This application claims priority to European Patent Application number 09305368.4, filed Apr. 28, 2009, titled “Microreactors with Connectors Sealed Thereon; Their Manufacturing”.
The present invention concerns connection of microreactors. It more particularly relates to glass, glass-ceramic and ceramic microreactors equipped with connection systems, to a method of manufacturing the same and to blocks of material suitable as connection systems.
Microreactors (microstructures), more particularly glass, glass-ceramic and ceramic microreactors (microstructures), are described in numerous patents, for example in U.S. Pat. No. 7,007,709.
They are drilled on back or (and) front face(s) to ensure reactant(s) inlet and product(s) outlet as well as generally thermal fluid inlet and outlet. Specific connection systems have already been described.
Such connection systems have more particularly been described in patent applications FR 2 821 657 and WO 2005/107 937 (in both said prior art documents, multiport connectors with polymer seal are described. A face connection is ensured and it induces a mechanical stress on the microreactor), also in patent application EP 1 925 364 (the described connection implies the cooperation of female and male parts) and patent application US 2007/280855 (the connector is here secured to the microreactor via mechanical means (by screw, peg or other fastener)). The applicant has also proposed a specific connection system in patent application EP 1 854 543. Said specific connection system is shown in annexed prior art
According to EP 1 854 543, fluidic face connection at each inlet and outlet is ensured thanks to a single port connector 50 tight on the microreactor 20 through a C-clamp mechanical part 55. Parts in contact with fluids are:
the O-ring seal 26, usually made of a perfluoroelastomer material,
the connector adapter 53 typically made of PTFE; and
the fitting 57, generally a Swagelock® fitting, usually made of PFA.
The material choices allow getting high and broad chemical resistant fluidic connection. However, internal pressure and temperature ranges of use are limited, as shown on
Several microfluidic devices 200′, each comprising a microstructure 20, for example a glass microstructure, and single port connectors 50, are assembled together in a module 61, 62 of a multi-step engineered reactor 60. Such a reactor is actually able to comprise numerous modules. Reactors of that type are so able to ensure a lot of chemical reactions, especially multi-step reactions, integrating several functions like pre-heating or cooling, mixing (single injection or multi-injections), residence time . . . . Each module 61 and 62 of the reactor 60 includes three microstructures 20. The typical distance between the microstructures 20 of a module is 120 mm. Such a distance allows the face connection with the single port connectors 50.
Considering these reactors composed of several microstructures linked together using such single port connector and piping, several issues have to be considered. The first main one is limiting the connection complexity that leads to a lot of tightness locations (which are always potential sources of leakage), to long assembly and/or maintenance time, to quite large reactor footprint and significant mechanical parts cost. The second main issue to consider is the limited combined pressure and temperature operation ranges. It would be opportune to address an enlarged market with applications running at higher pressure and temperature. Some other issues may also be addressed like reducing internal volume into connection, avoiding any potential mechanical stress induced on the microstructures, proposing transparent connection zones.
The inventors have considered these numerous issues and hereafter propose a new connection concept for microreactors.
The present invention provides a microfluidic device including a microreactor with fluidic inlet(s) and outlet(s) and a connector with fluidic channel(s) into its volume, at least one of said inlet(s) and outlet(s) of said microreactor being connected through said connector. Said microreactor is made of a first material selected from the group consisting in glasses, ceramics, glass-ceramics and metals coated with a glass, ceramic or glass-ceramic coating. Said connector is made of a second material selected from the group consisting in glasses, ceramics, glass-ceramics and metals coated with a glass, ceramic or glass-ceramics coating. Said connector is sealed on said microreactor via a fit layer made of a third material; said third material being selected from the group consisting in glasses, ceramics and glass-ceramics, having a lower softening point than the softening point of any glass, ceramic and glass-ceramic of said microreactor and connector and also having an expansion coefficient compatible with the expansion coefficient of any glass, ceramic and glass-ceramic of said microreactor and connector, (advantageously having a lower softening point than the softening points of both said first and second materials selected from glasses, ceramics and glass-ceramics or of both said coatings of said first and second metallic materials and also having an expansion coefficient compatible with the expansion coefficients of both said first and second materials selected from glasses, ceramics and glass-ceramics or of both said coatings of said first and second metallic materials).
