis; etherification; enzymatic synthesis; ketalization; saponification; isomerisation; quaternization; formylation; phase transfer reactions; silylations; nitrile synthesis; phosphorylation; ozonolysis; azide chemistry; metathesis; hydrosilylation; coupling reactions; and enzymatic reactions. 
     The present inventors and/or their colleagues have previously developed various microfluidic devices useful in process intensification and methods for producing such devices. These previously developed devices include apparatuses of the general form shown in prior art  FIG. 1 .  FIG. 1 , not to scale, is a schematic perspective showing a general layered structure of certain type of microfluidic device. A microfluidic device  10  of the type shown generally comprises at least two volumes  12  and  14  within which is positioned or structured one or more thermal control passages not shown in detail in the figure. The volume  12  is limited in the vertical direction by horizontal walls  16  and  18 , while the volume  14  is limited in the vertical direction by horizontal walls  20  and  22 . 
     The terms “horizontal” and “vertical,” as used in this document are relative terms only and indicative of a general relative orientation only, and do not necessarily indicate perpendicularity, and are also used for convenience to refer to orientations used in the figures, which orientations are used as a matter of convention only and not intended as characteristic of the devices shown. The present invention and the embodiments thereof to be described herein may be used in any desired orientation, and horizontal and vertical walls need generally only be intersecting walls, and need not be perpendicular. 
     A reactant passage  26 , partial detail of which is shown in prior art  FIG. 2 , is positioned within the volume  24  between the two central horizontal walls  18  and  20 .  FIG. 2  shows a cross-sectional plan view of the vertical wall structures  28 , some of which define the reactant passage  26 , at a given cross-sectional level within the volume  24 . The reactant passage  26  in  FIG. 2  is shaded for easy visibility of the fluid contained therein and forms a two-dimensionally tortuous and winding passage of constant width, in the form of a serpentine, which covers a maximum area of the surface of the plate defining the volume  24 . The fluidic connections between the other parts of the microfluidic device  10  and the inlet  30  and outlet  32  of the tortuous reactant passage  26  shown in the cross section of  FIG. 1  are provided in a different plane within the volume  12  and/or  14 , vertically displaced from plane of the cross-section shown in  FIG. 2 . 
     The reactant passage  26  has a constant height in a direction perpendicular to the generally planar walls. 
     The device shown in  FIGS. 1 and 2  serves to provide a volume in which reactions can be completed while in a relatively controlled thermal environment. 
     In  FIG. 3 , another prior art device is shown for the specific purpose to mix reactants, especially multiphase systems like immiscible fluids and gas liquid mixtures, and to maintain this dispersion or mixture over a wide range of flow rates. In this device of the prior art, the reactant passage  26  comprise a succession of chambers  34 . 
     Each of such chamber  34  includes a split of the reactant passage into at least two sub-passages  36 , and a joining  38  of the split passages  36 , and a change of passage direction, in at least one of the sub-passages  36 , of at least 90 degrees relative to the immediate upstream passage direction. In the embodiment shown, it may be seen in  FIG. 3  that both sub-passages  36  change direction in excess of 90 degrees relative to the immediate upstream passage direction of the reactant passage  26 . 
     Also in the embodiment of  FIG. 3 , each of the multiple successive chambers  34 , for those having an immediately succeeding one of said chambers, further comprises a gradually narrowing exit  40  which forms a corresponding narrowed entrance  42  of the succeeding chamber. The chambers  34  also include a splitting and re-directing wall  44  oriented crossways to the immediately upstream flow direction and positioned immediately downstream of the chamber&#39;s entrance  42 . The upstream side of the splitting and re-directing wall  44  has a concave surface  46 . The narrowing exit  40  from one chamber  34  to the next is desirably on the order of about 1 mm width. The channel desirably may have a height of about 800 μm. 
     Although good performance has been obtained with devices of this type, in many cases even exceeding the state of the art for a given reaction, it has nonetheless become desirous to improve fluid dynamic performance. In particular, it is desirable to obtain a controlled and well-balanced residence time while simultaneously decreasing the pressure drop caused by the device, while increasing throughput. 
