Method for producing a chromatography analysis column

Abstract

The invention concerns a method for producing a chromatography analysis column, the resulting column, and a device comprising such a column. The method according to the invention comprises the following steps: (a) depositing on the flat surface of a substrate a first layer of particles which are intended to form the stationary phase; (b) depositing on the layer at least one second layer of compactly assembled particles; (c) impregnating the first and second layers with a light radiation-sensitive material, to form at least two compactly assembled particle layers impregnated with sensitive material; (d) insolating these layers in the regions corresponding to the desired internal shape of the chromatography analysis column, if the light radiation-sensitive material behaves like a positive resin, or outlining this internal shape if the light radiation-sensitive material behaves like a negative photosensitive resin; (e) eliminating either the regions insolated in step (d) if the light radiation-sensitive layer behaves like a positive photosensitive resin, or the regions not insolated in step (d) if the light radiation-sensitive material behaves like a negative photosensitive resin; and (f) covering and sealing the structure obtained in step (e) with a cover covered on the face facing the layers with at least one layer of compactly assembled particles which are identical to or different from those deposited on the substrate surface. The invention is used in particular in the field of chemical analysis.

Claims

1. A process for the manufacture of a chromatography analytical column of the open tube having a porous layer type, characterized in that it comprises the following steps: a) deposition of a first layer (2) of identical or different particles, which are intended to form the stationary layer, on the flat surface of a substrate (1), b) deposition of at least one second layer (12) of particles as a compact assemblage on the layer (2), c) impregnation of the layers (2, 12) with a material sensitive to light radiation (4), in order to form at least two layers (3) of particles as a compact assemblage impregnated with sensitive materials, d) insolation of the layers (3) in the regions corresponding to the internal shape desired for the chromatography analytical column, when the material sensitive to light radiation (4) behaves as a positive resin, or outlining this internal shape, when the material sensitive to light radiation (4) behaves as a negative photosensitive resin, e) removal: of the regions insolated in step d), when the material sensitive to light radiation (4) behaves as a positive photosensitive resin, or of the regions not insolated in step d), when the material sensitive to light radiation (4) behaves as a negative photosensitive resin, and f) covering and sealing the structure obtained in step e) with a covering cap (7) covered, on its face turned towards the layers (3), with at least one layer of particles as a compact assemblage identical to or different from those deposited on the surface of the substrate (1).

2. The process as claimed in claim 1, characterized in that it additionally comprises, before step a), a step a1) of activation of said surface of the substrate (1), preferably by O2 plasma, UV radiation, a mixture of sulfuric acid and of hydrogen peroxide, or ozone.

3. The process as claimed in claim 2, characterized in that it additionally comprises, after step a1) of activation of said surface of the substrate (1), a step a2) of thermal annealing of said surface of the substrate (1) which has been subjected to step a1).

4. The process as claimed in claim 1, characterized in that it additionally comprises, after step c) of impregnation of the layers (2), a step c1) of thermal annealing of the substrate (1) and of the layers (3).

5. The process as claimed in claim 1, characterized in that it additionally comprises, after step d) of insolation of the layers (3), a step d1) of thermal annealing of the substrate (1) coated with the insolated layers (3).

6. The process as claimed in claim 1, characterized in that it additionally comprises, after step e) of removal of the insolated or non-insolated regions, a step e1) of annealing of the substrate (1) covered with the layers (3), certain regions of which have been removed.

7. The process as claimed in claim 1, characterized in that it additionally comprises a step of formation of at least one layer of particles as a compact assemblage on a face of the covering cap (7).

8. The process as claimed in claim 1, characterized in that said particles have a mean diameter of between 50 nm and 500 μm inclusive.

9. The process as claimed in claim 1, characterized in that the total thickness of the layers (2, 12) is between 50 and 700 μm inclusive.

10. The process as claimed in claim 1, characterized in that the particles are particles made of a metal oxide, or made of a ceramic, or made of a polymer, or made of a polysaccharide, or made of a metal; these particles optionally being functionalized.

11. The process as claimed in claim 1, characterized in that step a) is carried out by the Langmuir-Blodgett method, or by the Langmuir-Schaefer method, or by Marangoni self-assembling, or by the vortical surface method, or by floating-transferring, or by dip coating, or by spin coating.

12. The process as claimed in claim 1, characterized in that the material sensitive to light radiation (4) behaves as a positive resin and is sensitive to radiation with wavelengths of between 150 and 700 nm inclusive.

13. The process as claimed in claim 1, characterized in that the material sensitive to light radiation (4) behaves as a negative resin and is sensitive to radiation with wavelengths of between 150 and 700 nm inclusive.

