Method for producing valve for microinjector of liquid or gas chromatography device

Abstract

The invention relates to a method for manufacturing a valve for a microinjector of a chromatography device, comprising: depositing a polymer layer (20) on a support substrate (10); 0 a first partial cross-linking treatment of the polymer layer (20); 0 etching the support substrate (10) to expose a free region (21) of the polymer layer (20); -assembling the support substrate (10) and the fluid dispenser (300) by means of the polymer layer (20) such that:-the free region (21) forms a membrane having two opposite free surfaces (23, 24); and-the bonding region (25) of the polymer layer is in rigid contact with the support substrate and the dispenser (300), forming an adhesive interface between the support substrate and the dispenser; 0 a second treatment comprising continuing the crosslinking of the polymer layer (20).

Description

Technical Field

[0001] This invention generally relates to the field of liquid chromatography or gas chromatography. More specifically, it provides a method for manufacturing a valve for a micro-injector used in a liquid or gas chromatography apparatus. Background Technology

[0002] A measurement system for analyzing liquids or gases by liquid chromatography or gas chromatography includes a syringe, at least one separation column, and at least one detector. It also includes elements that provide an interface between the components.

[0003] Recently, compact analytical systems have been developed that can be transported or easily integrated into existing analytical facilities. Micro-injectors have been developed to inject a defined volume of fluid into the separation column of such a device. This fluid can be the gas or liquid to be analyzed.

[0004] These miniature syringes typically consist of a set of dual-state valves, each capable of being either closed or open. The closed state cuts off fluid flow, while the open state allows fluid to flow. Multiple valves are interconnected to form the syringe. Figure 1 The assembly shown comprises nine valves V1 to V9 linked together by a fluid connection to form a ten-channel microinjector. Other numbers and fluid connection configurations are possible. The opening and closing of the valves are driven by a microprocessor.

[0005] To obtain narrow injection peaks for accurate chromatographic analysis, it is necessary to minimize the volume of fluid interconnections between valves, in addition to the fluid capture volume containing the sample to be analyzed. Pneumatically or piezoelectrically actuated miniature valves are known for this purpose. In the case of pneumatic actuation, one or more electronically controlled valves drive pressurized fluid to deflect a flexible membrane, typically an elastic polymer such as polyimide.

[0006] The membrane is typically in the form of a film bonded between a glass substrate and a silicon substrate, including valve seats and fluid connections. The membrane can be bonded using adhesive films, multilayer films capable of being sealed by thermocompression, epoxy adhesives, or sintered glass or solder seals. For example, bonding a membrane with an adhesive film is described in U.S. Standard 6896 238 B2. Solder or sintered glass seals are described in U.S. Standard 4869 282A.

[0007] However, this bonding requires the adhesive film to be precisely positioned between the glass and the silicon substrate. This positioning is achieved by using a mask, which makes the valve assembly more complex.

[0008] Furthermore, this bonding of the membrane requires the application of two adhesive layers and two alignment steps during valve assembly.

[0009] Because some applications require the valve to remain closed for extended periods, the membrane is pushed against the valve seat during these usage phases. However, the operating temperature of microinjectors often induces adhesion properties in the membrane material, leading to static friction between the membrane surface and the valve seat. When this static friction begins to occur, the valve will no longer operate correctly.

[0010] Therefore, it is necessary to prevent the valve seat from becoming attached to the membrane. US Standard 6896 238 B2 proposes treating the membrane with one or more thin metal layers. However, this treatment complicates syringe manufacturing, adding one or more deposition steps and requiring one or more additional masks.

[0011] Further post-processing to avoid such adhesion is described in Shann○n et al., J. Micro○mech. Micro○eng. 18 (2008) 095015 (9pp).

[0012] Further improvements are expected in terms of ease of assembly, manufacturing cost, and the tightness of the syringe seal. Summary of the Invention

[0013] One object of the present invention is to design a method for manufacturing a microinjector valve that is easy to implement and automate. In particular, one object is to facilitate the alignment and sealing of the fluid passage during valve assembly and to achieve precise actuation of the membrane during use of the microinjector.

[0014] To this end, the present invention provides a method for manufacturing a valve for a micro-injector used in a liquid or gas chromatography apparatus, comprising the following steps:

[0015] ○ A polymer layer is deposited in liquid phase on the lower surface of the supporting substrate.