     In U.S. Pat. No. 7,241,423 (corresponding to US2002106311), “Enhancing fluid flow in a stacked plate microreactor,” parallel channels (see  FIG. 37 ) are used in order to implement an internally parallelized chemical reaction plant for the purpose of provide a microscale reaction apparatus that can provide substantially equal residence time distribution for fluid flow. However this reference does not solve all the issues related to controlled and even distribution of fluid flow. 
     SUMMARY OF THE INVENTION 
     A microfluidic device comprises at least one reactant passage ( 26 ) defined by walls and comprising at least one parallel multiple flow path configuration, said parallel multiple flow path configuration comprising a group of elementary design patterns of the flow path which are arranged in series with fluid communication so as to constitute flow paths, and in parallel so as to constitute a multiple flow path elementary design pattern in the parallel flow paths, said elementary design pattern being able to provide mixing and/or residence time, wherein the parallel multiple flow path configuration comprises at least two communicating zones between elementary design patterns of two adjacent parallel flow paths, said communicating zones being in the same plane as that defined by said elementary design patterns between which said communicating zone is placed and allowing passage of fluid (flow interconnections) in order to minimize mass flow rate difference between adjacent parallel flow paths which have the same flow direction. 
     In some cases, an equalization of the mass flow rate (and also of the fluid pressure) between the adjacent parallel flow paths of the parallel multiple flow path configuration can be achieved. 
     Moreover, this solution allows, thanks to the communicating zones, a uniformity of Residence Time in several parallel micro channels or flow paths of each parallel multiple flow path configuration. 
     Therefore, provided each flow path is of equal length, width and height to get a constant residence time and hydraulic properties, the parallel multiple flow path configuration according to the invention bring an increased of microreactor chemical production throughput. 
     Additional features and advantages of the invention will be set forth in the detailed description which follows, and in part will be readily apparent to those skilled in the art from that description or recognized by practicing the invention as described herein, including the detailed description which follows, the claims, as well as the appended drawings. 
     It is to be understood that both the foregoing general description and the following detailed description present embodiments of the invention, and are intended to provide an overview or framework for understanding the nature and character of the invention as it is claimed. The accompanying drawings are included to provide a further understanding of the invention, and are incorporated into and constitute a part of this specification. The drawings illustrate various embodiments of the invention, and together with the description serve to explain the principles and operations of the invention. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG. 1  (prior art) is a schematic perspective showing a general layered structure of certain prior art microfluidic devices; 
         FIG. 2  (prior art) is a cross-sectional plan view of vertical wall structures within the volume  24  of  FIG. 1 ; 
         FIG. 3  (prior art) is a cross-sectional plan view of vertical wall structures within the volume  24  of  FIG. 1  according to another prior art microfluidic device; 
         FIG. 4  is a cross-sectional plan view of vertical wall structures with elementary design patterns of a first type defining parallel multiple flow path configurations according to a first embodiment of the present invention; 
         FIG. 5  is a cross-sectional plan view of vertical wall structures defining parallel multiple flow path configurations according to a variant of the first embodiment of the present invention; 
         FIG. 6  is an enlarged view of detail VI of  FIG. 5 ; 
         FIG. 7  to  FIG. 9  are partial cross-sectional plan view of vertical wall structures with elementary design patterns of the first type according to some alternative of the location of the communicating zones in the parallel multiple flow path configuration; 
         FIGS. 10A-10G  are partial cross-sectional plan views of multiple vertical wall structures defining alternative elementary design patterns of the first type; 
         FIG. 11  is a cross-sectional plan view of an elementary design pattern of a second type; 
         FIG. 12  is a cross-sectional plan view of alternative vertical wall structures using the elementary design patterns of the second type of  FIG. 11  for defining portions of a parallel multiple flow path configuration according to yet another alternative embodiment of the present invention; 
         FIG. 13  is a cross-sectional plan view of vertical wall structures with elementary design patterns of the second type defining a parallel multiple flow path configuration according to a second embodiment of the present invention; 
         FIGS. 14 and 15  are cross-sectional plan views of two alternative vertical wall structures with elementary design patterns of a third type; 
         FIG. 16  are schematic representations of possible manifold structures to be placed upstream of each of the parallel multiple flow path configuration; 
         FIG. 17  and  FIG. 18  are cross-sectional plan view of vertical wall structures defining alternative structures respectively to  FIGS. 4 and 13 ; 
         FIG. 19  is a cross-sectional plan view of vertical wall structures combining parallel multiple flow path configurations shown on  FIGS. 4 and 5 ; 
         FIG. 20  is a graph of pressure drop across a microfluidic device in millibar, as a function of flow rate in milliliters per minute, comparing two embodiments of the invention to a prior art device; 
         FIG. 21  is a graph showing the correlation between flow rate and design for the same pressure drop comparing two embodiments of the invention to a prior art device (simulation done for 1 bar pressure drop). 
