JP2003344400A - Fiber cross section arranged body and manufacturing method thereof - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a fiber arranged sheet and a method of manufacturing the sheet which is excellent in the precision of arrangement of each fiber cross section in a thin leaf. <P>SOLUTION: The fiber cross section arranged sheet obtained by cutting a plurality of fibers fixedly bundled body in a direction perpendicular to the axial direction of the fibers is characterized in that: the main diameter of the fiber is ≤1 mm, density of the arranged fiber is ≥100/cm<SP>2</SP>; the fibers are regularly arranged in a matrix pattern with adjacent center line distance (P) in the matrix; the deviation rate of adjacent center line distance is ≤25%, wherein the deviation rate = (X/P)×100, where X=(max. value of the center distance between the fiber cross sections adjacent in the matrix)--(min. value of the center distance between the fiber cross sections adjacent in the matrix). <P>COPYRIGHT: (C)2004,JPO

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a high-precision fiber cross-section array sheet and a method for manufacturing the same. This fiber cross-section array sheet is used for the analysis of specimens that show specific interactions with these probes by immobilizing biologically relevant substances such as nucleic acids, proteins, polypeptides and polysaccharides on the fiber cross section as probes. Used.

[0002]

2. Description of the Related Art In recent years, genome projects in various organisms have been under way, and many genes including human genes and their nucleotide sequences are rapidly being clarified. The function of a gene whose sequence has been elucidated can be investigated by various methods, and as one of its powerful methods, gene expression analysis using the elucidated nucleotide sequence information is known. For example, a method utilizing various nucleic acid-nucleic acid hybridization reactions and various PCR reactions represented by Northern hybridization has been developed, and the relationship between various genes and their biological function expression is investigated by the method. be able to. However, these methods are limited in the number of genes that can be applied. Therefore, from the perspective of the entire complex reaction system consisting of an extremely large number of genes at the individual level, which is being clarified through today's genome project, it is necessary to perform a comprehensive and systematic analysis of genes by the above method. It is difficult.

Recently, a new analysis method or methodology called a DNA microarray method (DNA chip method) that enables collective expression analysis of a large number of genes has been developed and attracted attention. These methods are the same as conventional methods in principle in that all of them are nucleic acid-nucleic acid detection / quantification methods based on a nucleic acid-hybridization reaction, but many on a flat substrate piece called a microarray or chip. The major feature is that the DNA fragments of (1) are aligned and immobilized at high density. As a specific method of using the microarray method, for example, a sample obtained by labeling an expression gene of a cell to be studied with a fluorescent dye or the like is hybridized on a flat substrate piece to bind mutually complementary nucleic acids (DNA or RNA). There is a method in which the portion is labeled with a fluorescent dye or the like and then read at high speed with a high resolution analyzer. In this way, the amount of each gene in the sample can be estimated quickly. In other words, the essence of this new method is basically the integration of the amount of reaction sample miniaturized and the technology for arranging and arranging the reaction sample in a form capable of reproducibly conducting large-scale, rapid, systematic analysis and quantification. Understood to be.

As a method for arranging nucleic acids on a substrate, similar to the Northern method described above, a method of immobilizing the nucleic acid on a nylon sheet or the like at a high density, or a polylysine on a substrate such as glass for further increasing the arrangement density A method for coating and immobilizing such substances, or a method for directly solid-phase synthesizing a short-chain nucleic acid on a substrate such as silicon has been developed.

