Abstract:
Disclosed is a method of manufacturing a multiple-phase particle comprising preparing a channel whose outlet port is adapted to a first fluid, feeding a second fluid into the channel, the second fluid being higher in affinity to the outlet port as compared with the first fluid, feeding a third fluid into the channel, the third fluid being lower in affinity to the outlet port as compared with the second fluid, and introducing the third fluid into the second fluid in the channel while retaining the second fluid at the outlet port by an effect of the affinity of the second fluid, thereby entrapping the third fluid in the second fluid to form the multiple-phase particle.

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
     This application is based upon and claims the benefit of priority from prior Japanese Patent Application No. 2005-096550, filed Mar. 29, 2005, the entire contents of which are incorporated herein by reference. 
     BACKGROUND OF THE INVENTION 
     1. Field of the Invention 
     This invention relates to a method for manufacturing a multiple-phase particle and to an apparatus for manufacturing the multiple-phase particle. 
     2. Description of the Related Art 
     Multiple-phase particles such as microcapsules and composite fine particles are used extensively in various technical fields including biotechnology, the drug industry, the food industry, the cosmetic industry, and the paint industry, etc. When a multiple-phase particle is manufactured using lipid as an emulsifier, the product is referred to as a lipid multiple-phase particle. Further, the multiple-phase particle can be classified, according to the thickness of the membrane thereof, into a double emulsion and a vesicle (a reversed vesicle). Depending on the number of inner gas phase, aqueous phase or oil phase, the double emulsion can be classified into a multiple-phase-type emulsion and a single-phase-type emulsion. 
     In the DDS (Drug Delivery System) where the enhancement of pharmacological effects and the suppression of side effects are aimed at, the lipid multiple-phase particle is advantageous in that it is capable of controlling the release of medicine, improving the absorbability and enhancing the target directivity, and is also more excellent as compared with polymeric carrier in terms of toxity, antigenicity, irritation, etc. However, since the lipid multiple-phase particle is relatively instable as compared with polymeric carrier, it is difficult to supply a sufficient quantity as required of the particle immediately when immediate supply thereof is needed. 
     Although it is relatively easy to manufacture a multiple inner aqueous phase type emulsion, the double emulsion to be obtained lacks uniformity of particle size. Therefore, when the lipid multiple-phase particle is to be employed as a microcarrier, there will be raised the problems that it is difficult to control the dosage of chemicals as well as the rate of releasing the chemicals. 
     In order to manufacture a vesicle which is excellent in uniformity of particle size, it will be required to undergo a series of complicated steps such as drying of lipid, stirring, ultrasonic treatment, pressing, etc. Since the manufacturing process thereof includes the employment of harmful volatile organic substance such as chloroform, it is difficult to directly entrap a bioactive substance in the vesicle. Further, it is difficult to quickly and automatically manufacture a vesicle excellent in uniformity of particle size and to manufacture a vesicle enclosing therein a bioactive substance. It is also difficult to manufacture a vesicle where the inner membrane and the outer membrane thereof are asymmetric. Moreover, since the particle diameter of vesicle to be manufactured is as small as about 20 nm-50 nm, it is difficult to entrap a sufficient quantity, per unit volume, of a high-molecular substance such as protein, DNA, RNA, etc., so as to secure high activity thereof. 
     BRIEF SUMMARY OF THE INVENTION 
     A method of manufacturing a multiple-phase particle according to one aspect of the present invention comprises preparing a channel whose outlet port is adapted to a first fluid; feeding a second fluid into the channel, the second fluid being higher in affinity to the outlet port as compared with the first fluid; feeding a third fluid into the channel, the third fluid being lower in affinity to the outlet port as compared with the second fluid; and introducing the third fluid into the second fluid in the channel while retaining the second fluid at the outlet port by an effect of the affinity of the second fluid, thereby entrapping the third fluid in the second fluid to form the multiple-phase particle. 
     An apparatus for manufacturing a multiple-phase particle according to another aspect of the present invention comprises a continuous-phase supply portion feeding a first fluid as a mobile phase or a stationary phase; a channel communicated via an outlet port with the continuous-phase supply portion; a second fluid supply portion feeding the second fluid to the channel; and a third fluid supply portion feeding the third fluid to the channel. 
    
    
     
       BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWING 
         FIG. 1  is a diagram schematically illustrating the apparatus for manufacturing a multiple-phase particle according to a first embodiment of the present invention; 
         FIG. 2  is a diagram illustrating the process of forming a multiple-phase particle according to a first embodiment of the present invention; 
         FIG. 3  is a diagram illustrating a full automatic manufacturing apparatus for a multiple-phase particle according to a first embodiment of the present invention; 
         FIG. 4  is a diagram for illustrating a single-step emulsification method for forming a water-in-oil-in-water (W/O/W) emulsion of multiple-phase particle according to a first embodiment of the present invention; 
         FIG. 5  is a diagram for illustrating a single-step emulsification method for forming an oil-in-water-in-oil (O/W/O) emulsion of multiple-phase particle according to a first embodiment of the present invention; 
         FIG. 6  is a diagram schematically illustrating the apparatus for manufacturing a multiple-phase particle according to a first application example of the first embodiment of the present invention; 
         FIG. 7  is a diagram schematically illustrating a main portion of the apparatus for manufacturing a multiple-phase particle according to a second application example of the first embodiment of the present invention; 
         FIG. 8  is a diagram schematically illustrating a main portion of the apparatus for manufacturing a multiple-phase particle according to a third application example of the first embodiment of the present invention; 
         FIG. 9A  is a diagram schematically illustrating the method of manufacturing a single inner aqueous phase type W 1 /Os/W 2  emulsion having ink entrapped therein by using suction method according to Example 1 of the first embodiment of the present invention; 
         FIG. 9B  is a photograph illustrating a state wherein a third fluid  13  is poured into a second fluid  12  in Example 1 of the first embodiment of the present invention; 
         FIG. 9C  is a photograph showing the multiple-phase particle which was manufactured in Example 1 of the first embodiment of the present invention; 
         FIG. 9D  is a photograph showing a state where a blue ink solution is dropped into an aqueous solution; 
         FIG. 9E  is a photograph showing the multiple-phase particle which was manufactured in Example 1 of the first embodiment of the present invention; 
         FIGS. 10A and 10B  are photographs illustrating the process of manufacturing a single inner aqueous phase type W 1 /Os/W 2  emulsion having ink entrapped therein by using suction method according to Example 2 of the first embodiment of the present invention; 
         FIG. 10C  is a photograph showing the multiple-phase particle which was manufactured in Example 2 of the first embodiment of the present invention; 
         FIGS. 11A to 11D  are photographs illustrating the process of manufacturing a single inner vapor phase type V/Os/W 2  emulsion according to Example 3 of the first embodiment of the present invention; 
         FIGS. 12A and 12B  are photographs illustrating the process of manufacturing a single inner aqueous phase type W 1 /Os/W 2  emulsion according to Example 4 of the first embodiment of the present invention; 
         FIGS. 13A to 13C  are photographs illustrating the process of manufacturing a single inner aqueous phase type W 1 /Os/W 2  emulsion according to Example 4 of the first embodiment of the present invention; 
         FIGS. 14A and 14B  are photographs illustrating Comparative Example 2 of the first embodiment of the present invention; 
         FIG. 15  is a photograph illustrating Example 5 of the first embodiment of the present invention; 
         FIGS. 16A to 16C  are photographs illustrating Example 6 of the first embodiment of the present invention; 
         FIGS. 17A to 17C  are photographs illustrating Example 7 of the first embodiment of the present invention; 
         FIGS. 18A and 18B  are photographs illustrating Example 8 of the first embodiment of the present invention; 
         FIGS. 19A and 19B  are enlarged views of the channel installed in the apparatus for manufacturing a multiple-phase particle according to the second embodiment of the present invention; 
         FIGS. 19C to 19E  are enlarged views each schematically illustrating a first application example of the channel in the apparatus for manufacturing a multiple-phase particle according to the second embodiment of the present invention; 
         FIGS. 20A to 20F  are diagrams each illustrating the configuration of the outlet port of the channel according to the second application example of the second embodiment of the present invention; 
         FIGS. 21A to 21D  are diagrams each illustrating the configuration of the outlet port of the channel according to the third application example of the second embodiment of the present invention; 
         FIGS. 22A and 22B  are enlarged views of the channel according to the fourth application example of the second embodiment of the present invention; 
         FIGS. 23A and 23B  are enlarged views of other channels according to the fourth application example; 
         FIGS. 24A to 24C  are photographs for illustrating Example 1 of the second embodiment of the present invention; 
         FIGS. 25A and 25B  are photographs for illustrating Example 2 of the second embodiment of the present invention; and 
         FIG. 26  is a photograph for illustrating Example 3 of the second embodiment of the present invention. 
     
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
     Next, various embodiments of the present invention will be illustrated in detail with reference to drawings. In these drawings, the same or similar components are referred to by the same or similar reference numerals. It should be noted however that since these drawings are depicted schematically, the proportions in dimension of parts or components may differ from actual ones. Therefore, specific dimensions of each of parts or components should be judged by referring to the following explanations. Further, even between or among FIGS, the dimensional relationships or proportions thereof may differ from each other. 
     First Embodiment 
     In this first embodiment of the present invention, there are explained a method as well as an apparatus for manufacturing multiple-phase particles of various states such as a single inner aqueous phase type water-in-oil-in-water (W/O/W) emulsion, a multiple inner aqueous phase type water-in-oil-in-water (W/O/W) emulsion, vesicle, liposome, a single inner oil phase type oil-in-water-in-oil (O/w/O) emulsion, a multiple inner oil phase type oil-in-water-in-oil (O/W/O) emulsion, reversed vesicle, a single inner vapor phase type vapor-in-water-in-oil (V/W/O) emulsion, a multiple inner vapor phase type vapor-in-water-in-oil (V/W/O) emulsion, a single inner vapor phase type vapor-in-oil-in-water (V/O/W) emulsion, a multiple inner vapor phase type vapor-in-oil-in-water (V/O/W) emulsion, etc. 