         FIG. 22  is a graph showing mean time decantation in seconds, comparing an embodiment of the invention to a prior art device (at T=35° C., a total quantity of 120 g/min, using a Solvent flowrate of 110 g/min, and a diol flowrate of 10 g/min); and 
         FIG. 23  shows the mass flow rate in milliliters per minute through cross-sections for the configuration of vertical wall structures of  FIG. 8 . 
     
    
    
     DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS 
     Reference will now be made in detail to the presently preferred embodiments of the invention, examples of which are illustrated in the accompanying drawings. Whenever possible, the same reference numerals will be used throughout the drawings to refer to the same or like parts. 
     Without limitation, in the microfluidic devices of the invention the reactant passage and its portion constituted by parallel multiple flow path configurations are generally extending in an horizontal plane and defined by vertical walls. The “width” refers to a direction which is perpendicular to the flow direction and parallel to said horizontal plane of the parallel multiple flow path configuration. The “height” refers to a direction which is perpendicular to the flow direction and perpendicular to said horizontal plane of the parallel multiple flow path configuration. The “length” refers to a direction which is parallel to the flow direction and parallel to said horizontal plane of the parallel multiple flow path configuration. 
     In  FIG. 4  is visible a microfluidic device having a reactant passage  26  according to a first embodiment with six parallel multiple flow path configurations  50  placed in series. Each parallel multiple flow path configuration  50  has two parallel path flows  52  formed by the succession of nine chambers  34  placed in series in adjacent manner. Each chamber  34  forms an elementary design pattern of a first type, which is similar to that of  FIG. 3 , able to provide good mixing quality and to maintain liquid immiscible or gas liquid dispersion. 
     The two parallel path flows  52  are adjacent to each other. Also the adjacent chambers  34  of the two parallel path flows  52  form pairs of chambers  34  (more generally a multiple flow path elementary design pattern  57  with a communicating zone  54  between them. This communicating zone  54  is formed by a direct fluid connection between the pairs of chambers  34  so that when the flow of fluid passes in parallel in the two parallel path flows  52 , there is a possible passage of fluid between the two parallel path flows  52  at the location of these communicating zone  54 . Therefore, there is a contact point (common portion of wall) with an aperture/opening (communicating zone  54 ) between the adjacent chambers  34  of the parallel path flows  52 . 
     This specific possible passage of fluid or flow interconnection between the parallel path flows allows correction of any potential flow misbalance which can be due, among others, to the design of the reactant passage  26  (especially the manifold design) and/or the tolerance of the manufacture process and/or plugging of a flow path. 
     The fluid flow rate can therefore be balanced between all the flow paths  52  of the parallel multiple flow path configuration  50 . 
     Moreover, having the communicating zones  54  in the same volume  24  as that of the reactant passage  26  or the chamber  34 , i.e. having the communicating zones  54  in the same plane as that of the parallel flow paths  52 , brings some meaningful advantages: such a configuration is simple to manufacture (same plate), optimizes the thermal transfer with the thermal control passages of the volumes  12  and  14  placed on both sides of the volume  24  and avoid additional pressure drop and dead zones that are detrimental for an even Residence Time distribution and safety. 
