WO2009082535A2

WO2009082535A2 - Method and device for microreactor pressure control

Info

Publication number: WO2009082535A2
Application number: PCT/US2008/080200
Authority: WO
Inventors: R. Michael Van Dam; Kan Liu; Kwang-Fu Clifton Shen; Hsian-Rong Tseng
Original assignee: The Regents Of The University Of California
Priority date: 2007-10-16
Filing date: 2008-10-16
Publication date: 2009-07-02
Also published as: WO2009082535A3

Abstract

A microfluidic device has a device body, wherein the device body defines a microfluidic reactor and a pressure control system therein, the pressure control system being arranged proximate the microfluidic reactor. The microfluidic device also has a fluid-permeable membrane arranged between the microfluidic reactor and the pressure control system, the fluid-permeable membrane having a surface area and thickness such that a fluid can pass from a high pressure side to a low pressure side of said fluid-permeable membrane during operation of the microfluidic device to at least one of change a pressure in the microfluidic reactor in a preselected manner, to maintain a substantially constant pressure in the microfluidic reactor, to change a composition of fluids in the microfluidic reactor, or maintain a composition of fluids in the microfluidic reactor. A method on performing chemical reactions includes introducing a plurality of chemical substances into a microfluidic reactor, wherein the microfluidic reactor has a fluid-permeable membrane between at least a portion of the microfluidic reactor and a microfluidic pressure control system; and at least one of pressurizing with a fluid or evacuating a region of the pressure control system proximate the fluid-permeable membrane to cause fluid to pass through the fluid-permeable membrane in a predetermined manner in order to cause a predetermined effect on a chemical reaction in the microfluidic reactor.

Description

METHOD AND DEVICE FOR MICROREACTOR PRESSURE CONTROL CROSS-REFERENCE TO RELATED APPLICATION

[0001 ] This application claims priority to U.S. Provisional Application No. 60/960,844 filed October 16, 2007, the entire contents of which are hereby incorporated by reference.

[0002] This invention was made using U. S. Government support under DOE Grant No. DE-FG-06ER64249 and NIH Grant No. U54 CAl 19347-02. The U.S. Government has certain rights in this invention.

BACKGROUND

1. Field of Invention

[0003] The present invention relates to methods and devices for microreactor pressure control, and more particularly to methods and devices for microreactor pressure control using gas-permeable membranes in microfluidic devices.

2. Discussion of Related Art

[0004] The perfoπnance (e.g. chemical yield) of chemical reactions depends on many parameters, such as temperature, reaction time, and pressure, in addition to reagent concentrations, solvent, and other factors. Pn the construction of microfluidic chips for chemical synthesis, it is desirable to have individual control of each reaction parameter as this facilitates optimization and ensures that reaction conditions can be consistently reproduced. Pressure is an important parameter because it has been shown in many cases in conventional synthesis that reaction performance can be improved by superheating the solution above the boiling point of the solvent. To avoid significant evaporation of the solvent (and therefore changes in concentration), it is necessary to seal the reaction vessel, inside which the pressure increases until reaching the solvent vapor pressure at the current temperature (a physical property of the liquid). Alternatively, solvent vapor can be added to the system to replace that being lost.

[0005] Reactions in microfluidic chips can be extremely precisely controlled. The rapid heat transfer and mixing results in extremely high uniformity of concentrations and temperatures inside the system. There is considerable literature showing improved performance (yield, speed, selectivity) of reactions carried in microreactors instead of conventional apparatus.

[0006J In continuous flow reactors such as those made from glass, silicon, or other inert, rigid, non-permeable materials, it is straightforward to achieve independent control of temperature, reaction time (function of fixed channel length and flow rate), and pressure (by adjustment of backpressure). Commercial systems based on these principles exist (e.g. from Syrris, Inc.). However, a drawback of continuous flow reactors is that they are not suited to discrete "batch" microfluidic operations, especially when very tiny volumes of liquid must be manipulated, such as in radiochemistry and biological-molecule-labeling applications.

[0007] Manipulation of extremely tiny volumes can, however, easily be achieved by "digital" platforms such as droplet based devices or by elastomeric microfluidic chips with integrated pneumatic/hydraulic valves and pumps. A key feature of the latter is the ability to perform chemical process steps that cannot easily be performed in continuous flow microfluidic chips, such as solvent-exchange (Lee, C-C et al. Multistep Synthesis of a Radiolabeled Imaging Probe Using Integrated Microfluidics. Science 310(5755), 1793-1796 (2005)). However, the gas-permeability that enables this process (by evaporation through the polymer chip itself) is also sometimes a disadvantage. For example, when performing a reaction at high temperature in a volatile solvent, the solvent can evaporate through the walls of the microreactor ("chip") causing changes in concentration of solutes over time, and ultimately leading to drying that halts the reaction (possibly prematurely). There thus remains a need for improved methods and devices for microreactor pressure control.

