Method for preparing a tubular microchannel for gas chromatography

Abstract

Method (100) for preparing a tubular microchannel for gas chromatography, the microchannel being etched on a chip (1), the method (100) comprising the following steps: - chemical functionalization (101) of a support, in the microchannel, to adapt the chemical nature of the support for a deposition of a stationary phase on said support, - deposition (103) of the stationary phase on said support in which the chemical functionalization (101) of the support comprises an introduction into the microchannel of a reagent, the reagent being introduced in a concentrated form according to a purity level of between 95% and 100%, preferably according to a purity level of between 99% and 100%. Figure 3

Description

Title of the invention: Method for preparing a tubular micro-channel for gas chromatography

[0001] The present invention relates to the field of chromatography, and in particular to methods of manufacturing gas chromatography columns.

[0002] It is known to manufacture one or more micro-columns on a silicon or glass chip, according to the so-called MEMS (Micro-Electro-Mechanical System) technology, the chip having for example a thickness of 500 μm; according to an exemplary embodiment, the micro-columns form a micro-channel, with a square section of 120 μm, and a length of 5 m, etched in a serpentine fashion on the silicon chip, with a fluidic inlet and outlet of the micro-channel machined on the silicon chip.

[0003] It is also known to deposit, according to a so-called static method, a stationary phase in the micro-columns.

[0004] The known methods of deposition of the stationary phase applied to the microcolumns complicate the implementation of a chemical functionalization of the surface of the micro-columns, functionalization which is usually carried out at high temperature, typically at temperatures between 300°C and 400°C.

[0005] Furthermore, the performance of micro-columns obtained with known methods of stationary phase deposition has insufficient performance for certain applications.

[0006] The invention therefore aims to propose a solution to all or part of these problems.

[0007] To this end, the present invention relates to a method for preparing a tubular microchannel for gas chromatography, the microchannel being etched on a chip, the method comprising the following steps: - chemical functionalization of a support, in the micro-channel, to adapt the chemical nature of the support for deposition of a stationary phase on said support, - deposition of the stationary phase on said support in which the chemical functionalization of the support comprises an introduction into the micro-channel of a reagent, the reagent being introduced in a concentrated form according to a purity level of between 95% and 100%, preferably according to a purity level of between 99% and 100%.

[0008] According to these provisions, the method makes it possible to obtain better attachment of the stationary phase to the support, due to better deactivation of the support. This better attachment of the stationary phase results in a reduction of the asymmetry of the chromatographic detection peaks by the chip. In other words, according to these arrangements, particular chromatographic performances are obtained, associated with an increase in retention, stability and efficiency of the deposit, with a reduction in the asymmetry of the chromatographic peaks, said asymmetry tending towards 1 after the implementation of the process on the micro-channel.

[0009] According to one embodiment, the invention comprises one or more of the following characteristics, alone or in a technically acceptable combination.

[0010] According to one embodiment, the chip is made of silicon or glass.

[0011] According to one embodiment, a section of the micro-channel has a dimension between 10 pm and 200 pm, preferably between 50 pm and 150 pm, preferably equal to 120 pm.

[0012] According to one embodiment, the section is square or rectangular.

[0013] According to one embodiment, the micro-channel has a length of between 0.5 m and 10 m, preferably equal to 5 m.

[0014] According to one embodiment, the length of the micro-channel is extended in the shape of a serpentine.

[0015] According to one embodiment, the support is an interior surface of the microchannel.

[0016] According to one embodiment, the reagent is one of: hexamethyldisilazane, N,N-Dimethyltrimethylsilylamine, N-trimethylsilylimidazole.

[0017] According to these provisions, the chemical functionalization of the support comprises a grafting of trimethylsilyl chemical groups onto the support.

[0018] According to one embodiment, the introduction of the reagent into the micro-channel is carried out continuously and at a constant introduction speed.

[0019] According to these provisions, the functionalization step is dynamic, in other words the functionalization step takes place continuously over a period of time corresponding to a duration of introduction of the reagent.

[0020] According to one embodiment, the rate of introduction of the reagent is between 0.01 ml / h and 0.03 ml / h, preferably equal to 0.02 ml / h.

