JP5837429B2 - Method for regenerating reaction device for nucleic acid analysis and nucleic acid analyzer having washing mechanism used in the method - Google Patents

Description

  The present invention relates to a device regeneration method for reusing a reaction device for nucleic acid analysis and a nucleic acid analyzer having a cleaning mechanism used in the method.

  New techniques for determining the base sequences of DNA and RNA have been developed.

  In the currently used method using electrophoresis, a cDNA fragment sample synthesized in advance by reverse transcription reaction from a DNA fragment or RNA sample for sequencing is prepared, and a dideoxy reaction is performed by a well-known Sanger method. After that, electrophoresis is performed, and the molecular weight separation development pattern is measured and analyzed.

  On the other hand, in recent years, a method has been proposed in which a large number of DNA fragments as samples are fixed to a substrate and the sequence information of many fragments is determined in parallel.

  For example, in Non-Patent Document 1, a so-called bead is used as a carrier for carrying a DNA fragment, and PCR (Polymerase Chain Reaction) is performed on the microparticle. Thereafter, fine particles carrying PCR-amplified DNA fragments are put in a plate provided with a number of holes in which the hole diameter is adjusted to the size of the fine particles, and read by the pyro sequence method.

  In Non-Patent Document 2, PCR is performed on microparticles using microparticles as a carrier for supporting DNA fragments. Thereafter, the microparticles are dispersed and fixed on the glass substrate, an enzyme reaction (ligation) is performed on the glass substrate, a fluorescent dye is incorporated, and the sequence information of each fragment is obtained.

  Furthermore, in Non-Patent Document 3, a large number of DNA probes having the same sequence are fixed on a substrate. In addition, after cutting the DNA sample, a DNA probe sequence and an adapter sequence of a complementary strand are added to the end of each DNA sample fragment. By hybridizing these on the substrate, the sample DNA fragments are immobilized on the substrate randomly one molecule at a time. In this case, after taking in a substrate with a fluorescent dye that does not cause a DNA elongation reaction on the substrate, the unreacted substrate is washed, the immobilized molecules are detected by fluorescence, and the sequence information of the sample DNA is obtained. Yes.

  As described above, a method for determining the sequence information of a large number of fragments in parallel by fixing a large number of nucleic acid fragment samples on a substrate has been developed and put into practical use.

  Incidentally, Patent Document 1 discloses a nucleic acid analysis reaction device and a nucleic acid sample immobilization method for realizing a method for determining a large amount of sequence information in parallel. In a reaction device for nucleic acid analysis, a substrate having a sample fixing layer and a spacer with a central portion pulled out are installed in a chamber, and the upper surface of the chamber, the spacer, and the lower surface of the substrate are pressure-bonded by pressure. A flow path is formed from the hollow formed by the upper surface of the chamber and the spacer and the lower surface of the substrate. The liquid is taken in and out of the flow path from the two tubes at the top of the chamber. During use, the chamber and the substrate are pressurized with a spacer interposed therebetween, thereby preventing liquid leakage from the interface between the chamber and the spacer and the interface between the spacer and the substrate.

  In the sample fixing layer of Patent Document 1, consideration is given to improving the adhesion between the nucleic acid sample and the substrate. That is, the adhesiveness is improved by introducing a functional group into the nucleic acid sample and causing the functional group introduced into the nucleic acid sample to interact with the functional group of the sample fixing layer. As the sample fixing layer, an organic substance such as acrylamide, polylysine, streptavidin, or a silane coupling agent is used. In the method using a silane coupling agent, functional groups such as amino groups, carboxylic acids, and aldehyde groups are introduced into the sample fixing layer. The functional group introduced into the sample fixing layer and the functional group introduced into the nucleic acid sample are reacted via an optional linker reagent to fix the nucleic acid sample. As a functional group introduced into a nucleic acid sample, an acrydite, biotin, an amino group and the like are disclosed.