SUMMARY

[0008] A microfluidic device according to an embodiment of the current invention has a device body, wherein the device body defines a microfluidic reactor and a pressure control system therein, the pressure control system being arranged proximate the microfluidic reactor. The microfluidic device also has a fluid-permeable membrane arranged between the microfluidic reactor and the pressure control system, the fluid-permeable membrane having a surface area and thickness such that a fluid can pass from a high pressure side to a low pressure side of said fluid-permeable membrane during operation of the micro fluidic device to at least one of change a pressure in the micro fluidic reactor in a preselected manner, to maintain a substantially constant pressure in the microfluidic reactor, to change a composition of fluids in the microfluidic reactor, or maintain a composition of fluids in the microfluidic reactor.

[0009] A method on performing chemical reactions according to some embodiments of the current invention includes introducing a plurality of chemical substances into a microfluidic reactor, wherein the microfluidic reactor has a fluid-permeable membrane between at least a portion of the microfluidic reactor and a microfluidic pressure control system; and at least one of pressurizing with a fluid or evacuating a region of the pressure control system proximate the fluid-permeable membrane to cause fluid to pass through the fluid-permeable membrane in a predetermined manner in order to cause a predetermined effect on a chemical reaction in the microfluidic reactor.

BRIEF DESCRIPTION OF THE DRAWINGS

[0010] Additional features of this invention are provided in the following detailed description of various embodiments of the invention with reference to the drawings. Furthermore, the above-discussed and other attendant advantages of the present invention will become better understood by reference to the detailed description when taken in conjunction with the accompanying drawings, in which:

[001 1] Figure 1 is a schematic illustration of a conventional microfluidic devices; [0012] Figure 2 is a photograph of an embodiment of a microiliiidic device according to the current invention;

[0013] Figure 3 is a schematic illustration that shows a cross sectional perspective view of a micro fluidic device according to an embodiment of the current invention;

[0014] Figure 4 is a schematic illustration of a cross sectional view of a structure of a micro fluidic device according to an embodiment of the current invention; and

[0015] Figure 5 is a schematic illustration of the mcrofluidic chip cross-section when applying vacuum to the pressure-control device or when applying pressure.

DETAILED DESCRIPTION OF VARIOUS EMBODIMENTS

[0016] We provide a method and device for controlling pressure inside a microreactor, and controlling the flow of gas/vapor into and out of the reactor. Our invention can be useful in microfluidic chips fabricated from gas-permeable or semi-gas-permeable materials including elastomers such as PDMS (poly-dimethylsiloxane) or PFPE (perfluoropolyether), for example.

[0017] Our invention can address the above-noted limitations of elastomeric chips by manipulating the pressure in a channel adjacent to the microreactor, such that microreactor pressure and the flow of gas/vapor in and out of the reactor can be controlled. This can facilitate on-chip operations including: (i) speeding of solvent removal by evaporation, even when intrinsic permeability of chip material to solvent is relatively low; (ii) removing air from a reactor prior to filling reagents to speed up the filling process (i.e. if dead-end filling); and (iii) applying pressure to a reaction mixture to prevent evaporation under ambient conditions or to allow superheating or simply to allow control of pressure as an independent parameter.

[0018] There is very little prior art in this area because elastomeric chips have not been extensively used to perform chemical reactions, especially multi-step ones, and so such capabilities have not been necessary. This is primarily due to the unsuitability of the PDMS chip platform for chemistry, due to incompatibility with many organic solvents and reagents (Mukhopadhyay R. When PDMS isn't the best. Analytical Chemistry 79(9), 3248-3253 (2007); Lee, J.N., Park, C, Whitesides, G.M. Solvent compatibility of poly(dimethylsiloxane)-based microfluidic devices. Analytical Chemistry 75, 6544-6554 (2003)). With the advent of PFPE and other inert elastomers, it has become a real possibility to consider multi-step chemistry applications in conjunction with elastomeric chips (Rolland, J. P., Van Dam, R. M., Schorzman, D. A., Quake, S. R. & DeSimone, J. M. Solvent-resistant photocurable "liquid teflon" for microfluidic device fabrication. Journal of the American Chemical Society 126, 2322-2323 (2004)). Published work in this area is so far limited to the synthesis of DNA (Huang, Y., Castrataro, P., Lee, C-C, Quake, S. R. Solvent resistant microfluidic DNA synthesizer. Lab on a Chip 7, 24-26 (2007)), but the reaction conditions are very mild (ambient temperature and low pressures) and it undergoes solvent-exchange under ambient conditions because it is a solid-phase procedure.

