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WO2009082535A2 - Procédé et dispositif de régulation de la pression dans un microréacteur - Google Patents

Procédé et dispositif de régulation de la pression dans un microréacteur Download PDF

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Publication number
WO2009082535A2
WO2009082535A2 PCT/US2008/080200 US2008080200W WO2009082535A2 WO 2009082535 A2 WO2009082535 A2 WO 2009082535A2 US 2008080200 W US2008080200 W US 2008080200W WO 2009082535 A2 WO2009082535 A2 WO 2009082535A2
Authority
WO
WIPO (PCT)
Prior art keywords
fluid
microfluidic
reactor
pressure
permeable membrane
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/US2008/080200
Other languages
English (en)
Other versions
WO2009082535A3 (fr
Inventor
R. Michael Van Dam
Kan Liu
Kwang-Fu Clifton Shen
Hsian-Rong Tseng
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
University of California Berkeley
University of California San Diego UCSD
Original Assignee
University of California Berkeley
University of California San Diego UCSD
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by University of California Berkeley, University of California San Diego UCSD filed Critical University of California Berkeley
Publication of WO2009082535A2 publication Critical patent/WO2009082535A2/fr
Publication of WO2009082535A3 publication Critical patent/WO2009082535A3/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J19/0093—Microreactors, e.g. miniaturised or microfabricated reactors
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00781—Aspects relating to microreactors
    • B01J2219/00783—Laminate assemblies, i.e. the reactor comprising a stack of plates
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00781—Aspects relating to microreactors
    • B01J2219/00905—Separation
    • B01J2219/00907—Separation using membranes
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00781—Aspects relating to microreactors
    • B01J2219/0095—Control aspects
    • B01J2219/00952—Sensing operations
    • B01J2219/00968—Type of sensors
    • B01J2219/0097—Optical sensors

Definitions

  • 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.
  • the perfo ⁇ nance (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.
  • the solvent 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).
  • chip microreactor
  • 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 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.
  • 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.
  • Figure 1 is a schematic illustration of a conventional microfluidic devices
  • Figure 2 is a photograph of an embodiment of a microiliiidic device according to the current invention
  • 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
  • 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.
  • Figure 5 is a schematic illustration of the mcrofluidic chip cross-section when applying vacuum to the pressure-control device or when applying pressure.
  • 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.
  • 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.
  • FIG. 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.
  • the microfluidic reactor 104 is a ring reactor.
  • 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.
  • 108 is intended to refer to the membrane below upper layers of material.
  • 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.
  • 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.
  • the pressure control system 106 can include a fluid input channel 110 and a fluid output channel 1 12.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • other embodiments may include less, more or different microfluidic structures built in along with the microfluidic reactor 104 and a pressure control system 106.
  • 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.
  • 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.
  • 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.
  • gas e.g. N2, or solvent vapor
  • expansion of the pressure channel causes deformation that physically pushes on the reactor, increasing the pressure of its liquid contents.
  • 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.
  • the top layer is the fluid channel where the reactor channel would be located.
  • 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.
  • 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.
  • 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.
  • 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.
  • various embodiments of the current invention can be incorporated with no additional complexity into existing multilayer elastomeric micro fluidic chip designs.
  • 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.
  • placing more channels in this layer creates problems with the routing of fluids in one plane.
  • 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.
  • 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.
  • Material of the chip 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.
  • material choice can affect performance of various embodiments of the current invention.
  • 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.
  • 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).
  • 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.
  • 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.
  • 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.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Physical Or Chemical Processes And Apparatus (AREA)

