Patent Publication Number: US-2015064071-A1

Title: Disposable Module For Device For Synthesizing Radioisotopes And Process For Manufacturing Said Module

Description:
TECHNICAL FIELD 
     The present invention relates to a disposable module for a device for synthesizing radioisotopes and to a method for manufacturing said module. 
     DESCRIPTION OF THE STATE OF THE ART 
     Positron emission tomography is a medical imaging technique giving the possibility of viewing the metabolic activity of an organ subsequent to injection of a radioactive tracer, the biological properties of which are known in this organ. One of the most used tracers in nuclear medicine is 18F-fluoro-deoxy-D-glucose abbreviated as [18F]-FDG. This tracer similar to glucose will accumulate in tissues which consume large amounts of sugar like cancer cells, the heart or the brain. The synthesis of [18-F]-FDG is described in the document of Hamacher et al. J. Nucl. Med. 27, 235-238 (1986). 
     Several automated devices for synthesizing radioactive tracers have been developed. Such a synthesis device is advantageously positioned in a shielding cell. 
     A device marketed by the applicant under the name of Synthera® is described in document U.S. Pat. No. 7,235,216. This device comprises a fixed module and a disposable module which is positioned on the fixed module. 
     The fixed module comprises a processor and an interface for the disposable module. The interface of the fixed module is provided with rotary actuators and fluidic connectors leaving the interface and comprises a structure for positioning in an ejectable way a disposable module on said interface so that the rotary actuators and the fluidic connectors may be inserted into the disposable module. 
     The disposable module comprises:
         an interface capable of positioning itself against the interface of the fixed module;   two-way and three-way valves which may be actuated by said actuators of the fixed module;   fluidic connectors capable of being connected with the fluidic connectors of the fixed module;   a plate supporting flasks of reagents and a reactor, each of the flasks being connected to a valve through a flexible pipe and several valves being connected to said reactor through a flexible pipe.       

     The processor of the fixed module controls the fluid flow rates as well as the opening and the closing of the valves so as to carry out the different steps for the synthesis reaction of the radiopharmaceutical tracer. Once the radiopharmaceutical product is obtained, the latter is transferred into a container by passing through purification cartridges. 
     Advantageously, the Synthera® is positioned in a shielding cell comprising a container provided with a hatch located at the front of the fixed module and under the disposable module, so as to be able to collect the disposable module when the latter is ejected at the end of the synthesis. 
     The Synthera® is relatively compact, and several Synthera® devices may be inserted into a same shielding cell. The Synthera® has the advantage of not requiring any human intervention for removing the disposable module once the synthesis of the radiopharmaceutical tracer has completed. Nevertheless, the disposable module of such a device requires a particular assembly of flexible tubes. These flexible tubes are assembled manually on the plate and the customer has to check that each of the tubes is properly attached. Human errors during the positioning of the tubes are always possible. 
     Further, the area of the supporting plate is relatively compact (14×5 cm) and comprises locations reserved for flasks of reagents as well as for purification cartridges, leaving not very much room for the positioning of the fluidic connection means for the tubes. Certain tubes may have ends close to each other and may be subject to certain tensile stresses which may cause dislodging of the tube. Certain tubes may also bend upon assembling and cause poor flow of the liquid. 
     The flasks of reagents are sealed by a septum in rubber and maintained on the supporting plate by attachment means. The supporting plate comprises a movable support on which are positioned metal needles connected to the flexible tubes, each of the needles being positioned under a flask of reagents. Before the synthesis, the movable support is actuated so as to insert the needles into the septum of the flasks of reagents. In order to allow proper insertion of the needles into the flasks, the septa of the flasks have reduced thickness, which may sometimes cause an evaporation of certain volatile solvents. Also, when the movable support is actuated, it happens that flasks are dislodged from their attachment means. Microfluidic devices for the synthesis of radiopharmaceutical products were designed for the purpose of producing very small amounts of radiopharmaceutical products, for applications in scientific research. These devices allow the handling of microliters of solutions concentrated with reagents for productions of radiopharmaceutical products, the activity of which does not exceed 100 mCi. Such a device is described in document WO2007041486. This device is intended to produce small doses of radiopharmaceutical products and comprises a plate of 20×20×4 mm, 25×25×5 mm, 7×7×3 mm or 30×30×6 mm into which are integrated:
         a network of microfluidic channels, i.e. a network of channels with a cross-section of at least less than 1 mm and;   a cylindrical reactor, for which the ratio of the diameter over the height is greater than 3, the height being comprised between 25 and 1,000 μm, the diameter being comprised between 1 and 20 mm.       

