JP2009031023A - Production method of substrate for surface enhanced raman spectroscopic analysis, manufacturing method of micro-tas, and the micro-tas - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To create a micro-TAS (total analysis system) by making silver nanoparticles deposit locally on a substrate. <P>SOLUTION: A self-organizing monomolecular film (SAM) 12 is patterned on a glass substrate 14 by a micro-contact printing method, and then, silver nanoparticles 24 are deposited locally on a pattern substrate 16 by a silver mirror reaction, wherein a dispersant is added to a solution containing silver complex ions, to thereby produce a SERS substrate 18. After producing SERS activation sites 31-33 of the silver nanoparticles 24 on the substrate 18 by this method, the self-assembled monolayer (SAM) 12 is removed from the SERS substrate 18 by oxygen plasma, and the surface of the SERS substrate 18 is cleaned. Thereafter, a cover 40, having recessed parts formed on parts corresponding to the SERS activation sites 31-33 and a channel 34, is subjected to surface activation by oxygen plasma and is then fixed, to thereby manufacture the micro-TAS 30. <P>COPYRIGHT: (C)2009,JPO&INPIT

Description

  The present invention relates to a method for producing a substrate for surface-enhanced Raman spectroscopy suitable for use in surface-enhanced Raman spectroscopy, a method for producing a micro TAS (Total Analysis System) using this method, and a method produced by this method. It relates to micro TAS.

  Raman spectroscopic analysis is an analysis method that detects Raman scattered light generated by irradiating a sample with a laser. It is an extremely effective analytical technique for identification of biochemical substances such as viruses and proteins, environmental chemical substances, biosensors, etc. is there. However, the problem is that the Raman scattered light is extremely weak compared to the reflected light of the laser (Rayleigh scattering). This is solved by surface enhanced Raman spectroscopy (SERS) using the electric field enhancement effect on the surface of the metal nanoparticles. This SERS is an extremely effective analytical technique capable of identifying biochemical substances with extremely high sensitivity by utilizing the electric field enhancement effect generated on the surface of metal nanoparticles such as gold and silver.

  In SERS, the creation of a substrate having metal nanoparticles is a key. As conventional techniques, (1) one in which silver colloid is dispersed in a solution (patent documents 1, 2, non-patent documents 1, 2, 3), (2) silver nanoparticles are adsorbed on a glass substrate (patent documents) 3), (3) A method such as patterning silver by electron beam lithography may be used.

  In addition, as a method for depositing silver fine particles, an example in which a silver mirror reaction is performed after adding a dispersant for the production of a silver thin film has been reported (Non-patent Document 4).

  Further, the inventor has established a method for producing a silver nanoparticle substrate for SERS that is highly sensitive, highly reproducible, easy to produce and inexpensive in Non-Patent Document 5.

  On the other hand, a self-assembled monomolecular film (SAM) is a monomolecular film formed by adsorption of a compound having a reactive sensitive group such as silane as a hydrophilic group onto a solid substrate. It is an effective means for changing. As a conventional technique, there is a method of selectively depositing a film or etching using a SAM as a mask (Non-Patent Documents 6 and 7). As a SAM patterning method, there are a UV irradiation method and a microcontact printing method in which a SAM is formed on a stamp surface having a fine pattern and transferred to a substrate (Non-patent Document 8).

  Non-Patent Document 9 describes the use of polydimethylsiloxane (PDMS) for producing a SERS substrate.

Japanese Patent Laid-Open No. 7-146295 JP 11-61209 A Japanese Patent No. 3714671 S. Nie and S. R. Emory, Science. 275, 1102 (1997) K. C. Grabar, P.A. C. Smith, M.M. D. Musick, J.M. A. Davis, D.D. G. Walter, M.M. A. Jackson, A.M. P. Guthrie and M.M. J. et al. Natan, J .; Am. Chem, Soc. , 118, 1148 (1996) R. M.M. Bright, M.C. D. Musick and M.M. H. Natan, Langmuir, 14, 5695 (1998) Tsutomu Akazawa, Susumu Kakinuma “Development of silver ultrafine particle film production technology” Saitama Industrial Technology Center Research Report Vol. 2 (2004) pp. 194-196 K. Kurokaka and N.K. Miki, Proceedings of μTAS 2006, 2, 1268 (2006). H. Sugimura et al. , Electrochimica Acta, 47, 103 (2001). Y. Masuda et al. , Journal of Ceramic Society of Japan, 112, S1495 (2004). A. Kumar, H .; A. Biebuyck, and G.B. M.M. Whiteides, Langmuir, 10, 1498 (1994). G. L. Liu and L. P. Lee, Applied Physics Letters 87, 074101 (2005).