[0016] ○ Crosslinking treatment of the first part of the polymer layer,

[0017] ○ Etch the support substrate to expose the free regions of the polymer layer.

[0018] Assemble the support substrate and the fluid dispenser, the fluid dispenser including a cavity and at least one microcatheter, the cavity including a seat configured to receive the membrane, the at least one microcatheter being fluidly connected via the cavity to form a fluid channel.

[0019] The assembly is carried out by means of the polymer layer, such that

[0020] - The free regions of the polymer layer form a membrane with two opposing free surfaces, such that when an actuating force is applied to the membrane, the membrane contacts the seat to seal at least one microcatheter.

[0021] - The bonding region of the polymer layer is in integral contact with the bonding region of the lower surface of the support substrate and the bonding region of the upper surface of the dispenser, and the bonding region of the polymer layer forms an adhesive sealing interface between the support substrate and the dispenser.

[0022] ○ A second process, the second process comprising continuing the crosslinking of the polymer layer such that the first surface of the bonding region can be sealed with the dispenser.

[0023] The partial cross-linking of the polymer layer enables its adhesive properties to be used directly to bond the membrane in a sealing manner between the support substrate and the distributor, which includes the valve seat and fluid connections.

[0024] Polymers are used because of their elasticity and compatibility with photolithographic structuring. Furthermore, polymers in liquid form prior to polymerization can be easily deposited by centrifugation.

[0025] Particularly advantageously, the method further includes the step of etching the support substrate and polymer layer to create at least one fluid channel before assembling the support substrate and fluid dispenser, wherein at least one microchannel of the dispenser is adapted to communicate with the fluid channel, and the assembly is performed such that each fluid channel is aligned with the microchannel to form a corresponding fluid channel between the support substrate and the dispenser.

[0026] According to a preferred embodiment, the polymer is polyimide. A particular advantage of polyimides is their high-temperature resistance and their inertness to a wide range of chemicals.

[0027] The crosslinking step may include a first annealing at a temperature between 80°C and 150°C.

[0028] In some embodiments, the crosslinking step includes an ultraviolet irradiation step and / or a second annealing step.

[0029] In some embodiments, the step of depositing a polymer layer includes depositing an additional functional layer, such as a metal layer, a polysilicon layer, or a piezoelectric material layer, which is disposed on the surface of or within the polymer layer.

[0030] According to a preferred embodiment, the support substrate is made of silicon.

[0031] The etching step may include plasma etching.

[0032] In some embodiments, the step of crosslinking the polymer layer includes the steps of forming a vacuum and / or compressing the valve in pressure and / or annealing.

[0033] The method may also include the step of aligning the fluid channel with the inlet of the microcatheter disposed on the upper surface of the fluid dispenser.

[0034] Advantageously, the method also includes the step of assembling the fluid distributor by welding a glass substrate to the lower surface of the microfluidic circuit.

[0035] The present invention also relates to a microinjector valve for a liquid chromatography apparatus or manufactured according to the method described above, and comprises:

[0036] ○ A supporting base with an upper and lower surface.

[0037] ○ A fluid distributor comprising a cavity and at least two microchannels, the cavity including a seat, the at least two microchannels being fluidly connected via the cavity to form a fluid channel, and

[0038] ○ Polymer layer, advantageously made of polyimide, comprising:

[0039] The bonding region is in integral contact with the bonding region of the lower surface of the support substrate and the bonding region of the upper surface of the dispenser, such that the bonding region of the polymer layer forms an adhesive interface between the lower surface of the support substrate and the upper surface of the dispenser.

[0040] A free region is formed of a membrane having two free surfaces facing the cavity, such that when an actuating force is applied to the membrane, the membrane contacts the seat and closes at least one microcatheter to interrupt the passage of fluid.

[0041] Particularly advantageously, the fluid distributor comprises a silicon substrate and a glass substrate, wherein cavities and microchannels are formed in the silicon substrate, and the glass substrate forms the lower surface of the distributor, the glass substrate being fluid-tightly bonded to the lower surface of the silicon substrate.