     This device comprises valves positioned in proximity to the inlets and outlets of the reactor. For producing 18FDG, the reactor is heated to temperatures ranging from 60 to 75°. Overpressures may occur in the reactor during the reaction, due to the small volume of the reactor and to the requirement of closing all the valves for maintaining the liquid in the reactor, which may cause leaks at one or several valves of the reactor. In order to avoid losses of liquids, additional valves or double valves have to be used, which complicates the making of the device. 
     On the other hand, the reactor is included in the plate; its height is of the order of the diameter of the microfluidic channels and is located in a same plane with the microfluidic channels. The inlets and outlets of the reactor are located on the cylindrical portion of the reactor. The arrangement of the reactor and of the microfluidic channels in the plate as well as the dimensions of the reactor, do not allow good homogenization of the reaction mixture. Several solutions to this problem are proposed in document WO2007041486, nevertheless, the latter complicate the making of the plate. Therefore there is a need for designing a disposable module not having the drawbacks of the aforementioned devices. 
     Advantageously, such a disposable module has to be able to be inserted on existing fixed modules. 
     It is also necessary to produce a method for manufacturing disposable modules which is faster and more reliable. 
     SUMMARY OF THE INVENTION 
     The present invention relates to a disposable module for use in a device for the synthesis of radiopharmaceutical products starting with chemical reagents according to any of the appended claims. In particular, this is a disposable module comprising:
         a supporting plate comprising rigid means for connecting to at least one flask of chemical reagents in solution in a solvent, and a reactor;   interface means with a fixed module of said synthesis device, in contact with or integrated into said supporting plate, said interface means comprising at least one valve and/or at least one fluid inlet and/or at least one outlet for fluids;   at least one conduit connected to said at least one valve or to said at least one fluid inlet or to said at least one outlet of fluids,
 
characterized in that at least one of said conduits is integrated into the body of the disposable module.
       

     In a preferred embodiment of the module, the interface means appear as (i.e. consist in): an interface plate comprising said at least one valve, said at least one fluid inlet and said at least one outlet of fluids and in contact with said supporting plate, characterized in that at least one of said conduits is integrated into said supporting plate and/or into said interface plate. 
     Preferably, the totality of said conduits are integrated into the body of the disposable module, or—in the case of the shape according to the previous paragraph—into said supporting plate and/or into said interface plate. 
     According to an embodiment, the connection between the supporting plate and the interface plate is achieved by side wings secured with the supporting plate, and attached to the interface plate by clips. 
     The integration of conduits into the supporting plate and/or into the interface plate in particular gives the possibility of avoiding the use of flexible tubes for connecting the flasks, the reactor, the fluid inlets and the fluid outlets with the valves, which considerably reduces the risks of confusion, errors during the mounting of the module, the risk of leaks and of disconnecting the tubes. 
     Advantageously, said rigid connecting means appear in the form of at least one needle molded with a supporting plate, the flasks to be connected being closed by means of a septum. 
     According to preferred embodiments of the invention, the disposable module includes at least one, or any suitable combination of the following features:
         the rigid connecting means are molded with said supporting plate, or said supporting plate is overmolded on at least one metal needle;   the disposable module comprises said at least one flask of chemical reagents in solution in a solvent;   the disposable module comprises:
           conduits arranged so as to allow transfer of said chemical reagents towards said reactor;   a conduit arranged so as to allow the introduction of a gas flow into said reactor;   a conduit arranged so as to apply vacuum in the reactor;   a conduit arranged for allowing the discharge of the product obtained in said reactor;   
           said supporting plate comprises attachment means for said at least one flask;   said reactor is in a chemically inert plastic material in the presence of solutions encountered in the synthesis of radiopharmaceutical products and thermoresistant to temperatures above 150° C., preferably said plastic material is an ethylene-norbornene copolymer, the glassy transition temperature is above 150° C.       

