JP2018087747A - Biochemical sample collection nozzle - Google Patents

Abstract

PROBLEM TO BE SOLVED: To prevent a biochemical sample to be collected from adhering to a nozzle surface.SOLUTION: A biochemical sample collection nozzle is provided, including a first member 1 provided with a first through-hole 1A extending from a first end 1a to a second end 1b and shaped to have an outer diameter that gradually decreases toward the first end 1a. The first member 1 is made of a ceramics principally containing zirconium oxide.SELECTED DRAWING: Figure 1

Description

  The present disclosure relates to biochemical sampling nozzles.

  In an analyzer such as a liquid chromatograph for analyzing a liquid sample, a sample collecting nozzle for collecting and carrying the liquid sample is provided. As such a sampling nozzle, stainless steel, which is an alloy mainly composed of iron, is mainly used. Since iron has a property of adsorbing hydroxyl groups, when the liquid sample contains hydroxyl groups, the liquid sample adheres relatively firmly to the surface of the nozzle. Since biochemical samples such as blood containing proteins contain hydroxyl groups and proteins tend to adhere to the nozzle surface relatively firmly, even if an attempt is made to eject the collected biochemical sample from the nozzle, the adsorbed biochemical sample is not There is a risk that the amount of discharge from the nozzle may be insufficient or the amount of discharge may vary. As a nozzle that suppresses such sample adsorption on the nozzle surface, for example, in Patent Document 1, a nozzle in which a noble metal plating layer is provided on the nozzle surface in the vicinity of the tip is known.

JP 2013-137227 A

  In the nozzle described in Patent Document 1, when the noble metal plating layer provided on the nozzle surface is peeled off, the stainless steel is exposed by peeling, and the sample to be analyzed may be firmly attached to the exposed portion of the stainless steel. . Further, when a plurality of types of samples are continuously collected and discharged using the nozzle, the sample remaining on the nozzle surface is mixed with other types of samples to be collected next. Furthermore, when the noble metal plating layer provided on the nozzle surface peels, the peeled plating layer may be mixed into the sample as contamination.

  As described above, the adhesion of the sample to the nozzle surface and the peeling of the noble metal plating layer provided on the nozzle surface led to a decrease in analysis accuracy.

  In order to solve the above-mentioned problem, the first member has a first through hole extending from the first end to the second end, and has a first member whose outer diameter decreases toward the first end, and the first member is And a nozzle for collecting biochemical samples, characterized by comprising a ceramic mainly composed of zirconium oxide.

  According to the biochemical sample collection nozzle of the present disclosure, adhesion of the biochemical sample to be collected to the nozzle surface can be suppressed. By using the biochemical sample collection nozzle of the present disclosure, it is possible to collect a necessary amount of biochemical sample with high accuracy, and even in collecting a plurality of types of samples, the possibility of contamination can be suppressed. The analysis accuracy in can be made relatively high.

An example of the biochemical sample collection nozzle of this embodiment is shown, (a) is a perspective view, (b) is a cross-sectional view along the central axis, and (c) is an enlarged view of the enlarged diameter portion. . The other example of the biochemical sample collection nozzle of this embodiment is shown, (a) is a perspective view, (b) is sectional drawing along a central axis.

  Hereinafter, embodiments of the present disclosure will be described in detail with reference to the drawings. 1A and 1B show an example of a biochemical sample collection nozzle according to the present embodiment. FIG. 1A is a perspective view, FIG. 1B is a cross-sectional view taken along a central axis, and FIG. It is an enlarged view. FIG. 2 shows another example of the liquid sampling nozzle according to the present embodiment, in which (a) is a perspective view and (b) is a cross-sectional view along the central axis. In FIG. 2, the same components as those in FIG. 1 are denoted by the same reference numerals as those in FIG.