However, for example, a method of spotting and immobilizing nucleic acid on a substrate whose surface such as glass is chemically or physically modified [Science 270, 467-470 (1995)] is better than the sheet method in terms of spot density. Although excellent, the spot density and the amount of nucleic acid that can be immobilized per spot are directly synthesized on a silicon substrate (US Patent 5,445,934, US Paten
It has been pointed out that it is difficult to reproduce because it is a small amount compared with (5,774,305). In addition, regarding the method of regularly performing solid phase synthesis of various kinds of short-chain nucleic acids on the spot by using photolithography technology on a substrate such as silicon, the number of nucleic acid species that can be synthesized per unit area (spot density) and Although the amount of immobilization per spot (synthesis amount) and reproducibility are superior to those of the spotting method, the compound species that can be immobilized are limited to relatively short-chain nucleic acids that can be controlled by photolithography. further,
Due to the expensive manufacturing equipment and multi-stage manufacturing process, it is difficult to greatly reduce the cost per chip. In addition, a method of using minute beads is known as a method for solid phase synthesizing nucleic acid on a minute carrier to form a library.
This method is capable of synthesizing a variety of long-chain nucleic acids at a lower cost than the chip method, and is also considered to be capable of immobilizing longer-chain nucleic acids than cDNA and the like. However, unlike the chip method, it is difficult to fabricate a specified compound with reproducible alignment based on a specified sequence standard.

In view of the above situation, the present applicant has proposed a microarray by the fiber bundle slicing method which is inexpensive and can be mass-produced, and a manufacturing method thereof (Japanese Patent Application No. 2000-5565).
No. 8). A similar method is disclosed in Japanese Patent Laid-Open No. 11-1
08928, WO99 / 13313, WO99 / 1
No. 9711.

[0007]

In the above fiber bundle slicing method, a plurality of fibers holding a probe such as a nucleic acid is formed into a bundle, and the bundle is fixed with an adhesive or a resin and crosses the longitudinal direction of the fibers. This is a method of obtaining slices by slicing in the direction. This method is superior to other methods in that the same thin piece, that is, a large number of microarrays can be obtained at one time. However, it is necessary that the position of each fiber cross section included in the thin piece, that is, the position of the immobilized probe is regularly arranged.

Focusing on this point, the present inventors quantified and examined the alignment accuracy of the fiber cross-section of the thin piece obtained by the array of fiber bundles, and as a result, found that the array accuracy of the array obtained by the conventional method is the thin piece. It was found that the distance between each fiber also greatly changed within one thin piece.

SUMMARY OF THE INVENTION Therefore, an object of the present invention is to provide a fiber array sheet having excellent alignment accuracy of each fiber cross section arrayed in a thin piece, and a method for producing the same.

[0010]

DISCLOSURE OF THE INVENTION As a result of intensive studies in view of the above problems, the present inventors have found that when manufacturing a fiber cross-section array sheet, the array accuracy is controlled by controlling the diameter variation rate of the fibers used. It has been found that it is possible to obtain an excellent fiber cross-section array sheet of, and the present invention has been completed. Further, they have found that the use of a jig having a taper when arranging such fibers improves the workability of the arranging work and improves the productivity of the arranging sheet, and thus completed the present invention. It was

That is, according to the present invention, in a fiber fragment array sheet obtained by cutting a fiber bundle-fixed product having a plurality of fibers bundled and fixed in a direction crossing the longitudinal direction of the fibers, the average diameter of the fibers is 1 mm or less, the array density of fibers is 100 / cm ² or more, and the fibers are regularly arranged in the vertical and horizontal directions at the center-to-center distance P of the fibers, and the variation rate of the center-to-center distance of the fiber fragments adjacent in the vertical and horizontal directions is 25% or less. A fiber fragment array sheet, characterized in that Variability = (X / P) × 100, where X = (maximum distance between centers of adjacent fiber cross sections in the vertical and horizontal directions) − (minimum distance between centers of adjacent fiber cross sections in the vertical and horizontal directions)

Further, according to the present invention, in a fiber fragment array sheet obtained by repeatedly cutting a fiber bundle-fixed product having a plurality of fibers bundled and fixed in a direction intersecting the longitudinal direction of the fibers, the average diameter of the fibers is It is 1 mm or less, the arrangement density of the fiber cross sections is regularly arranged at 100 pieces / cm ² or more, and the standard deviation value of the distance between the fiber cross section centers adjacent to each other in the vertical and horizontal directions is calculated from the standard deviation value of the distance between the fiber cross section centers adjacent to each other in the vertical and horizontal directions. A fiber cross-section array sheet, wherein a value (CV value) divided by an average value is 3% or less.