     Another aspect of the invention relates to a method for manufacturing a disposable module for use in a device for the synthesis of radiopharmaceutical products, said method comprising a step for assembling (adhesively bonding) a film, a sheet or a plate onto a substantially planar disposable module plate and provided with grooves, so as to hermetically cover said grooves so as to form conduits or conduit portions able to transfer chemical reagents, gases or products. 
     Advantageously, the method of the invention comprises the following steps:
         i) adhesively bonding a film, a sheet or a plate on a supporting plate comprising:
           a first face provided with grooves and with first fluidic connection means connected to said grooves;   a face perpendicular to said first face, said perpendicular face comprising second fluidic connection means in communication with said grooves,   
            so as to hermetically cover said grooves;   ii) adhesively bonding a film, a sheet or a plate on an interface plate comprising:
           a face provided with grooves and;   fluidic connection means positioned so as to be able to connect to said second fluidic connection means of said supporting plate;   
            so as to cover said grooves of said interface plate;   iii) hermetically assembling said supporting plate with said interface plate, so as to connect said fluidic connection means of said interface plate with said second fluidic connection means of said supporting plate.       

     Preferably, said hermetically assembling step is carried out by inserting a gasket between said supporting plate and said interface plate. 
     According to another preferred embodiment of the invention, the method comprises the following steps:
         i) embossing a first plate comprising:
           a first face provided with grooves and first fluidic connection means connected to said grooves;   a face perpendicular to said first face, said perpendicular face comprising second fluidic connection means in communication with said grooves,   
           and a second plate comprising:
           a first face provided with grooves and with first fluidic connection means connected to said grooves;   a face perpendicular to said first face, said perpendicular face comprising second fluidic connection means in communication with said grooves,   
            so as to form a supporting plate, said first face of said first plate being put into contact with said first face of said second plate, said grooves of said first plate and of said second plate being positioned so as not to come into contact with each other;   ii) adhesively bonding a film, a sheet or a plate on an interface plate comprising:
           a face provided with grooves and;   fluidic connection means positioned so as to be able to be connected to said second fluidic connection means of said supporting plate;   
            so as to cover said grooves of said interface plate;   iii) hermetically assembling said supporting plate with said interface plate, so as to connect said fluidic connection means of said interface plate with said second fluidic connection means of said supporting plate. Advantageously, said supporting plate and said interface plate are in ethylene-norbornene copolymer, the glassy transition temperature of which is above 150° C. and in that said films, sheets or plates covering said grooves are in polypropylene.       

     A third aspect of the invention relates to a device for the synthesis of radiopharmaceutical products characterized in that it comprises a disposable module according to the invention. Advantageously, the disposable module of the invention is made by means of the method of the invention. 
    
    
     
       SHORT DESCRIPTION OF THE DRAWINGS 
         FIG. 1  shows a view of the disposable module according to the present invention; 
         FIG. 2  shows a view of the upper portion of the disposable module according to the present invention; 
         FIG. 3  shows a view of the low portion of the disposable module according to the present invention; 
         FIG. 4  shows a view of the rear of the interface plate of the disposable module according to the present invention. 
         FIG. 5  shows a view of a synthesis device comprising the disposable module according to the present invention 
         FIG. 6  shows a view of the upper portion of the disposable module according to a second embodiment of the invention. 
         FIG. 7  shows a view of a supporting plate and of an interface plate of a disposable module according to a third embodiment of the present invention. 
         FIG. 8  shows a diagram of a first embodiment of a method for manufacturing a disposable module according to the present invention. 
         FIG. 9  shows a diagram of a second embodiment of a method for manufacturing a disposable module according to the present invention. 
         FIG. 10  shows a global view of a disposable module according to the present invention. 
         FIG. 11  shows the portions of the supporting plate of the module shown in  FIG. 10 . 
         FIG. 12  shows another view of the supporting plate of the module shown in  FIG. 10 . 
         FIG. 13  shows the portions of the interface plate of the module shown in  FIG. 10 . 
     