       FIG. 1  shows an apparatus for manufacturing a multiple-phase particle  20  according to a first embodiment of the present invention. The manufacturing apparatus  1  shown herein comprises a continuous-phase supply portion  2 , a channel  3  communicating via an outlet port  31  with the continuous-phase supply portion  2 , a second fluid supply portion  4 , and a third fluid supply portion  5 . The continuous-phase supply portion  2  feeds a first fluid  11  as a continuous-phase constituted by either a mobile phase or a stationary phase. The second fluid supply portion  4  feeds a second fluid  12  containing an emulsifier  14  to the channel  3 . The affinity between this emulsifier  14  and the outlet port  31  is stronger than the affinity between the outlet port  31  and the first fluid  11 . 
     The third fluid supply portion  5  feeds a third fluid  13  to the channel  3 . The affinity between the third fluid  13  and the outlet port  31  is weaker than the affinity between the outlet port  31  and the second fluid  12  containing the emulsifier  14 . Further, the manufacturing apparatus  1  comprises a recovering portion  6  for recovering a multiple-phase particle  20  that has been generated as it is pushed into the continuous-phase supply portion  2 . 
     The manufacturing apparatus shown in  FIG. 1  is designed such that the second fluid  12  containing an emulsifier (for example, the reference number  14  shown in  FIG. 4 ) and being supplied from the second fluid supply portion  4 , and the third fluid  13  being supplied from the third fluid supply portion  5  are fed alternately to the channel  3 . At the outlet port  31 , while the third fluid  13  is enclosed by the second fluid  12 , the second fluid  12  is pushed into the first fluid  11 , thereby producing an intermediate body  10  of the multiple-phase particle  20 . From this intermediate body  10 , it is possible to manufacture the multiple-phase particle  20  wherein the third fluid is entrapped in the second fluid. 
     The second fluid  12  contains at least one emulsifier  14 . The second fluid  12  containing this emulsifier  14  is enabled, owing to the affinity thereof, to adhere to the outlet port  31 . When the third fluid  13  is enclosed in the second fluid  12 , the second fluid  12  is enabled to act as a boundary film between the third fluid  13  and the first fluid  11 . As a result, it is possible to produce the intermediate body  10  where the second fluid  12  enclosing the third fluid  3  therein is enabled to act as a boundary film. When the introduction of the third fluid  13  into the second fluid  12  is terminated, the intermediate body  10  can be kept in a stable state as it is. 
     Further, when the third fluid  13  is continuously introduced into the second fluid  12 , the intermediate body  10  is expanded to form a semi-spherical or micro-spherical body having a larger diameter than the inner diameter of the outlet port  31 , thus ultimately making it possible to produce a single phase type multiple-phase particle  20  where the third fluid is entrapped in the second fluid. The multiple-phase particle  20  thus formed may be a single inner vapor phase type, aqueous phase type or oil phase type liquid membrane emulsion (Double emulsion), vesicle or reversed vesicle. This multiple-phase particle  20  is then released from the outlet port  31 , resisting to the affinity thereof to the outlet port  31 . 
     When the first fluid (continuous-phase)  11  retained in the continuous-phase supply portion  2  is a mobile phase, the multiple-phase particle  20  flows in the flow direction of the first fluid  11  and is recovered at the recovering portion  6 . When the first fluid  11  is a stationary phase, the multiple-phase particle  20  that has been pushed out from the outlet port  31  can be unidirectionally adhered to the outer surface of the channel  3  by securing a suitable degree of affinity between the multiple-phase particle  20  and the outer surface of the channel  3 . Alternatively, the multiple-phase particle  20  can be adhered onto the outer surface of the channel  3  in such a manner that the multiple-phase particle  20  is arrayed regularly or irregularly. 
       FIG. 2  shows the process of forming a multiple-phase particle according to a first embodiment of the present invention. As shown in  FIG. 2 , by using the second fluid  12   a  containing an emulsifier  14  which has been fed initially and the third fluid  13   a , a multiple-phase particle  20   a  is formed at the outlet port  31 . Before this multiple-phase particle  20   a  is completely separated from the outlet port  31 , the second fluid  12   b  containing the emulsifier  14  is again fed to the multiple-phase particle  20   a . By using the second fluid  12   b  and the third fluid  13   b , a multiple-phase particle  20   b  is formed. Then, by using the second fluid  12   c  containing the emulsifier  14  and the third fluid  13   c , a multiple-phase particle  20   c  is formed. In this case, it is possible to form a single phase type multiple-phase particle  20 A wherein the third fluids  13   a ,  13   b  and  13   c  which have been coalesced into one body are enclosed in the second fluids  12   a ,  12   b  and  12   c  containing a coalesced emulsifier  14  and coalesced into one body. The multiple-phase particle formed in this case can be referred to as a single phase type emulsion, vesicle or reversed vesicle. 
     Alternatively, it is possible to manufacture a multiple-phase type multiple-phase particle  20 B wherein the third fluids  13   a ,  13   b  and  13   c  are independently dispersed in a coalesced body of the second fluids  12   a ,  12   b  and  12   c . The multiple-phase particle in this case is a multiple-phase type emulsion. 
     In order to introduce the second fluid  12  and the third fluid  13  into the channel  3 , it is possible to employ a method such as a direct introduction method or a suction method. One example of the direct introduction method is shown in  FIG. 3 . As shown in  FIG. 3 , the second fluid  12  is fed from the second fluid supply portion  4  via an inlet port  4 A into the channel  3  and the third fluid  13  is fed from the third fluid supply portion  5  via the inlet port  5 A into the channel  3 . The second fluid  12  and the third fluid  13  are alternately fed into the channel  3 . For example, while a segment of the second fluid  12  is intermittently fed at a constant intervals into the channel  3 , a segment of the third fluid  13  is fed into the channel  3  concurrent with the supply of the second fluid  12 . It is possible, in this manner, to alternately feed the second fluid  12  and the third fluid  13  into the channel  3 . Alternatively, while the third fluid  13  is continuously fed into the channel  3 , a segment of the second fluid is intermittently squeezed into the continuous flow of the third fluid  13  at a constant interval. It is possible, in this manner, to alternately feed the second fluid  12  and the third fluid  13  into the channel  3 . 
     In order to alternately feed the second fluid  12  and the third fluid  13  into the channel  3 , it is possible to employ a fluid-switch provided with a fluid supply control valve and a valve controlling apparatus for controlling the control valve. According to the direct introduction method, it is possible to continuously and fully automatically manufacture the multiple-phase particle while both of the second fluid  12  and the third fluid  13  feed directly into the channel  3 . Therefore, this method is advantageous in the respect that the multiple-phase particle  20  can be mass-produced. Further, when the first fluid  11  is a mobile phase, the multiple-phase particle  20  manufactured can be easily recovered at the recovery portion  6 . 
     On the other hand, the suction method is a method for alternately sucking the second fluid  12  and the third fluid  13  into the channel  3  from the outlet port  31  of the channel  3 . In this suction method, the second fluid  12  and the third fluid  13  are separately sucked into the channel  3  from the same outlet port  31 . Therefore, it is possible to realize miniaturization of the apparatus. Further, it is now possible to easily supply a required quantity of the multiple-phase particle  20  to a location where the supply of the multiple-phase particle  20  is needed such as a syringe. 
     At least the outlet port  31  of the channel  3  is made from a material to which the second fluid can be adhered due to the affinity of the material to the second fluid  12 . The surface characteristics, especially wettability thereof, can be relatively determined by taking into consideration the features of the emulsifier  14  included in the second fluid  12  and the features of the third fluid  13 . Incidentally, it is also possible to control the surface characteristics of the outlet port  31  by treating the surface of the outlet port  31 . For example, it is possible to enhance the wettability of the outlet port  31  to the second fluid  12  (or adhesion of the second fluid  12 ) by performing a roughening treatment of the surface of the outlet port  31 . 
     Next, the single-step emulsifying method of the multiple-phase particle of W/O/W emulsion according to the first embodiment will be explained with reference to  FIG. 4 . For example, the outlet port  31  of channel (for example, microchannel)  3  is made hydrophobic. By using an aqueous phase (W 2 ) as the first fluid  11  and by using an oil phase (Os) containing an emulsifier  14  as a segment of the second fluid  12 , these fluids are fed into the channel  3 . Further, by using an aqueous phase (W 1 ) as a segment of the third fluid  13 , segments of both second fluid  12  and third fluid  13  are alternately fed into the channel  3 . The second fluid  12  and the third fluid  13  introduced into the flow of the second fluid  12  are successively pushed into the first fluid  11  from the outlet port  31 . As a result, an intermediate body  10  and a multiple-phase particle  20  of single inner aqueous phase type W 1 /Os/W 2  emulsion or vesicle where the third fluid is to be enclosed in the second fluid can be manufactured. In this case, by a hydrophobic interaction between the hydrophobic group of the second fluid  12  or the emulsifier  14  and the hydrophobic channel  3 , the second fluid  12  containing an emulsifier  14  adhere onto the outlet port  31 . 
     At the interface where the emulsifier  14  and the third fluid  13  are contacted with each other, the hydrophilic group of the emulsifier  14  is arrayed so as to surround the third fluid  13 . Further, at the interface where the emulsifier  14  and the first fluid  11  contact each other, the hydrophilic group of the emulsifier  14  is arrayed so as to face the first fluid  11 . As the third fluid  13  is gradually introduced into the second fluid  12 , a semi-spherical or microspherical body with the emulsifier  14  acting as a boundary film can be obtained. When these semi-spherical and microspherical bodies are grown into a size which is large enough for releasing, the resultant body is released from the outlet port  31 , thereby manufacturing the multiple-phase particle  20  of single inner aqueous phase type W 1 /Os/W 2  emulsion. 