According to some variants:
the connector is sealed on the microreactor via a frit plate (generally of a thickness e: 0.5 mm≦e≦2 mm) or via a thin layer of a frit (having generally a thickness e′: e′<500 μm);
the sealing(s) is(are) glass/glass/glass sealing(s) or ceramic/ceramic/ceramic sealing(s) or ceramic/glass/ceramic sealing(s);
the fluidic channel(s) inside the connector is(are) not straight channels, so as to create side connections. Side connections are particularly advantageous (with regards to face connections);
the connector is located on a edge of the microreactor, is advantageously located on a edge and in a corner of said microreactor;
at least two fluidic inlet(s) and outlet(s) are connected through a single connector; all fluidic inlet(s) and outlet(s) are advantageously connected through a single connector. Multiport connections are particularly advantageous;
a single connector for all fluidic inlet(s) and outlet(s) is sealed parallel to a edge of the microreactor and close to said edge, advantageously in a corner, all said inlet(s) and outlet(s) being preferably arranged on a line;
the microfluidic device is connected to a plate through a single connector arranged parallel to a edge of the microreactor and close to said edge via O-ring seals and fixed to said plate via mechanical fixing means only contacting said plate and said connector (without any mechanical contact and stress on the microreactor).
The present invention also provides a method for manufacturing such a microfluidic device. Said method comprises the sealing of at least one connector to a microreactor, said sealing being carried out during the manufacturing of said microreactor or being carried out once said microreactor has been manufactured.
According to some variants:
a sealing comprises the arrangement of a fit plate between the two surfaces to seal;
a sealing comprises the deposit of a thin layer of frit on at least one of the two surfaces to seal.
The present invention also provides a block made of a material selected from the group consisting of glasses, ceramics, glass-ceramics and metals coated with a glass, ceramic or glass-ceramic coating, having two main faces and at least a lateral one, with at least one fluidic channel through its volume, from a face to an other face, advantageously from one of its main face to a(the) lateral one, allowing fluidic connection(s), advantageously side fluidic connections. Such a block is suitable as connector for microreactors.
According to some variants:
the fluidic channel(s) has(have) an equivalent diameter within the range of 1-10 mm, advantageously within the range of 1.5-5 mm;
the block includes fluidic channels of different internal volumes within its volume;
the block includes at least one fluidic channel which separates and/or at least two fluidic channels which join together within its volume;
the block includes at least one recess for a sensor, such a recess emerging into a fluidic channel, within its volume.
Additional features and advantages of the invention will be set forth in the detailed description which follows, and in part will be readily apparent to those skilled in the art from that description or recognized by practicing the invention as described herein, including the detailed description which follows, the claims, as well as the appended drawings.
It is to be understood that both the foregoing general description and the following detailed description present embodiments of the invention, and are intended to provide an overview or framework for understanding the nature and character of the invention as it is claimed. The accompanying drawings are included to provide a further understanding of the invention, and are incorporated into and constitute a part of this specification. The drawings illustrate various embodiments of the invention and together with the description serve to explain the principles and operations of the invention.
Reference will now be made in detail to the presently preferred embodiments of the invention, examples of which are illustrated in the accompanying drawings. Whenever possible, the same reference numerals will be used throughout the drawings to refer to the same or like parts.
It should be emphasized that such a block constitutes the key of the claimed invention.
The fluidic channels 4 connect the main face 2′ to a single lateral one 3′, i.e. connect two perpendicular faces, so allowing side connections. Such side connections are particularly advantageous. According to variants not shown, such channels are able to connect a main face 2, 2′ to at least two different lateral faces chosen amongst faces 3,3′,3″ and 3′″ and/or are able to connect opposite faces of a block and/or are able to connect both perpendicular and opposite faces, so allowing both side and face connections.
The block 1 of
The diameter of the fluidic channel(s) is generally within the range of 1-10 mm, advantageously within the range of 1.5-5 mm. Said diameter is determined by the properties of the fluid intended to be circulated within said fluidic channel(s), by the specific application needed. A diameter of 1.5 mm may be suitable in contexts of low volumes without thermal control, a diameter of 5 mm may be required with fluids of high viscosity or with high flow rate inducing high pressure drop . . . .
As shown in
The diameter of any fluidic channel is more precisely an equivalent diameter insofar as any fluidic channel is not compulsorily cylindrical (with circular section). It is quite possible to have any channel with a non circular section, for example with a rectangular section, more particularly when the connector is obtained by hot forming.
The multiport connector 10 of the invention, as shown in
The block 1 of material also comprises alignment pins 5 used to correctly position and maintain it during its sealing by heat to a microreactor (so as to constitute a microfluidic of the invention). The holes (inlet(s) and outlet(s)) of the microreactor (see
According to a variant not shown, the connector 10 may allow cross-connections, i.e. the block 1 may include fluidic channels which cross (so that, for example, at least one inlet and at least one outlet cross).