14. The process as claimed in claim 1, characterized in that the material sensitive to light radiation (4) is obtained by a sol-gel process.

15. The process as claimed in claim 1, characterized in that step c) is carried out by spin deposition of the material sensitive to light radiation (4) on the layer (2) or by immersion of the substrate (1) coated with the layer (2) in the material sensitive to light radiation (4).

16. The process as claimed in claim 1, characterized in that step d) of insolation of the layers (3) with the light radiation (4) is carried out through a mask (11) comprising regions transparent to said light radiation (4), these transparent regions corresponding to: the internal shape desired for the chromatography analytical column, when the material sensitive to light radiation (4) behaves as a positive resin, or outlining this internal shape, when the material sensitive to light radiation (4) behaves as a negative resin.

17. The process as claimed in claim 1, characterized in that step d) of insolation of the layers (3) is carried out by laser writing in order to form the internal shape desired for the column, when the material sensitive to light radiation (4) behaves as a positive resin, or in the regions outlining this internal shape, when the material sensitive to light radiation (4) behaves as a negative resin.

18. The process as claimed in claim 1, characterized in that the substrate is rigid or flexible and made of a material chosen from a metal oxide, a metal, a ceramic or a polymer.

19. The process as claimed in claim 1, characterized in that the particles are made of a material chosen from silica, titanium dioxide, alumina, latex, polydimethylsiloxane (PDMS), gold, copper and the mixtures of these.

20. A chromatography analytical column, characterized in that it comprises a substrate (1), a flat surface of which is coated with at least one layer (3) of particles, this layer (3) of particles, which are optionally functionalized, comprising a region (5) devoid of the particles and forming the internal portion of the column and in that at least one wall of the column consists of a mixture of said particles, which are optionally functionalized, and of a material sensitive to light radiation, which is crosslinked.

21. The column as claimed in claim 20, characterized in that the particles are particles made of a metal oxide, polymer, polysaccharide, metal or ceramic, these particles optionally being functionalized.

22. The column as claimed in claim 20, characterized in that the particles have a mean diameter of between 50 nm and 500 μm inclusive.

23. The column as claimed in claim 20, characterized in that the substrate (1) is flexible or rigid and is made of a material chosen from a metal oxide, a metal, a ceramic or a polymer.

24. The column as claimed in claim 20, characterized in that the particles are made of a material chosen from silica, alumina, titanium oxide, latex, polydimethylsiloxane (PDMS), gold, copper or mixtures of these.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

(1) FIG. 1 shows depositing of particles as a compact assemblage in a channel and on a sealing covering cap.

(2) FIG. 2 shows the process for the manufacture of a chromatography analytical column according to the invention.

(3) FIG. 3 illustrates the principal of the preparation of the sol-gel hybrid.

(4) FIG. 4 presents a diagrammatical representation of an inorganic network and an organic network.

EXAMPLE

Example 1

(5) a silicon substrate having a diameter of 7.62 cm (3 inches) comprising a layer of silica with a thickness of 100 nm obtained by thermal growth was subjected to a step a1) of activation of the surface by Brown treatment, that is to say dipping in a 0.1N sodium hydroxide bath.

(6) Silica particles with a diameter of 1 μm functionalized by dipping with 5 mM 5,6-epoxyhexyltriethoxysilane in toluene at 80° C. for 16 hours, followed by rinsing with distilled water and drying at 110° C. for 3 hours, were deposited by the Langmuir-Blodgett method. A heat treatment at 110° C. for 3 hours was carried out on the substrate coated with the first layer of particles.

(7) Due to the activation of the substrate, which comprises OH bonds, the first layer of particles functionalized with 5,6-epoxyhexyltriethoxysilane created covalent bonds between the particles and the substrate. In order to fix this first layer to the substrate, a heat treatment at 110° C. for 3 hours was carried out.

(8) 50 layers of the same particles as above were deposited by the Langmuir-Blodgett method at a draw rate of 1 cm/min.

(9) The stack of layers was then impregnated with a positive photosensitive resin TELR-P0003PM, sold by TOK Europe (Tokyo Ohka Kogyo Co. Ltd), by spin deposition at 1000 rpm for 1 min.

(10) The stack of layers was stabilized by thermal annealing at 110° C. for 2 min.

(11) The combination obtained was then insolated by UV radiation with a wavelength of 365 nm, at 200 MJ/cm.sup.2 for 15 seconds.

(12) The resin was subsequently developed, that is to say that the regions of insolated resin were removed by immersion in TMA 238 WA, sold by JSR. The TMA comprises tetramethylammonium hydroxide. The immersion lasted a few seconds. The substrate coated with the layers was subsequently rinsed with water. The insolation was carried out by virtue of an MA750 laser appliance emitting wavelengths of 365 nm.