[0019] Our group at UCLA has previously explored synthesis of radiopharmaceuticals (Lee, C-C et al. Multistep Synthesis of a Radiolabeled Imaging Probe Using Integrated Microfluidics. Science 310(5755), 1793-1796 (2005)). In these chips, solvents must be evaporated through the whole elastomeric matrix of the chip. Because vapors travel through the entire chip there is a high likelihood that some solvent remains within the chip. This can be a problem if it diffuses back to the reactor during later steps (e.g., if water is evaporated but remains in the elastomer matrix, it can contaminate a later water-sensitive reaction). We further observed the problem that pressure cannot be controlled independently (though superheating is possible by raising the temperature above the solvent boiling point). Due to the tiny liquid volume and permeability of the chip material, the solvent is typically gone within seconds to minutes and reaction times cannot be controlled (especially if long reactions are desired) and reagent concentrations vary continuously.

[0020] In other work, we (at Caltech/Siemens) have built a closed "coin-shaped" reactor chip in principle capable of superheating (Elizarov, A.M., KoIb, H. C, van Dam, R.M., Heath, J. R., Padgett, H. C, Huang, J., Daridon, A. Coin-shaped reactor in microfluidic devices used for radiopharmaceutical synthesis. Proc. Nanotech 2006. 2006; 2: 542-545; Elizarov, A.M., van Dam, R.M., Heath, J.R., KoIb, H.C., Huang, J., Daridon, A. Microfluidic device with coin-shaped reactor for radiopharmaceutical synthesis. Proc. ACS 2006 2006; van Dam, R.M., Elizarov, A.M., Ball, E., Shen, CK-F , KoIb, H., Rolland, J., Diener, L., Williams D., Edgecombe, B., Stephen, T., Heath, J.R. Automated microfluidic chip and system for the synthesis of radiopharmaceuticals on human-dose scales. Proc. Nanotech 2007. 2007; 3: 300-303) but, like above, pressure was not an independent variable; rather the pressure obtained was simply the vapor pressure at the working temperature and could not be separately controlled. Due to the larger volume of liquid, the solvent took longer to dry at a given temperature, but reaction time was still entangled with temperature, permeability, and ever-changing reagent concentrations. However, the coin- reactor design (Figure 1 ) was not used for performing operations we describe here. Furthermore, the coin-shaped reactor suffered from issues of poorly controlled mixing, and some structural integrity issues when working at high temperatures (and therefore pressures), so the combination of our microchannel-based reactor and associated pressure/vacuum channel can provide superior control over all aspects of the reaction.

[0021] Another way to apply pressure as an independent variable is to have an open channel into the reactor. It is essential that this be done at a position where there is no liquid to prevent loss of the reactor contents. This approach is being pursued by Siemens and is essentially the basis of the SYRRIS continuous-flow microreactor mentioned above. A disadvantage of this approach is the risk of losing liquid from the reaction mixture (especially for precious reagents) either in a bulk leak or due to splashing etc causing a minor volume leak. Our system according to various embodiments of the current invention uses a completely closed reactor with permeable membrane on at least one side so fluid is always fully contained.