US2009 / 0062129 JP 2006-87974 US7115400B1

Nature 2005, vol. 437, pp. 376-380. Science 2005, voL. 309, pp.1728-1732 Science 2008, vol. 320, pp. 106-109. Langmuir 2007, vol. 23, pp.377-381 Anal.Biochem. 2003, vol. 320, pp.55-65 Applied Catalysis A: General.2005, vol. 286, pp.128-136 J. Environ. Monit.2000, vol.2, pp550-555 Proc. Natl. Acad. Sci. USA. 1996, Vol. 93, pp. 10614-10619,

  The amount of spacer deformation depends on the film thickness of the spacer. When the film thickness is large, the amount of deformation of the spacer is large, and the spacer easily follows the unevenness of the substrate, so that liquid leakage hardly occurs. However, if the spacer is thinned, the amount of deformation due to pressurization decreases, so the risk of liquid leakage increases and the spacer cannot be thinned. The reaction device of Patent Document 1 tends to have a thick spacer and a large capacity in the flow path.

  In general, since the reagent used for nucleic acid analysis is expensive, the nucleic acid analysis system of Patent Document 1 uses a large amount of reagent and the running cost of analysis is high.

  On the other hand, Patent Document 2 discloses a reaction device in which a chamber, a spacer, and a substrate are integrated as a reaction device having a small flow path volume. As the spacer material, epoxy resin, acrylic resin, or polydimethylsiloxane is used. However, since the processing temperature of the spacer material and the bonding temperature between the spacer material and the sample layer are as high as 100 ° C. or higher, the organic substance that is the sample fixing layer is a factor that deteriorates due to thermal denaturation. The deterioration of the sample layer causes the nucleic acid sample to peel off during the extension reaction.

  Non-Patent Document 4 and Non-Patent Document 5 disclose methods using an inorganic oxide such as titania or zirconia as a sample fixing layer. Inorganic oxides are stable even at temperatures of 100 ° C. or higher. It is possible to prevent thermal denaturation during processing of the spacer material and joining with the sample layer.

  In general, it is known that a functional group containing oxygen specifically adsorbs to an inorganic oxide. Non-patent document 4 discloses phosphoric acid, non-patent document 6 discloses sulfuric acid, and non-patent document 7 discloses acetic acid as such functional groups. Non-Patent Document 4 discloses a method of immobilizing an oligonucleotide whose terminal is phosphorylated on zirconia.

  These nucleic acid analysis reaction devices are often provided with a plurality of channels in one device so that a plurality of samples can be simultaneously evaluated. However, if the number of samples is less than the designed number of channels, the channels will remain. Also, when the number of samples is large, the number of devices is increased, but there are many cases where the number of samples is not satisfied after all.

  Here, many problems can be solved if a sample can be added to the unused flow path of the device once used next time, but as a result of the inventor's evaluation, the unused flow path of the device once used is resolved. It was found that when the sample was fixed as it was, the sample nucleic acid sample was peeled off during the extension reaction.

  This is due to the heat applied when the device is used for the first time. In other words, in order to perform the extension reaction of the nucleic acid sample that is the sample in the flow channel, heat of about 70 degrees is applied to the entire device. This heat oxidizes the sample fixing layer in the unused flow channel, and the sample fixing ability is reduced. By lowering.

  Yet another reason is that when the device is used for the first time, due to the specifications of the device, even if some chemical reagent has entered the unused flow path slightly, the oxidation of the sample fixing layer is further increased. It became clear that it progressed remarkably.

  For this reason, conventionally, when the analysis is performed with the number of samples less than the designed number of channels and with unused channels remaining, the expensive reaction device for nucleic acid analysis is discarded without being fully used. As a result, the user is wasted.

  Yet another reason is that even with an unused reaction device for nucleic acid analysis, if the sample is removed from the sealed state and left in the air for a long time, the sample fixing layer will oxidize and the sample fixing ability will decrease. Is clear. In this case as well, it is unavoidable for the user to discard the expensive nucleic acid analysis reaction device without using it.

  The present invention has been made in view of the above points. When the reaction device for nucleic acid analysis is used for the first time, an unused flow path is left, or the reaction device for nucleic acid analysis is unused. A method for regenerating (repairing) the function of a sample fixing layer in an unused flow path that has deteriorated due to oxidation and allowing the reaction device for nucleic acid analysis to be reused when used for a long time. An object of the present invention is to provide a nucleic acid analyzer having a washing mechanism.

The inventor of the present invention, as described above, uses an unused flow path remaining in a nucleic acid analysis reaction device that has been used once, deterioration of an unused nucleic acid analysis reaction device left in the air, that is, fixation to a nucleic acid sample. To investigate the cause of deterioration of the capacity or adsorption capacity (oxidation of the sample fixed layer), and based on that knowledge, as described below, a method of regenerating the fixed capacity or adsorption capacity of the sample fixed layer that has deteriorated (attenuated), And the nucleic acid analyzer which has the washing mechanism used for it was completed.
(1) One aspect of the present invention relates to a method for regenerating a reaction device for nucleic acid analysis.