[0042] In some embodiments, the valve further includes:

[0043] At least one first fluid channel, formed by at least two microchannels fluidly connected via the cavity, the first fluid channel being adapted to establish a fluid connection between the fluid dispenser and the device for supplying the fluid to be analyzed.

[0044] ○ At least one second fluid channel, the at least one second fluid channel being adapted to establish a fluid connection between the membrane and a pneumatic device, the pneumatic device being configured to actuate the membrane between a closed position and an open position, wherein in the closed position the membrane fluidly seals the first fluid channel, and in the open position the first fluid channel is opened.

[0045] In some embodiments, a first fluid passage and a second fluid passage are arranged in the first face of the valve.

[0046] The valve may also include a third fluid channel for establishing a fluid connection between the fluid distributor and the chromatographic column, the third opening being arranged in a second side of the valve opposite to the first side.

[0047] Another object of the present invention relates to a microinjector for a liquid or gas chromatography apparatus, comprising a plurality of interconnected valves as described above, at least one inlet for a carrier gas, at least one inlet for an analyte fluid, at least one fluid outlet for injecting a sample of the analyte fluid carried by the carrier gas into a chromatographic column, means for actuating the valves, and a microprocessor configured to control the actuation of the respective valves.

[0048] In some embodiments, the device for actuating the valve is a pneumatic device, and the micro-injector further includes at least one gas inlet configured to supply valve actuation gas to the pneumatic device.

[0049] Finally, the present invention relates to a liquid or gas chromatography apparatus comprising a liquid or gas chromatography column, a microinjector as described above, and a detector, the microinjector being configured to inject a fluid sample to be analyzed into the inlet of the chromatography column, and the detector comprising an inlet adapted for fluid connection to the outlet of the chromatography column. Attached Figure Description

[0050] Other features and advantages of the invention will become apparent from the following detailed description with reference to the accompanying drawings, in which:

[0051] Figure 1 This is a schematic top view of the valve and tubing components in a syringe.

[0052] Figure 2A This is a schematic cross-sectional view of the valve according to the present invention.

[0053] Figure 2B yes Figure 2A A detailed schematic diagram of the valve in the diagram.

[0054] Figure 3 This is a schematic diagram designed to form the upper silicon substrate.

[0055] Figures 4A to 4D The steps for manufacturing the upper part of the valve are shown.

[0056] Figure 5 This is a schematic diagram of the upper part of the valve.

[0057] Figure 6A and 6B The manufacturing stages of the dispenser are shown.

[0058] Figure 7 This is a 3D diagram of the distributor.

[0059] Figure 8 This is a schematic diagram of a gas distributor.

[0060] Figure 9 This is a schematic diagram of the valve before the assembly stage.

[0061] Figure 10 This is a 3D view of the assembled valve. Detailed Implementation

[0062] For clarity and simplicity, use as... Figure 2A The bottom-up orientation is shown, in which the valve is positioned such that the diaphragm is arranged above its fluid conduit, which is intended to be closed.

[0063] Therefore, the terms “front,” “rear,” “upper,” “bottom,” and “lower” will be used in the description without limiting the invention.

[0064] The valve according to the invention comprises an upper portion and a lower portion, the upper portion comprising a polymer layer forming a membrane, and the lower portion comprising a seat formed in a fluid distributor. This fluid can be a gas or liquid to be analyzed. During manufacturing, the polymer layer is deposited in a liquid phase. This deposition technique allows the polymer layer to be deposited on the entire surface of the upper portion. Therefore, the bonding regions of the polymer layer form an adhesive interface between the two upper and lower portions of the valve, and the free regions of the polymer layer are intended to form the valve membrane. The polymer layer is cross-linked in two stages. The separation of these two cross-linking stages allows different regions of the membrane to be assigned different functions depending on their location within the valve.

[0065] Figure 2A This is a schematic diagram of a valve according to the present invention. The valve is intended for use in a microinjector in a liquid or gas chromatography apparatus. The valve includes an upper portion 100 and a lower portion, the upper portion 100 including a polymer layer 20 forming a valve diaphragm, and the lower portion including a dispenser 300 forming a valve seat. The upper portion 100 is rigidly attached to the dispenser 300 via the polymer layer 20. Microcatheters 51, 53A, and 53B allow fluid to pass through the valve.