  In the conventional SERS substrate preparation method proposed by the inventors, silver nanoparticles can be deposited on the entire glass substrate, but local deposition is difficult.

  In order to combine a microchannel or the like with a SERS substrate and put it to practical use as a highly sensitive analysis chip, a technique for locally depositing silver nanoparticles is indispensable. However, there is no self-deposition type substrate using SAM.

  On the other hand, when silver nanoparticles are etched using a photosensitive resist that can be patterned by light as a mask, if the resist is peeled off after etching, silver fine particles are also peeled off together with the resist. Further, there is a problem that the resist and the organic solvent for removing the resist remain on the substrate, and the substrate becomes dirty.

  The present invention has been made to solve the above-mentioned conventional problems, and an object thereof is to enable silver nanoparticles to be deposited locally.

  The present invention has been made by paying attention to the fact that the deposition on the silver nanoparticles can be controlled by applying the substrate surface modification with SAM to the self-deposition type substrate and can be left on the substrate without damaging the silver nanoparticles. is there.

  In the production of a substrate for surface-enhanced Raman spectroscopic analysis, the present invention comprises a silver mirror reaction in which a self-assembled monolayer is patterned on a substrate by a microcontact printing method, and then a dispersant is added to a solution containing silver complex ions. The present invention solves the above problem by locally depositing silver nanoparticles on a substrate.

  The self-assembled monolayer can be silane-based.

  According to another aspect of the present invention, an active site of silver nanoparticles is generated on a substrate by the above-described method, and then a cover having a recess formed in a portion corresponding to the active site and the channel is fixed. A method for producing TAS is provided.

  Prior to the fixing, the self-assembled monolayer can be removed from the substrate surface and the substrate surface can be cleaned by oxygen plasma.

  The present invention also provides a micro TAS manufactured by the above method.

  According to the present invention, silver nanoparticles can be locally deposited on a substrate, and for example, a microchip having a local SERS active site can be manufactured. In addition, a substrate having a highly accurate silver nanoparticle pattern can be produced in a large amount by a simple operation, and is inexpensive and excellent in mass productivity. Furthermore, high Raman signal sensitivity and reproducibility can be obtained from any local site obtained by the present invention.

  Hereinafter, embodiments of the present invention will be described in detail with reference to the drawings.

  In the present embodiment, a substrate having a SERS active site locally is realized by patterning a silane-based SAM on a glass substrate using a microcontact printing method.

  Hereinafter, a specific procedure will be described with reference to FIG.

  First, a PDMS stamp 10 having a fine pattern as shown in FIG. 1A is created by using a soft lithography technique for producing a polymer using a resist patterned by photolithography as a mold, for example. Next, octadecyltrichlorosilane (OTS), which is a silane-based SAM, is dissolved in anhydrous toluene to prepare a 1% OTS-SAM solution, and the PDMS stamp 10 is immersed in the solution for 5 minutes, for example, to make soft contact. Next, the PDMS stamp 10 coated with the SAM 12 is taken out and contact printed on the glass substrate 14 as shown in FIG.

  Immediately thereafter, for example, a heat treatment is performed on a heater to obtain a pattern substrate 16 having a SAM pattern formed on the glass substrate 14 as shown in FIG.

  Silver nanoparticles 24 are deposited on the pattern substrate 16 by a silver mirror reaction. Specifically, as shown in FIG. 1C, a reducing agent 22 is added to a silver fine particle liquid 20 in which a dispersing agent is added and stirred in a solution containing silver complex ions (for example, an aqueous solution of silver nitrate added with aqueous ammonia). At the same time, the pattern substrate 16 is immersed. As a result, since the silver nanoparticles 24 are deposited only at locations other than the SAM 12, as shown in FIG. 1D, the SERS substrate 18 having the SERS active site where the silver nanoparticles 24 are locally deposited can be formed. it can.

  As the dispersant, for example, a copolymer having an acidic group can be used, and as the reducing agent 22, for example, hydrazine can be used.

  The SEM image of the glass substrate which has a silver nanoparticle when the immersion time of PDMS in an OTS-SAM solution and the heat processing time after soft contact are changed is shown in FIG. It is the silver nanoparticle which the white part in the figure deposited. (A) No heating at immersion time of 30 seconds, (b) No heating at immersion time of 5 minutes, (c) Heating at immersion time of 30 seconds for 5 minutes, (d) Heating time of 5 minutes at immersion time of 5 minutes It is an example. Thus, a favorable silver nanoparticle pattern can be obtained by controlling the conditions at the time of contact printing (immersion time in the SAM solution and heat treatment time of the substrate).