[0013]

BEST MODE FOR CARRYING OUT THE INVENTION The present invention will be described in detail below.
The fiber cross-section array sheet of the present invention means one satisfying any of the following conditions.

(1) In a fiber fragment array sheet obtained by cutting a fiber bundle-fixed product having a plurality of fibers bundled and fixed in a direction intersecting the longitudinal direction of the fibers, the average diameter of the fibers is 1 mm or less, Fiber arrangement density is 100 / cm
² or more, the fibers are regularly arranged in the longitudinal and lateral directions at the center distance P of the fibers, and the variation rate of the center distance between the longitudinally and laterally adjacent fiber fragments is 25% or less. . Variability = (X / P) × 100, where X = (maximum distance between centers of adjacent fiber cross sections in the vertical and horizontal directions) − (minimum distance between centers of adjacent fiber cross sections in the vertical and horizontal directions)

(2) In a fiber fragment array sheet obtained by repeatedly cutting a fiber bundle-fixed product having a plurality of fibers bundled and fixed in a direction intersecting the longitudinal direction of the fibers, the average diameter of the fibers is 1 mm or less. And the array density of the fiber cross sections is regularly arranged at 100 pieces / cm ² or more, and the standard deviation value of the distance between the center points of the fiber cross sections that are vertically and horizontally adjacent is the average value of the distance between the center points of the fiber cross sections that are vertically and horizontally adjacent. A highly accurate fiber cross-section array sheet, wherein the value (CV value) divided by is 3% or less.

The "average diameter of the fiber" is the average value of the values obtained by continuously measuring the diameter of the fiber over the entire length of the fiber. The smaller the average diameter of the fibers, the higher the array density of the fiber cross-section array sheet described later can be produced. Therefore, the diameter of the fiber is preferably 1 mm or less. The “array density of fiber cross sections” is the number of fiber cross sections existing per unit area of the fiber cross section array sheet. The array density is preferably 100 pieces / cm ² or more. Further, it is preferable that one fiber cross section array sheet includes 100 or more fiber cross sections.

In the present invention, the accuracy of the fiber cross section arrangement in the fiber cross section array sheet is evaluated by the variation rate or the CV value. The fluctuation rate is calculated by the following formula. Variability = (X / P) × 100, where X = (maximum distance between centers of adjacent fiber cross sections in the vertical and horizontal directions) − (minimum distance between centers of adjacent fiber cross sections in the vertical and horizontal directions)

Specifically, the center-to-center distance P between the fiber cross sections adjoining in the vertical and horizontal directions is measured, and the difference between the maximum value and the minimum value thereof is evaluated. Here, the distance P between the fiber cross-section centers that are vertically and horizontally adjacent to each other will be described with reference to FIG. FIG. 1 schematically shows a fiber cross-section array sheet having a fiber cross-section group arranged in n rows × n columns at a desired center-to-center distance P between fiber cross-sections. In this case, if the center position of the fiber cross section in the i-th row and the j-th column is represented by (i, j), since the fiber cross-sections are arranged at substantially equal intervals, the fiber cross-sections adjacent to each other in the vertical and horizontal directions of (i, j) are ( i-1, j) (i + 1, j) (i, j + 1) (i, j
There are four types of -1). In the present invention, the distance P between the fiber cross-section centers is calculated for 100 fiber cross-sections, the maximum value and the minimum value thereof are calculated, and the difference is defined as X, and X is divided by the target fiber cross-section center distance P. Defined as a rate.

The CV value is a value obtained by calculating the standard deviation of the distances between the fiber cross-section centers that are adjacent in the vertical and horizontal directions and dividing it by the average value of the distances between the fiber cross-section centers. Also in this case, 100 is selected as the number of fiber cross-sections and the CV is calculated in the same manner as the calculation of the variation rate.
Calculate the value.

In any of the above methods, the fiber cross section array sheet having a fiber cross section number of 100 or less has the whole fiber cross section, and the fiber cross section array sheet having the fiber cross section number of 100 or more has 100 at the central portion.
Measure for each piece.