     According to the invention, the design of manifold  56  placed upstream of each parallel multiple flow path configuration  50  and the strict similarity of the chambers  34  and of the parallel fluid flows  52  are therefore less critical. 
     The two channels or flow paths  52  are adjusted in such a way that they are regularly in contact at their edges with an opening (communicating zone  54 ) between them being adjusted to allow a modification of flow repartition in case of different pressure drop between parallel fluid flows  52  (manufacturing tolerances or plugging for example), and small enough not to modify significantly the flow pattern at the said contact points. 
     The successive chambers  34  make up a significant portion of the reactant passage  26  of the embodiment of a microfluidic device represented in  FIG. 4 . The chambers  34  desirably have a constant height H, shown in  FIG. 1 , in a direction generally perpendicular to the walls  18  and  20 , which height H generally corresponds to the distance between the walls  18  and  20 . In other words, the portion of passage  26  having the chambers  34  generally occupies the maximum space possible in the direction of height H, matching the maximum dimension of the volume  24  in the direction of H. This is significant because (1) the volume of a given lateral size microfluidic device is thus maximized, allowing longer residence times at higher throughput rates and (2) the amount of material and distance between reactant passage  26  and the volumes  12  and  14  in which one or more thermal control fluid passages are contained is minimized, allowing for greater heat transfer. Further, although the height H may desirably be on the order of 800 μm to in excess of a few millimeters, the thickness of boundary layers in the direction of H are generally reduced by secondary flows induced within the reactant passage by passing of the reactant fluid through the directional changes caused by the splitting and re-directing walls  44 , and by repeated passage though gradually narrowing exits  40  into the wider space of the successive chambers  34 . 
     For devices in which heat exchange and residence time is to be maximized, it is desirable that the multiple successive chambers  34  extend along at least 30%, preferably at least 50% of the total volume of the reactant passage  26 , more desirably at least 75% or more, as is the case in the embodiment of  FIG. 4 . 
     As may also be seen in the embodiment of the present invention in  FIG. 4 , the successive chambers  34  desirably share common walls with the next chambers in the up- and down-stream directions. This helps assure that the maximum number of chambers  34  is positioned within a given space, and thus also maximizes the volume of the reactant passage  26  as a fraction of total volume available between the walls  18 ,  20 . In particular, it is desirable that the reactant passage  26  has an open volume of at least 30% of the total volume consisting of (1) said open volume (2) the volume of the wall structures  28  that define and shape the reactant passage between the horizontal walls  18 ,  20 , and (3) any other volume such as empty volume  48  between the wall structures  28  that define and shape the reactant passage  26 . More desirably, the reactant passage has open volume of at least 40%. 
     In the variant of  FIG. 5  the reactant passage  26  has four parallel multiple flow path configurations  50  placed in series between the inlet  30  and the outlet  32 . Each parallel multiple flow path configuration  50  has four parallel and adjacent path flows  52  each formed by the succession of eighteen chambers  34  placed in series in adjacent manner. 
     In this configuration, the four adjacent chambers  34  in fluid communication with each other, each of which is part of a different path flows  52 , form together a multiple flow path elementary design pattern  57  in which the fluid flows at a same level in the four parallel path flows  52 . 
     As may be seen in the enlarged partial view of  FIG. 6 , communicating zones  54  are formed between all the pairs of two adjacent elementary design patterns or chambers  34  of all of said multiple flow path elementary design patterns  57  of the four parallel multiple flow path configurations  50 . 
     The key advantage of multiple flow paths approach according to this invention is to reduce significantly pressure drop for a given flow rate. As an example, for an elementary design pattern formed by chambers  34  as shown on  FIGS. 4 to 6 , dual flow (two channels in parallel as shown on  FIG. 4 ) allows dividing pressure drop by a factor 2.7 at 200 ml/min as compared to a pattern with only one channel ( FIG. 3 ). Then the use of four parallel flows as shown on  FIGS. 5 and 6  still provides a further pressure drop reduction by a factor 2.5 as compared to a pattern with two channels, leading to a reduction by a factor 6.8 as compared to a single channel (see  FIG. 20 ). 