    
    
     The figures are not drawn to scale. 
     DETAILED DESCRIPTION OF THE INVENTION 
     The present invention was described in terms of specific embodiments which are illustrative of the invention and which should not be interpreted in a limiting way. More generally, one skilled in the art will appreciate that the present invention is not limited by what has been particularly illustrated and/or described below. 
     The use of the verbs &lt;&lt;comprise&gt;&gt;, &lt;&lt;include&gt;&gt;, &lt;&lt;consist of&gt;&gt;, &lt;&lt;be provided with&gt;&gt;, or any other alternative, as well as their respective conjugations, does not exclude the presence of elements other than those indicated. 
     The use of the article &lt;&lt;one&gt;&gt;, &lt;&lt;the&gt;&gt; preceding an element does not exclude the presence of a plurality of such elements. 
     According to a first aspect, the present invention relates to a disposable module  100  for a macrofluidic device for automated synthesis of a radioactive tracer. 
     Preferably, the disposable module comprises:
         at least one flask of chemical reagents  102 ,  103 ,  104 ,  105  in solution in a solvent;   a reactor  106 ;   fluid transfer means comprising a conduit and a valve for opening or closing said conduit and;   a supporting plate  101  supporting said reactor  106  and said at least one flask.       

     A macrofluidic device for synthesis is defined as a synthesis device for which at least the reactor may contain volumes of liquids greater than 1 ml. Preferably, the flasks of reagents are also able to contain volumes of liquids of more than 1 ml. Still more preferably, the section of the conduits is greater than 1 mm in diameter. 
     The disposable module  100  is characterized in that at least one conduit is integrated into the body of the disposable module  100 . Preferably, the whole of all the conduits is integrated into the body of the disposable module. 
     The use of flexible pipes as fluid transfer means is thus suppressed. 
     Preferably, the body of said disposable module  100  is formed with said supporting plate  101  and with a second interface plate  115  perpendicular to said supporting plate  101 . 
     Preferably, said supporting plate  101  is attached against the interface plate  115  by an attachment means. 
     Preferably, a sealing gasket is comprised between said supporting plate and said interface plate  115 . 
     Preferably, the disposable module  100  comprises:
         a first fluid transfer means being arranged so as to allow transfer of said chemical reagents from said flask to said reactor;   a second fluid transfer means being arranged so as to allow the introduction of a gas flow into said reactor and;   a third fluid transfer means being arranged so as to allow the discharge of the product obtained in said reactor.       