The variation rate of the fiber cross-section array sheet of the present invention is 25% or less, preferably 20% or less when measured by the above evaluation method. The CV value is 3% or less, preferably 2.5% or less. When the fluctuation rate or the CV value is equal to or less than the above value, the positioning of each fiber in each fiber cross section becomes easy, and the accuracy of analysis is improved and the analysis time is shortened. The following method can be exemplified as a method for producing such a fiber fragment array sheet.

A method for producing a fiber cross-section array sheet, which comprises the following steps: (1) Forming a fiber-immobilized material having a diameter fluctuation rate of 5% or less, (2) Immobilizing a biological substance on the fiber, (3) Crossing the fiber-immobilized material in the longitudinal direction of the fiber The process of cutting into thin pieces by cutting in the direction.

As the fibers to be used, fibers having a diameter fluctuation rate of 5% or less are used. Where "diameter variation rate"
Is the ratio of the maximum value (minimum value) of the values obtained by continuously measuring the diameter of the fiber over the entire length of the fiber and the average diameter, that is, can be calculated by the following formula. Diameter fluctuation rate = [(maximum (small) value-average value) / average value] x
100. It is preferable that the range of the diameter variation is within ± 5% of the standard diameter by the spinning technique. When the fibers spun by such a method are used, both the variation rate and the CV value of the fiber fragment array sheet are improved. In addition, monofilament with small diameter fluctuation of fiber,
It is preferable to use hollow fibers.

In the present invention, examples of the material of the fibers include synthetic fibers, semi-synthetic fibers, regenerated fibers, and chemical fibers such as inorganic fibers. As a typical example of synthetic fiber,
Nylon 6, nylon 66, various polyamide fibers such as aromatic polyamide, polyethylene terephthalate, polybutylene terephthalate, polyester fibers such as polylactic acid and polyglycolic acid, various acrylic fibers such as polyacrylonitrile, polyethylene, etc. From various polyolefin fibers such as polypropylene, polyvinyl alcohol fibers, polyvinylidene chloride fibers, polyvinyl chloride fibers, polyurethane fibers, phenolic fibers, polyvinylidene fluoride, polytetrafluoroethylene, etc. Examples of such fluorine-based fibers, polyalkylene paraoxybenzoate-based fibers, fibers using a (meth) acrylic resin such as polymethylmethacrylate, and the like. Typical examples of the semi-synthetic fibers include various cellulose-based derivative fibers made from diacetate, triacetate, chitin, chitosan, etc., and various protein-based fibers called promix. As a typical example of regenerated fiber, various cellulosic regenerated fibers obtained by viscose method, copper-ammonia method, or organic solvent method (rayon, cupra, polynosic, etc.)
And so on. A glass fiber is a typical example of the inorganic fiber.

When the fiber array is produced, a step of applying tension to the fibers may be included, so that the fibers to be used are preferably fibers having a high elastic modulus, such as methyl methacrylate fibers and aromatic polyamide fibers. . Hollow fibers using the above substances as materials can be produced by a known method using a special nozzle. A melt spinning method is preferable for polyamide, polyester, polyolefin and the like, and a horseshoe-shaped nozzle, a C-shaped nozzle, a double tube nozzle and the like can be used as the nozzle.

Solvent spinning is preferably used for the spinning of synthetic polymers which cannot be melt-spun, semi-synthetic fibers or polymers used for recycled fibers. In this case as well, as with melt spinning, 2
A hollow fiber having a continuous hollow portion can be obtained by performing spinning while filling the hollow portion with an appropriate liquid as a core material using a heavy pipe nozzle. These hollow portions are suitable for immobilizing a biological substance. The fiber used in the present invention may be used as it is in an untreated state, or may be a fiber having a reactive functional group introduced, if necessary,
Further, it may be a fiber that has been subjected to plasma treatment or radiation treatment such as γ-ray or electron beam.