  A biochemical sample collection nozzle 10 (hereinafter, also simply referred to as nozzle 10) shown in FIGS. 1 and 2 is used in an analyzer such as a liquid chromatograph for analyzing a biochemical sample. The nozzle 10 is used for collecting and transporting a sample to be analyzed in this analyzer. The nozzle 10 uses a biochemical sample such as blood containing protein as an analysis target sample (hereinafter also referred to as an analysis sample). Specifically, the nozzle 10 sucks up the analysis sample in the first through hole 1A by immersing a part of the first end 1a side in the analysis sample, and the analysis sample in the first through hole 1A. Hold. The suction of the analysis sample into the first through-hole 1A may be effected only by the so-called capillary phenomenon, or the effect of the pressure difference due to the negative pressure inside the first through-hole 1A can be used. .

  The nozzle 10 of the present disclosure is a biochemical sample collection nozzle having a first through hole 1A extending from the first end 1a to the second end 1b, and having a shape in which the outer diameter becomes narrower toward the first end 1a. The first member 1 includes a ceramic mainly composed of zirconium oxide (hereinafter also referred to as zirconium oxide ceramics).

  Here, the main component of the ceramic means a component occupying 70% by mass or more out of a total of 100% by mass of the components constituting the ceramic. It is preferable that the content of zirconium oxide is 75% by mass or more in a total of 100% by mass of the components constituting the ceramic. Each component constituting the ceramic can be identified by an X-ray diffractometer, and the content thereof can be determined by a fluorescent X-ray analyzer or an ICP emission spectroscopic analyzer.

  In the nozzle 10 of the present embodiment, the first member 1 is made of zirconium oxide ceramics, so that the inner peripheral surface of the first through hole 1A is also made of zirconium oxide. Thus, when the inner peripheral surface of the first through hole 1A is made of zirconium oxide, the nozzle 10 moves to the inner peripheral surface of the first through hole 1A as compared with the case where stainless steel or the like is used as the inner peripheral surface. The adhesion of proteins and the like is suppressed. The nozzle 10 made of zirconium oxide ceramics as the first member 1 itself does not easily adhere to the analysis sample even if a noble metal plating layer or the like is not provided on the surface, and mixing of the peeled plating layer into the analysis sample does not occur. In the first member 1, since the first end 1 a and the outer peripheral surface of the first member 1 are also made of zirconium oxide ceramics, it is difficult for the analysis sample to adhere to the entire surface of the first member 1. By using such a nozzle 10, residue due to adhesion of the collected analytical sample to the nozzle surface is suppressed, so that the necessary amount of analytical sample can be collected with high accuracy. Moreover, the mixing at the time of collecting a plurality of types of analysis samples can be suppressed. In addition, since the zirconium oxide ceramic has relatively high toughness, it is difficult to break when an external force is applied to the first member 1.

  Moreover, the nozzle 10 may have the 2nd member 2 provided with 2 A of 2nd through-holes connected to 1 A of 1st through-holes in the 2nd end 1b side of 1 A of 1st through-holes. The inner diameter of the first through hole 1A may be smaller than the inner diameter of the second through hole 2A. When the second member 2 is provided and the inner diameter of the first through-hole 1A is smaller than the inner diameter of the second through-hole 2A, an analysis of an amount larger than the size of the first through-hole 1A of the first member 1 is performed. The sample can be held by the nozzle 10.

Further, in the nozzle 10, the first end 1 a side of the first member 10 serves as an inlet for an analysis sample to be collected and a discharge port for the collected analysis sample. When the analysis sample is discharged from the nozzle 10, the analysis sample is discharged as a droplet. The size of each droplet varies depending on the size of the inner diameter of the first through hole 1A. When the inner diameter of one through hole 1A is small, each droplet is small. In the nozzle 10, since the inner diameter of the first through hole 1A is smaller than the inner diameter of the second through hole 2A, the second through hole 2A having a relatively large inner diameter holds a relatively large amount of analysis sample and is relatively small. Since the first through-hole 1A having the inner diameter can be ejected with a small droplet, it has a high ejection accuracy while maintaining a large amount.

  In addition, although the material of the 2nd member 2 is not limited, It is preferable to consist of the material similar to the 1st member 1, ie, a zirconium oxide ceramic. Since the second member 2 is made of zirconium oxide ceramics, it is possible to suppress the residue due to adhesion of the collected analysis sample to the nozzle surface also in the second through-hole 2A. Thereby, the nozzle 10 can quantify the analysis sample with high accuracy. In addition, it is possible to further suppress contamination when collecting a plurality of types of analysis samples.