     Another way to highlight a key benefit of this multiple flow path approach is to look at maximum working flow rate corresponding to the same pressure drop. The data of  FIG. 21  shows that the maximum possible flow rate corresponding to 1 bar pressure drop is respectively 120 ml/min for a pattern with only one channel ( FIG. 3 ), 200 ml/min for a pattern with two channels in parallel as shown on  FIG. 4  and 350 ml/min for a pattern with four channels in parallel as shown on  FIGS. 5 and 6 . 
     Therefore, multiple flow paths architecture according to this invention allowing a significant pressure drop reduction, it is an efficient way to increase chemical production throughput without increasing energy consumption to pump the fluids, and to keep pressure drop below typical design pressure of equipments and/or the complexity of the system through external numbering up. 
     Moreover, another key advantage of this high throughput design approach is to significantly reduce pressure drop (at a given flowrate) without any negative impact on pressure resistance and mixing/dispersions quality. So no compromise is needed, especially regarding: 
     Pressure resistance: a parallel multiple flow path configuration  50  is formed by implementing in parallel channels formed by a series of elementary design patterns (for instance chamber  34  with a heart shape of  FIGS. 3 to 5 ). Putting in parallel elementary design patterns able to withstand a given pressure rupture doesn&#39;t reduce total pressure rupture, so pressure resistance is conserved. 
     Dispersions (or mixing) quality: as the base elementary design pattern is conserved, the efficiency of mixing is comparable to the prior art single channel designs. In case of emulsions, the quality of emulsion has been assessed using solvent &amp; diol non-miscible liquid system. The emulsion is created in the microstructures and the fluid flowing out of the microstructure collected. Time needed for decantation was taken as a measure of the quality of the emulsion formed inside the microstructure (the higher the time, the better the quality). As reported in  FIG. 22 , the design with two channels in parallel according to the invention as shown on  FIG. 4  gives a result (at the left side of  FIG. 22 ) as good as a pattern with a single flow path according to the prior art as shown on  FIG. 3  (at the right side of  FIG. 22 ). In this test, the design with a single flow path has a lower internal channel height (1 mm) than the design with dual flow path (1.1 mm). And the lower the channel height is, the better suspension quality is. 
     As shown on  FIG. 7  for a parallel multiple flow path configuration  50  with two flow paths  52 , the communicating zones  54  between parallel adjacent chambers  54  can have different distribution or physical arrangement: 
       FIG. 7   a  is a configuration in which said communicating zones  54  are formed between all the pairs of two adjacent elementary design patterns (chambers  34 ) of all of said multiple flow path elementary design patterns  57  of said parallel multiple flow path configuration  50 , 
       FIG. 7   b  shows an alternative in which said communicating zones  54  are formed only between the pairs of two adjacent elementary design patterns (chambers  34 ) of the first two multiple flow path elementary design patterns  57  located in the upstream part of said parallel multiple flow path configuration  50 , and 
       FIG. 7   c  shows another alternative in which said communicating zones  54  are formed only between every other pair of two adjacent elementary design patterns (chambers  34 ) of all of said multiple flow path elementary design patterns  57  of said parallel multiple flow path configuration  50 . 
       FIGS. 8 and 9  partially show a parallel multiple flow path configuration  50  with four parallel fluid paths  52 : 
     on  FIG. 8  the communicating zones  54  are formed between all the pairs of two adjacent elementary design patterns (chambers  34 ) of all of said multiple flow path elementary design patterns  57  of said parallel multiple flow path configuration  50 , and 
       FIG. 9  shows another alternative in which said communicating zones  54  are formed only between some pairs of two adjacent elementary design patterns (chambers  34 ): more precisely the communicating zones  54  forming flow interconnections are located in a staggered configuration. 