[0022] Figure 2 is a photograph of a micro fluidic device 100 according to an embodiment of the current invention. The micro fluidic device 100 has a device body 102 attached to or formed on a substrate (not visible in Figure 1). The channel structures defined by the device body are enhanced in the photograph of Figure 2 by filling them with colored dyes to indicate the different types of channel structures. The device body 102 of the micro fluidic device 100 defines a micro fluidic reactor 104 and a pressure control system 106 arranged proximate the micro fluidic reactor 104. In this example, the microfluidic reactor 104 is a ring reactor. However, the broad concepts of the current invention are not limited to only ring reactors. The microfluidic device 100 comprises a fluid-permeable membrane 108 arranged between the microfluidic reactor 104 and the pressure control system 106. In Figure 2, 108 is intended to refer to the membrane below upper layers of material. There is a membrane vertically between a portion of this upper section and the section of 104 directly beneath. In this particular example there are a plurality of fluid-permeable membranes arranged proximate the micro fluidic reactor 104, only one of which is labeled in Figure 2 (fluid-permeable membrane 108). The fluid- permeable membrane 108 has a surface area and thickness such that a fluid can pass from a high pressure side to a low pressure side of the fluid-permeable membrane 108 during operation of the micro fluidic device 100 to at least one of change a pressure in the micro fluidic reactor 104 in a preselected manner or to maintain a substantially constant pressure in the micro fluidic reactor 104. Some embodiments could have a single fluid- penneable membrane, while other may have a plurality of fluid-permeable membranes, in some cases ten, twenty or more fluid-permeable membranes. In the example of Figure 2, the large number of fluid-permeable membranes provide a large surface area between the micro fluidic reactor 104 and the pressure control system 106 while maintaining good structural integrity.

[0023] The pressure control system 106 can include a fluid input channel 110 and a fluid output channel 1 12. In the example of Figure 2, the fluid input channel 110 branches into three fluid input channels. The invention is not limited to any particular number of fluid input and output channels in the pressure control system 106. Furthermore, the fluid input channel 1 10 and/or the fluid output channel 1 12 could be used for both input and output of fluid to pressurize and/or evacuate the pressure control system at different times, or could be blocked at certain times during operation. [0024] The microfluidic reactor 104 can include one or more fluid input/output channels such as fluid input/output channels 1 14, 116, 1 18 and 120. Each of the fluid input/output channels could branch into multiple channels as show in Figure 2 for fluid input/output channels 1 14, 1 16 and 120. In addition, each main fluid input/output channel 1 14, 116, 1 18 and 120 and/or the branch channels can have a valve structure to control fluid flow, as is illustrated in the example of Figure 2. For example, the channel 122 leads to a valve mechanism on the fluid input/output channel 1 14 indicated as the heavy crass line segment in the figure. Similarly, the channels 124, 126 and 128 lead to valves to each of three branch channels that lead to main fluid input/output channel 114. The valves can be pneumatic and/or hydraulic valves, for example. Other microfluidic structures can be included in various embodiments of a microfluidic device according to the current invention. The microfluidic device 100 in the example of Figure 2 also includes a microfluidic pump 130 that has the pneumatic/hydraulic control channels 132, 134 and 136. However, other embodiments may include less, more or different microfluidic structures built in along with the microfluidic reactor 104 and a pressure control system 106. Further, microfluidic reactors and a pressure control systems according to various embodiments of the current invention are not limited to only the particular examples illustrated herein.

[0025] Figure 2 shows a plan view of a microfluidic device 100 according to an embodiment of the current invention. A system according to an embodiment of the current invention can also include pumps, sources of pressurized fluids such as pressurized gas or liquids, and other auxiliary equipment. The additional features of embodiments of the current invention will now be describe with reference to schematic illustrations of Figures 3 and 4. A channel structure according to embodiments of the current invention is arranged adjacent to a microreactor structure, as is shown schematically in Figure 3 and Figure 4. This illustrates one possible fabrication method.

[0026] Through this channel, the following operations can be facilitated in the microreactor:

applying vacuum to the pressure channel provides a pressure drop across the membrane for assisting in the removal of solvent vapor from the reactor during an evaporation

applying vacuum to the pressure channel provides a pressure drop across the membrane across which trapped air in a closed reactor can flow, such as to pre- evacuate the reaction chamber. This can dramatically speed the process of filling the reactor with reagents.

applying pressure to the pressure channel increases the pressure in the reactor by two processes: (i) flow of gas (e.g. N2, or solvent vapor) across the membrane from the pressure channel into the reactor, and (ii) expansion of the pressure channel causes deformation that physically pushes on the reactor, increasing the pressure of its liquid contents. This permits control of pressure inside the reactor, independent of other parameters, for purposes such as:

o slowing or preventing evaporation of solvent from the reactor under ambient to modest temperatures (to avoid changing reagent concentrations, and to prolong reaction time). Changing concentrations are undesirable in many cases as this makes reactions difficult to reproduce, and can complicate optimizations; furthermore, one particular concentration may be optimal and it may be desired to remain at that level for the duration of the reaction.

o permit superheating of reaction mixture such that it can remain in liquid form far above the boiling point of the solvent.