     By the same principle, an intermediate body  10  as well as a multiple-phase particle  20  of a single inner vapor phase type V/Os/W 2  emulsion where the third fluid is enclosed in the second fluid can be manufactured. In this case, an oil phase (Os) containing an emulsifier  14  is fed, as a segment of the second fluid  12 , into the channel  3  and a vapor phase (V) is fed, as a segment of the third fluid  13 , into the channel  3 . The segments of these second fluid  12  and third fluid  13  are alternately introduced into the channel  3 . The second fluid  12  and the third fluid  13  introduced into the flow of the second fluid  12  are successively pushed into the first fluid  11  from the outlet port  31 . As a result, an intermediate body  10  as well as a multiple-phase particle  20  of a single inner vapor phase type V/Os/W 2  emulsion can be manufactured. 
     By a hydrophobic interaction between the hydrophobic group of the second fluid  12  or the emulsifier  14  and the hydrophobic channel  3 , the second fluid  12  adhere onto the outlet port  31 . In the case of the single inner vapor phase type V/Os/W 2  emulsion, the hydrophobic group of emulsifier  14  is arrayed so as to face the third fluid  13  at the interface where the emulsifier  14  and the third fluid  13  contact each other. At the interface where the emulsifier  14  and the first fluid  11  contact each other, the hydrophobic group of emulsifier  14  is arrayed so as to face the first fluid  11 . 
     Next, the single-step emulsifying method of the multiple-phase particle of O/W/O emulsion according to the first embodiment will be explained with reference to  FIG. 5 . The outlet port  31  of channel  3  is made hydrophilic. By using an oil phase (O 2 ) as the first fluid  11  and by using an aqueous phase (Ws) containing an emulsifier  14  as a segment of the second fluid  12 , these fluids are fed into the channel  3 . Further, by using an oil phase (O 1 ) as a segment of the third fluid  13 , segments of both second fluid  12  and third fluid  13  are alternately fed into the channel  3 . The second fluid  12  and the third fluid  13  introduced into the flow of the second fluid  12  are successively pushed into the first fluid  11  from the outlet port  31 . As a result, an intermediate body  10  and a multiple-phase particle  20  of single inner oil phase type O 1 /W s /O 2  emulsion and reversed vesicle where the third fluid is enclosed in the second fluid can be manufactured. 
     In this case, by a hydrophilic interaction between the hydrophilic group of the second fluid  12  or the emulsifier  14  and the hydrophilic channel  3 , the second fluid  12  adhere onto the outlet port  31 . At the interface where the emulsifier  14  and the third fluid  13  contact each other, the hydrophobic group of the emulsifier  14  is arrayed so as to surround the third fluid  13 . Further, at the interface where the emulsifier  14  and the first fluid  11  are contacted with each other, the hydrophobic group of the emulsifier  14  is arrayed so as to face the first fluid  11 . As the third fluid  13  is gradually introduced into the second fluid  12 , a semi-spherical or microspherical expanded body with the emulsifier  14  being acting as a boundary film can be obtained. When these semi-spherical and microspherical bodies are further grown into a size which is large enough for releasing, the resultant body is released from the outlet port  31 , thereby manufacturing the multiple-phase particle  20  of single inner oil phase type O 1 /Ws/O 2  emulsion. 
     By the same principle, an intermediate body  10  as well as a multiple-phase particle  20  of a single inner vapor phase type V/Ws/O 2  emulsion can be manufactured. In this case, an aqueous phase (Ws) containing an emulsifier  14  is fed, as a segment of the second fluid  12 , into the channel  3  and a vapor phase (V) is fed, as a segment of the third fluid  13 , into the channel  3 . The segments of these second fluid  12  and third fluid  13  are alternately introduced into the channel  3 . Thereafter, the second fluid  12  and the third fluid  13  introduced into the flow of the second fluid  12  are successively pushed into the first fluid  11  from the outlet port  31 . As a result, an intermediate body  10  as well as a multiple-phase particle  20  of a single inner vapor phase type V/Ws/O 2  emulsion can be manufactured. 
     In the manufacture of the multiple-phase particle  20  according to the first embodiment of the present invention, the control of temperature and pressure is very important. In the case of controlling the temperature of manufacturing system, as long as it is possible to separately or totally control the temperature of the second fluid  12  containing an emulsifier as well as the temperature of the third fluid  13  directly or indirectly from the inside or outside of the channel  3 , there is no particular limitation with regard to the means for controlling the temperature. Further, even in the continuous-phase supply portion  2 , it is preferable to suitably control the temperature thereof. 
     In this first embodiment, the intermediate body  10  and the multiple-phase particle  20  can be manufactured so as to have a semi-ellipsoidal configuration or a spheroidal configuration depending on the molecular structure of emulsifier. Therefore, there is no particular limitation with regard to the configuration of the intermediate body  10  and the multiple-phase particle  20 . 
     In the manufacture of the multiple-phase particle  20  according to this first embodiment, each of the first fluid  11 , the second fluid  12  containing an emulsifier  14 , and the third fluid  13  may be any one of vapor phase (V), aqueous phase (W) and oil phase (O) depending on the kinds of the multiple-phase particle  20  desired to be obtained. For example, in order to manufacture a W 1 /Os/W 2  emulsion as the multiple-phase particle  20 , the first fluid  11  may be an aqueous phase (W 2 ), the second fluid  12  may be an oil phase (Os) containing an emulsifier, and the third fluid  13  may be an aqueous phase (W 1 ) containing a substance. 
     The first fluid  11  may comprise a surfactant a polymer or a saccharide in order to stabilize the multiple-phase particle  20 . Further, as for the third fluid, it is possible to employ liquid crystal. The third fluid may not be restricted to a single phase but may be a multiple-phase wherein a vapor phase, a liquid phase or liquid crystal is suitably mixed therewith. 
     The second fluid  12  can be adhered to the outlet port  31  through an interaction between the channel  3  and the second fluid  12  containing an emulsifier  14 . The second fluid  12  may not be restricted to either water or oil. As for water, it is possible to employ pure water (distilled water) or an aqueous solution containing various materials. As for oil, it is possible to employ hydrocarbons such as hexane, octane, isooctane, decane, dodecane, hexadecane, cyclohexane, etc.; a hydrophobic solvent such as chloroform, etc.; a hydrophilic solvent such as methanol, butanol, acetonitrile, etc.; and aromatic hydrocarbons such as benzene, toluene, etc. These solvents can be employed singly or as a mixture. Further, in order to dissolve a water-soluble living matter-related substance in the second fluid  12 , a small quantity of water may be added to the second fluid  12 . As long as the solvent or mixed solvent to be employed is capable of dissolving or dispersing the emulsifier  14 , there is no limitation with regard to the kinds of solvent, mixing ratio and the state of mixture. 
     In the manufacture of multiple-phase particle (for example, double emulsion, vesicle, liposome, etc.) for DDS, non-toxic oil such as non-toxic glycerin, ethylene glycol, ethanol, soybean oil, etc. can be employed as an oil phase. As for the second fluid  12  containing an emulsifier  14 , it may be constituted by only an emulsifier. For example, an emulsifier containing at least one material excluding water and oil may be employed as the second fluid. An emulsifier which is low in HLB value is high in affinity to oil and hence lipophilic. On the other hand, an emulsifier which is high in HLB value is highly hydrophilic. 
     As for the second fluid  12 , it may be constituted by only an emulsifier. Therefore, a plural kinds of emulsifiers differing HLB value may be suitably mixed together to form a mixture of emulsifiers exhibiting a wide range of HLB values for use in the manufacture of a multiple-phase particle. For example, when sorbitan monolaurate and polyoxyethylene sorbitan monolaurate are mixed together at a suitable ratio, it is possible to obtain a mixture of emulsifiers exhibiting an HLB value ranging from 9 to 17. Further, when sorbitan monostearate and polyoxyethylene sorbitan monostearate, or sorbitan monooleate and polyoxyethylene sorbitan monooleate are mixed together at a suitable ratio, it is possible to obtain a mixture of emulsifiers exhibiting an HLB value ranging from 5 to 15. Further, when two different kinds of sucrose fatty acid esters are mixed together at a suitable ratio, it would be possible to obtain a mixture of emulsifiers exhibiting an HLB value ranging from 1 to 19. 
     A mixture of emulsifiers (the second fluid  12 ) retain at the outlet port  31  by the affinity thereof to the outlet port  31  of channel  3 . When the mixture of emulsifiers is pushed into the first fluid  11  while introducing the third fluid  13  into the mixture of emulsifiers, an intermediate body  10  of multiple-phase particle  20  is produced. From this intermediate body  10 , it is possible to manufacture the multiple-phase particle  20  wherein the third fluid is enclosed in the mixture of emulsifiers. This process can be achieved by using a mixture of emulsifiers exhibiting a suitable HLB value. 
     When a multiple-phase particle is manufactured using, as the second fluid  12 , only an emulsifier or an emulsifier containing some kind of substance, multilamellar vesicle, multilamellar reversed vesicle, vesicle or reversed vesicle can be manufactured. 
     Since the emulsion is thermodynamically unstable, creaming, flocculation, Ostwald ripening or coalescence generates with time, thereby phase-separating the emulsion into an oil phase and an aqueous phase. According to the method according to one embodiment of the present invention, a multiple-phase particle can be manufactured by using only an emulsifier. As a result, it is now possible to manufacture thermodynamically stable multilamellar vesicle, multilamellar reversed vesicle, vesicle or reversed vesicle. 
     When water or oil is included in the second fluid  12  containing an emulsifier  14 , the multiple-phase particle  20  to be formed initially is a double emulsion. When the membrane of the multiple-phase particle  20  becomes thinner subsequently, multilamellar vesicle, multilamellar reversed vesicle, vesicle or reversed vesicle can be formed. 
     The second fluid  12  containing an emulsifier  14  may further contain at least one material. Specific examples of such a material include, for example, protein (for example, enzyme, molecular chaperone, antigen, antibody, hormone, etc.), nucleic acid, nucleic acid-related substances, molecule, glycolipid, cholesterol, fluorescent pigment, ligand, photosensitive molecule, ion channel, electron-conjugated substance, supplemental surfactant, crown ether, fullerene, carbon nanotube, carbon nanohone, porphyrin, cyclodextrin, molecular tongs, microparticle, dendrimer, steroid, peptide, polypeptide and saccharide. It is possible, through the inclusion of these materials in the second fluid, to manufacture double emulsion, vesicle or reversed vesicle which are modified by these materials. 