  An example of a micro TAS created using the present invention is shown in FIG. In FIG. 3, 31 to 33 are SERS active sites prepared according to the present invention, 34 is a microchannel, 36 is a channel inlet, and 38 is a channel outlet.

  The micro TAS 30 is created in the procedure as shown in FIG.

  First, as shown in FIG. 4 (A), silver nanoparticles 24 are locally deposited on the SERS active sites 31 to 33 (FIG. 4 shows 31 and 32) by the method shown in FIG. A SERS substrate 18 is prepared.

  Next, as shown in FIG. 4B, the surface of the SERS substrate 18 is irradiated with, for example, 50 W of oxygen plasma for 0.5 seconds to remove the SAM 12 and clean and activate the surface.

  On the other hand, as shown in FIG. 4 (C), recesses are formed in the microchannel 34 portion and the SERS active sites 31 to 33 (31 and 32 are shown in FIG. 4), and the channel inlet 36 and the channel outlet 38 are formed. For example, a PDMS cover 40 having a hole punched with a punch is prepared.

  As shown in FIG. 4D, the surface of the PDMS cover 40 is activated by irradiation with, for example, 50 W oxygen plasma for 0.5 seconds.

  Next, as shown in FIG. 4E, the micro TAS 30 is manufactured by reversing and bonding the PDMS cover 40 to the surface of the SERS substrate 18.

  FIG. 5 shows the SERS active site when oxygen plasma treatment is performed for 0.5 seconds and the Raman signal of 10 mM / l rhodamine 6G from the glass substrate. It can be seen that the oxygen plasma does not damage the SERS active site.

  FIG. 6 shows a Raman signal of 10 mM / l rhodamine 6G from each SERS active site of the micro TAS shown in FIG. It can be seen that the local SERS active sites prepared by the present invention are very high in both sensitivity and reproducibility.

  The PDMS stamp 10 used in this embodiment can be used repeatedly, and a low-cost substrate can be manufactured.

  In the embodiment, the stamp and the cover are made of PDMS, and the OTS is used as the SAM. However, the types of the stamp, the cover, and the SAM are not limited to these.

  Moreover, in the said embodiment, the copolymer which has an acidic group was used as a dispersing agent, and the hydrazine was used as a reducing agent, However, The kind of dispersing agent and a reducing agent is not limited to this. The solution containing silver ions is not limited to the silver nitrate solution, and the substrate is not limited to the glass substrate.

Process drawing which shows embodiment of this invention The figure which shows the example at the time of the contact printing in the said embodiment, and the silver nanoparticle pattern obtained The top view which shows embodiment of the micro TAS manufactured by this invention Process drawing showing the manufacturing method of the micro TAS Diagram showing the effect of oxygen plasma treatment on the SERS site The figure which shows the Raman signal in each site of micro TAS

Explanation of symbols

DESCRIPTION OF SYMBOLS 10 ... PDMS stamp 12 ... SAM pattern 14 ... Glass substrate 16 ... Pattern substrate 18 ... SERS substrate 20 ... Silver fine particle liquid 22 ... Reducing agent 24 ... Silver nanoparticle 30 ... Micro TAS
31-33 ... SERS active site 34 ... micro flow path 36 ... flow path inlet 38 ... flow path outlet 40 ... PDMS cover

Claims (5)

After patterning the self-assembled monolayer on the substrate by micro contact printing method,
A method for producing a substrate for surface enhanced Raman spectroscopy (SERS) analysis, wherein silver nanoparticles are locally deposited on a substrate by a silver mirror reaction in which a dispersant is added to a solution containing silver complex ions.   The method for producing a substrate for surface enhanced Raman spectroscopic analysis according to claim 1, wherein the self-assembled monolayer is a silane system. After generating SERS active sites of silver nanoparticles on a substrate by the method of claim 1,
A method for producing a micro TAS, comprising fixing a cover having a recess in a portion corresponding to the SERS active site and the flow path.   4. The method for producing a micro TAS according to claim 3, wherein the self-assembled monomolecular film is removed from the substrate surface by oxygen plasma and the substrate surface is cleaned before the fixing.   A micro TAS manufactured by the method according to claim 3 or 4.