Next, a fiber bundle-fixed product in which a plurality of the above fibers are bundled and fixed is prepared. An example of the focusing method is a tool having small holes, in which a fiber is passed through each small hole of a jig having an array pattern formed of a large number of small holes to focus the fibers.

The small holes penetrating the jig used in the present invention may be arranged in a predetermined pattern. For example, a circular hole may be arranged vertically and horizontally (see FIG. 2). When such a jig is used, the fibers are passed through the holes of the jig and then the distance between the jigs is expanded. However, it is preferable that the hole positions of the jigs are aligned and contact with each other in order to match the hole positions of the adjacent jigs.

When a jig having holes having the same pattern as a desired array pattern is used as a jig for focusing fibers,
The distance between the fibers in the fiber array is the same as the hole pitch of the jig (the distance between the center of the hole and the center of the adjacent hole). Such a jig having a constant hole pitch is preferably manufactured by photoetching because it is the cheapest and can be mass-produced with high precision. The material of the jig is usually stainless steel, copper or copper alloy, but in the present invention, a stainless steel plate (SUS304 material) is most suitable from the viewpoint of material strength, processing cost and material cost.

Each hole diameter of the jig is
It should be the same as the outer diameter of the fiber used. If workability and fiber diameter fluctuation are taken into consideration, the pore size is 100 to 12 of the fiber diameter.
5% is preferable, and about 105% is the most preferable.

Further, as shown in FIG. 3, by providing a taper from the insertion side to the discharge side in which the hole diameter becomes small for a while, the fibers can be efficiently moved to the jig even when the respective hole diameters of the jig are close to the outer diameter of the fiber. Can be inserted into the hole. In this case, the hole diameter on the insertion side is preferably as large as possible, and is preferably the same as the maximum hole pitch value. Further, the hole diameter on the discharge side is the same as the maximum value of the diameter variation range of the fiber, and the work is very easy as compared with the case where a jig having no taper is used for each hole.

Two such jigs are arranged in series, or if necessary, two or more jigs are arranged so that the positions of the holes are aligned and are in contact with each other, and fibers are passed through the holes of the jig to perform an arraying work.

After that, the distance between the jigs is increased. The interval is not particularly specified and may be set appropriately.
If the interval is wide, a long product of the fiber array can be molded, and the manufacturing cost can be reduced by reducing the loss in the subsequent process such as slicing into thin pieces. If the spacing is excessively widened, the binding force of the fibers may decrease near the center of the span and the alignment may be disturbed.
It is adjusted appropriately so as not to cause such disturbance. Also,
The number of jigs may be appropriately added for the purpose of strengthening the array regulation near the center of the span.

Next, tension is applied to all the fibers that have passed through the jig, and in that state, the gaps between the fibers are filled with resin and fixed. Although the tension varies depending on the cross-sectional shape and material of the fiber, that is, the elastic modulus, the expansion rate, etc., the tension is set so that the fiber does not sag and does not break. Then, the tension is maintained in order to maintain the tension of the fibers without slack. As a method,
Examples include a method of pulling all the fibers with a spring, a method of non-contact suction with an air sucker, a method of collecting the fibers with an appropriate adhesive tape and attaching the fibers to a jig, a method of utilizing gravity, and the like.

The fibers bundled as described above are fixed with a resin or the like to prepare a fiber bundled and fixed product. If the fixing means is each resin, it exhibits a low-viscosity liquid so that it can be easily filled in the voids between the fibers, and can be filled and cured at room temperature,
For example, a two-component reaction curable resin such as urethane resin is preferable.

Next, a bio-related substance is fixed to each fiber of the fiber-focused fixing material. Examples of biological substances include deoxyribonucleic acid (DNA), ribonucleic acid (RNA), peptide nucleic acid (P
NA), nucleic acids such as oxypeptide nucleic acid (OPNA),
Alternatively, proteins, polysaccharides, etc. may be mentioned. The biological substance used in the present invention may be commercially available or may be obtained from living cells or the like.