     If double emulsion is to be manufactured, other kinds of substance may be dispersed or dissolved in the second fluid  12  in addition to the emulsifier  14  and the aforementioned materials. Specific examples of such a substance include, for example, redox agent, peptide, metallic fine particle, magnetic fine particle, polymeric fine particle, microparticle, dendrimer, carbon nanohone, oil-soluble or water-soluble medicine, etc. These substances may be employed singly or in combination of two or more kinds and may be dispersed or dissolved in the second fluid. 
     As long as it is possible to obtain stable multiple-phase particle  20 , the emulsifier  14  to be included therein may be selected from lipid, boundary lipid, sphingolipid, fluorescent lipid, cationic surfactant, anionic surfactant, amphoteric surfactant, nonionic surfactant, synthetic polymer, natural polymer such as protein. As for the kinds and combination of the emulsifier  14 , there is no particular limitation. 
     When a lipid is to be employed as the emulsifier  14 , the following substances can be employed as lipid. Namely, they include triolein, monoolein, egg yolk lecithin, phospholipid, synthetic lipid, lysophospholipid, glycosyl diacyl glycerol, plasmalogen, sphingomyelin, ganglioside, fluorolipid, sphingolipid, sphingoglycolipid, steroid, sterol, cholesterol, oxicholesterol, dihydrocholesterol, glyceryl distearate, glyceryl monooleate, glyceryl dioleate, isosorbate monobrassidate, sorbitan tristearate, sorbitan monooleate, solbitan monopalmitate, sorbitan monolaurate, sorbitan monobrassidate, dodecyl phosphate, dioctadecyl phosphate, tocopherol, chlorophyll, xanthopyll, phosphatidylethanol amine, phosphatidylserine, inositol, hexadecyltrimethyl ammonium bromide, diglycosyl diglyceride, phosphatidylcholine, retinal/oxycholesterol/lectin/rhodopsin, cerebral total lipid, human erythrocyte total lipid, etc. Other kinds of lipid and synthetic lipid can be also used as long as they are useful in the manufacture of multiple-phase particle  20 . 
     When a surfactant is to be employed as the emulsifier  14 , the following substances can be employed as lipid. Namely, they include alkyl quaternary ammonium salt (such as CTAB, TOMAC, etc.), alkyl pyridinium salt (such as CPC, etc.), dialkyl sulfosuccinate (such as AOT, etc.), dialkyl phosphate, alkyl sulfate (such as SDS, etc.), alkyl sulfonate, polyoxyethyelene-based surfactant (such as Tween type, Brij type, Triton type, etc.), alkyl sorbitan (Span type, etc.), lecithin-based surfactant, betaine-based surfactant, sucrose fatty acid ester, etc. It is also possible to employ other kinds of surfactant other than mentioned above. 
     When a polymeric emulsifier is to be employed as the emulsifier  14 , the following substances can be employed as lipid. Namely, they include polysoap, polyethylene glycol, polyvinyl alcohol, polypropylene glycol, etc. 
     When a protein emulsifier is to be employed as the emulsifier  14 , casein can be employed for instance. 
     As long as it is possible to stably retain a multiple-phase particle, the third fluid  13  may be suitably selected so as to comprise water or oil as in the case of the second fluid  12  containing an emulsifier  14 . It is also possible to employ gas or liquid crystal as the third fluid  13 . 
     By incorporating various materials into each segment of the third fluid  13 , double emulsion, vesicle or reversed vesicle each enclosing therein a foreign matter can be manufactured. Namely, it is possible to obtain double emulsion, vesicle or reversed vesicle, wherein the inner membrane and the outer membrane thereof are modified by a foreign matter. As for the material to be incorporated into the third fluid  13 , it is possible to employ aromatic or odorous substances, drug, chemicals, dyestuffs, fluorescent agents, sugar, redox agents, peptide, polypeptide, protein, nucleic acid, nucleic acid-related substances, metallic fine particle, dendrimer, carbon nanohone, fine particle, micelle containing oil-soluble drug, reversed micelle containing water pool-soluble drug or protein, cell, liquid crystal, etc. Namely, it is possible to employ gas, liquid, solid, molecular assembly, etc. These materials can be employed singly or in combination thereof. 
     As for the first fluid  11 , water or oil can be employed. Further, gas can be also employed as the first fluid  11 . In order to enhance the stability of the multiple-phase particle  20 , a surfactant, a polymer or sugar may be optionally incorporated into the first fluid  11 . 
     In the manufacturing method of the multiple-phase particle  20  wherein the channel  3  is utilized according to the first embodiment of the present invention, it is desirable to suitably control the volume ratio between the second fluid  12  and the third fluid  13 . By doing so, the film thickness and particle diameter of the multiple-phase particle  20  can be easily controlled. Further, it is also desirable to suitably select and control the diameter, configuration and surface characteristics of the outlet port  31  as well as the extrusion rate of fluids, the flowing rate and temperature of the first fluid  11 , the kinds of emulsifier  14  to be included in the second fluid  12 , and the kinds of solvent to be employed. When these factors are suitably controlled, it would become possible to quickly and automatically manufacture a multiple-phase particle  20  which is minimal in non-uniformity with regard to the particle diameter, configuration and film thickness. 
     In the manufacturing apparatus  1  of the multiple-phase particle  20  shown in  FIG. 1 , if the multiple-phase particle  20  is positively or negatively charged, the multiple-phase particle  20  can be easily recovered by using an electroosmosis flow. In this case, an electrode is disposed at the continuous-phase supply portion  2  or at the recovery portion  6 . The same can be applied to the manufacturing apparatus shown in  FIG. 3 . When a nanoporous filter is disposed at the outlet port of channel, a multiple-phase particle which is much smaller in particle diameter can be obtained. For example, a hydrophilic nanoporous filter to be employed in the manufacture of a W/O/W double emulsion or multilamellar vesicle or in the manufacture of vesicle can be made to have a hydrophobic surface by surface-treating it by nonelectrolytic plating, etc. 
     First Application Example 
     The application of the present invention to the method of manufacturing different kinds of multiple-phase particles will be explained with reference to  FIG. 6 .  FIG. 6  shows a schematic view of the manufacturing apparatus for manufacturing multiple-phase particles according to this first application example of the first embodiment. 
     The manufacturing apparatus  1  shown herein comprises a second fluid supply portion  4  having a plurality of supply portions  41 - 43  which are juxtaposed each other. The supply portions  41 - 43  are communicated via a supply-control valve  44  and on/off valves  45  with a channel  3 . Further, the manufacturing apparatus  1  comprises a third fluid supply portion  5  having a plurality of supply portions  51 - 53  which are juxtaposed each other. The supply portions  51 - 53  are communicated via a supply-control valve  44  and on/off valves  45  with a channel  3 . A pencil pump  7  is disposed in between the continuous-phase supply portion  2  and the supply-control valve  44 . 
     In each of the supply portions  41 - 43  of the second fluid supply portion  4 , a second fluid containing a different kind of emulsifier  14  is filled so as to be controlled by the on/off valves  45 . In each of the supply portions  51 - 53  of the third fluid supply portion  5 , a different kind of material is filled so that a third fluid containing a different kind of material can be fed into the channel  3 . The supply of the third fluid can be controlled by using the supply-control valve  44  and the on/off valves  45 . 
     In addition to the emulsifier  14 , the second fluid may further contain a different kind of substance. Specific examples of such a substance include ligand, glycolipid, protein, electron-conjugated substance, fluorolipid, cyclodextrin, fullerene, molecular tong, porphyrin, steroid, photosensitive molecule, fluorescent pigment, sugar, crown ether, dendrimer, polypeptide, metallic fine particle, magnetic fine particle, polymeric fine particle, micro-particle, micelle or reversed micelle containing glycolipid, fluorolipid or protein, etc. As for the substance to be included in the second fluid, there is no particular limitation as long as the substance is capable of being stably existed in the second fluid or between the molecules of emulsifier  14 , or on the inner or outer membrane of double emulsion, vesicle or reversed vesicle. 
     As for the substance to be incorporated into the third fluid, it is possible to employ aromatic or odorous substances, drug, chemicals, dyestuffs, fluorescent agents, redox agents, amino acid, peptide, polypeptide, sugar, protein, nucleic acid, nucleic acid-related substances, metallic fine particle, magnetic fine particle, polymeric fine particle, micro-particle, dendrimer, carbon nanohone, micelle containing oil-soluble drug, reversed micelle containing water pool-soluble drug or protein, cell such as lactic acid bacterium and  E. coli , liquid crystal, or micelle or reversed micelle containing glycolipid, fluorolipid or protein, etc. 
     Owing to the interaction with the second fluid, the substances to be added to the third fluid are enabled to exist in the second fluid or between the molecules of emulsifier  14 , or adhere onto the inner or outer membrane of double emulsion, vesicle or reversed vesicle. As in the case of the substances to be added to the second fluid, the substances to be added to the third fluid are capable of acting as a modifying medium that can modify the membrane of double emulsion, vesicle or reversed vesicle. On the other hand, the substances to be added to the third fluid may be enclosed in a multiple-phase. 
     In the manufacturing apparatus  1  shown in  FIG. 6 , the second fluid  12  containing a different emulsifier  14  and the third fluid  13  containing a different substance will be alternately fed into the channel  3 . As a result, various kinds of multiple-phase particles  20  each enclosing a different substance can be manufactured. Furthermore, it is possible, through the employment of the manufacturing apparatus shown in  FIG. 6 , to manufacture a double emulsion or a vesicle where the inner membrane and the outer membrane are asymmetrical to each other, a double emulsion, a multilamellar vesicle or a vesicle which contain various kinds of bioactive substance, a double emulsion, a multilamellar reversed vesicle or a reversed vesicle where the membrane thereof is modified by protein. 