     Preferably, said supporting plate  101  comprises attachment means  107  for said at least one so-called flask. 
     Preferably, said supporting plate  101  comprises fluidic connection means  114  for the flasks of reagents and fluidic connection means  114 ′ for the reactor. 
     Preferably, said at least one flask of reagents is sealed with a rubber septum and said fluid transfer means comprise a pointed fluidic connection means  114  able to pierce through said septum, said fluidic connection means being in a molded plastic material with said supporting plate. The flasks may thus be attached by hand with the required pressure, which gives the possibility of sealing the flasks with thicker septa and avoiding possible evaporations of liquid. With this configuration, the problems of dislodgement of the flasks from their attachment means are also avoided. 
     Preferably, the supporting plate  101  comprises a tube  108  immersed in said reactor, said plunger tube  108  being connected to said third fluid transfer means in order to discharge the product of the reaction. 
     Preferably, the plunger tube is molded against the wall of the reactor. 
     Preferably, a portion of said disposable module  100  is made in polypropylene of medical grade (for example marketed under the name of . . . ) and another portion of said disposable module is made in an ethylene-norbornene copolymer marketed under the name of Topas®. These materials are approved by the FDA (Food and Drug Administration) for producing devices for production of radiopharmaceuticals. 
     According to a first embodiment of the invention, said reactor  106  is attached on the supporting plate by an attachment means. According to a second embodiment of the invention, the reactor is welded against the body of the supporting plate  101 . According to a third embodiment of the invention, a first portion of the reactor is molded with the supporting plate  101  and a second portion of the reactor is welded against the first portion of the reactor. The reactor  106  is preferably made of a plastic material transparent to visible light and chemically inert in the presence of the solutions encountered in the synthesis of radiopharmaceutical products such as for example solutions comprising acetonitrile, acids or bases, and thermoresistant to temperatures above 150° C. 
     Preferably, the reactor is in ethylene-norbornene copolymer, the glassy transition temperature of which is above 150° C. Such copolymers are marketed by TOPAS Advanced Polymers GmbH, under the names of series 6015 and 6017 having a glassy transition temperature of 160° C. and 178° C. respectively, the glassy transition temperature of the ethylene-norbornene copolymer being proportional to the norbornene level in the copolymer. This material has the advantage of not including any silicon or other metals such as aluminium or boron, which in the state of trace amounts may have an influence on the yield of the nucleophilic substitution reaction as this is described in document WO2011084763. 
     Preferably, the interface plate  115  of the disposable module  100  comprises an interface  113  ( FIG. 4 ) for connecting to a fixed module  200  of a synthesis device  300  for radiopharmaceutical products such as for example the fixed module of a Synthera® marketed by the applicant and described in more detail in document U.S. Pat. No. 7,235,216 incorporated by reference. Preferably, said interface  113  comprises inlets and outlets for fluids. 
     First Exemplary Embodiment of the Invention 
       FIGS. 1 to 5  relate to a non-limiting example of a disposable module intended for the synthesis of  18 F-fluorodeoxyglucose (18[F]-FDG). The synthesis of 18[F]-FDG is not a limitation of the use of the disposable module, other radiopharmaceutical tracers may be synthesized by adapting the disposable module, for example by changing the arrangement of the transfer means, the number and the contents of the flasks of chemical reagents. 
     According to a particular embodiment of the present invention, the body of the disposable module  100  comprises a supporting plate  101  and a second interface plate  115  substantially perpendicular to said supporting plate  101 , as illustrated in  FIGS. 1 to 3 . The supporting plate  101  comprises a first face  109 , illustrated in  FIGS. 1 and 2 , comprising:
         a first flask of reagent  102  comprising an acetonitrile solution of 4,7,13,16,21,24-hexaoxa-1,10-diazabicyclo[8.8.8]hexacosane more known under the name of Kryptofix 2.2.2.;   a second flask of reagents  103  comprising a solution in acetonitrile of β-D-mannopyranose 1,3,4,6-tetra-O-acetate 2-O-trifluoromethanesulfonate, 1,3,4,6-tetra-O-acetyl-2-O-trifluoromethanesulfonyl-β-D-manno-pyranose, more known under the name of mannose triflate;   a third flask of reagents  105  comprising NaOH in solution in water;   a fourth flask  104  containing water.       

     The flasks  102 ,  103 ,  104  and  105  are preferably sealed with a rubber septum. The first face  109  also comprises fluidic connection means  114 , for example needles capable of piercing the septum of said flasks. The first face  109  also comprises first inlet  110  and outlet  110 ′ fluidic connection means for an F-18 extraction cartridge containing an anion exchanger resin, preferably a QMA Waters cartridge (not shown for the sake of clarity of the drawing), and the second inlet  111  and outlet  111 ′ fluidic connection means for an 18F-FDG purification cartridge (not shown for the sake of clarity of the drawing). The supporting plate  101  comprises a second face  112 , illustrated in  FIG. 3 , on which is attached a reactor  106  (not shown in  FIG. 3  for the sake of clarity of the drawing), either via an attachment means or via a weld or via a molding with the plate or via any other attachment method. The second face  112  further comprises a liquid outlet O 4  for discharging the 18F-FDG obtained at the end of the synthesis. 
     The interface plate  115  comprises a front face  116  supporting said supporting plate  101  and a rear face  113  being used as interface for attaching the disposable module  100  on a fixed module as for example described in document U.S. Pat. No. 7,235,216. 
       FIG. 2  illustrates a view of the disposable module  100  centered on said first face  109  of the supporting plate and a portion of the front face  116  of the interface plate  115 . Two-way valves V 2 , V 4 , V 5  and V 6  are located in an upper portion of the interface plate  115 . 
       FIG. 3  illustrates a view of the disposable module centered on the second face  112  of the supporting plate and a lower portion of the interface plate  115 . Three-way valves V 1 , V 3 , V 7 , V 8  are located in a lower portion of the interface plate  115 . 
       FIG. 4  illustrates a rear view of the disposable module, and more particularly of the rear portion  113  of the interface plate  115 , being used as an interface with a fixed module. 
     The rear portion  113  of the interface plate  115  comprises:
         an inlet E 1  for the fluid flowing out of a target for production of radioisotopes, the fluid generally being water enriched with O-18 ( 18 O)) containing F-18;   a first outlet O 1  of liquid for discharging water enriched with O-18;   an inlet E 2  of inert gas such as for example helium;   an outlet O 2  for applying vacuum   an outlet O 3  for discharging wastes from the reaction.       