     Referring to  FIG. 23 , is shown a simulation of the mass flow rate in milliliters per minute through cross-sections of the flow paths of a parallel multiple flow path configuration  50  with four parallel flow paths ( FIG. 8 ) having communicating zones  54  between all the pairs of two adjacent elementary design patterns (chambers  34 ). More precisely the mass flow rate is expressed at the outlet portion of each chamber  34  of the first four levels of the parallel multiple flow path configuration  50 , these locations having a reference number fxy, where x is the position of the level along the flow paths  52  and y the lateral position. The simulation shown on  FIG. 23  is putting into evidence efficiency of flow interconnection for four parallel flow paths: flow misbalance existing at the entrance (cross-sections f 11 , f 12 , f 13  and f 14  of the first level) almost completely disappears after four flow interconnections (cross-sections f 41 , f 42 , f 43  and f 44  of the fourth level have very close flow rates). 
       FIGS. 10A-10G  are cross-sectional plan views of multiple alternative wall structures defining portions of reaction passages according to some alternative embodiments of the present invention, in particular, defining alternative forms of the successive chambers  34 . The chambers shown in the embodiments above generally correspond to those of  FIG. 10F , wherein a post  58  may potentially serve to increase the pressure resistance of the chamber  34  relative to a chamber  34  having a larger open area or “free span” as in the embodiment of  FIG. 10A . On the other hand, embodiments without the post  58  may have less tendency toward having a small dead volume (a slow moving spot in the fluid flow pattern) upstream of the post  58 . The embodiment of  FIG. 10G  essentially avoids all risk of dead volume by including a triangular backing structure  60  on the downstream side of the splitting and re-directing wall  44 , being therefore particularly recommended for handling solids such as solid suspensions or precipitating reactions, which can tend to collect in areas of dead volume to clog a reactant passage. 
     In the embodiment of  FIG. 10B , the splitting and re-directing wall  44  is segmented in four segments, thus dividing the reactant passage into two main sub-passages around the splitting and re-directing wall  44  and three secondary sub-passages between the segments of the wall  44 . The small size of the secondary sub-passages can help to maintain fine emulsions. 
     In the embodiment of  FIG. 10C , the splitting and re-directing wall  44  is asymmetrical, being offset to alternating sides in successive chambers  34  so as to provide especially strong secondary flows. The post  58  is also offset from the center of the chamber  34  in alternating fashion, and by being positioned in the larger of the two sub-passages formed by the wall  44 , the post  58  serves as an additional flow divider. 
     The embodiments of  FIGS. 10D and 10E  correspond to those of  10 F and  10 B, respectively, with the following difference: the gradually narrowing exit  40  of the previously discussed embodiments is replaced by a wider exit  62  filled with small secondary flow dividers  64  positioned to as to finely divide the incoming flow to the chamber  34 , thereby assisting to create and maintain an emulsion or other immiscible mixture. 
     Referring to  FIGS. 11 to 13 , an elementary design pattern of a second type is proposed in the form of an open cell/space  134  with several pillars  166  placed in staggered configuration (five pillars  166  on  FIGS. 11 and 12 ). The pillars  166  have the height of the reactant passage  26  and are elongated and parallel to the fluid flow direction (arrows on  FIGS. 11 and 12 ). 
     The pillars  166  are structures serving as turbulence promoter or static mixer along the fluid flow path  152 . In this context, the pillars could present other designs, including designs which have portions which are not parallel to the fluid flow direction in order to promote turbulence. 
     The open cells  134  are placed in series to form a flow path  152  and in parallel to form a multiple flow path elementary design pattern  157  which is limited by lateral vertical wall structures  28 . 
     The two (or more) open cells  134  placed in parallel to form a multiple flow path elementary design pattern  157  can be aligned in the lateral direction ( FIG. 13 ) or shifted in upstream or downstream direction with respect to the fluid flow direction ( FIG. 12 ). 
     The flow path elementary design patterns  134  are placed in series to form a parallel multiple flow path configuration  150  which is a continuous straight channel or a tortuous channel with important straight portions ( FIG. 13 ). 