     Second Application Example 
       FIG. 7  shows a schematic view of the main portion of manufacturing apparatus of multiple-phase particle according to the second application example of the first embodiment. Namely,  FIG. 7  shows a region in the vicinity of the outlet port  31  of the manufacturing apparatus  1  shown in  FIG. 1 . As shown in  FIG. 7 , a first branch channel  32  and a second branch channel  33  are extended from the outlet ports  4 A and  5 A of the channel  3  to the outlet port  31 . The first branch channel  32  is designed to redifferentiate the second fluid  12  containing an emulsifier  14  and the third fluid  13  which are introduced into the channel  3 . The second branch channel  33  is designed to further redifferentiate the second fluid  12  and the third fluid  13  that have been redifferentiate at the first branch channel  32 . 
     In  FIG. 7 , the cross-sectional structures of the channel  3 , the first branch channel  32  and the second branch channel  33  as well as the configuration of the outlet port  31  are shown. The third fluid  13  is introduced into the second fluid  12  which has been redifferentiated at the second branch channel  33 . As the third fluid  13  is introduced in this manner, the second fluid  12  is pushed into the first fluid  11 . As a result, it is possible to form a multiple-phase particle  20  where the third fluid is enclosed in the second fluid. 
     By using the manufacturing apparatus provided with the channel  3  comprising the first branch channel  32  and the second branch channel  33 , a plural kinds of multiple-phase particles  20  corresponding to the ultimate number of the second branch channel  33  can be simultaneously manufactured. 
     Incidentally, there is no particular limitation with regard to the number of branch channels, so that one or not less than three branch channels can be disposed at the channel  3 . 
     Third Application Example 
       FIG. 8  shows a schematic view of the main portion of manufacturing apparatus of multiple-phase particle according to the third application example of the first embodiment. In the apparatus shown in  FIG. 8 , the outer surface of the channel  3  has the same surface characteristics as those of the outlet port  31 . Alternatively, the outer surface of the channel  3  has affinity to the multiple-phase particle. By controlling the manufacturing conditions such as the state of the first fluid  11  at the continuous-phase supply portion  2 , the multiple-phase particles  20  can be adhered to and arrayed regularly along the outer surface of the channel  3 . These multiple-phase particles  20  can be manufactured as a single inner aqueous phase type multiple-phase particle  20 A as shown in  FIG. 2  or as a multiple inner aqueous phase type multiple-phase particle  20 B. 
     When the sidewall of the continuous-phase-generating portion has the same surface characteristics as those of the channel  3 , the multiple-phase particle can be, likewise, regularly arrayed on the sidewall of the continuous-phase-generating portion. The same can be said also in the case where the sidewall of the continuous-phase-generating portion has affinity to the multiple-phase particle. 
     When the channel  3  is connected with a movable apparatus (for example, an XYZ stage) in the process of manufacturing the multiple-phase particle, the channel  3  can be moved three-dimensionally. Therefore, the multiple-phase particle can be manufactured at a predetermined location. 
     As explained above, in the method of manufacturing the multiple-phase particles  20  according to the first embodiment of the present invention, it is possible to realize a single stage emulsification method. Thus, it is possible to quickly and automatically manufacture a multiple-phase particle  20  which is minimal in non-uniformity with regard to the particle diameter, film thickness and sealed content, more specifically, a multiple inner aqueous phase type emulsion, a multiple inner oil phase type emulsion, a multiple inner vapor phase type emulsion, a single inner aqueous phase type emulsion, a single inner vapor phase type emulsion, a single inner oil phase type emulsion, vesicle, liposome or reversed vesicle. 
     Further, according to the manufacturing method of the first embodiment, the multiple-phase particle  20  can be manufactured under moderate conditions. It is also possible to obtain a multiple-phase particle  20  where a bioactive substance of high activity is efficiently sealed therein. 
     Further, according to the manufacturing method of the first embodiment, it is possible to manufacture the multiple-phase particle  20  where the inner membrane thereof differs from the outer membrane thereof. Additionally, according to the manufacturing method of the first embodiment, it is possible to manufacture the multiple-phase particle  20  which includes different kinds of phases. 
     In the manufacturing method of the first embodiment, it is possible to manufacture the multiple-phase particle  20  where more than one kind of substance is enclosed therein. According to the manufacturing apparatus  1  of the first embodiment, it is possible to easily execute the aforementioned manufacturing methods. 
     Next, specific examples according to the first embodiment of the present invention will be explained. 
     Comparative Example 1 
     A soft glass capillary (inner diameter=200 μm, outer diameter=300 μm, length=40 mm) which was not surface-treated was prepared. This capillary was then connected with the needle of microsyringe for gas chromatography (10 μL, HAMILTON Co., Ltd., type 84853) by using a Teflon (registered trademark) heat tube, thereby forming a channel  3 . Then, a microsyringe was fixed to a repeating dispenser. 
     Monoolein was employed as an emulsifier  14 , and decane was used as a solvent of the monoolein. The second fluid  12  containing the emulsifier  14  was prepared by dissolving the monoolein in decane in the concentration of 5 wt %. As for the third fluid  13 , an aqueous solution of water-soluble blue ink was employed. Further, pure water was employed as the first fluid  11 . 
     Then, by suction method, a W 1 /Os/W 2  emulsion was manufactured. More specifically, a distal end portion (outlet port  31 ) of the glass capillary connected with the microsyringe was alternately dipped into the second fluid  12  containing the emulsifier  14  and into the third fluid  13 , thereby respectively sucking about 35 nL-100 nL of these fluids. Then, a distal end portion (outlet port  31 ) of the glass capillary was introduced into a tube filled with pure water employed as the first fluid  11 , and then, by using a repeating dispenser, the second fluid  12  and the third fluid  13  were alternately pushed out of the microsyringe. By using an optical microscope (Keyence VH-5910), the behavior of formation of a blue-ink-entrapped W 1 /Os/W 2  emulsion was observed. By using the glass capillary, a solution of monoolein/decane (5 wt %) (Os) lipid employed as the second fluid  12  containing an emulsifier  14  and a solution of blue ink employed as the third fluid  13  were alternately pushed out. As a result, an Os/W 2  emulsion was mainly obtained. 
     Example 1 
     A polypropylene microtube (inner diameter=200 μm, outer diameter=300 μm) was connected with the needle of microsyringe for gas chromatography (10 μL, HAMILTON Co., Ltd., type 84853), thereby forming a channel  3 . In the following description, this channel  3  will be referred to as a microtube. 
     Then, in the same manner as in the case of Comparative Example 1, the second fluid  12  (Os) containing an emulsifier  14 , the third fluid  13  (W 1 ), and the first fluid  11  (W 2 ) were employed to manufacture a single inner aqueous phase type W 1 /Os/W 2  emulsion entrapping blue ink by the same suction method as described above. 
       FIG. 9A  shows a schematic diagram illustrating the manufacture of the single inner aqueous phase type W 1 /Os/W 2  emulsion entrapping ink by suction method according to Example 1.  FIG. 9B  shows a state where an aqueous solution of blue ink employed as the third fluid  13  was being introduced into the monoolein/decane (5 wt %) (Os) (a lipid solution phase) employed as the second fluid  12  containing an emulsifier  14 . 
     What is appeared white around the microtube (channel  3 ) illustrates a phenomenon that generated due to the refraction of light by the monoolein/decane (5 wt %) (Os) (a lipid solution phase). As shown in  FIG. 9B , the microtube exhibiting hydrophobicity was capable of trapping the second fluid  12  (Os) exhibiting hydrophobicity. Further, the microtube was capable of trapping an intermediate body  10  which was being expanded as the third fluid  13  was being introduced into the intermediate body  10  following the extrusion of the second fluid  12 . 
     As the third fluid  13  was continued to be introduced into this intermediate body  10  and this intermediate body  10  was continued to expand, the intermediate body  10  was grown into a semispherical body and then a microspherical body. When the microspherical body was expanded to a size which was large enough to release, the microspherical body was permitted to leave from the tip (outlet port  31 ) of tube and enter into the first fluid  11 . In this manner, it was confirmed that it was possible to manufacture, as a multiple-phase particle  20 , a single inner aqueous phase type W 1 /Os/W 2  emulsion entrapping ink. 
     The photograph of the multiple-phase particle  20  manufactured according to Example 1 is shown in  FIG. 9C . This multiple-phase particle is a single inner aqueous phase type W 1 /Os/W 2  emulsion entrapping a water-soluble blue ink at a high concentration. It was observed that when this multiple-phase particle was pierced using a needle, the ink-entrapped emulsion was instantaneously collapsed and at the same time, blue ink was simultaneously released from the ink-entrapped emulsion. 
     For the purpose of comparison, the photograph illustrating a state when a solution of blue ink was poured into an aqueous solution is shown in  FIG. 9D . As shown in  FIG. 9D , since the blue ink was water-soluble, it was difficult for the blue ink to retain a fixed configuration in an aqueous solution. Thus, the blue ink was quickly dispersed in the aqueous solution. In view of these facts, the emulsion enclosing blue ink at a high concentration was apparently a single inner aqueous phase type W 1 /Os/W 2  emulsion. 
     On the other hand, when the first fluid  11  is in a state of stationary phase in  FIG. 9A , even if a single inner aqueous phase type W 1 /Os/W 2  emulsion entrapping blue ink at a high concentration is manufactured as a multiple-phase particle  20 , it is difficult to enable the multiple-phase particle  20  to separate from the microtube (channel  3 ). Thus, the multiple-phase particle  20  was moved along the outer sidewall of the microtube. Alternatively, as shown in  FIG. 9E , the multiple-phase particle  20  adhered onto the microtube. According to this method, it is possible to array the multiple-phase particle  20  along the microtube. 
     As described above, according to Example 1, it was possible to manufacture a single inner aqueous phase type W 1 /Os/W 2  emulsion entrapping blue ink. 
     Example 2 
     A single inner aqueous phase type W 1 /Os/W 2  emulsion was manufactured under the same conditions as Example 1 except that a thin blue ink was employed as the third fluid  13 . This emulsion contained a thin blue ink and was minimal in scattering of particle diameter.  FIGS. 10A and 10B  illustrate the process of manufacturing the emulsion. The second fluid  12  containing an emulsifier  14  was introduced into the tube and then the third fluid  13  was introduced into the tube, thereby expanding the second fluid  12  at first into a semispherical body. Then, it was observed that the semispherical body deformed while being gradually shifted laterally. The single inner aqueous phase type W 1 /Os/W 2  emulsion thus formed is shown in  FIG. 10B . 