[0066] The term “microchannel” refers to a channel with a cross-section of less than or equal to 500 μm × 500 μm, and the term “microfluidic channel” refers to a fluid channel formed by one or more microchannels.

[0067] The upper portion 100 includes a support substrate 10 and a polymer layer 20. The support substrate 10 has a lower surface 11 and an upper surface 12, with the polymer layer 20 disposed on the lower surface 11 and the upper surface 12 corresponding to the outer surface of the valve. In an illustrative and non-limiting manner, the support substrate has a thickness between 0.2 mm and 2 mm. The support substrate 10 is made of a rigid material that is inert relative to the fluid being analyzed, typically glass or silicon. In some embodiments, the support substrate may be a silicon-on-insulator (SOI) substrate, titanium, sapphire, or a material compatible with microelectronic processes.

[0068] The polymer layer 20 is made of a flexible, elastic material that can withstand the temperatures used during chromatographic analysis and is inert relative to the fluid being analyzed. This polymer is suitable for liquid-phase deposition. Preferably, the polymer is photosensitive so that it can be structured using photolithography. Typically, the polymer layer is made of polyimide, preferably photosensitive polyimide, so that the structure can be etched into the layer using photolithography. In some cases, the polymer can be a photosensitive composition, such as a SU-8 type composition, or a benzocyclobutene (BCB)-based polymer.

[0069] The bonding region 25 of the polymer layer 20 forms an adhesive interface between the bonding region 17 on the lower surface 11 of the support substrate 10 and the bonding region 37 on the upper surface of the dispenser 300. The adhesive interface can be a single surface, or it can consist of several different portions of the polymer layer 20.

[0070] The free regions of the polymer layer form a membrane 21 with two free surfaces 23 and 24. The outer free surface 23 is oriented to face the outside of the valve, and the inner free surface 24 is oriented to face the dispenser 300. Typically, on its outer surface, the membrane 21 is completely surrounded by the region of the supporting substrate 10.

[0071] In some embodiments, the polymer layer includes an additional functional layer, such as a layer of metal, polycrystalline silicon, or piezoelectric material. Such an additional layer may be disposed on one facet of the polymer layer or within the polymer layer, and may accordingly consist of two stacked polymer layers. This type of additional layer can be used to add functionality to a valve diaphragm, for example, to provide actuation of the diaphragm or to determine the actuation or efficiency of the valve.

[0072] The dispenser 300 includes a structured substrate 30 and a substrate 40, the structured substrate 30 including a cavity 35 and microcatheters 53A and 53B, and the substrate 40 forming the lower surface of the dispenser 300.

[0073] The structured substrate 30 is fluid-tightly bonded to the substrate 40 forming the lower surface of the dispenser 300. The substrate 40 forming the lower surface of the dispenser 300 is made of a rigid, inert, fluid-impermeable material, typically glass. The structured substrate 30 is typically made of silicon or another material capable of forming structures by etching.

[0074] refer to Figure 2B The structured substrate 30 includes a cavity 35 disposed on the upper surface of the dispenser 300 and facing the membrane 21. The structured substrate 30 also includes a seat 39 disposed opposite the membrane 21. The seat 39 is configured to receive the membrane 21 when an actuation force is applied to it. In the absence of an actuation force, a distance d between the membrane 21 and the seat 39 allows fluid to pass through. In the absence of an actuation force, the distance d is typically between 10 μm and 50 μm.

[0075] refer to Figure 2A The structured substrate 30 also includes at least two microcatheters 53A and 53B, which are in fluid communication with the outside of the valve via a microcatheter 51 disposed in the upper portion 100 of the valve. The microcatheters 53A and 53B are in fluid communication with each other via a cavity 35. When an actuation force is applied to the membrane 21, the membrane 21 contacts the seat 39 and closes at least one microcatheter 53A or 53B. In this way, fluid flow between the microcatheters 53A and 53B is interrupted.

[0076] exist Figure 2A and 2B In the illustrated embodiment, the microfluidic channel is arranged on the outer surface of the valve. In other embodiments, additional conduits may be arranged on the upper, side, and / or lower surface of the valve. For example, a first passage formed by two microchannels can establish a fluid connection between a fluid dispenser and a device for supplying the fluid to be analyzed. A second fluid channel may be present for establishing a fluid connection between a membrane and a pneumatic device configured to actuate the membrane. This pneumatic device can apply an actuating force to the membrane to bring it into a closed position in contact with a seat. In this closed position, the membrane tightly seals the first fluid channel. When the pneumatic device releases the actuating force, the membrane returns to the open position, thereby opening the first fluid channel.