[0027] Micro fluidic devices according to some embodiments of the current invention could be fabricated using a typical approach for micro fluidic chips, namely by stacking several chip layers. Here the top layer is the fluid channel where the reactor channel would be located. Below that is the control channel, typically containing valves, but here also containing any pressure-control channels. Where the channels cross, one obtains a pressure-control membrane rather than a valve membrane.

[0028] This basic design is suitable for use under a wide range of conditions and the best practice depends on the specific application. Some of the relevant parameters include thickness of the fluid-permeable membrane, fabrication method, surface area and materials used.

[0029] The thickness of the fluid-permeable membrane affects the permeability and thus the maximal rate of flow of gas or vapors across the membrane. If speed is desired, this should be thin. However, there may be a minimum size depending on pressures used and the intrinsic material strength as well as the geometry and the maximum elongation expected at maximum deformation.

[0030] A simple method of fabrication is to use the conventional multilayer method of Figure 3 and place the pressure control channels in the same layer as valve control channels. Thus various embodiments of the current invention can be incorporated with no additional complexity into existing multilayer elastomeric micro fluidic chip designs. Typically a 10-20um valve membrane can be used in these types of PDMS and PFPE chips, so this approach would give a 10-20um pressure control membrane. Another approach is to fabricate pressure control channels in the same layer as the fluid channels in close proximity to the reactor, but this limits the membrane surface area (because typically channels are much wider than they are tall), and there are practical difficulties in placing features extremely close together within a single layer. Furthermore, placing more channels in this layer creates problems with the routing of fluids in one plane.

[0031 ] The fluid-permeable membrane surface area between reactor channel and pressure control channel affects the total permeability and thus the maximal rate of flow of gas or vapors across the membrane. If speed is desired, then this should be as large as possible. A practical limit on this is that the pressure control membrane tends to act as a valve due to the membrane flexibility/elasticity as illustrated in Figure 5. In Figure 2, we illustrate a particular design example. It has the ring microreactor 104, valves, pumps, and pressure control channels (spoked structure 106). To get maximal surface area, we should create a pressure control channel directly above the ring reactor. However, this would permit the whole membrane between the channels to collapse (i.e. if pressurized, it would collapse into the fluid channel; if evacuated, it would collapse into the pressure control channel). After collapse, there would be little free surface area for gas transport. By dividing the surface area up into discrete pieces, we have the advantage that each region has significant non-collapsed surface area (due to elastic forces) and only a small amount of surface area is lost in the areas between "spokes^"'. [0032] Note that if the pressure/vacuum is sufficiently high, the permeable membrane will deflect and could act as a valve; however, gas transport can still occur over the deflected membrane with only a small loss in surface area where the membrane is in contact with the wall(s) of the fluid channel. This effect is illustrated in Figure 5. Since the pressure control membrane can have the same dimensions as valve membranes in the chip, sufficiently high pressures can cause valve-like deflections of the pressure control membrane. This can interfere with flow, but does not significantly interfere with permeability. In addition, many uses of this system rely on stagnant fluid in the reactor. The top in Figure 5 illustrates an undeflected membrane gas flow from pressure control channel to reactor across the permeable membrane. The middle illustration is a zoomed view of a condition in which a higher pressure causes deflection. Gas flow is blocked at the point of contact but can still enter the reactor through the remainder of the membrane. At the bottom of Figure 5, vacuum is applied and causes deflection. Again, no flow can occur at the contact point, but the remainder of the membrane continues to transport solvent vapor out of the reactor.

[0033] Material of the chip (and hence membrane) will affect the permeability and thus the rate of gas flow across the membrane. The material may selectively allow some gases/vapors to pass more easily than others. Thus material choice can affect performance of various embodiments of the current invention. However, material can be selected based on requirements for the particular application because the material is in contact with reactor contents; e.g., an inert elastomer such as PFPE may be required in some cases rather than PDMS if harsh chemicals are being used in that case. One advantage according to some embodiments of the current invention can be that even if the permeability is intrinsically low (e.g. water permeability of PFPE), the layer can be sufficiently thin that the gas/vapor flow rate can remain sufficiently high to meet the needs of the application.

[0034J Various embodiments of the current invention can be simple to incorporate into multilayered elastomeric microfluidic chips and can provide functionality useful for chemical reactions and other processes. Major advantages can be the abilities to rapidly evaporate solvent and remove it completely from the chip, to evacuate air from a dead-end chamber prior to filling, and to apply pressure to slow or prevent evaporation of solvent under ambient or superheated conditions. Embodiments of the current invention can extend the range of elastomeric microfluidic chip applications to those involving high temperatures and pressures (superheated conditions).