       FIG. 4  also shows the rear portion of the valves V 1 , V 2 , V 3 , V 4 , V 5 , V 6 , V 7  and V 8 , included in the interface plate  115 , each of these valves comprising a housing for valve actuators for a fixed module  200 . 
     The disposable module comprises a plurality of channels entirely integrated into the body of the disposable module:
         a first channel  14  connecting the inlet E 1  to the valve V 1 ;   a second channel  1  crossing the supporting plate and connecting the valve V 1  to the valve V 2 ;   a third channel  2  connecting the first reagent flask  102  containing Kryptofix to the valve V 2     a fourth channel  15  connecting the valve V 1  by means of an inlet fluidic connection  110  of the 18F capture cartridge;   a fifth channel  16  connecting the outlet fluidic connection means  110 ′ of the 18F capture cartridge to the valve V 3 ;   a sixth channel  17  connecting the valve V 3  to the outlet O 1 ;   a seventh channel  4  connecting the valve V 3  to the reactor  106 ;   an eighth channel  3  connecting the second flask of reagents  103  containing mannose triflate to the valve V 4 ;   a ninth channel  5  connecting the valve V 4  to the reactor  106 ;   a tenth channel  6  connecting the gas inlet E 2  to the reactor  106 ;   an eleventh channel  7  connecting the reactor  106  to the outlet O 2  for the vacuum;   a twelfth channel  11  connecting the third flask  105  containing NaOH to the valve V 5 ;   a thirteenth channel  8  connecting the valve V 5  to the reactor  106 ;   a fourteenth channel  12  connecting the fourth flask  104  containing water to the valve V 6 ;   a fifteenth channel  9  connecting the valve V 6  to the reactor  106 ;   a sixteenth channel  10  connecting the plunger tube  108  in the reactor  106  to the valve V 7 ;   a seventeenth channel  18  connecting the valve V 7  to the inlet fluidic connection means  111  of the FDG purification cartridge;   an eighteenth channel  20  connecting the outlet fluidic connection means  111 ′ of the FDG purification cartridge to the valve V 8 ;   a nineteenth channel  19  connecting the valve V 8  to the outlet O 3  for discharging the waste from the reaction and;   a twentieth channel  13  connecting the valve V 8  to the outlet O 4  for discharging the FDG.       

     Second Exemplary Embodiment of the Invention 
       FIG. 6  shows a second exemplary embodiment of the invention comprising all the features of the first example and wherein:
         the connection between the second channel  1  forms an angle of 90° with the valve V 2  and the connection between the valve V 2  and the third channel  2 ;   the connection between the eighth channel  3  forms an angle of 90° with the valve V 4  and the connection between the valve V 4  and the ninth channel  5 ;   the connection between the twelfth channel  11  forms an angle of 90° with the valve V 5  and the connection between the valve V 5  and the thirteenth channel  8  and;   the connection between the fifteenth channel  9  forms an angle of 90° with the valve V 6  and the connection between the valve V 6  and the fourteenth channel  12 .       