[0077] The valve may include a third fluid channel for establishing a fluid connection between the fluid distributor and the chromatographic column. In this case, it is advantageous to arrange the openings of the first and second fluid channels on the outer surface of the valve, and the opening of the third fluid channel on the inner surface opposite the outer surface of the valve.

[0078] A method for manufacturing the valve according to the present invention will now be described.

[0079] Upper part of the production valve

[0080] refer to Figure 3A support base 10 is provided, which has:

[0081] A lower surface 11 is intended to form the lower surface of the supporting membrane, and a surface 12 is intended to form the upper surface, which corresponds to the outer surface of the valve opposite to the lower surface 11. (See reference) Figure 4A The polymer layer 20 is deposited in liquid phase on the lower surface 11 of the supporting substrate 10. During deposition, the substrate is reversed in orientation relative to the valve, i.e., the lower surface 11 is oriented upwards to facilitate liquid phase deposition. This liquid phase deposition is typically performed by centrifugation to obtain a thin layer suitable for forming a deformable film.

[0082] The deposited polymer layer 20 is then annealed. In an illustrative and non-limiting manner, this annealing can be carried out at a temperature between 80°C and 150°C for a duration between 1 and 20 minutes. Reference Figure 4B Then, the first step is performed: structuring the partially cross-linked polymer layer using photolithography to form microducts 51 passing through the polymer layer. Specifically, this step includes using a mask M that defines the location of the microducts and applying radiation, such as ultraviolet (UV) radiation, through the mask. The energy of the UV radiation is typically around 300 mJ / cm². 2 and 900mJ / cm 2 between.

[0083] Partial crosslinking of the deposited polymer layer 20 continues via heat treatment, typically for a duration between 10 and 60 minutes at temperatures between 30°C and 150°C. Following this step, the polymer layer 20 is fully cured and chemically stabilized to form a film. Simultaneously, the polymer layer remains sufficiently flexible and tacky to allow the supporting substrate to bond to the dispenser in subsequent steps.

[0084] If the polymer layer includes other functional layers, these functional layers can be deposited after the polymer layer is deposited. In some cases (not shown), a second polymer layer is deposited to complete the membrane.

[0085] refer to Figure 4C The second photolithographic structuring step, particularly photographic development, then enables the polymer layer 20 to be... Figure 4B The irradiated region in the first structuring step shown is etched. This type of development allows the polymer to be removed from the region irradiated by ultraviolet radiation in order to create openings in the microconductor 51, which is designed to form microfluidic channels for valves.

[0086] In the next step, refer to Figure 4D Partial etching is performed to remove the first portion 13 of the supporting substrate 10. (See reference...) Figure 5The free regions 21 of the polymer layer 20 are thus exposed, resulting in two free surfaces 23 and 24. Etching can be performed using localized plasma processing. The free regions are intended to form the membrane 21 of the valve. The bonding regions 25 where the polymer layer 20 contacts the support substrate 10 are intended to form an adhesive layer during valve assembly.

[0087] Production Distributor

[0088] refer to Figure 6A The distribution substrate 30 is used to form a distributor, which is designed to house microchannels for fluid circulation within the valve. The distribution substrate 30 is typically made of silicon. The thickness of the distribution substrate 30 is typically between 0.2 mm and 2 mm. (Reference) Figure 6B The structure is created through multiple photolithography and / or plasma etching steps. These steps produce the valve's cavity 35 and seat 39, fluid passages, and microfluidic channels 53A, 53B. The cavity 35 and seat 39 are typically created on the upper surface of the dispensing substrate 30 via successive plasma etching steps, the upper surface being designed to face the membrane after valve assembly. Some microfluidic channels 53A, 53B pass between the upper and lower surfaces of the dispensing substrate 30 and can be created by etching from the upper and / or lower surfaces of the substrate. Other microfluidic channels 53A, 53B pass between the cavity and the lower surface of the dispensing substrate 30 and are created by etching from the lower surface of the substrate. Microfluidic channels 53A, 53B are also disposed on the lower surface of the dispensing substrate 30 and can be fluidly connected to one or more through channels.