[0035] The example reactor and pressure control channel in Figure 2 achieves all of these functions in a single chip component, thus not requiring additional chip real-estate or off-chip connections to provide the various different functionalities. In Figure 2, this particular example has a ring microreactor 104 and fluid channels 1 14, 116, 118, 120 and the corresponding branch channels. Valves and pumps are also shown in Figure 2 and exist in the control layer below the fluid layer. In addition the central spoked structure 106 is also in the control layer and comprises the pressure control channel. It crosses the microreactor 104 at many points to provide a large membrane surface area but without significantly collapsing. A single channel 112 is connected to the top-right part of this structure which we normally plug according to this embodiment. A triple channel is connected to the lower-left part of this spoked structure 106 and this is where we apply vacuum or pressure. [0036] The invention has been described in detail with respect to various embodiments, and it will now be apparent from the foregoing to those skilled in the art that changes and modifications may be made without departing from the invention in its broader aspects, and the invention, therefore, as defined in the claims is intended to cover all such changes and modifications as fall within the true spirit of the invention.

Claims

WE CLAIM:

1 . A micro fluidic device comprising a device body, said device body defining: a microfluidic reactor; and a pressure control system arranged proximate said microfluidic reactor, wherein said microfluidic device comprises a fluid-permeable membrane arranged between said microfluidic reactor and said pressure control system, said fluid-permeable membrane having a surface area and thickness such that a fluid can pass from a high pressure side to a low pressure side of said fluid-permeable membrane during operation of said microfluidic device to at least one of change a pressure in said microfluidic reactor in a preselected manner, to maintain a substantially constant pressure in said microfluidic reactor, to change a composition of fluids in said microfluidic reactor, or maintain a composition of fluids in said microfluidic reactor.

2. A microfluidic device according to claim 1, wherein said fluid-permeable membrane can change shape in response to pressure changes to thereby cause a change in pressure exerted on a fluid in said microfluidic reactor to contribute to a change in pressure of said fluid in said microfluidic reactor.

3. A microfluidic device according to claim 1, wherein said device body comprises a plurality of layers having structures that were formed separately and then bonded together.

4. A micro fluidic device according to claim 3, wherein said device body further comprises a substrate wherein at least one of said plurality of layers of material of said device body is bonded to said substrate to form a control layer and at least one of said plurality of layers is bonded to said control layer to form a flow layer that includes said microfluidic reactor as well as at least one input channel and at least one output channel to said microfluidic reactor.

5. A microfluidic device according to claim 1, wherein said pressure control system comprises at least one fluid channel to provide at least one of a fluid pressure or vacuum to said fluid-permeable membrane.

6. A microfluidic device according to claim 1, wherein said fluid is a gas.

7. A microfluidic device according to claim 4, wherein said control layer comprises structures to control valves and pumps in said flow layer.

8. A microfluidic device according to claim 1, wherein said microfluidic reactor is a ring-shaped microfluidic reactor and said pressure control system comprises a plurality fluid-permeable membranes spaced apart and arranged proximate said ring-shaped microfluidic reactor in a spoke-like pattern.

9. A microfluidic device according to claim 8, wherein said plurality fluid-permeable membranes are at least ten fluid-permeable membranes that provide a fluid-permeable region across at least about 40% of said ring-shaped microfluidic reactor.

10. Λ micro fluidic device according to claim 1 , wherein said fluid-permeable membrane of said pressure control system is a perfluoropolyether fluid-permeable membrane.

1 1. A micro fluidic device according to claim 1 , wherein said fluid-permeable membrane of said pressure control system is a poly-dimethylsiloxane fluid-permeable membrane.

12. A micro fluidic device according to claim 1, wherein said device body comprises perfluoropolyether in its composition.

13. A micro fluidic device according to claim 1, wherein said device body comprises poly-dimethylsiloxane in its composition.

14. A method on performing chemical reactions, comprising: introducing a plurality of chemical substances into a micro fluidic reactor, wherein the micro fluidic reactor has a fluid-permeable membrane between at least a portion of said micro fluidic reactor and a microfluidic pressure control system; at least one of pressurizing with a fluid or evacuating a region of said pressure control system proximate said fluid-permeable membrane to cause fluid to pass through said fluid-permeable membrane in a predetermined manner in order to cause a predetermined effect on a chemical reaction in said microfluidic reactor.