     The pillars  166  are arranged such that in all transverse sections (all widths) of the parallel multiple flow path configuration  150 , there is at least one pillar  166  ( FIGS. 12 and 13 ). 
     The communicating zones  154  between two adjacent elementary design patterns or open cells  134  are openings or passages defined between at least two pillars  166  of each of these two adjacent elementary design patterns or open cells  134 , notably two pillars  166  in alignment. 
     In the alternative staggered configuration of the pillars of  FIG. 13 , which shows a second embodiment of the present invention, each cross-section of the open cell  134 , which is perpendicular to the fluid flow direction, contains at least one portion of pillar(s). The parallel multiple flow path configuration  150  of  FIG. 13  forms an enlarged multiple fluid flow path disposed downstream a manifold  156  having a very simple configuration. 
     With these elementary design pattern of the second type in the form of an open cell  134  with pillars  166 , sub passages of the flow path  152  are defined by the pillars  166 , between the pillars  166  which are offset in the lateral direction, i.e. which are not in alignment along the flow path  152 . 
     The elementary design pattern of the second type  134  is particularly dedicated for homogenous fluid residence time. 
     In  FIGS. 12 and 13 , there are two flow paths  152  in parallel, each multiple flow path elementary design pattern  157  having two design patterns of the second type or open cells  134  placed in parallel, but more than two open cells  134  could be placed in parallel between the lateral vertical wall structures  28 . 
       FIGS. 14 and 15  show another possible form for the elementary design pattern: this is an elementary design pattern of the third type or wavy chamber  234 . This wavy chamber  234  defines a flow path portion and has a width which is progressively enlarged and then progressively reduced in the flow direction, before the reduced width forming the entrance of the following downstream wavy chamber  234  having the same design. 
     The variation of width allow for a better pressure resistance of the wall structures. Moreover, such a configuration allow a contact between two parallel elementary design patterns at the location of their larger width, which is a simple way to create a communicating zone only by creating an opening in this location of contact with a common wall. 
     The wavy chambers  234  are placed in series to form a flow path  252  and in parallel to form a multiple flow path elementary design pattern  257 . The flow path elementary design patterns  257  are placed in series to form a parallel multiple flow path configuration  250 . 
     In  FIG. 14 , the communicating zones  254  between two adjacent elementary design patterns or wavy chambers  234  are fowled by an opening between two adjacent wavy chambers  234  which are in contact along by their enlarged width. 
     In the alternative form of  FIG. 15 , the wavy chambers  234  are staggered in the flow direction between two adjacent parallel flow paths  252  so that a single wavy wall  228  serves to delimit two adjacent parallel flow paths  252 . In other words, two adjacent parallel flow paths  252  are bordered by the two opposite face of the same single wavy wall  228  which optimises the space occupied by the reactant passage in the volume  24 . 
     In that case, the communicating zones  254  between two adjacent elementary design patterns or wavy chambers  234  are formed by an opening in the single wavy wall  228 . 
     As shown on  FIG. 15 , the elementary design pattern of the third type or wavy chamber  234  can contain a splitting and re-directing wall  244 . 
     The two (or more) wavy chambers  234  placed in parallel to form a multiple flow path elementary design pattern  257  can be aligned in the lateral direction ( FIG. 14 ) or shifted in upstream or downstream direction with respect to the fluid flow direction ( FIG. 15 ). 
       FIG. 14  shows the implementation of two parallel flow paths  252  and  FIG. 15  shows the implementation of eight parallel flow paths  252  but any other number of parallel flow paths can be implemented in each parallel multiple flow path configuration  250 . 
     As previously indicated, elementary design pattern of the first type or chamber  34 , elementary design pattern of the second type or open cell  134  and elementary design pattern of the third type or wavy chamber cell  234  provide mixing and/or residence time, have a width which is not constant along the direction of the flow path and can be in flow interconnection with another elementary design pattern of the same type of the adjacent flow path. 