[0089] Figure 7 The arrangement of the lumen 35, seat 39, and microcatheters 53A and 53B is shown in perspective. The seat may include a central portion 39A and / or a plurality of studs 39B distributed around the lumen 35. (Reference) Figure 8 The structured silicon substrate 30 is then welded to the glass substrate 40 to form the lower surface of the valve. For example, the substrate can be welded to the glass substrate via an anodic seal. The glass substrate 40 typically has a thickness between 0.2 mm and 2 mm. Therefore, the fluid channels 53A, 53B on the lower surface of the dispensing substrate 30 are closed, except for any fluid inlets and / or outlets and associated fluid connections.

[0090] Assembly valves

[0091] refer to Figure 9 Assemble the upper part 100 and the dispenser 300 so that the membrane 21 is positioned facing the seat 39, and the microcatheter 51 of the upper part 100 is aligned with the microcatheters 53A and 53B of the dispenser 300. Alignment can be performed manually using an optical device such as a microscope, or it can be performed using a dedicated alignment machine.

[0092] The bonding region 25 of the polymer layer 20 is designed to form an adhesive interface between the bonding region 17 on the lower surface 11 of the support substrate 10 and the bonding region 37 on the upper surface of the dispenser 300. During assembly, this bonding region 25 of the polymer layer contacts the bonding region 37 of the dispenser to achieve bonding with the upper part 100. The upper part 100 and the dispenser 300 are then held in contact by applying pressure. In an illustrative and non-limiting manner, the pressure is between 2 N and 30 kN, and the duration of compression is between 5 minutes and 5 hours.

[0093] Once alignment and contact are complete, crosslinking of the polymer layer 20 continues to bond the upper portion 100 to the dispenser 300. Continuous crosslinking is performed via thermocompression in an illustrative and non-limiting manner. During this step, the support substrate and dispenser can be aligned and placed in contact within a vacuum chamber, under pressure, for example, at 1 x 10⁻⁶. -8 Between mbar and 1 bar. Heat the assembled upper and lower parts to, for example, a temperature between 30°C and 400°C.

[0094] After cross-linking, the associated portions are cooled to a temperature, for example, between 20°C and 80°C. (See reference) Figure 10 The upper part 100 and the distributor 300 are sealed, and the valve is complete.

[0095] At this stage, the polymer layer has lost its adhesive properties in its partially cross-linked state. The cross-linked bonding region 25 forms a sealing connection between the supporting substrate and the corresponding surface of the dispenser. The polymer layer allows the valve diaphragm to be manufactured simultaneously with the upper part bonded to the dispenser.

[0096] In some embodiments, other substrates or materials may be deposited on the surface of the valve or on one or more interfaces during manufacturing. For example, metals, polycrystalline silicon, or piezoelectric materials may be deposited on the surface or between two consecutively deposited polymer layers.

[0097] Use valves

[0098] After assembling the valve, the inlet of a microfluidic channel can be connected to a device for supplying the fluid to be analyzed, and the outlet of the same microfluidic channel can be connected to an analytical device, particularly a liquid chromatography or gas chromatography column. Because the microfluidic channel includes at least two conduits connected via a cavity fluid, the microfluidic channel can be opened or closed by actuating a membrane formed of a polymer layer.

[0099] A dedicated pneumatic device can be used to actuate the membrane to open and close the valve. In this case, in addition to the microfluidic tubing forming a passage through the cavity, the valve includes at least one second fluid passage for establishing a fluid connection between the membrane and the pneumatic device. This fluid passage includes an inlet designed to connect to the pneumatic device and an outlet in fluid communication with the membrane.

[0100] A pneumatic device is used to apply pneumatic pressure to the membrane. The membrane can then be pressed against the dispenser seat to close the microfluidic channels. When the pneumatic pressure decreases, the membrane returns to its initial position and opens the microfluidic channels. Alternatively, another technique, such as a piezoelectric device, can be used to apply pressure to the membrane.

[0101] When the membrane is pressed against the distributor seat, no static friction effect occurs between the membrane surface and the valve seat due to the complete cross-linking of the membrane. No additional anti-static friction treatment is required for the membrane or seat.

