SAPPHIRE MICROREACTORS

Abstract

The present invention concerns the field of microreaction devices and of micro-process engineering. It particularly involves devices having micro-channels (internal chambers of micrometric to submicrometric dimensions) for conveying chemical or biochemical mixtures and/or reactions. More specifically, such devices are optimized to achieve high temperature and pressure stresses (i.e. 500° C. and 500 bar). For observation and analysis purposes, the microreaction devices have a wide range of transparency in terms of wavelengths. The subject matter of the present invention relates to a microfluid or microreactor device made of transparent sapphire, preferably in the wavelength range of 150 to 6500 nm, its manufacturing method and to its use.

Claims

1. A microreactor made of transparent sapphire in the wavelength range from 150 to 6500 nm.

2. The microreactor according to claim 1, wherein the sapphire is mono-crystalline or polycrystalline.

3. The microreactor according to claim 1, further comprising a first wafer and a second wafer, wherein at least one of said wafers comprises at least one micro-channel.

4. The microreactor according to claim 3, wherein the micro-channel has an average depth H ranging from 0.1 to 500 μm.

5. The microreactor according to claim 3, wherein the micro-channel has an average width W ranging from 0.1 to 1000 μm.

6. The microreactor according to claim 3, wherein the ratio of wafer thickness/micro-channel depth is greater than or equal to.

7. The microreactor according to claim 5, wherein the total surface area of the at least one micro-channel, is less than or equal to half of the total wafer surface area.

8. The microreactor according to claim 1, having a volume of less than 500 μl.

9. (canceled)

10. A process of manufacturing a sapphire microreactor according to claim 1, comprising the steps of: 1) etching at least one micro-channel on at least one wafer, and 2) assembling the etched wafer obtained in step 1) on a second etched or unetched wafer.

11. The process according to claim 10, wherein the etching step 1) further comprises the substeps of: (a) printing an image of interest, by means of a resin, on at least one wafer, said wafer being covered by a layer of sacrificial material, (b) chemical etching of the layer of sacrificial material present on the wafer, (c) removing the residual resin layer, and (d) chemical etching of the micro-channels according to the desired final depth.

12. The process according to claim 10, further comprising a step of drilling the inlet and/or outlet ports of the wafer(s).

13. The process according to claim 10, wherein the assembly of step 2) further comprises a pre-bonding step, wherein said pre-bonding step comprises at least one wafer cleaning step followed by pre-bonding in aqueous solution and then heat treatment in a press system.

14. The process according to claim 13, wherein the cleaning step is carried out by means of a solution of sulphuric acid (H.sub.2SO.sub.4) and hydrogen peroxide (H.sub.2O.sub.2), (4:1, v/v), followed by a rinsing with ultra-pure water at a temperature higher than or equal to 60° C. and a treatment in a phosphoric acid crystallizer at a temperature higher than or equal to 150° C.

15. The process according to claim 13, wherein the pre-bonding consists of bringing the wafers into contact with each other, with the etched side(s) on the inside, the set thus constituted is then heat treated at a temperature ranging from 200 to 300° C. and for a time ranging from 2 to 4 hours in a press system.

16. The process according to claim 10, wherein the assembly of step 2) is performed by the Spark Plasma Sintering (SPS) or Field Activated Sintering Technique (FAST) method.

17. (canceled)

18. The microreactor according to claim 2, wherein the sapphire is mono-crystalline and the c-plane is perpendicular to the microreactor surface.

19. The microreactor according to claim 3, wherein the ratio of wafer thickness/micro-channel depth is greater than or equal to 4.

20. The microreactor according to claim 5, wherein the minimum distance Z between two micro-channels, or between two parts of the same micro-channel is greater than or equal to W.

21. The microreactor according to claim 1, having a volume ranging from 0.5 to 500 μl.

22. The method of claim 10, wherein the etching is done by a photolithography method followed by chemical or plasma etching, or by direct laser writing method or machining.

Description

[0049] FIG. 1 shows the transmission diagram of a sapphire microreactor according to the invention with a total thickness of 1 mm (transmission in % as a function of wavelength λ in μm).

[0050] FIG. 2 shows a cross-sectional view of micro-channels etched into two wafers (A and C) and micro-channels etched into a single wafer (B and D).

[0051] FIG. 3 shows a cross-sectional view of a wafer comprising a chemically etched micro-channel.

[0052] FIG. 4 shows a cross-sectional view of a wafer comprising a plasma etched micro-channel.

[0053] FIG. 5 shows a cross-sectional view of a microreactor according to the invention comprising a first wafer (1), a second wafer (2) and a micro-channel (3).

[0054] FIG. 6 shows two examples of patterns (A) and (B). Pattern (A) represents a “porous medium” type microreactor composed of microplots with different diameters. The pattern (A) has an inlet E1 and an outlet S1 as well as two ports P1 and P2 allowing the pressure to be measured upstream and downstream of the micro-plots. Pattern (B) represents a “segmented flow” microreactor composed of two inlets E′1 and E′2 and an outlet S′1. The two micro-channels connected to the inlets E′ 1 and E′2 join to form a single channel that continues to have a certain length of channel up to the outlet S′1.