[0021] According to one embodiment, the introduction of the reagent into the micro-channel comprises the use of a syringe pump to deliver a volume of reagent contained in a syringe, for example 1 ml, at a constant flow rate into the micro-channel, the syringe pump being connected to an inlet of the micro-channel by a capillary tube.

[0022] According to these provisions, pressure exerted by the syringe pump makes it possible to compensate for a significant viscosity of the reagent linked to its use without dilution.

[0023] According to one embodiment, the chip is maintained at a determined temperature during the functionalization step.

[0024] According to one embodiment, the determined temperature is between 50°C and 150°C, preferably equal to 100°C.

[0025] According to one embodiment, the chip is placed in an oven maintained at the determined temperature.

[0026] According to these provisions, the method makes it possible to avoid functionalization usually carried out at high temperature, i.e. at temperatures between 300°C and 400°C in a closed system, which cannot be carried out on certain systems, in particular on miniaturized systems based on MEMS technologies.

[0027] According to one embodiment, the deposition of the stationary phase comprises deposition by evaporation.

[0028] According to one embodiment, the deposition by evaporation comprises a control of a deposition speed.

[0029] According to one embodiment, the control of the deposition speed comprises evaporation by applying a suction pressure lower than a determined pressure.

[0030] According to one embodiment, the determined pressure is between 350 mBar and 450 mBar, preferably equal to 400 mBar.

[0031] According to one embodiment, the application of a suction pressure comprises the use of a vacuum pump directly connected to the inlet of the micro-channel by a capillary tube to create the desired depression, an outlet of the micro-channel being closed during the step of applying the suction pressure.

[0032] According to these provisions, the speed of the deposition is limited to a maximum value.

[0033] According to these provisions, the chromatographic performances are improved.

[0034] According to one embodiment, during the step of depositing the stationary phase, the chip is placed in a thermostatically controlled bath.

[0035] According to one embodiment, the stationary phase is one of: polysiloxane, or PDMS, and polyethylene glycol, or PEG.

[0036] According to one embodiment, the method comprises a step of treating the support with the application of a coating on the support, before the step of depositing the stationary phase on the support.

[0037] According to one embodiment, the coating is an alumina coating or a titanium oxide coating.

[0038] For a better understanding, an embodiment and / or implementation of the invention is described with reference to the attached drawings representing, by way of non-limiting example, an embodiment or implementation respectively of a device and / or a method according to the invention. The same references in the drawings designate similar elements or elements whose functions are similar.

[0039] [Fig. 1] is a schematic representation of an assembly for implementing a functionalization step of the process according to an implementation mode of the invention.

[0040] [Fig.2] is a schematic representation of an assembly for implementing a stationary phase deposition step of the method according to an embodiment of the invention.

[0041] [Fig.3] is a schematic representation of the sequence of steps of the method according to one embodiment of the invention.

[0042] The present invention relates to a method 100 for preparing a tubular micro-channel, etched on a chip 1, and configured for the implementation of gas chromatography.

[0043] The microchannel has, for example, a square or rectangular section. A section of the microchannel has a dimension between 10 pm and 200 pm, preferably between 50 pm and 150 pm, preferably equal to 120 pm.

[0044] The microchannel has, for example, a length of between 0.5 m and 10 m, preferably equal to 5 m. In particular, the length of the microchannel is extended in a serpentine shape on the chip 1.

[0045] Chip 1 is, for example, made of silicon or glass.

[0046] The method 100 comprises the following steps:

[0047] - chemical functionalization 101 of a support, in the micro-channel, to adapt the chemical nature of the support for deposition of a stationary phase on said support; said support is, for example, an interior surface of the micro-channel. - deposition 103 of the stationary phase on said support.

[0048] The chemical functionalization 101 of the support comprises an introduction into the micro-channel of a reagent, the reagent being introduced in a concentrated form according to a purity level of between 95% and 100%, preferably according to a purity level of between 99% and 100%.

[0049] According to these particular provisions, the method 100 makes it possible to obtain better attachment of the stationary phase to the support, due to better deactivation of the support. This better attachment of the stationary phase results in a reduction in the asymmetry of the chromatographic detection peaks by the chip evaluated using the asymmetry factor whose formula is:

[0050] Fs = [Math.l] 2 X

[0051] Where Fs is the peak asymmetry factor, b5% is the right half-width of the peak at 5% of the peak height, and a5% is the left half-width of the peak at 5% of the peak height.