Abstract

L'invention concerne un dispositif microfluidique doté d'un corps de dispositif définissant un réacteur microfluidique et d'un système de régulation de la pression dans celui-ci, le système de régulation de la pression étant disposé à proximité du réacteur microfluidique. Le dispositif microfluidique est également doté d'une membrane perméable aux fluides disposée entre le réacteur microfluidique et le système de régulation de la pression, la membrane perméable aux fluides présentant une aire et une épaisseur telles qu'un fluide peut passer d'un côté haute pression à un côté basse pression de ladite membrane perméable aux fluides pendant le fonctionnement du dispositif microfluidique afin de modifier une pression dans le réacteur microfluidique d'une manière prédéfinie, maintenir une pression sensiblement constante dans le réacteur microfluidique, modifier une composition de fluides dans le réacteur microfluidique et / ou maintenir une composition de fluides dans le réacteur microfluidique. L'invention concerne également un procédé destiné à réaliser des réactions chimiques et comportant les étapes consistant à introduire une pluralité de substances chimiques dans un réacteur microfluidique, le réacteur microfluidique étant muni d'une membrane perméable aux fluides entre au moins une partie du réacteur microfluidique et un système microfluidique de régulation de la pression; et à pressuriser à l'aide d'un fluide et / ou à évacuer une région du système de régulation de la pression à proximité de la membrane perméable aux fluides pour faire passer du fluide à travers la membrane perméable aux fluides d'une manière prédéterminée afin de provoquer un effet prédéterminé sur une réaction chimique dans le réacteur microfluidique.
PCT/US2008/080200 2007-10-16 2008-10-16 Procédé et dispositif de régulation de la pression dans un microréacteur Ceased WO2009082535A2 (fr)

Applications Claiming Priority (2)

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US96084407P 2007-10-16 2007-10-16
US60/960,844 2007-10-16

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WO2009082535A2 true WO2009082535A2 (fr) 2009-07-02
WO2009082535A3 WO2009082535A3 (fr) 2010-03-18

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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8266791B2 (en) 2007-09-19 2012-09-18 The Charles Stark Draper Laboratory, Inc. Method of fabricating microfluidic structures for biomedical applications
WO2014190258A1 (fr) * 2013-05-23 2014-11-27 The Regents Of The University Of California Déclenchement microfluidique entraîné par dégazage proximal
US9067189B2 (en) 2012-03-30 2015-06-30 General Electric Company Microfluidic device and a related method thereof
WO2016044532A1 (fr) * 2014-09-17 2016-03-24 The Regents Of The University Of California Système de batterie sous vide pour pompage microfluidique portatif

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6375901B1 (en) * 1998-06-29 2002-04-23 Agilent Technologies, Inc. Chemico-mechanical microvalve and devices comprising the same
US20050266582A1 (en) * 2002-12-16 2005-12-01 Modlin Douglas N Microfluidic system with integrated permeable membrane
US7413712B2 (en) * 2003-08-11 2008-08-19 California Institute Of Technology Microfluidic rotary flow reactor matrix
US20070178133A1 (en) * 2005-11-09 2007-08-02 Liquidia Technologies, Inc. Medical device, materials, and methods

Cited By (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8266791B2 (en) 2007-09-19 2012-09-18 The Charles Stark Draper Laboratory, Inc. Method of fabricating microfluidic structures for biomedical applications
US9181082B2 (en) 2007-09-19 2015-11-10 The Charles Stark Draper Laboratory, Inc. microfluidic structures for biomedical applications
US10265698B2 (en) 2007-09-19 2019-04-23 The Charles Stark Draper Laboratory, Inc. Microfluidic structures for biomedical applications
US9067189B2 (en) 2012-03-30 2015-06-30 General Electric Company Microfluidic device and a related method thereof
WO2014190258A1 (fr) * 2013-05-23 2014-11-27 The Regents Of The University Of California Déclenchement microfluidique entraîné par dégazage proximal
US9737888B2 (en) 2013-05-23 2017-08-22 The Regents Of The University Of California Proximal degas driven microfluidic actuation
WO2016044532A1 (fr) * 2014-09-17 2016-03-24 The Regents Of The University Of California Système de batterie sous vide pour pompage microfluidique portatif
CN106687216A (zh) * 2014-09-17 2017-05-17 加利福尼亚大学董事会 用于便携微流泵送的真空电池系统
US9970423B2 (en) 2014-09-17 2018-05-15 The Regents Of The University Of California Vacuum battery system for portable microfluidic pumping
CN106687216B (zh) * 2014-09-17 2019-05-28 加利福尼亚大学董事会 用于便携微流泵送的真空电池系统
US10864517B2 (en) 2014-09-17 2020-12-15 The Regents Of The University Of California Vacuum battery system for portable microfluidic pumping

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