[0055] FIG. 7 shows (A) the microreactor C obtained in Example 1 with the porous medium type pattern A of FIG. 4 and (B) a microreactor with the segmented flow type pattern B of FIG. 4 (fluid alternations).

[0056] FIG. 8 represents in 3D modeling, two patterns (A and C) of microreactor of porous medium type with (A) a uniform porous medium (identical diameter of the micro-plots) and (C) a porous medium composed of micro-plots having three different diameters. FIG. 8 shows a 3D model of a segmented flow pattern (B).

[0057] FIG. 9 shows schematically the main steps in the manufacture of a microreactor according to the invention.

[0058] FIG. 10 shows the device set up for chemical etching.

[0059] FIG. 11 shows an injection system, also known as a compression piece, which connects the microreactor inlets and outlets to reagents. This injection system keeps the microreactor under pressure.

[0060] FIG. 12 shows a photograph taken by optical microscopy (×40 objective) of the interior of an all-sapphire microreactor under pressure during a reaction between water, iron particles and a gas.

[0061] FIG. 13 shows in (A) the image obtained by optical microscopy (×15 objective) during an in situ infrared spectroscopy analysis of a microreactor filled with a water/pentane/air mixture; in (B) the absorption spectrum of the all-sapphire microreactor used as a background for the in situ analyses; in (C) and (D) respectively, the absorption spectra of pentane and water obtained by infrared spectroscopy on the microreactor.

[0062] FIG. 14 represents a mask made with AUTOCAD software (registered trademark) containing the image of interest or design to be etched in the wafer.

[0063] FIG. 15 shows the parameters used in the Spark Plasma Sintering assembly step, specifically the temperature and pressure ramps applied as a function of time.

[0064] FIG. 16 shows: (A) a sapphire microreactor pattern that has an inlet and an outlet as well as two ports P1 and P2 allowing the pressure upstream and downstream of the micro-plots to be measured, said pattern simulating a heterogeneous porous medium with different sized pads (25 to 300 μm) as well as preferential passage areas simulating cracks. (B) visible light images at different growth times (0 and 8 h) of microorganisms of the strain Thermococcus Barophilus that were grown under pressure (100 bar)/temperature (85° C.) in a microreactor having the design of FIG. 16-A. It is possible to follow the evolution of the microbial development in real time.

[0065] The invention will be better understood by reading the following non-limiting examples.

Example 1: Manufacture of a Sapphire Microreactor According to the Invention

[0066] 1) Etching.

[0067] The pattern of a micro-channel (previously drawn on a mask via AUTOCAD software (trademark), see FIG. 14) is printed on the sapphire wafer by the photolithography process.

[0068] This step is preferably performed in a clean room (clean room according to ISO 14644-1). A sapphire wafer of 101.6 mm diameter (wafer), covered with a 500 nm SiO.sub.2 oxide layer, is cleaned with isopropanol and ethanol and then dried with a microfiber cloth, in order to remove all dust/traces from the surface. The lithography process starts with the uniform application of a film of a few μm thickness of photosensitive resin (advantageously: 4 μm), on the substrate via the use of a spin coating device. A baking step on a hot plate follows the resin deposition (the temperature and the duration are to be adapted according to the resin, in this example the baking was 5 minutes at 115° C.). Once the wafer has cooled down to room temperature, the resin is exposed for 45 seconds to ultraviolet rays in an exposing aligner (for example type UV-KUB KLOE). When the wafer is placed in this apparatus, a mask is placed on top so that the mask patterns are positively formed on the resin.

[0069] The wafer is then immersed in a chemical developer bath containing a diluted solution of tetramethylammonium hydroxide which removes the insolated areas. These areas are no longer protected by the resin and will therefore be sensitive to etching. To stop the development of the resin, the wafer is then rinsed with water and dried before being heated for a few minutes on a hot plate (about 6 minutes at 115° C.).

[0070] The oxide layer, exposed after irradiation of the resin, is removed by acid etching. The wafer is placed, with the side to be etched facing upwards, in a Teflon crystallizer and the area to be etched is covered with a 1% hydrofluoric acid (HF) solution buffered in water for 7 minutes. Once the chemical etching is complete, the wafer is rinsed with water and the final design imprint appears. The residual resin layer is removed by cleaning the wafer with acetone.

[0071] Once the oxide layer has been removed, the sapphire is etched. The etching is done with sulfuric acid (H.sub.2SO.sub.4) and phosphoric acid (H.sub.3PO.sub.4) in the proportions 4 to 1 (v/v), following the set-up shown in FIG. 10. The temperature of the mixture stabilizes between 250 and 300° C. After several minutes at the maximum temperature, the wafer is etched to form the desired micro-channel pattern. Since the wafer etch is anisotropic, the etch profile is along the c-plane of the sapphire, making asymmetric angles 0=35° and 70° to the surface. Once etched, the wafer is rinsed with water and ethanol.

[0072] The inlet and outlet ports of the wafer are drilled, for example with a laser or by using diamond drill bits. A final HF bath (7 min) is performed to remove the residual oxide layer.