[0052] In other words, according to these provisions, an improvement in chromato- graphics is obtained, associated with an increase in retention, stability and deposition efficiency, the improvement resulting in a reduction in the asymmetry of the chromatographic peaks, said asymmetry tending towards 1 after the implementation of the process on the micro-channel.

[0053] In particular, the reagent may be one of the following components: hexamethyldisilazane (HDMS), N,N-Dimethyltrimethylsilylamine (TMSDMA), or N-trimethylsilylimidazole. Thus, the step of chemical functionalization 101 of the support comprises a grafting of trimethylsilyl chemical groups onto the support.

[0054] The table below illustrates the improvement in performance obtained with a microchannel prepared according to method 100, using one of these reagents to deactivate the surface of the support, when the reagent is introduced in a concentrated form, with a purity level preferably between 99% and 100%.

[0055] A reference gas mixture comprising the different gaseous compounds of the first column of the table, each compound of the mixture having a particular role indicated in the second column of the table, in a chromatographic column equipped at the outlet with a chip with a chromatographic microchannel prepared according to a known method (see detection results presented in the 3rd column of the table), then in a chromatographic column equipped at the outlet with a chip with a chromatographic microchannel prepared according to the invention with a reagent of the HDMS type in the pure state (see detection results presented in the 4th column of the table), then in a chromatographic column equipped at the outlet with a chip with a chromatographic microchannel prepared according to the invention with a reagent of the TMSDMA type in the pure state (seedetection results presented in the 5th column of the table), then in a chromatographic column equipped at the outlet with a chip with a chromatographic micro-channel prepared according to the invention with a pure N-trimethylsilylimidazole type reagent (see detection results presented in the 6th column of the table).

[0056] For each compound of the reference gas mixture, the numerical value indicated in the table, at the intersection of the row corresponding to this compound and the column corresponding to the chromatographic device evaluated, is a measure of the asymmetry of a chromatographic peak, measured at a height of 10% of the chromatographic peak corresponding to this compound. Ideally the asymmetry factor should be close to 1. In the worst case the spread over time of the detection of the compound is such that the asymmetry factor is almost infinite, which is shown in the table by NE.

[0057] It appears that, when the chromatograph used comprises a chip with a microchannel prepared with one of the reagents cited, in accordance with the method according to the invention, that is to say that said reagent has been introduced into the functionalization step in a virtually pure state, according to the purity levels indicated above, then the asymmetry factor of the chromatographic peak approaches 1 (columns 4, 5 and 6 of the table) for compounds (rows 5 to 9 of the table) for which this asymmetry factor is much greater than 1 with chromatographs comprising a known column (column 3 of the table).

[0058] [Tables 1] Compounds Role Known column + Chip with microchannel prepared according to known method Known column + Chip with microchannel prepared according to the invention with pure HDMS reagent Known column + Chip with microchannel prepared according to the invention with pure TMSDMA reagent Known column + Chip with microchannel prepared according to the invention with pure N-trimethylsilyl imidazole reagent n-octane Efficiency measurement 1.03 1.02 1.03 1.03 n-decane Efficiency measurement 1.03 1.04 1.05 1.04 Propylbenzene Efficiency measurement 0.98 0.98 1.00 0.98 3-octanone Efficiency measurement 1.26 0.97 0.99 0.98 4-picoline Acid site detection 13.55 2.62 2.93 4.78 1-heptanol Detection of site with hydrogen bond NE 1.79 1.84 2.05 Propionic acid Detection of basic site NE 1.58 2.05 1.56 Trimethyl Phosphate Detection of acidic site NE 1.08 1.06 1.49

[0059] In particular, the introduction of the reagent into the microchannel can be carried out continuously and at a constant introduction rate. Thus, the functionalization step is dynamic, i.e. the functionalization step takes place continuously over a period of time corresponding to a duration of introduction of the reagent.

[0060] More particularly, the introduction rate may be between 0.01 ml / h and 0.03 ml / h, preferably equal to 0.02 ml / h.