For example, when nucleic acid is used as a biological substance, DNA or RNA can be prepared from living cells by a known method, for example, the method of Blin et al. (Blin et al., Nucleic Acids Res for extraction of DNA). .3: 2303 (1976)
) Etc., and for RNA extraction, Favaloro
Favaloro et al., Methods Enzymol. 65: 71
8 (1980)) etc. Furthermore, linear or circular plasmid DNA or chromosomal DNA, a DNA fragment obtained by chemically cutting these with a restriction enzyme,
It is also possible to use DNA synthesized by an enzyme or the like in a test tube, or chemically synthesized oligonucleotides.

The immobilization method may be immobilization on the fiber as it is, or a derivative obtained by chemically modifying a biomaterial, or a biomaterial modified as necessary may be immobilized. For example, when nucleic acid is used as a biological substance, amination, biotinylation, digoxigenation, etc. are known as the chemical modification of nucleic acid [Current Pro
tocols In Molecular Biology, Ed .; Frederick M. Aus
ubel et al. (1990), Deisotope experimental protocol
(1) DIG hybridization (Shujunsha)], these modification methods can be adopted in the present invention. In the case of immobilizing a bio-related substance on these fibers, various chemical or physical interactions between the fiber and the bio-related substance, that is, the functional group of the fiber and the bio-related substance are constituted. Chemical or physical interactions with the components can be utilized. Regarding hollow fibers, after introducing a liquid containing a bio-related substance into the hollow portion of the fibers forming the array, the functional group present on the inner wall surface of the hollow portion of the fiber and the component forming the bio-related substance Bio-related substances can be introduced into these fibers by utilizing the interaction between them.

When the unmodified nucleic acid is immobilized on the fiber, the nucleic acid and the fiber are allowed to act on each other, and then they can be immobilized by baking or irradiation with ultraviolet rays. When immobilizing nucleic acid modified with an amino group on the fiber, a functional group of the fiber is used by using a cross-linking agent such as glutaraldehyde or 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide (EDC). Can be combined with. Further, when the immobilized bio-related substance is denatured by, for example, heat treatment, alkali treatment, or surfactant treatment, or when the bio-related substance obtained from a biomaterial such as cells or cells is used. Can also perform processing such as removing unnecessary cell components. Note that these processes may be performed separately or simultaneously. Further, it may be appropriately carried out before immobilizing the sample containing the bio-related substance on the fiber.

When hollow fibers are used in the present invention, as shown in FIG. 4, a fiber array 41 fixed with a resin is used.
And a fiber portion 42 that is not fixed with a resin are provided, and the tip portion of this fiber portion 42 is immersed in a container 43 containing a biological substance, so that the liquid can be introduced into the hollow portion of each fiber. That is, the fiber portion 42 not fixed with resin
Since it extends from the fiber array 41 fixed with resin,
After immersing the fiber portion 42 in a container 43 containing a biological substance, the side opposite to the immersed portion (fiber side fixed with resin)
When sucked from, the biomaterial is sucked up into the hollow portion of the fiber in the fiber array 41, and the biomaterial can be introduced.

The above is an example of a method of fixing a bio-related substance to each fiber after forming the fiber array, and after fixing the bio-related substance to each fiber, the fibers are converged to form an array. May be.

The types of bio-related substances immobilized on the fibers in the fiber array can be different from each other.

Next, by cutting the above-mentioned fiber bundle-fixed product in a direction intersecting the longitudinal direction of the fibers, preferably in a vertical direction, a sheet having a fiber cross-section array body on which a biological substance is fixed (see FIG. 5) is obtained. Obtainable. A microtome, a laser, etc. can be used as a cutting means. The thickness of the sheet is 5 mm or less, preferably 0.1 mm to 1 mm.

When the biological substance is, for example, a nucleic acid,
By reacting the above sheet with a sample and performing hybridization, a specific polynucleotide present in the sample can be detected using the nucleic acid as a probe.

[0045]

EXAMPLES The present invention will be specifically described by the following examples.