That is, a flow cell type reaction device for nucleic acid analysis comprising a sample fixing layer for fixing a nucleic acid sample and one or more flow paths formed on the sample fixing layer is used after using the partial flow path, or A method of regenerating the function of the sample fixing layer of the unused flow path when left unused in the air for a long time,
A first step of causing a reduction reaction in the sample fixing layer by injecting a sample fixing layer reducing liquid into an unused flow path of the device and adjusting the temperature of the device;
Thereafter, by flowing pure water through the unused flow path, a second step of washing away the sample fixed bed reducing liquid;
It is characterized by including.
(2) The other relates to the invention of a nucleic acid analyzer equipped with a washing mechanism used in the method for regenerating a reaction device for nucleic acid analysis of (1).

That is, nucleic acid extension reaction and nucleic acid analysis are performed using a flow cell type reaction device for nucleic acid analysis including a sample fixing layer for fixing a nucleic acid sample and one or more flow paths formed on the sample fixing layer. A nucleic acid analyzer comprising:
A liquid feeding unit for injecting liquid into the flow path;
A holder unit for adjusting the temperature of the device;
Pure water as cleaning water,
And a solution for sample fixed layer reduction reaction that causes temperature reduction to cause a reduction reaction in the sample fixed layer.

  According to the present invention, when an unused flow path is left when the reaction device for nucleic acid analysis is used for the first time, or when it is left unused in the air for a long time, it deteriorates due to oxidation. By reducing and washing the unused flow path, the function of the sample fixing layer can be regenerated so that it can be used for the next use.

The figure which shows the structure of the nucleic acid analyzer which concerns on one Example of this invention. Explanatory drawing which shows the process example of the regeneration method of the reaction device for nucleic acid analysis of this invention. The disassembled perspective view before an assembly which shows an example of the reaction device for nucleic acid analysis used for the said Example. The perspective view after the assembly of the reaction device for nucleic acid analysis.

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

  Here, specific embodiments will be described in detail in order to understand the present invention, but the present invention is not limited to the contents described here.

  An embodiment of a nucleic acid analyzer having a cleaning mechanism for regenerating a reaction device for nucleic acid analysis of the present invention will be described with reference to FIG.

  The nucleic acid analyzer 101 includes a holder unit 103 for a reaction device for nucleic acid analysis, a stage unit 104 having an X-axis and Y-axis moving mechanism, various reagent containers 105, and a liquid feeding unit 106 including a nozzle 107. , A nozzle moving unit 108 for moving the nozzle 107, a detection unit 109 for nucleic acid analysis, a waste liquid container 110 for storing waste liquid, and a nozzle cleaning mechanism 113.

  The holder unit 103 has a function of fixing a flow cell type nucleic acid analysis reaction device 102 having a plurality of flow paths 111 and adjusting the temperature of the nucleic acid analysis reaction device 102.

  As described in the background art, the flow cell type reaction device 102 for nucleic acid analysis may have various modes. In the present embodiment, as an example, as shown in FIG. 3, the substrate 31 and the substrate 41 and a spacer 51 interposed therebetween are configured. The spacer 51 has a plurality of elongated cutouts 111 ′ for forming a flow path, and is formed by adhering or welding the substrate 31, the spacer 51, and the substrate 41 so as to sandwich the spacer 51 (FIG. 4). reference). A plurality of flow paths 111 are formed by the cutout 111 ′ of the spacer 51, one surface (lower surface) of the substrate 31, and one surface (upper surface) of the substrate 41.

  Reference numerals 32, 52, and 42 are holes used for positioning when the substrate 31, the spacer 51, and the substrate 41 are bonded together.

  As the substrate 31 or the substrate 41 in addition thereto, it is preferable to use a transparent glass, particularly a glass that can transmit fluorescence in a fluorescence detection method used for nucleic acid analysis, or a resin such as an acrylic resin or a cycloolefin polymer. The substrate 31 is provided with respective inlets 33 and outlets 34 corresponding to the plurality of flow paths 111 (cutouts 111 ′). A sample fixing layer 60 is formed on at least one of the substrate 31 and the substrate 41 (the substrate 31 in this embodiment) on one surface facing the flow path 111. The sample fixing layer 60 fixes the nucleic acid sample by reacting its own functional group with the functional group introduced into the nucleic acid sample.