     Further, when the first fluid  11  was in a state of stationary phase, it was possible to enable the single inner aqueous phase type W 1 /Os/W 2  emulsion of the similar configuration to array along the microtube (channel  3 ) as shown in  FIG. 10C . 
     Example 3 
     A single inner vapor phase type V/Os/W 2  emulsion was manufactured under the same conditions as Example 1 except that air was employed as the third fluid  13 .  FIGS. 11A to 11D  illustrate the process of successively manufacturing the single inner vapor phase type V/Os/W 2  emulsion, i.e., one, four, six and seven pieces thereof, respectively. 
     Example 4 
     An emulsion was manufactured under the same conditions as Example 1 except that the second fluid  12  containing an emulsifier  14  was formulated such that sorbitan monooleate was employed as the emulsifier  14 , n-hexadecane was used as a solvent of the sorbitan monooleate. The second fluid  12  containing the emulsifier  14  was prepared by dissolving the sorbitan monooleate in n-hexadecane in the concentration of 0.088 M or 0.1. 
       FIGS. 12A and 12B  illustrate a single inner aqueous phase type W 1 /Os/W 2  emulsion entrapping blue ink where the concentration of the emulsifier  14  in the solution was set to 0.088 M. In this case, the single inner aqueous phase type W 1 /Os/W 2  emulsion was left free and permitted to adhere onto the outer sidewall of microtube (channel  3 ). 
       FIG. 13A  shows a process of introducing blue ink into the second fluid  12  containing the emulsifier  14  (0.1 M). The single inner aqueous phase type W 1 /Os/W 2  emulsion entrapping blue ink can be manufactured by introducing blue ink employed as the third fluid  13  into the second fluid  12  as in the case where monoolein was employed as the emulsifier  14 . 
       FIGS. 13B and 13C  illustrate a state where the single inner aqueous phase type W 1 /Os/W 2  emulsion entrapping blue ink was adhered onto the outer sidewall of microtube and a state where blue ink was released after the collapse of the emulsion. Concurrent with the instantaneous collapsing of the emulsion enclosing blue ink, the blue ink was permitted to release. Accordingly, the emulsion manufactured under the manufacturing conditions of this example was apparently a single inner aqueous phase type emulsion. 
     Comparative Example 2 
     An emulsion was manufactured under the same conditions as Example 4 except that the volume of aqueous solution of blue ink employed as the third fluid  3  was increased to about ten times as large as that of Example 4. It was possible, as shown in  FIGS. 14A and 14B , to manufacture a multiple inner aqueous phase type emulsion. However, it was difficult to minimize the scattering in size of inner aqueous phase. 
     Example 5 
     A single inner aqueous phase type emulsion was manufactured under the same conditions as Example 4 except that the manufacturing velocity (extrusion velocity) was altered. According to the principle shown in  FIG. 2 , a single inner aqueous phase type emulsion was manufactured. As a result, it was possible to obtain a multiple inner aqueous phase type emulsion ( 20 B) where the inner aqueous phase was minimal in scattering of particle diameter as shown in  FIG. 15 . In this example, the first fluid  11  was formed of a stationary system and the outer sidewall of the microtube was hydrophobic. Therefore, the multiple inner aqueous phase type emulsion thus manufactured was retained at the distal end of the microtube. 
     Example 6 
     An emulsion was manufactured under the same conditions as Example 4 except that the inner diameter and outer diameter of microtube were altered (inner diameter=100 μm, outer diameter=150 μm) and that the quantity of the second fluid  12  containing an emulsifier  14  as well as the quantity of the third fluid  13  (an aqueous solution of blue ink) were altered. 
     The single inner aqueous phase type emulsion enclosing an aqueous solution of blue ink thus obtained is shown in  FIG. 16A .  FIGS. 16B and 16C  illustrate a multiple inner aqueous phase type emulsion where the inner aqueous phase was minimal in scattering of particle diameter. The single inner aqueous phase type emulsion manufactured in Example 6 was smaller in particle diameter as compared with that of emulsion manufactured in Example 4. Further, the particle diameter of the inner aqueous phase of multiple inner aqueous phase type emulsion manufactured in Example 6 was smaller in particle diameter as compared with that of emulsion manufactured in Example 5. It was possible, through the control of the inner diameter of microtube and the quantity of the second fluid  12  as well as the quantity of the third fluid  13 , to control not only the particle diameter of the multiple-phase particle but also the particle diameter of the inner aqueous phase thereof. 
     Example 7 
     An emulsion was manufactured under the same conditions as Example 4 except that air and an aqueous solution of thin blue ink were employed as the third fluid  13  and 0.1 M NaCl solution was employed as the first fluid  11 . Further, an emulsion was manufactured under the same conditions as Example 4 except that air and an aqueous solution of thin blue ink were respectively employed as the third fluid  13  and that these third fluid  13  were alternately introduced into the microtube with the second fluid  12  being interposed therebetween. 
       FIGS. 17A and 17B  illustrate a single inner aqueous phase type emulsion entrapping blue ink and adhered to the microtube, and a single inner vapor phase type emulsion, respectively. 
       FIG. 17C  illustrates an emulsion where air and a thin blue ink were introduced respectively as a segment of the third fluid  13  into the microtube. As shown in  FIG. 17C , it was possible to manufacture an emulsion where an inner vapor phase and an inner aqueous phase were coexisted. 
     Example 8 
     An emulsion was manufactured under the same conditions as Example 4 except that a microtube whose distal end portion (the outlet port  31  of channel  3 ) was cut out at an angle of 20 degrees was employed as the microtube, that a solution containing a high concentration of blue ink and air were employed as the third fluid  13 , and that 0.1 M NaCl was employed as the first fluid  11 . 
       FIGS. 18A and 18B  illustrate a single inner aqueous phase type emulsion entrapping blue ink, and a single inner vapor phase type emulsion, respectively. 
     Second Embodiment 
     In the manufacturing apparatus  1  for a multiple-phase particle  20  according to the first embodiment, the construction of the channel  3  can be modified. The second embodiment of the present invention illustrates this modification. In the explanation of this embodiment, the constituent elements which function in the same manner as those employed in the aforementioned first embodiment will be referred to by the same reference numerals, thereby omitting the duplication of explanation thereof. 
     In this second embodiment of the present invention, there are explained a method as well as an apparatus for manufacturing multiple-phase particles  20  of various states such as a single inner aqueous phase type W/O/W emulsion, a multiple inner aqueous phase type W/O/W emulsion, vesicle, a single inner oil phase type O/W/O emulsion, a multiple inner oil phase type O/W/O emulsion, reversed vesicle, a single inner vapor phase type V/O/W emulsion, a multiple inner vapor phase type emulsion, etc. 
     The manufacturing apparatus  1  for a multiple-phase particle  20  according to the second embodiment is fundamentally the same in construction as the manufacturing apparatus  1  for a multiple-phase particle  20  according to the first embodiment. As shown in  FIG. 19A , the construction of the channel  3  differs from that of the  FIG. 3 . The channel  3  is formed of a dual passage structure consisting of an outer circumferential passage (outer passage)  301 , and an inner circular passage (inner passage)  302  disposed inside the outer circumferential passage  301 . The outer circumferential passage (outer passage)  301  guides the second fluid  12  containing an emulsifier  14  from the inlet port  4 A of the channel  3  to the outlet port  31 . On the other hand, the inner circular passage (inner passage)  302  guides the third fluid  13  from the inlet port  5 A of the channel  3  to the outlet port  31 . 
     The outlet port  31  is an outlet port of entire channel  3 . At the circumferential portion of the outlet port  31 , the outlet port  311  of the outer circumferential passage (outer passage)  301  is disposed for discharging the second fluid  12 . At the central portion of the outlet port  31 , the outlet port  312  of the inner circular passage  302  is disposed for discharging the third fluid  13 . 
     As shown in  FIG. 19B , the channel  3  is formed of a dual passage structure consisting of an outer circumferential passage (outer passage)  301 , and an inner circular passage (inner passage)  302 . The outer circumferential passage (outer passage)  301  guides the third fluid  13  from the inlet port  5 A of the channel  3  to the outlet port  31 . On the other hand, the inner circular passage (inner passage)  302  guides the second fluid  12  containing an emulsifier  14  from the inlet port  4 A to the outlet port  31 . 
     The outlet port  31  is an outlet port of entire channel  3 . At the circumferential portion of the outlet port  31 , the outlet port  311  of the outer circumferential passage  301  is disposed for discharging the third fluid  13 . At the central portion of the outlet port  31 , the outlet port  312  of the inner circular passage  302  is disposed for discharging the second fluid  12 . 
     In the manufacturing apparatus  1  (channel  3 ) shown in  FIG. 19A , the second fluid  12  containing an emulsifier  14  is fed from the second fluid supply portion  4  shown in  FIG. 3  to the outer circumferential passage (outer passage)  301  of the channel  3 , and the third fluid  13  is fed from the third fluid supply portion  5  to the inner circular passage  302 . At the outlet port  31  of the channel  3 , the third fluid  13  from the outlet port  312  of the inner circular passage  302  and the second fluid  12  from the outlet port  311  of the outer circumferential passage  301  are alternately discharged at constant intervals. At the outlet port  31 , the second fluid  12  is pushed into the first fluid  11  while introducing the third fluid  13  into the second fluid  12 . In this way, an intermediate body  10  of the multiple-phase particle  20  can be formed. 
     Further, from this intermediate body  10 , a multiple-phase particle  20  where the third fluid  13  is entrapped in the second fluid  12  can be formed. By alternately extruding the second fluid  12  and the third fluid  13  at fixed intervals from the outlet port  31  into the first fluid  11 , it is possible to obtain a multiple-phase particle  20  which is minimal in non-uniformity with regard to the particle diameter, film thickness and sealed content. 