<Example 1> As a jig, 35 mm x 35
φ0.1 mm at the center of a SUS304 plate having a thickness of 0.1 mm and a thickness of 0.1 mm.
32 rows of through-holes, 0.42 mm pitch, 10 rows x 10
Two perforated plates provided with 100 rows were overlapped, and one hollow fiber was passed through all 100 holes. The through hole is tapered (φ0.32mm → φ0.34mm).

The hollow fiber is made of PMMA (made by Mitsubishi Rayon Co., average outer diameter 0.300 mm, outer diameter variation range ±).
0.015 mm, inner diameter 0.2 mm, length 500 mm) was used. Then, with the hollow fiber passed through, the distance between the two porous plates was expanded to 50 mm, and both ends of the hollow fiber were lightly pulled to remove looseness. Between the perforated plates, Coronate 4401 and Nipporan 422, which are two-component mixed polyurethane resin
1 (all manufactured by Nippon Polyurethane Industry Co., Ltd.)
Filled with the mixture of 1. It was cured at room temperature for 24 hours to obtain a hollow fiber array having both ends which were not fixed with a resin. Then, the hollow fiber array was subjected to a microtome (microflake cutting device for microscope: POLYCUT-S (R
Eichert-Jung) was used, and the cutting was repeated by crossing the hollow fibers perpendicularly to the longitudinal direction. As a result of cutting, a slice piece having a thickness of 0.5 mm was obtained.

The center of gravity of the hollow fiber cross section exposed on the surface was measured for all 100 fibers using a contour projector V-12 (manufactured by Nikon). Then, when the distance between the positions of the centers of gravity of the hollow fiber cross sections adjacent to each other vertically and horizontally was calculated, the average value was 0.417 mm, the maximum value was 0.429 mm, and the minimum value was 0.401 mm. Therefore, the variation rate was 6.6%. The standard deviation value was 0.006 mm and the CV value was 1.3%.

Comparative Example 1 An example except that polyethylene hollow fiber MHF200TL (manufactured by Mitsubishi Rayon Co., average outer diameter 0.29 mm (± 0.03 mm), inner diameter 0.2 mm, length 500 mm) was used as the fiber. The same operation as in 1 was performed to obtain sliced pieces. Further, the distance between the positions of the centers of gravity of the hollow fiber cross-sections exposed on the surface of 180 points was calculated by the same method as in Example 1. As a result, the average value is 0.4
13 mm, maximum value is 0.508 mm, minimum value is 0.31
It was 5 mm, and the variation rate was 46.9%. The standard deviation value was 0.028 mm and the CV value was 6.8%.

[0050]

INDUSTRIAL APPLICABILITY The present invention makes it possible to extremely efficiently manufacture a fiber array consisting of a fiber bundle in which each fiber is arranged in high density and orderly by introducing a high precision fiber array technology using a jig. And By applying this method to the production of an array of fibers on which a biological substance such as a nucleic acid, a protein or a polysaccharide is immobilized, a thin piece having a cut surface intersecting the fiber axis can be obtained from the array. By using this thin piece, that is, the bio-related substance-immobilized fiber cross-section array sheet, the type and amount of a specific bio-related substance in a sample can be detected.

As an advantage and utility of the present invention compared with the conventional method, for example, a jig for assisting fiber arrangement without performing the bio-related substance alignment process and the immobilization process on the same two-dimensional carrier. A fiber array body in which bio-related substances are arranged in an orderly manner is obtained by using, and the bio-related substance-immobilized fiber cross-section array sheet is obtained by subjecting the array to a cutting and thinning process that is not available in the conventional method. It is possible to manufacture the above-mentioned product, and it is possible to dispense with the error-prone microdispensing operation as in the conventional spotting method, and to enable mass production through continuous thinning.

[0052]

[Brief description of drawings]

FIG. 1 is a schematic diagram showing the maximum value and the minimum value of the distance between fiber cross-section centers that are vertically and horizontally adjacent to each other.

FIG. 2 is an example of a jig used in the present invention.

FIG. 3 is a sectional view of a hole portion of a jig having a tapered hole.