  As the sample fixing layer 60, an inorganic oxide that is known to specifically adsorb functional groups containing oxygen is used. In particular, a compound having a Lewis acid site or a Bronsted acid site on the surface is desirable. Such an inorganic oxide is selected from the group consisting of titania, zirconia, alumina, zeolite, vanadium pentoxide, silica, sapphire, tungsten oxide and tantalum pentoxide, and may be a mixture or compound of at least two of these. Good. In particular, a compound selected from titania, zirconia, alumina, zeolite, and vanadium pentoxide having a high density of Lewis acid sites and Bronsted acid sites on the surface is desirable. Inorganic oxides are less likely to be thermally denatured, and are not denatured when a flow cell (reaction device for nucleic acid analysis) is manufactured by heating and welding the spacer 51, the substrate 31, and the substrate 51.

  Alternatively, the reaction device for nucleic acid analysis may be configured by the substrates 31 and 41 without the spacer 51, and a groove serving as a flow path may be provided in one or both of the substrates 31 and 41.

  The reagent container 105 is a plurality of various reagent containers. For example, various reagents used for the extension reaction and analysis of nucleic acid samples (fluorescence detection of nucleic acid molecules), nucleic acid extension reaction processes, and unnecessary substances generated in the fluorescent substrate incorporation process. For example, a container for washing water for washing. Although the number of the reagent containers 105 is expressed in a simplified manner in FIG. 1, a larger number of reagent containers 105 are actually prepared than shown. In the present embodiment, the reagent container 105 includes a sample fixed layer reducing liquid container 105 ′ used in the device regeneration method of the present invention. The sample fixed bed reducing liquid is oxidized in the unused flow path remaining in the reaction device for nucleic acid analysis that has been used once, or in the unused flow path of the reaction device for unused nucleic acid analysis that has been left in the air for a long time. The sample fixed layer is used to regenerate by a reduction reaction. In this embodiment, as the solution, for example, an aqueous solution containing potassium hydroxide (hereinafter referred to as KOH) is used. The liquid for sample fixed layer reduction causes a reduction reaction in the oxidized sample fixed layer 60 by adjusting the temperature. The reagent container 105 further includes a container for storing ethanol. The use of ethanol will be described later.

  The stage unit 104 moves the holder unit 103 to which the nucleic acid analysis reaction device 102 is attached.

  The nozzle 107 moves between the reagent container 105, the nucleic acid analysis reaction device 102, and the nozzle cleaning mechanism 113 via the nozzle moving unit 108.

  Here, the operation of the nucleic acid analyzer according to the present embodiment will be described.

  First, nucleic acid analysis will be described. The reaction device 102 for nucleic acid analysis holding the nucleic acid sample in the preliminary process is installed in the holder unit 103. In the preliminary process, a nucleic acid sample is introduced into a selected channel among the channels 111, and the nucleic acid sample is fixed to the sample fixing layer 60 via a functional group or a carrier.

  In this state, the nozzle 107 accesses a reagent container necessary for the nucleic acid extension reaction and fluorescence detection, and sucks the reagent through the nozzle 107 and the liquid feeding unit 106. The nozzle 107 is conveyed to the upper surface of the nucleic acid analysis reaction device 102 by the nozzle moving unit 108 and injects the reagent through the inlet 33 of the selected flow path of the nucleic acid analysis reaction device 102. After the reagent injection, the nozzle 107 is moved to the cleaning mechanism 113 and cleaned. The nozzle cleaning mechanism 113 includes a nozzle cleaning tank (not shown) and a mechanism for supplying detergent liquid and cleaning water thereto.