  Moreover, the 1st member 1 has the insertion part 11 inserted in 2A of 2nd through-holes in the 2nd end 1b side, and the inside diameter of the 1st through-hole 1 becomes large as it approaches the 2nd end side 1b. You may have the enlarged diameter part 12 which becomes. In the case where the insertion portion 11 in the first member 1 is inserted into the second through hole 2A, when the first member and the second member are joined via the joining layer 3 as in the present embodiment, the insertion portion 11 Since it can be set as the wide range and joining area | region of the whole opposing area | region of an outer peripheral surface and 2 A of internal holes of 2nd through-hole, the 1st member 1 can be firmly couple | bonded with the 2nd member 2. FIG.

  In addition, when it has an enlarged diameter portion whose inner diameter increases as it approaches the second end side 1b, the analysis sample can easily flow smoothly from the inside of the second through hole 2A toward the inside of the first through hole 1A. Therefore, it is possible to suppress the generation of microbubbles at the boundary portion between the second through hole 2A and the first through hole 1A. In addition, when there is no worry about generation | occurrence | production of a microbubble etc., the structure which does not have the enlarged diameter part 12 like other embodiment shown in FIG. 2 may be sufficient. The shape of the enlarged diameter portion 12 is, for example, a truncated cone shape, and the apex angle θ in a sectional view along the central axis may be, for example, 70 ° or more and 110 ° or less.

  When the first member 1 of the nozzle 10 has the insertion portion 11 to be inserted into the second through hole 2A on the second end 1b side, the outer peripheral surface of the insertion portion 11 and the inner periphery of the second through hole 2A. The bonding layer 13 may be positioned between the surfaces. When satisfying such a configuration, since the first member 1 and the second member 2 are firmly joined, the possibility that the first member 1 is detached from the second member 2 is reduced.

Moreover, when the insertion part 11 has the level | step difference surface 14 in the 1st end 1a side, the joining layer 13 may be located between the level | step difference surface 14 and the 2nd member 2. FIG. When the bonding layer 13 is located between the stepped surface 14 and the second member 2 in addition to the outer peripheral surface of the insertion portion 11 and the inner peripheral surface of the second through hole 2A, the first member 1 Since the second member 2 and the second member 2 are more firmly joined, there is less possibility that the first member 1 is detached from the second member 2.

  The bonding layer 13 may contain silicon oxide as a main component and include barium oxide, calcium oxide, and aluminum oxide. The bonding layer 13 containing silicon oxide as a main component is a so-called glass bonding layer. The bonding layer 13 containing barium oxide has relatively high water resistance, and also contains calcium oxide, so that the chemical durability is relatively high. Further, the bonding layer 13 containing aluminum oxide has a relatively high glass softening temperature and a relatively high heat resistance.

Note that the main component in the bonding layer 13 refers to the largest component among the total of 100% by mass of the components constituting the bonding layer 13. Of the total 100% by mass of the components constituting the bonding layer 13, silicon oxide is preferably 50% by mass or more. For example, the bonding layer 13 has a barium oxide content of 15% by mass to 30% by mass, a calcium oxide content of 5% by mass to 20% by mass, and an aluminum oxide content of 1% by mass to 10% by mass. The remainder is silicon oxide. The content of each component constituting the bonding layer 13 can be obtained by an ICP emission spectroscopic analyzer.

  The first through hole 1A has a region having a constant inner diameter (D1) from the first end 1a to the second end 1b, and the ratio of the length (L1) of the first through hole 1A to the inner diameter (D1) ( L1 / D1) may be 50 or more. In the nozzle 10 of the embodiment shown in FIG. 1, the inner diameter (D1) of the first through hole 1A is, for example, 0.25 mm to 0.3 mm, and the length (L1) of the first through hole 1A is, for example, 12 mm to 16 mm. The ratio (L1 / D1) is 40 or more and 64 or less.