[0073] We obtain the wafer A.

[0074] 2) Assembly.

[0075] The wafer pre-bonding step is performed in clean condition (clean room) to avoid any dust or impurities to be placed between the two wafers and compromise the assembly. The two wafers, wafer A and a wafer B (preferably of the same lateral dimensions as wafer A) are cleaned with a Piranha solution (sulfuric acid (H.sub.2SO.sub.4) and hydrogen peroxide (H.sub.2O.sub.2, 4:1 v/v) for 15 min. Then the two wafers are placed for 5 min in ultra pure water heated to 60° C. and transferred to a phosphoric acid crystallizer heated to 150° C. After 30 minutes, both wafers are placed in a dilute sulfuric acid solution with a pH of 1 for 5 min. The wafers are then placed in a crystallizer containing ultra pure water for 5 minutes.

[0076] The two wafers are then assembled one against the other, the etched side(s) on the inside. The set thus constituted is then heat treated at 200° C. for 2 hours in a press system (screw tightening).

[0077] The assembly of the wafers is carried out by Spark Plasma Sintering (SPS), also called Field Activated Sintering Technique (FAST). The parameters are shown in FIG. 15, which specifies in particular the temperature and pressure ramps applied as a function of time to ensure good assembly.

[0078] Once the two wafers are bonded, the microreactor is cut by a diamond saw to obtain the microreactor C, depending on the dimensions of the pattern and the application envisaged for the thickness.

Example 2: Example of the Use of the Microreactor C of Example 1 Under Severe Conditions, Pressure and Temperature Test and In Situ Analysis

[0079] The microreactor in Example 1 is used for microbiology under extreme conditions.

[0080] The microreactor C of Example 1 is connected to a fluid injection system suitable for high pressure and high temperature conditions. FIG. 11 shows the three-dimensional drawing of the PEEK (polyetheretherketone) compression piece developed for these microreactors.

[0081] Pressure and Room Temperature Test of the Microreactor C.

[0082] To test the microreactor C in pressure, it is attached to the compression piece and connected to an ISCO Teledyne pump filled with water. The microreactor C has a pressure resistance of 400 bar under the conditions of the example.

[0083] Temperature and Atmospheric Pressure Test of the Microreactor C.

[0084] To test the microreactor C in temperature, it underwent a local temperature gradient: 400° C. at one end and 11.3° C. at the other. After several hours under this temperature gradient, the microreactor remained intact (no cracks, breaks or other changes).

[0085] It is thus demonstrated that the microreactor according to the invention can withstand the severe conditions according to the example of temperature and pressure tests described above.

[0086] In Situ Analysis in the Microreactor C.

[0087] Microreactor C is transparent over a very wide wavelength range: from infrared to ultraviolet. FIG. 1 shows a transmission spectrum of a sapphire microreactor as a function of wavelength. This characteristic allows to realize observations or analyses (FIG. 13) with for example an optical microscope or an infrared spectrometer.

[0088] Analysis by Optical Microscopy.

[0089] By optical microscopy, it is possible to observe in real time the reactions that occur inside the microreactors.

[0090] Analysis by Infrared Spectroscopy.

[0091] An in situ analysis of a microreactor C was performed using an infrared spectrometer equipped with a microscope (see FIG. 13A). First, the absorption spectrum of sapphire (visible in FIG. 13B) was made. This spectrum was used as a background to perform analyses. Next, we injected a water-pentane mixture into the microreactor. The absorption spectra of these two molecules are shown in FIGS. 13C and 13D.

[0092] These tests and analyses show that it is possible to follow in real time a reaction performed in an all-sapphire microreactor under pressure and temperature via in situ analysis techniques. For example, FIG. 12 shows an image obtained by optical microscopy of the interior of a microreactor (pattern with microdots) housing a reaction between water, CO.sub.2(g) and iron particles. One of the products of this reaction (FeCO.sub.3) can be identified by infrared spectroscopy.

Example 3: Example of the Use of a Sapphire Microreactor to Monitor the Growth of Extremophilic Microbial Strains In Situ and in Real Time

[0093] A sapphire microreactor was fabricated according to Example 1 with the pattern shown in FIG. 16-A.

[0094] The microreactor has been used for the study and cultivation of living microorganisms under extreme conditions, in particular microorganisms from deep ocean environments (i.e. Thermococcus barophilus).

[0095] This made it possible to perform in situ and real-time microbial growth monitoring for pressures up to 400 bar and temperatures <100° C. The microreactor pattern used for this study is shown in FIG. 16-A.

[0096] The microreactor is filled with a culture medium inoculated with the strain to be studied. This medium is then pressurized and placed in temperature conditions allowing the development of the microorganisms with the help of a heating element in direct contact with the microreactor. The microreactor is placed under a confocal microscope to perform in situ and real time imaging to follow the growth of the microorganisms.

[0097] FIG. 16-B shows visible light images at different growth times (0 and 8 h) of microorganisms of the Thermococcus Barophilus strain that were grown under pressure (100 bar)/temperature (85° C.) on a microreactor with the design shown in FIG. 16-A. It is thus possible to follow the evolution of microbial development in real time.