[0102] The arrangement of the microfluidic tubing can be designed according to the purpose of the valve and the design of the microinjector into which the valve may be incorporated. For example, the inlets of one or more microfluidic channels through the cavity and the inlets of fluid channels for connecting pneumatic devices can be arranged on the upper surface of the valve. When such a valve is used for a microinjector for chromatographic analysis, the inlets of the microfluidic channels can be connected to a fluid supply device for delivering the analyte and / or a device for delivering a carrier gas. Thus, all fluid connections to the outside of the chromatographic apparatus are arranged on the same surface of the valve. The valve may also include a third fluid channel for establishing a fluid connection between the fluid dispenser and the chromatographic column. In this case, the valve may be designed such that the opening of the third fluid channel is arranged on the lower surface of the valve opposite the upper surface. Thus, the lower surface of the valve may include one or more fluid connections to the interior of the chromatographic apparatus. In an illustrative and non-limiting manner, the upper surface may be formed by the supporting substrate 10 and the outer free surface 23 of the membrane, and the lower surface may be a surface formed by a glass substrate 40.

[0103] Miniature syringe

[0104] One or more valves according to the invention can be used to manufacture microinjectors for chromatographic analysis. For example, multiple valves can be assembled in an electronic circuit. Inputs and outputs are connected according to the application. For example, a first input is connected to a fluid source to be analyzed, and a second input is connected to a carrier gas source. One or more outputs can be connected to one or more chromatographic columns, such as an analytical column, and corresponding outputs are connected to a pre-column and / or a reference column. One or more inputs and outputs can also be used to interconnect multiple corresponding valves, such as... Figure 1As shown. Some valves can be used to manage flow during cleaning of the chromatography apparatus. Control devices can be connected to the chromatography apparatus to drive valves or valve assemblies using software. Such software drives the opening and closing parameters of each valve, such as the duration and / or force and / or actuation sequence of each corresponding valve in the valve assembly.

[0105] This component can be incorporated into a liquid or gas chromatography apparatus that includes one or more chromatographic columns and detectors.

[0106] References

[0107] US 6896 238 B2

[0108] United States 4869 282 A

[0109] "Micr○-fabricated membrane gas valves with an○n-sticti○nc○atingdep○sited by C4F8 / Ar plasma" Shann○n et al., J. Micr○mech. Micr○eng. 18(2008) 095015 (9pp)

Claims

1. A method for manufacturing a valve for a microsyringe for a liquid or gas chromatography apparatus, comprising the steps of: o liquid phase depositing a polymer layer (20) on a lower surface (11) of a support substrate (10), o partial cross-linking treatment of a first portion of the polymer layer (20), o etching of the support substrate (10) to expose a free area (21) of the polymer layer (20), o assembling the support substrate (10) and a fluid dispenser (300), the fluid dispenser (300) comprising a cavity comprising a seat (39) configured to receive the membrane and at least one microduct (53A, 53B) fluidically connected via the cavity to form a fluidic passage, the assembling being carried out by means of the polymer layer (20) so that - the free area (21) of the polymer layer (20) forms a membrane having two opposite free surfaces (23, 24) so that, when an actuation force is applied to the membrane, the membrane comes into contact with the seat (39) so as to seal the at least one microduct (53A, 53B), - a bonding area (25) of the polymer layer is in integral contact with a bonding area (17) of the lower surface (11) of the support substrate (10) and with a bonding area (37) of the upper surface of the dispenser (300), the bonding area (25) of the polymer layer forming an adhesive sealing interface between the support substrate (10) and the dispenser (300), o a second treatment comprising continuing the cross-linking of the polymer layer (20) so that a first face of the bonding area (25) can be sealed with the dispenser (300).

2. The method according to claim 1, further comprising the step of etching the support substrate (10) and the polymer layer (20) to create at least one fluidic passage (51, 52) before assembling the support substrate and the fluid dispenser, at least one microduct (53A, 53B) of the dispenser (300) being adapted to communicate with a fluidic passage (51, 52), the assembling being carried out so that each fluidic passage (51, 52) is aligned with a microduct (53A, 53B) to form a respective fluidic passage between the support substrate (10) and the dispenser (300).