Characteristically, the block 1 is intended to be sealed on a microreactor 20, fitting with the inlets and outlets of said microreactor 20, so as to be able to ensure its function of connector.
Details are now given on the constitutive materials of the microreactor 20 and of the block 1, suitable as connector 10.
The microreactor 20 is made of a first material selected from the group consisting in glasses, ceramics, glass-ceramics and metals coated with a glass, ceramic or glass-ceramic coating.
The block 1 intended to be used as connector 10 after sealing (by heat) on the microreactor 20 is made of a second material also selected from the group consisting in glasses (Pyrex or Pyrex-like glasses for example), ceramics (alumina for example), glass-ceramics and metal coated with a glass, ceramic or glass-ceramic coating.
One skilled in the art knows how to choose both said first and second materials to have them resist to the circulation of fluids. He easily realizes that the chemical durability of the connector has advantageously to be at least equal to the one of the microreactor. So the second material generally shows a chemical resistance equal to or greater than the one of said first material. These notions of chemical resistance and chemical durability are familiar to those skilled in the art. They are quantified by measures of weight loss of samples. There exist normalized tests well-known from one skilled in the art (for example, test DIN 12116 for the resistance to acids and test ISO 695 for the resistance to bases). Said second material selected from glasses, ceramics and glass-ceramics or said coating of said second metallic material can advantageously have a softening point (one skilled in the art knows that parameter, he knows normalized methods to measure it, more particularly the one according to the standard ASTM C 1351M) equal to or greater than, the one of said first material selected from glasses, ceramics and glass-ceramics or of said coating of said first metallic material. In that way, during the sealing thermal cycle, there will be no risk at all of deformation of the block 1 and so connection face will be kept flat enough to get tightness with suitable polymer O-ring seals.
The block 1 can be realized by standard machining or carrying out hot forming processes.
Precisions on the way of sealing the block 1 on the microreactor 20 are given below in reference to
The microreactor 20 has its surface delimited by four edges 20a, 20b, 20c and 20d. Edges 20a and 20b join in corner 20′b, edges 20b and 20c join in corner 20′c, edges 20c and 20d join in corner 20′d and edges 20d and 20a join in corner 20′a.
According to a preferred mode of the invention shown in
The sealing between a microreactor 20 and a connector of the invention such as 10 on
It may be carried out using a frit plate. Such a fit plate may exist according to different designs. Two designs are shown on
Using a fit plate 23′a or 23″a for carrying out a sealing of the connector 10 on the microstructure 20 will more particularly depend on the surface quality and geometrical flatness of the microstructure 20.
Such frit plates 23′a or 23″a can be realized by standard machining or using hot forming processes.
The method according to said second variant comprises:
The result of the sealing is a microfluidic device, a continuous structure including the microreactor and the connector(s), able to withstand more than 40 bars. Note also that several connectors 10′ (or 10) may be sealed on a microreactor 20, keeping in mind that a single connector 10′ (or 10) used for all inlets and outlets is a preferred variant.
The microreactor 20 is preconstituted. On a part of its external surface (where the connector 10′ is intended to be sealed), a thin layer of fit 23b1 is deposited.
At least a connector 10′ is also preconstituted and a thin layer of frit 23b2 is deposited on a part of its external surface, said part being intended to be sealed on said microreactor 20. The thin layer of fit 23b2 is generally deposited on a face of the connector 10, taking care of not blocking the fluidic channel(s) 4.
The two deposited thin layers of frit 23b1 and 23b2 are then contacted and following a suitable heat treatment, they generate the seal or fit layer 23b.
Said method thus comprises:
It is quite possible to obtain a good sealing using a single thin layer of frit deposited on one of the two surfaces to seal. So the present disclosed method includes both the use of a single and of two thin layers of frit.
It is also quite possible to carry out that method of sealing—using a single or two thin layers of fit hereabove described carried out on a pre-constituted microreactor, while constituting the microreactor (a thin layer of frit (the single one thin layer of frit or one of the two thin layers of fit intended to form the frit layer of the final microfluidic device) being deposited on a part of the external surface of a suitable constitutive layer of the microreactor).
It has been indicated that a fit layer 23a obtained from a fit plate 23′a or 23″a has generally a thickness comprised between 0.5 and 2 mm while a frit layer 23b (obtained from one or two thin layers 23b1 and 23b2) has generally a thickness equal or inferior to 500 μm.