     Other elementary design patterns able to provide mixing and/or residence time can be used according to the parallel multiple flow path configuration described above, i.e notably with elementary design patterns which are adjacent to each other both in series and in parallel. 
     Preferably, the communicating zones are formed by a direct flow interconnection between two adjacent elementary design patterns of said multiple flow path elementary design pattern. 
     For each parallel multiple flow path configuration a manifold  56 ,  156 ,  256  is placed along said reactant passage upstream said parallel multiple flow path configuration in order to divide or fork said reactant passage  26  into so many flow paths as there are in the parallel multiple flow path configuration. 
     Due to flow interconnection between adjacent parallel flow paths, which allow for correction of flow misbalance between the parallel flow paths, the manifolds design can be simple and need to take into account fluids physical properties with limited accuracy.  FIG. 16  show three possible simple designs for manifolds  56 ,  156 ,  256 . 
     These simple manifold designs are non chemical reaction dependant designs, with potentially some flow interconnection as well into manifold zone ( FIG. 16C ). Therefore these simple manifold designs do not require an important surface to accommodate different flow misbalance and to create uniform parallel flows. 
       FIG. 17  (respectively  FIG. 18 ) is similar to  FIG. 4  (respectively  FIG. 13 ) with the addition of a mixing portion  68  placed along the reactant passage  26 , upstream of any multiple flow path configuration  50 . This mixing portion  68  comprises a series of chamber  34 . 
       FIG. 19  shows another possible design for the reactant passage  26  in which there are several parallel multiple flow path configuration  50  placed in series which do not have the same number of parallel flow paths  52 : in this example some parallel multiple flow path configurations  50  have two parallel flow paths  52  and parallel multiple flow path configurations  50  have four parallel flow paths  52 . 
     Other design are possible according to the invention, notably having other numbers of parallel flow paths in one parallel multiple flow path configuration: for instance three, five, six, eight parallel flow paths. 
     Preferably, said communicating zones  54 ,  154  and  254  have a length ranging from 0.5 to 6 mm, preferably from 1 to 5 mm and preferably from 1.5 to 3.5 mm. 
     Preferably, the height of the volume  24  and of the reactant passage  26 , which is also the height of the elementary design patterns  34 ,  134 ,  234  and of the communicating zones  54 ,  154  and  254 , ranges from 0.8 mm to 3 mm. 
     Preferably, said communicating zones  54 ,  154  and  254  have a ratio height/length ranging from 0.1 to 6, and preferably from 0.2 to 2. 
     Preferably, the width of said elementary design patterns along the flow path is ranging from 1 to 20 mm, and preferably from 3 to 15 mm. 
     Preferably, the ratio between the width of said elementary design patterns along the flow path, at the location of the communicating zone  54 ,  154 ,  254 , and the length of said communicating zones is ranging from 2 to 40, and preferably from 2 to 14. 
     According to the invention, when considering two adjacent parallel flow paths  52 ,  152 ,  252 , there are at least two communicating zones  54 ,  154 ,  254  located somewhere between the inlet and the outlet of the parallel multiple flow path configuration  50 ,  150 ,  250 . 
     Depending on elementary design patterns along the flow path, number of parallel paths, global implementation into available surface and manifold design, different numbers of communicating zones  54 ,  154 ,  254  may be needed to get fully uniform flow distribution. But most of the correction is usually done within the first two communicating zones  54 ,  154 ,  254 . 
     The microfluidic devices according to the present invention are desirably made from one or more of glass, glass-ceramic, and ceramic. Processes for preparing such devices from glass sheets forming horizontal walls, with molded and consolidated frit positioned between the sheets forming vertical walls, are disclosed, for example, in U.S. Pat. No. 7,007,709, “Microfluidic Device and Manufacture Thereof,” but fabrication is not limited to this method. 
     The devices of the present invention may also include layers additional to those shown, if desired. 
     “Reactant” as used herein is shorthand for potentially any substance desirable to use within a microfluidic device. Thus “reactant” and “reactant passage” may refer to inert materials and passages used for such.