3. The method according to claim 1 or 2, wherein the polymer is a polyimide.

4. The method according to claim 3, wherein the partial cross-linking step comprises a first annealing at a temperature of 80°C to 150°C.

5. The method according to any one of claims 1 to 4, wherein the partial cross-linking step comprises a step of irradiation with ultraviolet radiation and / or a second annealing step.

6. The method of any one of claims 1 to 5, wherein, The step of depositing the polymer layer (20) comprises depositing an additional functional layer, such as a layer of metal, polysilicon or piezoelectric material, arranged on a face of the polymer layer or within the polymer layer.

7. The method of any one of claims 1 to 6, wherein, The support substrate (10) is made of silicon.

8. The method according to any one of claims 1 to 7, wherein the etching step comprises a plasma etching.

9. The method according to any one of claims 1 to 8, wherein the step of crosslinking the polymer layer comprises the step of forming a vacuum and / or compressing the valve in pressing and / or annealing.

10. The method according to claim 9, further comprising the step of aligning the fluidic passage (51) with microduct inlets (53A, 53B) arranged in an upper surface of the fluid distributor (300).

11. The method according to any one of claims 1 to 10, further comprising the step of assembling the fluid distributor (300) by welding a glass substrate (40) on a lower surface of the microfluidic circuit.

12. A microinjector valve for a liquid or gas chromatography device, manufactured according to the method of any one of claims 1 to 11, and comprising: o a support substrate (10) having an upper surface and a lower surface, o a fluid distributor (300) comprising a cavity comprising a seat and at least two microducts fluidically connected via the cavity to form a fluidic passage, and o a polymer layer, advantageously made of polyimide (20), comprising: a bonding area (25) integrally in contact with a bonding area (17) of the lower surface (11) of the support substrate (10) and a bonding area (37) of the upper surface of the distributor (300), so that the bonding area (25) of the polymer layer forms a bonding interface between the lower surface of the support substrate and the upper surface of the distributor (300), and a free area (21) forming a membrane having two free faces facing the cavity, so that when an actuation force is applied to the membrane, the membrane comes into contact with the seat and closes at least one microduct so as to interrupt the passage of fluid.

13. The microinjector valve according to claim 12, wherein the fluid distributor (300) comprises a silicon substrate (30) in which the cavity and the microducts are formed, and a glass substrate (40) forming a lower surface of the distributor, the glass substrate being bonded to a lower surface of the silicon substrate (30) in a fluid-tight manner.

14. The microinjector valve according to any one of claims 12 or 13, further comprising: o at least one first fluidic passage formed by at least two microducts fluidically connected via the cavity, the first fluidic passage being adapted to establish a fluidic connection between the fluid distributor and a device for supplying fluid to be analyzed, and o at least one second fluidic passage adapted to establish a fluidic connection between the membrane and a pneumatic device configured to actuate the membrane between a closed position in which the membrane seals the first fluidic passage in a fluid-tight manner and an open position in which the first fluidic passage is open.

15. The microinjector valve according to claim 14, wherein the first fluidic passage and the second fluidic passage are arranged in a first face of the valve.

16. The microsyringe valve of claim 15, further comprising a third fluid channel for establishing a fluid connection between the fluid dispenser and a chromatographic column, the third opening being arranged in a second face of the valve opposite the first face.

17. A microsyringe for a liquid or gas chromatography apparatus, comprising a plurality of interconnected valves according to any one of claims 12 to 16, at least one inlet for a carrier gas, at least one inlet for a fluid to be analyzed, at least one fluid outlet for injecting a sample of the fluid to be analyzed carried by the carrier gas into a chromatographic column, means for actuating the valves, and a microprocessor configured to control actuation of the respective valves.

18. The microsyringe of claim 17, wherein the means for actuating the valves are pneumatic means, the microsyringe further comprising at least one gas inlet configured to supply valve actuation gas to the pneumatic means.

19. A liquid or gas chromatography apparatus comprising a liquid or gas chromatographic column, a microsyringe according to claim 17 or claim 18 configured to inject a sample of a fluid to be analyzed into an inlet of the chromatographic column, and a detector comprising an inlet adapted to be fluidically connected to an outlet of the chromatographic column.

Images