[0061] Even more particularly, the introduction of the reagent into the micro-channel comprises the use of a syringe pump 4 to deliver a volume of reagent contained in a syringe, for example 1 ml, at a constant flow rate into the micro-channel, the syringe pump 4 being connected to an inlet 2 of the micro-channel by a capillary tube, as illustrated in [Fig.l].

[0062] According to these provisions, pressure exerted by the syringe pump makes it possible to compensate for a significant viscosity of the reagent, which is linked to its use without dilution.

[0063] Optionally, the chip 1 is maintained at a determined temperature during the functionalization step. For this purpose, the chip is placed in an oven 5 maintained at the determined temperature. The temperature is typically between 50°C and 150°C, preferably equal to 100°C. Thus, the method 100 according to the invention makes it possible to dispense with functionalization usually carried out at high temperature, i.e. at temperatures between 300°C and 400°C, which cannot be carried out on certain systems, in particular on miniaturized systems based on MEMS technologies.

[0064] The deposition 103 of the stationary phase comprises, for example, deposition by evaporation. The deposition by evaporation comprises, in particular, control of a rate of deposition.

[0065] The control of the deposition speed comprises, more particularly, an application of a suction pressure lower than a determined pressure, for example between 350 mBar and 450 mBar, preferably equal to 400 mBar.

[0066] For this purpose, it is for example possible to use a vacuum pump 6 directly connected to the inlet 2 of the micro-channel by a capillary tube to create the desired depression, as illustrated in [Fig.2], an outlet 3 of the micro-channel being closed during the step of applying the suction pressure.

[0067] Thus, the deposition speed is limited to a maximum value, and the chromatographic performances are improved.

[0068] During the stationary phase deposition step, the chip 1 can be placed in a thermostatically controlled bath 7.

[0069] The stationary phase is, for example, one of the following products: polysiloxane, or PDMS, and polyethylene glycol, or PEG.

[0070] The method may further comprise a step 102 of treating the support, the treatment step 12 consisting of applying a coating to the support, before the step 103 of depositing the stationary phase on the support.

[0071] The coating is for example an alumina coating or a titanium oxide coating.

Claims

Claims

1. Method (100) for preparing a tubular microchannel for gas chromatography, the microchannel being etched on a chip (1), the method (100) comprising the following steps: - chemical functionalization (101) of a support, in the microchannel, to adapt the chemical nature of the support for a deposition of a stationary phase on said support, - deposition (103) of the stationary phase on said support in which the chemical functionalization (101) of the support comprises an introduction into the microchannel of a reagent, the reagent being introduced in a concentrated form according to a purity level of between 95% and 100%, preferably according to a purity level of between 99% and 100%.

2. The method (100) of claim 1, wherein the support is an interior surface of the microchannel.

3. The method (100) of claim 1 or 2, wherein the reagent is one of: hexamethyldisilazane, N,N-Dimethyltrimethylsilylamine, N-trimethylsilylimidazole.

4. Method (100) according to one of claims 1 to 3, in which the introduction of the reagent into the micro-channel is carried out continuously and at a constant introduction speed.

5. Method (100) according to claim 4, wherein the rate of introduction of the reagent is between 0.01 ml / h and 0.03 ml / h, preferably equal to 0.02 ml / h.

6. Method (100) according to one of claims 1 to 5, in which the chip (1) is maintained at a determined temperature during the functionalization step.

7. Method (100) according to claim 6, wherein the determined temperature is between 50°C and 150°C, preferably equal to 100°

8. V-. Method (100) according to one of claims 1 to 7, in which the deposition (103) of the stationary phase comprises a deposition by evaporation.

9. The method (100) of claim 8, wherein the evaporative deposition comprises controlling a rate of the deposition.

10. The method (100) of claim 9, wherein controlling the rate of deposition comprises evaporation by applying a suction pressure lower than a determined pressure.

11. Method (100) according to one of claims 1 to 10, in which the stationary phase is one of: polysiloxane, or PDMS, and poly-ethylene glycol, or PEG.

12. Method (100) according to one of claims 1 to 11, comprising a step of treating (102) the support with an application of a coating on the support, before the step of depositing (103) the stationary phase on the support.

13. The method (100) of claim 12, wherein the coating is an alumina coating or a titanium oxide coating.

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