     The valves V 2 , V 4 , V 5  and V 6  in this case are three-way valves. All the valves of the disposable module are thus three-way valves, which make the disposable module easier and less costly to manufacture. 
     Third Exemplary Embodiment of the Invention 
       FIG. 7  shows a third exemplary embodiment of the invention comprising all the features of the first and of the second example but wherein the channel network is changed so as to avoid the intersection of the channels in the supporting plate  101 . 
     Also, the interface plate  115  is changed so that the channels  4  and  5  join up in order to form a common channel  4 + 5 , and so that the channel  9  joins up with channel  8  in order to form a common channel  8 + 9 . With this joining of the inlet channels of reagents it is possible to reduce the number of channels directed towards the reactor  106 , which simplifies the supporting plate  101 . 
     According to a second aspect, the present invention relates to a method for manufacturing a disposable module  100  for an automated macrofluidic device for synthesizing a radioactive tracer as described above. 
     The method comprises a step for assembling (by adhesively bonding or welding for example) a film, a sheet or a plate on a substantially planar disposable module plate and provided with grooves, so as to hermetically cover by means of a film or a plate said grooves in order to form conduits or conduit portions able to transfer chemical reagents, gases or products. According to a first embodiment of the method, the method for manufacturing the disposable module is carried out in the following way: 
     In a first step, a film, a sheet or a plate  400  is assembled onto a supporting plate  101  comprising:
         a first face provided with grooves and first fluidic connection means connected to said grooves;   a face perpendicular to said first face, said perpendicular face comprising second fluidic connection means in communication with said grooves,
 
so as to hermetically cover said grooves.
       

     In a second step, another film, another sheet or another plate  400 ′ is assembled onto an interface plate  115  comprising:
         a face  116  provided with grooves and;   fluidic connection means positioned so as to be able to connect to said second fluidic connection means of said supporting plate;
 
so as to hermetically cover said grooves of the interface plate.
       

     The film, sheet or plate  400 ′ assembled on the interface plate  115  is either perforated beforehand or pierced after adhesive bonding so that each of the fluidic connection means is de-obstructed. 
     Preferably, adhesive bonding of the films, sheet or plate on said supporting plate and on said interface plate is carried out by means of a thermal welding method without any solvents, for example a laser welding method, a heating method with ultrasound or a method using heated blades. 
     In a third step, the supporting plate  101  is assembled with said interface plate  115 , so as to connect said fluidic connection means of said interface plate  115  with said second fluidic connection means of said supporting plate  101 . 
     Preferably, a gasket  401  is inserted between the supporting plate  101  and the interface plate  115  during the assembling step. 
     Preferably, the interface plate  115  comprises an attachment means  403  in which the supporting plate  101  will be fastened with clips or vice versa. The interface plate  115  also comprises locations for valves positioned on the face  113  opposite to the face  116  provided with grooves. 
     According to an example of the first embodiment of the method, as illustrated in  FIG. 8 , said supporting plate  101  comprises:
         two opposite faces  109 ,  112  provided with grooves and with first fluidic connection means connected to said grooves;   a face  407  perpendicular to said two opposite faces, said perpendicular face comprising second fluidic connection means in communication with said grooves.       

     In the first step of the method as described above, a film, a sheet or a plate  400  are assembled on each of the opposite faces  109 ,  112  provided with grooves and with fluidic connections, so as to hermetically cover said grooves. 
     Preferably, an open cylindrical portion  406  extends perpendicularly downwards from the supporting plate  101  from its lower surface  112 . Preferably, a plunger tube  108  is molded against the wall of the open cylindrical portion  406 . In a subsequent step to the assembling of the film, sheet or plate  400  on the lower face  112  of the supporting plate  101 , a circular part  402  is welded to the base of the cylindrical portion so as to form a reactor  106 . 
     According to a second embodiment of the method illustrated in  FIG. 9 , the method for manufacturing the disposable module is carried out in the following way: 
     In a first step, a first plate  404  comprising:
         a first face  410  provided with grooves and with first fluidic connection means connected to said grooves;   a face  411  perpendicular to said first face, said perpendicular face comprising second fluidic connection means in communication with said grooves,
 
and a second plate  405  comprising:
   a first face  410 ′ provided with grooves and with first fluidic connection means connected to said grooves;   a face  411 ′ perpendicular to the said first face, said perpendicular face comprising second fluidic connection means in communication with said grooves,
 
are embossed so as to form a supporting plate  101 , said first face  410  of said first plate  404  being put into contact with said first face  410 ′ of said second plate  405 , said grooves of said first plate  404  and of said second plate  405  being positioned so as not to come into contact with each other. Preferably, the second plate  405  comprises an open cylindrical portion  406 ′ extending perpendicularly towards the bottom of the plate  405  from the lower surface  112 . Preferably, a plunger tube  108  is molded against the wall of the open cylindrical portion  406 ′. In a preliminary or subsequent step to the step for embossing the first plate  404  with the second plate  405 , a circular part  402  is welded to the base of the cylindrical portion so as to form a reactor  106 .
       