  When this ratio (L1 / D1) is 50 or more, since the inner diameter (D1) of the first through hole 1A is sufficiently small, the analysis sample can be sucked up stably by capillary action. In addition, since the first through hole 1A is sufficiently long, a relatively large amount of analysis sample can be held and transported. Further, in the first through hole 1A having a sufficiently small inner diameter D1 with respect to the length L1, turbulent flow hardly occurs in the sucked analysis sample. For this reason, at the time of aspiration of an analysis sample, it is controlled that the micro bubble resulting from turbulent flow arises in an analysis sample. Further, when the droplets are ejected, variations in the size of the droplets due to such turbulent flow are suppressed.

  The ceramics constituting the first member 1 and the second member 2 of the nozzle 10 may contain 2 mol% or more and 4 mol% or less of yttrium in terms of oxide. When the ceramic contains yttrium as an oxide in the above range, the first member 1 and the second member 2 made of this ceramic have a relatively high mechanical strength.

  Further, the ceramics constituting the first member 1 and the second member 2 of the nozzle 10 may include 8 mol% or more and 12 mol% or less in terms of oxides of at least one of magnesium and calcium. Such ceramics have a relatively high thermal shock resistance.

  Next, an example of a method for manufacturing a liquid sample collecting nozzle will be described. First, a ceramic raw material powder containing zirconium oxide as a main component and a clay containing a binder are put into an extrusion molding machine and pressed to extrude to obtain a cylindrical first molded body having first through holes.

  Using a method similar to the method described above, a cylindrical second molded body having a second through hole is obtained. In order to obtain a nozzle made of ceramic containing 2 mol% or more and 4 mol% or less of yttrium in terms of oxide, 2 mol% or more of the powder of yttrium oxide in the total 100 mol% of the ceramic raw material powder and the yttrium oxide powder. What is necessary is just to mix | blend so that it may become 4 mol% or less.

  In addition, in order to obtain a nozzle for collecting a liquid sample made of a ceramic containing 8 mol% or more and 12 mol% or less of at least one of magnesium and calcium as an oxide, the ceramic raw material powder and the oxide of the Group 2 element are used. What is necessary is just to mix | blend so that the powder of the oxide of a 2nd group element may be 8 mol% or more and 12 mol% or less in total 100 mol% of this powder.

  Next, the first molded body and the second molded body are placed in a firing furnace and fired in an air atmosphere at, for example, 1300 ° C. or higher and 1700 ° C. or lower to form a first fired body and a second fired body, respectively. be able to.

  Next, the surface of each of the first fired body and the second fired body is mechanically processed to obtain the first member 1 and the second member 2. At this time, polishing may be performed so that the outer peripheral surface of the first fired body on the first end 1a side becomes narrower toward the tip, and the second end 1b side may be ground to form the insertion portion 11. Moreover, what is necessary is just to process a part of opening end by the side of the 2nd end 1b of 1 A of 1st through-holes, and to form the enlarged diameter part 12. FIG.

Next, the central axis of the through hole 1A of the first member 1 and the central axis of the through hole 2A of the second member 2 are aligned, and the insertion portion 11 of the first member 1 is replaced with the second through hole of the second member 2. Inserted into 2A, the first member 1 and the second member 2 are joined together via a paste that becomes the joining layer 13. At this time, first, powders of silicon oxide, barium oxide, calcium oxide, and aluminum oxide, cellulose-based resin, and at least one of the outer peripheral surface of the insertion portion 11 of the first member 1 and the inner peripheral surface of the through-hole 2A, A paste containing an organic solvent such as terpineol is applied. In addition, the sum total of content of each powder of the oxide in 100 mass% of paste shall be 72 to 78 mass%. In addition, the content of the barium oxide powder is 15% by mass to 30% by mass and the content of the calcium oxide powder is 5% by mass to 20% by mass in the total 100% by mass of the oxide powders. The content of the aluminum oxide powder may be 1% by mass or more and 10% by mass or less, and the remainder may be silicon oxide.

  In this state, when the insertion portion 11 of the first member 1 is inserted into the second through hole 2A of the second member 2, a step is formed between the outer peripheral surface of the insertion portion 11 and the inner peripheral surface of the second through hole 2A. The paste spreads between the surface 14 and the second member 2. In this state, for example, the temperature is raised to 850 ° C. or higher and 950 ° C. or lower and heat-treated, and then the temperature is lowered to room temperature. Thereby, the nozzle 10 with which the 1st member 1 and the 2nd member 2 were joined via the joining layer 13 is obtained.