(13) The substrate coated with layers of particles comprising, as a hollow, the shape of the desired microcolumn was heat treated at 110° C. for 1 h.

(14) A covering cap coated on one of its faces with a layer of the same particles as described above was sealed by virtue of an adhesive at 110° C. for 30 min and then 160° C. for 1 hour under vacuum.

Example 2

(15) In this example, the sealing covering cap was covered with particles by the following process:

(16) A silicon substrate with a diameter of 7.62 cm (3 inches) coated with a layer of 100 nm of silica was activated by Brown treatment, that is to say dipped in a 0.1N sodium hydroxide bath.

(17) Silica particles with a mean diameter of 1 μm were functionalized with a 5 mM solution of 5,6-epoxyhexyltriethoxysilane in toluene at 80° C. for 16 hours. The substrate was rinsed with distilled water and then annealed by drying at 110° C. for 3 hours.

(18) The functionalized particles were deposited on a surface of the substrate by the Langmuir-Blodgett method at a draw rate of 1 cm/min.

(19) This first layer of particles was subsequently heat treated at 110° C. for 3 hours in order to anchor this layer to the substrate by establishment of covalent bonds, as in example 1.

(20) Subsequently, 50 layers of particles identical to those deposited for the first layer were deposited by the Langmuir-Blodgett method at a draw rate of 1 cm/min.

REFERENCES

(21) [1] Somobrata Acharya, Jonathan P. Hill and Katsuhiko Ariga, “Soft Langmuir-Blodgett Technique for Hard Nanomaterials”, Adv. Mater., 2009, 21, 2959-2981. [2] Maria Bardosova, Martyn E. Pemble, Ian M. Povey and Richard H. Tredgold, “The Langmuir-Blodgett Approach to Making Colloidal Photonic Crystals from Silica Spheres”, Adv. Mater., 2010, 22, 3104-3124. [3] Masahiro Shishido and Daisuke Kitagawa, “Preparation of ordered mono-particulate film from colloidal solutions on the surface of water and continuous transcription of film to substrate”, Colloids and Surfaces A: Physicochem. Eng. Aspects, 311 (2007), 32-41. [4] Sanjib Biswas and Lawrence T. Drzal, “A Novel Approach to Create a Highly Ordered Monolayer Film of Graphene Nanosheets at the Liquid-Liquid Interface”, Nano Left., Vol. 9, No. 1, 2009. [5] Feng Pan, Junying Zhang, Chao Cai and Tianmin Wang, “Rapid Fabrication of Large-Area Colloidal Crystal Monolayers by a Vortical Surface Method”, Langmuir, 2006, Vol. 22, No. 17, pp 7101-7104. [6] Y. J. Zhang, W. Li and K. J. Chen, “Application of two-dimensional polystyrene arrays in the fabrication of ordered silicon pillars”, Journal of Alloys and Compounds, 450 (2008), 512-516. [7] J. Rybczynski, U. Ebels and M. Giersig, “Large-scale, 2D arrays of magnetic nanoparticles”, Colloids and Surfaces A: Physicochem. Eng. Aspects, 219 (2003), 1-6. [8] D. Nagao, R. Kameyama and H. Matsumoto, “Single- and multi-layered patterns of polystyrene and silica particles assembled with a simple dip-coating”, Colloid and Surfaces A: Physiochem. Eng. Aspects, 2008, Vol. 317, pp 722-729. [9] S. Rakers, L. F. Chi and H. Fuchs, “Influence of the Evaporation Rate on the Packing Order of Polydisperse Latex Monofilms”, Langmuir, 1997, 13, 7121-7124. [10] V. Conedera, N. Fabre and H. Camon “Les matériaux élaborés par sol-gel et leur utilisation en micro Technologies [Materials prepared by the sol-gel process and their use in microtechnologies]”, LAAS Report No. 02217 (2002). [11] P. Coudray, P. Etienne and Y. Moreau, “Integrated optics based on organo-mineral materials”, Invited paper of European materials conference-Strasbourg (1999). [12] R. C. Liang, M. Chan-Park, S. C-J, Tseng, Z-A G. Wu and H. M. Zang, “Electrophoretic display”, Patent Publication No. WO 01/67171 A1, (2001). [13] R. C. Liang, Z-A. G. Wu and H. M. Zang, “Manufacturing process for multi-layer color displays”, Patent Publication No. WO2004/051353 (2004). [14] T. Ozawa, S. Ishiwata and Y. Kano, “Adhesive Properties of Ultraviolet Curable Pressure-Sensitive Adhesive Tape for Semiconductor Processing (I)-Interpretation via Rheological Viewpoint”, Furukawa Review, 20, 83 (2001).