  On the other hand, the temperature of the nucleic acid sample and the injection reagent in the nucleic acid analysis reaction device 102 is adjusted by the holder unit 103, thereby causing a nucleic acid extension reaction in which a substrate with a fluorescent dye is incorporated into the nucleic acid sample. In order to perform fluorescence observation of the nucleic acid sample subjected to the nucleic acid extension reaction, the reaction device 102 for nucleic acid analysis is moved to the observation position by the stage unit 104. At the observation position, excitation light is applied to the reaction device 102 for nucleic acid analysis via the detection unit 109 to detect fluorescence of each extension reaction in a plurality of nucleic acid samples in the observation region. After the detection, the reaction device 102 for nucleic acid analysis is moved minutely by a predetermined movement amount via the stage 104, and the operation of fluorescence detection is repeated a plurality of times in the same manner. When the fluorescence detection in all the observation areas is completed, the nozzle 107 accesses the washing water (pure water) container accommodated in the reagent container 105, and the washing water is sucked by the liquid feeding unit 106, and the reaction device for nucleic acid analysis. By injecting into the flow channel 102, the inside of the flow path 111 of the reaction device 102 for nucleic acid analysis is washed. Washing waste liquid (used reagents and unnecessary substances generated by the nucleic acid extension reaction) discharged through the outlet 34 of the flow path 111 by washing is sent to the drainage container 110 through a drainage passage and a drain tube 114 (not shown). .

  Thereafter, the sequence of the nucleic acid sample after completion of the nucleic acid extension reaction can be analyzed by repeating the operations of reagent injection, washing, and nucleic acid detection in the extension reaction a plurality of times.

  As shown in FIG. 1, the reaction device 102 for nucleic acid analysis that has been used once for nucleic acid analysis as described above, in addition to the used channel 111a that has already been used for analysis, There may be an unused flow path 111b in which no sample is held.

  As described above, the reaction device 102 for nucleic acid analysis once subjected to the nucleic acid analysis is subjected to heat of around 70 degrees on the entire device. Since the sample fixing layer 60 is oxidized by this heat in the unused channel 111b, the sample fixing ability is lowered. In the present embodiment, in order to regenerate the fixing function of the sample fixing layer of the unused flow path 111b, the following regeneration method is executed when the device 102 is not subjected to analysis.

  First step: First, the container 105 ′ containing the KOH aqueous solution is accessed by the nozzle 107, and the KOH aqueous solution (sample fixed layer reducing liquid) is sucked through the nozzle 107 and the liquid feeding unit 106, and the nozzle 107 is moved to the inlet 33 of the unused channel 111b, and an aqueous KOH solution is injected into the unused channel 111b. Further, the temperature of the entire reaction device 102 for nucleic acid analysis is adjusted by the holder unit 103, thereby causing a reduction reaction with the KOH aqueous solution on the sample fixing layer in the unused channel 111b that has been oxidized in the first analysis. Let

  Second step: After the sample fixing layer 60 in the unused flow path 111b has sufficiently undergone the reduction reaction, the nozzle 107 supplies the cleaning water (pure water) stored in the reagent container for the cleaning water to the nozzle 107 and the liquid supply. By sucking through the unit 106 and injecting it into the unused flow path 111b, the aqueous KOH solution is washed away.

  After the reduction reaction with the KOH aqueous solution and the washing with the washing water are repeated a plurality of times, only the washing with the washing water is repeated a plurality of times so that no KOH aqueous solution remains in the unused flow path 111b.

  Finally, idle suction by the nozzle 107 or discharge of only air is performed to eliminate the liquid remaining in the unused flow path 111b.

  Depending on the performance of the nozzle 107, the flow path configuration of the reaction device 102 for nucleic acid analysis, or the configuration of the sample fixing layer, it is difficult to completely remove the wash water from the flow path filled with the wash water. In this case, the washing water can be efficiently removed from the flow path by injecting ethanol contained in the reagent container and then performing idle suction of the nozzle 107.

  FIG. 2 shows a specific example in the regeneration method of the reaction device 102 for nucleic acid analysis. In addition, it cannot be overemphasized that the conditions illustrated in a process can be changed suitably, and are not limited to this example.

  In FIG. 2, in Step 1, 45 μl of 10% strength aqueous KOH solution is injected into the unused flow path 111b through the nozzle 107 at room temperature (25 ° C.). In step 2, the temperature of the aqueous KOH solution is adjusted at 55 ° C., and is retained in the unused flow path 111b for 2 minutes. Thereafter, in Step 3, 125 μl of pure water at room temperature is supplied to the unused flow path 111b to wash away the KOH aqueous solution. In step 4, the same KOH aqueous solution is injected as in step 1, and in step 5, the same temperature adjustment as in step 2 is performed. Thereafter, the cleaning of the unused flow path 111b is repeated three times in Steps 6, 7, and 8. Finally, in step 9, after injecting ethanol with a concentration of 100 percent and 125 μl into the unused flow path 111b, the nozzle 107 is sucked or discharged to remove residual cleaning water from the flow path. .