     In a second step, a film, a sheet or a plate  400 ′ is assembled to an interface plate  115  comprising:
         a face  116  provided with grooves and;   fluidic connection means positioned so as to be able to connect to said second fluidic connection means of said supporting plate;
 
so as to hermetically cover said grooves of said interface plate  115 .
       

     Preferably, the assembling of the films, sheet or plate  400  on said interface plate  115  is carried out by means of a thermal welding method without any solvents, for example a laser method, a heating method with ultrasound or a method using heated blades. 
     The film, sheet or plate  400  assembled on the interface plate  115  is either perforated beforehand, or pierced after adhesive bonding so that each of the fluidic connection means is de-obstructed. 
     In a third step, said supporting plate  101  is assembled with the interface plate  115 , so as to connect said fluidic connection means of the interface plate  115  with said second fluidic connection means of said supporting plate  101 . 
     Preferably, a gasket  401  is inserted between the supporting plate  101  and the interface plate  115  during the assembling step. 
     Preferably, the interface plate comprises an attachment means  403  in which will be fastened the supporting plate  101  with clips or vice versa. The interface plate  115  also comprises valves positioned on the face  113  opposite to the face  116  provided with grooves. 
     Preferably, independently of the embodiment of the method for manufacturing the disposable module, said supporting plate  101  and said interface plate  115  are in ethylene-norbornene copolymer, the glassy transition temperature of which is above 150° C. and said films, sheets or plate covering said grooves are in polypropylene. According to an embodiment, the supporting plate  101  and the interface plate  115  form a single unit part instead of two separate and assembled parts. 
     According to another embodiment, the module comprises a supporting plate  101  into which are integrated the interface means such as the valves V 1 -V 8 , the fluid inlets E 1 -E 2  and the fluid outlets O 1 -O 3 . This embodiment may be achieved by increasing the thickness of the supporting plate with respect to the embodiments described above, so as to house the interface means in a wall of said plate which is perpendicular to the plane of the plate. Another possibility is to provide a supporting plate provided with a central portion comprising rigid connection means  114  to at least one flask of chemical reagents, and the portions located laterally with respect to the central portion but in the same plane as the central portion, the lateral portions being provided with said interface means. In the embodiment illustrated in  FIGS. 10-13 , the connection between the supporting plate  101  and the interface plate  115  is ensured by side wings  500  secured with the supporting plate, and attached to the interface plate with clips  501 . 
     The supporting plate  101  is assembled from a first plate  502  provided with grooves  503  and a second plate  504  provided with apertures  505  and  506  for connecting to the conduits formed by the grooves  503  after the assembling. The wings  500  are secured with a second plate  504 . A first group of apertures  505  are connected to the flasks  506  mounted on the supporting plate. A second group of apertures  507  is connected through the inside of the portion  504  to apertures  508  at the perpendicular face  509  of the second plate  504 . Therefore this is an embodiment similar to the one shown in  FIG. 9 , except that the grooves  503  are all found in one of the two portions ( 404  and  405  in  FIG. 9 ). 
     The interface plate  115  is formed by the assembling of three portions:
         a plate  510  provided with grooves  511  and with apertures  512  configured so as to connect to the apertures  508  of the supporting plate  101 ,   a plate  513  comprising a planar face  514  which will be placed against the grooves  511  in order to generate channels, and a face  515  comprising means  516  for connecting valves and fluid inlets or outlets, and   a third plate  517  comprising apertures  518  for housing valves  519  of different types, as well as apertures  520  for fluid inlets or outlets. Sealing means  521  are inserted between both plates  101  and  115  as shown in  FIG. 12 .