Whatever the exact variant of sealing carried out, it is advantageous to seal materials of the same kind. So the microfluidic devices of the invention comprise advantageously a glass microreactor with glass connector(s), a ceramic microreactor with ceramic connector(s), or a glass-ceramic microreactor with glass-ceramic connector(s).
The microfluidic devices of the invention are very advantageously glass microreactors with glass connectors or ceramic microreactors with ceramic connectors. The sealings are obviously carried out with suitable frit material. So the preferred sealings microreactor/frit layer/connector(s) are glass/glass/glass sealings, ceramic/ceramic/ceramic sealings and ceramic/glass/ceramic sealings. A microfluidic device of the invention comprises a sealing microreactor/frit layer/connector or at least two sealings microreactor/frit layers/connectors.
Concerning the material of the frit layer (the third material), it has to show a suitable softening point and a suitable expansion coefficient (to be able to constitute an effective seal between the first and second material). Its softening point has to be lower than the softening point of any glass, ceramic and glass-ceramic of the microreactor and connector and its expansion coefficient has to be compatible with the expansion coefficient of any glass, ceramic and glass-ceramic of the microreactor and the connector (said microreactor and connector being made of these materials (glass, ceramic, glass-ceramic) or including these materials as coating of metal). Advantageously, said third material has a lower softening point than the softening points of both said first and second materials selected from glasses, ceramics and glass-ceramics or of both said coatings of said first and second metallic materials and also has an expansion coefficient compatible with the expansion coefficients of both said first and second materials selected from glasses, ceramics and glass-ceramics or of both said coatings of said first and second metallic materials. In reference to said expansion coefficient of the third material, it is suitable (“compatible”) if its value differs from the values of the expansion coefficients of both the first and second materials of less than 20×10−7K−1, advantageously less than 10×10−7 K−1 (all these CTE values being considered between 25 and 300° C., being expressed in 10−7 K−1).
One skilled in the art also knows how to choose said third material to have it resist to the circulation of fluids. He easily realizes that the chemical durability of said third material, as the one of the second material, has advantageously to be at least equal to the one of the first material. So said third material generally shows a chemical resistance equal or greater than the one of said first material.
We remind here that a single multiport connector is advantageously used.
The main advantage of the invention connection concept is visualized on
We have indicated that connections according to the prior art (EP 1 854 543—
A connector according to the invention sealed on a microstructure is a concept that suppresses as well as PTFE adapter and PFA Swagelok® fitting, the two limiting components. The single remaining component is the O-ring seal.
In consequence, the acceptable combined pressure and temperature operation ranges are increasing, towards 20 bars up to 250° C. and therefore covering enlarged chemical applications.
It has already been mentioned that a single port connector may be sealed according to the invention to an inlet or outlet of a microreactor but that multiport connectors are obviously preferred, that such multiport connectors are advantageously arranged on an edge of the microreactor, close to said edge, with all the inlet(s) and outlet(s) of said microreactor very advantageously arranged on a line. Such a design of a microreactor is illustrated in
In any way, the pattern of the microreactor and the one of the connector have obviously to be adapted (to match) to allow the connection(s).
According to the preferred variant shown in
According to the illustrated variant, 21 are inlets for different reactants, 21a is the inlet for the heat exchange fluid while 21′ are additional potential injection points; 22 is the outlet for the product(s) and 22a is the outlet for the heat exchange fluid.
Typical distance d (between the line 25 and the edge of the microfluidic device 20) is comprised between 5 and 30 mm, while typical distance e (which represents the length of a suitable connector to seal) is comprised between 20 and 150 mm. We have already indicated (in a non limitative way) that connectors of the invention are more particularly suitable to ensure 2 to 10 connections. So the number of fluidic inlets and outlets located in the area of the surface of the microfluidic device shown in
It has to be emphasized that the multiport side connection according to the invention, as more particularly illustrated in this
it involves a single side connection face tightened thanks to a single clamping system 27, without any mechanical contact (stress) on the microstructure 20;
it allows the arrangement of several microfluidic devices 200 in a limited space. The distance between the microstructures 200 can be limited, can be lower than 100 mm. Said distance value has to be compared with the prior art distance of 120 mm (see
it offers the possibility to design a reactor architecture based on fluidic backbone approach. Several microfluidic devices 200 can be plugged into a fluidic backbone like electronic cards, fluid communication between microstructures 20 being done through the fluidic backbone.