  According to the above-described embodiment, when an unused channel remaining when the reaction device for nucleic acid analysis is used for the first time, the unused channel that has deteriorated due to oxidation is reduced and washed to fix the sample. The layer function can be regenerated and used for the next use.

  In this example, an aqueous solution containing potassium hydroxide (hereinafter referred to as KOH) was used as the sample fixed bed reducing liquid. However, the present invention is not limited to this. For example, as an alternative, sodium hydroxide is used. Water, triethylamide ammonia water, sulfuric acid ammoniated water, etc. are considered to have the same effect.

  Moreover, the reduction reaction temperature of the liquid for sample fixed bed reduction can be 15 ° C to 70 ° C, and 40 ° C to 70 ° C can be considered as a more preferable temperature. Further, in order to drain the washing water from the flow path, isopropanol or methanol may be used instead of ethanol.

  In this example, the method for regenerating a reaction device for nucleic acid analysis that has been used once has been described. This regeneration method is applied to a reaction device for analyzing nucleic acid that has been left in the air for a long time after opening. It is also possible.

DESCRIPTION OF SYMBOLS 60 ... Sample fixed layer, 101 ... Nucleic acid analyzer, 102 ... Reaction device for nucleic acid analysis, 103 ... Holder unit, 104 ... Stage unit, 105 ... Reagent container, 105 '... Container for sample fixed layer reduction liquid, 106 ... Sending Liquid unit, 107... Nozzle, 108... Nozzle moving unit, 109 .. detection unit, 110 .. waste liquid container, 111 .. channel, 111 a .. used channel, 111 b .. unused channel, 113.

Claims (7)

A flow cell type reaction device for nucleic acid analysis comprising a sample fixing layer for fixing a nucleic acid sample and one or more flow paths formed on the sample fixing layer is used after a part of the flow paths or unused When the sample is left in the air for a long time, the function of the sample fixing layer of the unused flow path is regenerated,
The sample fixing layer is formed of an inorganic oxide that fixes the nucleic acid sample,
A first step of causing a reduction reaction in the sample fixing layer by injecting a sample fixing layer reducing liquid into an unused flow path of the device and adjusting the temperature of the device;
And a second step of washing out the sample fixed layer reducing liquid by flowing pure water through the unused flow path, and regenerating the reaction device for nucleic acid analysis,   The device according to claim 1, wherein the device has a plurality of flow paths, and the first and second flow paths are left in the unused flow paths remaining in the device after all the analysis on the used flow paths is completed. A method for regenerating a reaction device for nucleic acid analysis, characterized by applying a process.   3. The method for regenerating a reaction device for nucleic acid analysis according to claim 1, wherein the sample fixed layer reducing liquid is potassium hydroxide water.   The method for regenerating a reaction device for nucleic acid analysis according to claim 3, wherein the temperature of the reduction reaction using the potassium hydroxide water is between 40 ° C and 70 ° C. Nucleic acid analysis for performing nucleic acid extension reaction and nucleic acid analysis using a flow cell type reaction device for nucleic acid analysis comprising a sample fixing layer for fixing a nucleic acid sample and one or more flow paths formed on the sample fixing layer A device,
A liquid feeding unit for injecting liquid into the flow path;
A holder unit for adjusting the temperature of the device;
Pure water as cleaning water,
A sample fixing layer reducing liquid that is temperature-adjusted to cause a reduction reaction in the sample fixing layer , and
The sample fixing layer, nucleic acid analysis device according to claim that you have been formed by the inorganic oxide to fix the nucleic acid sample.   6. The nucleic acid analyzer according to claim 5, wherein the sample fixed bed reducing liquid is potassium hydroxide water. In claim 6,
The sample fixing layer is formed of an inorganic oxide that fixes the nucleic acid sample via a functional group containing oxygen or via a carrier, and the inorganic oxide is titania, zirconia, alumina, zeolite, vanadium pentoxide, silica. A nucleic acid analyzer comprising at least one inorganic oxide selected from the group consisting of sapphire, tungsten oxide and tantalum pentoxide, or a compound containing at least two of these .

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