FIG. 4 is a schematic diagram of a process of introducing a biopolymer into the hollow fiber array.

FIG. 5 is a thin piece obtained by slicing a hollow fiber array in a direction perpendicular to the fiber axis.

[0053]

[Explanation of symbols]

11 ... Minimum value of fiber cross-section center distance in FIG. 1 ... Maximum value of fiber cross-section center distance 13 in FIG. 1 ... Target fiber cross-section center distance 21 ... fiber 22 ... jig 31 ... fiber 32 ... jig 41 ... resin-fixed hollow fiber array 42 ... Hollow fiber part 43 not fixed with resin: container 44 containing a biomaterial, continuous surface 51: fiber cross section 52: fiber cross section array sheet

   ─────────────────────────────────────────────────── ─── Continued front page    (72) Inventor Chiho Ito             3-10-1, Daikokucho, Tsurumi-ku, Yokohama-shi, Kanagawa             Ryo Rayon Co., Ltd., Chemical Products Development Laboratory (72) Inventor, Teruta Ishimaru             3-10-1, Daikokucho, Tsurumi-ku, Yokohama-shi, Kanagawa             Ryo Rayon Co., Ltd., Chemical Products Development Laboratory (72) Inventor Yoko Miyauchi             3-10-1, Daikokucho, Tsurumi-ku, Yokohama-shi, Kanagawa             Ryo Rayon Co., Ltd., Chemical Products Development Laboratory F-term (reference) 4B024 AA19 CA01 CA11 HA12                 4B029 AA07 AA23 BB15 BB20 CC03

Claims (8)

[Claims] 1. A fiber fragment array sheet obtained by cutting a fiber bundle-fixed article, in which a plurality of fibers are bundle-fixed, in a direction crossing the longitudinal direction of the fibers, wherein the fibers have an average diameter of 1 mm or less, Of 100 / cm ² or more, the fibers are regularly arranged in the longitudinal and lateral directions at the center-to-center distance P of the fibers, and the fluctuation rate of the center-to-center distance of the fiber fragments adjacent to each other in the vertical and horizontal directions is 25% or less. And a fiber fragment array sheet. Variability = (X / P) × 100, where X = (maximum distance between centers of adjacent fiber cross sections in the vertical and horizontal directions) − (minimum distance between centers of adjacent fiber cross sections in the vertical and horizontal directions) 2. A fiber fragment array sheet obtained by repeatedly cutting a fiber bundle-fixed article having a plurality of fibers bundled and fixed in a direction crossing a longitudinal direction of the fibers, wherein the fibers have an average diameter of 1 mm or less. Yes, the arrangement density of the fiber cross section is 100 pieces / cm ² or more, and is regularly arranged,
A value obtained by dividing the standard deviation value of the distances between the fiber cross-section centers vertically and horizontally by the average value of the distances between the fiber cross-section centers vertically and horizontally (C
V value) is 3% or less, a fiber cross-section array sheet. 3. The sheet according to claim 1, wherein the fiber is a hollow fiber. 4. The sheet according to claim 4, wherein a bio-related substance is immobilized on the fiber. 5. A method for manufacturing a fiber cross-section array sheet, which comprises the following steps. (1) Forming a fiber-immobilized material having a diameter fluctuation rate of 5% or less, (2) Immobilizing a biological substance on the fiber, (3) Crossing the fiber-immobilized material in the longitudinal direction of the fiber The process of cutting into thin pieces by cutting in the direction. 6. A method for producing a fiber cross-section array sheet, which comprises the following steps. (1) A step of fixing a bio-related substance to a fiber having a diameter fluctuation rate of 5% or less, (2) A step of forming a fiber-immobilized fixture, (3) A fiber-immobilized fixture is crossed in the longitudinal direction of the fiber. The process of cutting into thin pieces by cutting in the direction. 7. A method for producing a sheet, comprising using two or more perforated plates in the step of forming the fiber bundle-immobilized article according to claim 5. 8. The method for producing a sheet according to claim 7, wherein at least one hole of the perforated plate has a tapered shape.