  In the present embodiment, as described above, the first member 1 and the second member 2 are manufactured by an extrusion method using an extruder. For this reason, unlike the processing method of mechanically forming the through-hole with a tool such as a drill, for example, the minute amount generated in the crystal particles arranged on the inner peripheral surface of the first through-hole 1A or the second through-hole 2A Since there are few cracks etc., crystal particle fragments and the like are rarely detached from the inner peripheral surfaces of the first through hole 1A and the second through hole 2A. Moreover, the variation in the diameter of the crystal grains exposed on the inner peripheral surface of the first through hole 1A and the second through hole 2A is small, and the occurrence of large local irregularities is also suppressed. For this reason, in the nozzle 10 manufactured by the manufacturing method of this embodiment, the residue of the analysis sample on the inner surface, which is likely to occur when there are large irregularities, is further suppressed. The manufacturing method of the first member 1 and the second member 2 is not particularly limited, but the viewpoint of suppressing the detachment of crystal particles from the inner surfaces of the first through hole 1A and the second through hole 2A, and the analysis sample From the viewpoint of further suppressing the residue, it is preferable to use an extrusion method.

  In the nozzle 10 manufactured in the present embodiment, the average particle diameter of the crystal particles mainly composed of zirconium oxide exposed on the surface of the first through hole 1A of the first member 1 is, for example, 0.2 μm or more and 0.4 μm. It is as follows. The average grain size of the crystal grains is 7.8 μm × 5.8 μm in which the fracture surface of the ceramic is magnified 10,000 times with a scanning electron microscope, and four straight lines having the same length are drawn. It can be obtained by dividing the number of crystal grains present on the substrate by the total length of these straight lines.

  Although the present embodiment has been described above, the present disclosure is not limited to the above-described embodiment, and various modifications and improvements can be made without departing from the gist of the present invention.

DESCRIPTION OF SYMBOLS 1 1st member 1a 1st end 1b 2nd end 1A 1st through-hole 2 2nd member 2A 2nd through-hole 10 Nozzle (nozzle) for biochemical sample collection
11 Insertion part 13 Bonding layer 14 Step surface

Claims (9)

A nozzle for collecting biochemical samples,
A first member having a first through hole extending from the first end to the second end, and having a shape with an outer diameter becoming narrower toward the first end,
The biochemical sample collection nozzle, wherein the first member is made of a ceramic mainly composed of zirconium oxide. A second member provided on the second end side of the first through hole, the second member including a second through hole communicating with the first through hole;
The biochemical sample collection nozzle according to claim 1, wherein the inner diameter of the first through hole is smaller than the inner diameter of the second through hole. The first member has an insertion portion to be inserted into the second through hole on the second end side,
3. The biochemical sample collection nozzle according to claim 2, wherein the first through hole has a diameter-expanded portion whose inner diameter increases as it approaches the second end side. The first member has an insertion portion to be inserted into the second through hole on the second end side,
The biochemical sample collection nozzle according to claim 2 or 3, wherein a bonding layer is located between the outer peripheral surface of the insertion portion and the inner peripheral surface of the second through hole.   The biochemistry according to claim 4, wherein the insertion portion has a step surface on the first end side, and the bonding layer is located between the step surface and the second member. Sample collection nozzle.   6. The nozzle for collecting a biochemical sample according to claim 4, wherein the bonding layer contains silicon oxide as a main component and contains barium oxide, calcium oxide, and aluminum oxide.   The first through hole has a region having a constant inner diameter (D1) from the first end toward the second end, and a ratio of the length (L1) of the first through hole to the inner diameter (D1). The nozzle for collecting a biochemical sample according to any one of claims 1 to 6, wherein (L1 / D1) is 50 or more.   8. The biochemical sample collection nozzle according to claim 1, wherein the ceramic contains 2 mol% or more and 4 mol% or less of yttrium in terms of an oxide. The bioceramic sampling nozzle according to any one of claims 1 to 7, wherein the ceramic contains at least one of magnesium and calcium in an amount of 8 mol% to 12 mol% in terms of an oxide.

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