     Further, in the manufacturing apparatus  1  (channel  3 ) shown in  FIG. 19B , the second fluid  12  containing an emulsifier  14  is fed from the second fluid supply portion  4  shown in  FIG. 3  to the inner circular passage  302  of the channel  3 , and the third fluid  13  is fed from the third fluid supply portion  5  to the outer circumferential passage  301 . At the outlet port  31  of the channel  3 , the second fluid  12  from the outlet port  312  of the inner circular passage  302  and the third fluid  13  from the outlet port  311  of the outer circumferential passage  301  are alternately discharged at constant intervals. As a result, at the outlet port  31 , the third fluid  13  is introduced into the second fluid  12 . At the same time, the second fluid  12  is pushed into the first fluid  11 . 
     In this way, an intermediate body  10  of the multiple-phase particle  20  can be formed. Further, from this intermediate body  10 , a multiple-phase particle  20  where the third fluid  13  is entrapped in the second fluid  12  can be formed. By alternately extruding the second fluid  12  containing an emulsifier  14  and the third fluid  13  at fixed intervals from the outlet port  31  into the first fluid  11 , it is possible to obtain a multiple-phase particle  20  which is minimal in non-uniformity with regard to the particle diameter, film thickness and sealed content. 
     According to the same principle as that explained with reference to  FIG. 8  of the aforementioned first embodiment, even in the channel  3  according to the second embodiment, the multiple-phase particle  20  can be adhered unidirectionally on the outer surface of the outer circumferential passage  301 . In this case, the wettability of the outer surface of the outer circumferential passage  301  and the manufacturing conditions such as flowing rate of the first fluid  11  should be suitably controlled. Further, the multiple-phase particle  20  may be arrayed at random. 
     As already explained with reference to the first embodiment, the multiple-phase particle  20  thus formed can be ultimately formed into a single inner aqueous phase type multiple-phase particle  20 A or into a multiple-phase type multiple-phase particle  20 B. 
     Incidentally, the wettability, in particular, of the outer surface of the outer circumferential passage  301  can be determined relative to the emulsifier  14  to be included in the second fluid  12 . Further, the wettability can be determined by suitably selecting the material for the outer circumferential passage  301  (channel  3 ) or by the roughening work of the surface of the outer circumferential passage  301 . 
     First Application Example 
     Application examples of the structure of the outlet port  31  of channel  3  are shown in  FIGS. 19C to 19E . The channel  3  shown in  FIG. 19C  is constructed such that the outlet port  312  of the inner circular passage  302  is protruded toward the first fluid  11  more than the outlet port  311  of the outer circumferential passage (outer passage)  301 . 
     The channel  3  shown in  FIG. 19D  is constructed such that the outlet port  312  of the inner circular passage  302  shown in  FIG. 19C  is provided with a branch passage  313  shown in  FIG. 7  and that the outlet port  312  is formed into a tandem structure in external appearance. 
     The channel  3  shown in  FIG. 19E  is constructed such that the location of the outlet port  312  of the inner circular passage  302  is made the same as that of the outlet port  311  of the outer circumferential passage  301  and it is provided with a branch passage  313  shown in  FIG. 19D . The outlet port  311  of the outer circumferential passage  301  is equipped with a nanoporous filter  303 . When the outer circumferential passage  301  is made of a material such as aluminum, titanium, silicon, etc., the nanoporous filter can be easily manufactured in the vicinity of the outlet port  311  by using electrochemical etching (ECE) technique, i.e. anodic oxidation or etching technique for instance. It is possible, through the control of etching conditions of ECE, to manufacture a nanoporous filter having a pore size ranging from 5 nm to 500 nm. 
     Second Application Example 
     Application examples of the structure of the outlet port  31  of channel  3  are shown in  FIGS. 20A to 20F  according to the fist application example shown in  FIG. 19A . The configuration of the outlet port  31  is fundamentally constructed such that the outlet port  312  of the inner circular passage  302  is disposed at a central portion of the outlet port  31  of channel  3 . At the peripheral portion of the outlet port  31 , the outlet port  311  of the outer circumferential passage  301  is disposed so as to surround the outlet port  312  of the inner circular passage  302 . The channel  3  is required to be constructed such that the second fluid  12  can be efficiently fed to the outlet port  311  of the outer circumferential passage  301  for feeding the second fluid  12  containing an emulsifier  14 . And the third fluid  13  can be efficiently fed to the outlet port  312  of the inner circular passage  302  for feeding the third fluid  13 . There is no particular limitation with regard to the configuration of outlet port  31  of channel  3 . 
     The channel  3  shown in  FIG. 20A  is constructed such that it comprises an annular outlet port  312  of the inner circular passage  302  and an annular outlet port  311  of the outer circumferential passage  301  which is disposed concentric with the outlet port  312 . In any of  FIGS. 20A to 20F , the outlet port  312  of the inner circular passage  302  is manufactured using a hydrophilic material. On the other hand, the outlet port  311  of the outer circumferential passage  301  is manufactured using a hydrophobic material in any of  FIGS. 20A to 20F , thereby enabling the second fluid  12  containing an emulsifier  14  to be discharged therefrom. The second fluid  12  further spreads out to form a film that adheres onto the outlet port  31 . 
     The channel  3  shown in  FIG. 20B  is constructed such that it comprises three annular outlet ports  312  of three inner circular passages  302  and an annular outlet port  311  of the outer circumferential passage  301  which is disposed to surround all of these outlet ports  312 . 
     The channel  3  shown in  FIG. 20C  is constructed such that it comprises seven annular outlet ports  312  of seven inner circular passages  302  and an annular outlet port  311  of the outer circumferential passage  301  which is disposed to surround all of these outlet ports  312 . 
     The channel  3  shown in  FIG. 20D  is constructed such that it comprises a plurality of annular outlet ports  312  disposed in a single inner circular passage  302  and an annular outlet port  311  of the outer circumferential passage  301  which is disposed to surround all of these outlet ports  312 . 
     The channel  3  shown in  FIG. 20E  is constructed such that it comprises a trianglar outlet port  312  of the inner circular passage  302  and an annular outlet port  311  of the outer circumferential passage  301  which is disposed to surround all of these outlet ports  312 . 
     The channel  3  shown in  FIG. 20F  is constructed such that it comprises an annular outlet port  312  of the inner circular passage  302  and a rectangular outlet port  311  of the outer circumferential passage  301  which is disposed to surround the outlet port  312 . 
     Each of the inlet ports of the inner circular passages  302  shown in  FIGS. 20B to 20D  may be constructed separately from each other. Alternatively, these inlet ports may be formed integral with each other. When these inlet ports are individually constructed, different kinds of multiple-phase particles  20  of inner vapor phase type, liquid phase type and oil phase type double emulsions can be manufactured. 
     Incidentally, as for the first fluid  11 , the emulsifier  14 , the second fluid  12  and the third fluid  13 , the same kinds of substances as described with reference to the aforementioned first embodiment can be used. These fluids including the first fluid  11  can be optionally combined with each other depending on the kind of multiple-phase particle  20  desired to obtain. 
     Third Application Example 
     Application examples of the structure of the outlet port  31  of channel  3  are shown in  FIGS. 21A to 21D  according to the fist application example shown in  FIG. 19B . The channel  3  shown in  FIG. 21A  is constructed is constructed in the same manner with respect to the configuration as that the outlet port  31  of channel  3  shown in  FIG. 20A  except that the outlet port  312  of the inner circular passage  302  and the outlet port  311  of the outer circumferential passage  301  are both made of hydrophobic materials. The inner circular passage  302  shown in  FIGS. 21A to 21D  is designed such that the second fluid  12  containing an emulsifier  14  is fed thereto. 
     The channel  3  shown in  FIG. 21B  is constructed in the same manner with respect to the configuration as that the outlet port  31  of channel  3  shown in  FIG. 20E  except that the outlet port  312  of the inner circular passage  302  and the outlet port  311  of the outer circumferential passage  301  are both made of hydrophobic materials. 
     The channel  3  shown in  FIG. 21C  is constructed in the same manner with respect to the configuration as that the outlet port  31  of channel  3  shown in  FIG. 20F  except that the outlet port  312  of the inner circular passage  302  and the outlet port  311  of the outer circumferential passage  301  are both made of hydrophobic materials. 
     The channel  3  shown in  FIG. 21D  is constructed such that the outlet port  31  of channel  3  is constructed opposite to the configuration of the outlet port  31  of channel  3  shown in  FIG. 20D . Namely, a single annular outlet port  312  of the inner circular passage  302  is surrounded by three annular outlet ports  311  of the outer circumferential passage  301 . At least the outer surface of a region of the outer circumferential passage  301  where the outlet ports  311  are located is made hydrophobic and the outer surface of other portions of the outer circumferential passage  315  is made hydrophilic. The outer surface of other portion  314 , which is surrounding the inner circular passage  302  and the outer circumferential passage  301 , is made hydrophobic. The outlet port  312  of the inner circular passage  302  is formed of a hydrophobic material. 
     Fourth Application Example 
     In the channel  3  having a dual passage structure according to the aforementioned second and third application examples of the second embodiment, the surface characteristics of the inner circular passage  302  and the outer circumferential passage  301  may be suitably combined with the features of the first fluid  11 , the second fluid  12  and the third fluid  13 , thereby making it possible to manufacture various kinds of multiple-phase particle  20 . 
     As shown in  FIG. 22A , it is possible to employ a channel  3  provided with a hydrophobic outer circumferential passage  301 . Alternatively, it is also possible to employ a channel  3  where the outer wall of the inner circular passage  302  and the outlet port  312 , or the inner wall of the outer circumferential passage  301  and the outlet port  311  are partially lipophilized. In the employment of this channel  3 , gas (V) or a hydrophilic liquid (W 1 ) is fed as the third fluid  13  to the inner circular passage  302  and a lipophilic second fluid  12  (Os) containing at least one emulsifier  14  is fed to the outer circumferential passage  301 . Then, the second fluid  12  and the third fluid  13  are alternately introduced from the outlet port  31  into a hydrophilic first fluid (W 2 ) at predetermined intervals. 