No doubt that one skilled in the art has realized the great interest of the invention, more particularly the great interest of the advantageous variant of the invention using a connector able to drive all the inlets and outlets on a single connection face, perpendicular to the microreactor surface.
We hereafter insist on the main advantages of the new fluidic connection approach of the invention. Some of said advantages are common to all variants, some of them are limited to specific (preferred) variants. Most of them have already been explained in reference to at least one of the accompanying figures. Most of them are hereafter explained in reference to the teaching of EP 1 854 543.
1) Large Temperature and Pressure Operation Ranges
Said operation ranges are larger than the one of the prior art connections according to EP 1 854 543 (see
2) Simplification of the Microfluidic Device Construction: Less Clamping Systems and Tightness Zones
Proposed multiport connector sealed on a microstructure allows simplifying the mechanical structure of the microfluidic device:
instead of having one clamping system per single port connector, so per inlet and outlet, a single global clamping system for the whole multiport connector is enough. So typically five C-clamps (55 in
sealing of the connector on the microreactor is a way to avoid the use of polymer sealing zone, with the associated risk of leakage.
In the case of prior art connections as described in EP 1 854 543 (see
3) Side Connections: Reactor Compactness and Compatibility with Fluidic Bus Reactor Architecture
Prior art connections (according to EP 1 854 543) are face connections, with single port connectors, on both sides of the microreactor (see
4) Low Internal Volume without Thermal Control
Typical single port connectors presented on
5) Ease of Maintenance
Another benefit of sealed multiport connectors, advantageously with side connections, is the ease of plug and play. Because of the single clamping system and because of no direct contact with adjacent microstructures, it is possible to rapidly remove and exchange one microstructure of an assembly without moving the others.
With prior art connections according to EP 1 854 543, mainly based on Swagelok® fitting, an operation is needed for each single port connector and it is necessary sometimes to move several microstructures in order to remove easily one.
6) Robustness
With connections as described in EP 1 854 543, tightening of single port connectors is done into the microstructure itself, where additional stresses like internal pressure and thermal gradient have to be handled. And beyond compression stresses, potential bending stresses could be applied on microstructures when connection between microstructures is done and when piping is added, especially heat exchange stainless steel piping.
According to the invention, the single tightening force is applied only on the connector sealed on microstructure: no mechanical force is applied on the microstructure itself (even no mechanical contact needed) which contributes to increase mechanical robustness of glass microstructure. (See
7) Transparent Connection
The connectors of the invention, made of a glass may be transparent. So it is possible to have visual contact of the reactant(s) and product(s), even inside connection zones (which is not possible according to prior art single port connector of EP 1 854 543). Interest is to detect any potential clogging into inlets and outlets zones. So the advantage of the transparency of a microreactor may be kept into a connector of the invention.
The microfluidic devices disclosed herein are generally useful in performing any process that involves mixing, separation, extraction, crystallization, precipitation, or otherwise processing fluids or mixtures of fluids, including multiphase mixtures of fluids—and including fluids or mixtures of fluids including multiphase mixtures of fluids that also contain solids—within a microstructure. The processing may include a physical process, a chemical reaction defined as a process that results in the interconversion of organic, inorganic, or both organic and inorganic species, a biochemical process, or any other form of processing. The following non-limiting list of reactions may be performed within the disclosed devices: oxidation; reduction; substitution; elimination; addition; ligand exchange; metal exchange; and ion exchange. More specifically, reactions of any of the following non-limiting list may be performed within the disclosed devices: polymerisation; alkylation; dealkylation; nitration; peroxidation; sulfoxidation; epoxidation; ammoxidation; hydrogenation; dehydrogenation; organometallic reactions; precious metal chemistry/homogeneous catalyst reactions; carbonylation; thiocarbonylation; alkoxylation; halogenation; dehydrohalogenation; dehalogenation; hydroformylation; carboxylation; decarboxylation; amination; arylation; peptide coupling; aldol condensation; cyclocondensation; dehydrocyclization; esterification; amination; heterocyclic synthesis; dehydration; alcoholysis; hydrolysis; ammonolysis; etherification; enzymatic synthesis; ketalization; saponification; isomerisation; quaternization; formylation; phase transfer reactions; silylations; nitrile synthesis; phosphorylation; ozonolysis; azide chemistry; metathesis; hydrosilylation; coupling reactions; and enzymatic reactions.
Number | Date | Country | Kind |
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09305368.4 | Apr 2009 | EP | regional |
Filing Document | Filing Date | Country | Kind | 371c Date |
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PCT/US10/32742 | 4/28/2010 | WO | 00 | 10/26/2011 |