     As a result, it is possible to manufacture a multiple-phase particle  20  of a single inner vapor phase type V/Os/W 2  emulsion, a multiple inner vapor phase type V/Os/W 2  emulsion, a single inner aqueous phase type W 1 /Os/W 2  emulsion, a multiple inner aqueous phase type W 1 /Os/W 2  emulsion, and vesicle. 
     Further, as shown in  FIG. 22B , it is possible to employ a channel  3  provided with a hydrophobic inner circular passage  302 . Alternatively, it is also possible to employ a channel  3  where the outer wall of the inner circular passage  302  and the outlet port  312 , and the inner wall of the outer circumferential passage  301  and the outlet port  311  are partially lipophilized. In the employment of this channel  3 , gas (V) or a hydrophilic liquid (W 1 ) is fed as the third fluid  13  to the outer circumferential passage  301  and a lipophilic second fluid  12  (Os) containing at least one emulsifier  14  is fed to the inner circular passage  302 . 
     Then, the second fluid  12  and the third fluid  13  are alternately introduced from the outlet port  31  into a hydrophilic first fluid (W 2 ) at predetermined intervals. As a result, it is possible, through a single-step emulsification method, to manufacture a multiple-phase particle  20  of a single inner vapor phase type V/Os/W 2  emulsion, a multiple inner vapor phase type V/Os/W 2  emulsion, a single inner aqueous phase type W 1 /Os/W 2  emulsion, a multiple inner aqueous phase type W 1 /Os/W 2  emulsion, and vesicle, wherein the third fluid is entrapped in the second fluid. 
     As shown in  FIG. 23A , it is possible to employ a channel  3  provided with a hydrophilic outer circumferential passage  301 . Alternatively, it is also possible to employ a channel  3  where the outer wall of the inner circular passage  302  and the outlet port  312 , and the inner wall of the outer circumferential passage  301  and the outlet port  311  are partially hydrophilized. In the employment of this channel  3 , gas (V) or a lipophilic liquid (O 1 ) is fed as the third fluid  13  to the inner circular passage  302  and a hydrophilic second fluid  12  (Ws) containing at least one emulsifier  14  is fed to the outer circumferential passage  301 . 
     Then, the second fluid  12  and the third fluid  13  are alternately introduced from the outlet port  31  into a lipophilic first fluid (O 2 ) at predetermined intervals. As a result, it is possible to manufacture, by a single-step emulsification method, a multiple-phase particle  20  of a single inner vapor phase type V/Ws/O 2  emulsion, a multiple inner vapor phase type V/Ws/O 2  emulsion, a single inner oil phase type O 1 /Ws/O 2  emulsion, a multiple inner oil phase type O 1 /Ws/O 2  emulsion, and reversed vesicle. 
     As shown in  FIG. 23B , it is possible to employ a channel  3  provided with a hydrophilic inner circular passage  302 . Alternatively, it is also possible to employ a channel  3  where the inner wall of the inner circular passage  302  and the outlet port  312 , and the inner wall of the outer circumferential passage  301  and the outlet port  311  are partially hydrophilized. In the employment of this channel  3 , gas (V) or a lipophilic liquid (O 1 ) is fed as the third fluid  13  to the outer circumferential passage  301  and a hydrophilic second fluid  12  (Ws) containing at least one emulsifier  14  is fed to the inner circular passage  302 . 
     Then, the second fluid  12  and the third fluid  13  are alternately introduced from the outlet port  31  into a lipophilic first fluid (O 2 ) at predetermined intervals. As a result, it is possible to manufacture, by a single-step emulsification method, a multiple-phase particle  20  of a single inner vapor phase type V/Ws/O 2  emulsion, a multiple inner vapor phase type V/Ws/O 2  emulsion, a single inner oil phase type O 1 /Ws/O 2  emulsion, a multiple inner oil phase type O 1 /Ws/O 2  emulsion, and reversed vesicle. 
     In the method of manufacturing the multiple-phase particles  20  according to the second embodiment of the present invention, it is possible to realize a single stage emulsification method. Thus, it is possible to automatically manufacture a multiple-phase particle  20  which is minimal in non-uniformity with regard to the particle diameter, film thickness and sealed content, more specifically, a single inner aqueous phase type emulsion, a single inner oil phase type emulsion, a single inner vapor phase type emulsion, vesicle, liposome, reversed vesicle, a multiple inner aqueous phase type emulsion, a multiple inner oil phase type emulsion, a multiple inner vapor phase type emulsion. 
     Further, according to the manufacturing method of the second embodiment, the multiple-phase particle  20  can be manufactured under moderate conditions. It is also possible to obtain a multiple-phase particle  20  where a bioactive substance of high activity is efficiently sealed therein. 
     Further, according to the manufacturing method of the second embodiment, it is possible to manufacture the multiple-phase particle  20  where the inner membrane thereof differs from the outer membrane thereof. 
     Additionally, according to the manufacturing apparatus  1  of the second embodiment, it is possible to easily execute the aforementioned manufacturing methods. 
     Next, specific examples according to the second embodiment of the present invention will be explained. 
     Example 1 
     By using the same structure as that of channel  3  shown in  FIG. 22A , a blue ink-enclosed W 1 /Os/W 2  emulsion. More specifically, a stainless steel pipe (inner diameter=130 μm, outer diameter=470 μm) which was cut out at an angle of 20 degrees was used as the inner circular passage  302 . As for the outer circumferential passage  301 , a polypropylene microtube was employed. Thus, a channel  3  of dual passage structure comprising these inner circular passage  302  and outer circumferential passage  301  was employed. 
     Sorbitan monooleate was employed as the emulsifier  14 , and n-hexadecane was used as a solvent of the Sorbitan monooleate. The second fluid  12  containing the emulsifier  14  was prepared by dissolving the Sorbitan monooleate in n-hexadecane in the concentration of 0.1 M. As for the third fluid  13 , an aqueous solution of water-soluble blue ink of low concentration was employed. Further, pure water was employed as the first fluid (continuous-phase)  11 . 
     A Teflon (registered trademark) heat tube was connected with the needle of microsyringe for gas chromatography (10 μL, HAMILTON Co., Ltd., type 84853). Then, a microsyringe was fixed to a repeating dispenser. Further, the outer circumferential passage  301  was also connected with the needle of microsyringe for gas chromatography (10 μL, HAMILTON Co., Ltd., type 84853). 
     In the manufacture of the blue ink-enclosed W 1 /Os/W 2  emulsion, the second fluid  12  containing the emulsifier  14  was at first pushed out of the outer circumferential passage  301  to enable this solution to adhere onto the inlet port  311 . Then, an aqueous solution of blue ink of low concentration employed as the third fluid  13  was pushed out of the inner circular passage  302 , thereby introducing the third fluid  13  into the second fluid  12 . As the third fluid  13  was continued to introduce into the second fluid  12 , the second fluid  12  was enabled to act as a boundary film between the third fluid  13  and the first fluid  11 , thereby forming an intermediate body  10  as shown in  FIG. 24A . When the third fluid  13  was further continuously introduced into the second fluid  12 , the intermediate body  10  was expanded to form a micro-spherical body. When this micro-spherical body was further expanded large enough to reach the releasing stage, the micro-spherical body was separated from the outlet port  31 . As a result, as shown in  FIG. 24B , the micro-spherical body adhered onto the outer surface of the outer circumferential passage  301 , thereby forming a thin blue ink-enclosed W 1 /Os/W 2  emulsion. 
     For the purpose of comparison, a thin blue ink employed as the third fluid  13  was continuously discharged from the inner circular passage  302  without continuously supplementing the second fluid  12  to the vicinity of the outlet port  311  from the outer circumferential passage  301 . In this case, it was difficult to observe the formion of blue ink-enclosed emulsion, and instead, the outflow of blue ink was observed as shown in  FIGS. 24B and 24C . 
     Example 2 
     The manufacture of an emulsion was executed under the same conditions as Example 1 of the second embodiment except that a thick blue ink was employed as the third fluid  13  and that the outlet port  312  of the inner circular passage  302  was extended longer than the outlet port  311  of the outer circumferential passage  301  as shown  FIGS. 25A and 25B . 
     As a result, an intermediate body  10  was formed as in the case of Example 1. When the third fluid  13  was further continuously introduced into the second fluid  12 , the intermediate body  10  was expanded to form a microspherical body. When this microspherical body was further expanded large enough to reach the releasing stage, the microspherical body was separated from the outlet port  31 . As a result, it was possible to form a thick blue ink-enclosed single inner aqueous phase type W 1 /Os/W 2  emulsion being adhered onto the outer surface of the outer circumferential passage  301 .  FIG. 25B  shows a couple of thick blue ink-enclosed single inner aqueous phase type W 1 /Os/W 2  emulsions that had been continuously formed by this manufacturing method. 
     Example 3 
     The manufacture of a blue ink-enclosed V/Os/W 2  emulsion as a multiple-phase particle  20  was performed by using a channel  3  having the same structure as the channel  3  shown in  FIG. 22A . More specifically, a stainless steel pipe (inner diameter=130 μm, outer diameter=470 μm) which was cut out at an angle of 90 degrees was prepared as the inner circular passage  302 . As for the outer circumferential passage  301 , a silicone tube was employed. Thus, a channel of dual passage structure consisting of these inner circular passage  302  and outer circumferential passage  301  was employed. 
     As for the second fluid  12  containing an emulsifier, a solution of decane containing 5 wt % of monoolein was employed. As for the third fluid  13 , air was employed. Other conditions were the same as those of Example 1 shown in  FIG. 22A . Under these conditions, it was possible to manufacture a multiple-phase particle  20  of single inner vapor phase type V/Os/W 2  emulsion which was excellent in uniformity of particle size. 
     Incidentally, it should be understood that the present invention is not limited to the aforementioned embodiments and that these embodiments can be variously modified without departing from the spirit or scope of the general inventive concept as defined by the appended claims and their equivalents. 
     Additional advantages and modifications will readily occur to those skilled in the art. Therefore, the invention in its broader aspects is not limited to the specific details and representative embodiments shown and described herein. Accordingly, various modifications may be made without departing from the spirit or scope of the general inventive concept as defined by the appended claims and their equivalents.