JP2006218611A - Plastic product having minute flow passage - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a plastic product having a flow passage excellent in transparent characteristics, especially a plastic micro analyzing chip having excellent transparent characteristics in the flow passage part and thereby excellent in accuracy and sensitivity in optical analysis, a micro reactor chip, or a bio chip. <P>SOLUTION: In the plastic product constituted by plastic, this invention is the plastic product having the minute flow passage having a width of 1mm or less and a depth of 1mm or less in the inside or on the surface and transmittance of light of 70% or more in the minute flow passage part, especially the plastic micro analyzing chip, the micro reactor chip, or the bio chip. <P>COPYRIGHT: (C)2006,JPO&NCIPI

Description

  The present invention relates to a plastic product having a fine channel, particularly to a plastic micro-analysis chip or microreactor chip with good analysis accuracy, and further to a plastic biochip.

  In recent years, biochips, which are devices in which a physiologically active substance is immobilized on a solid substrate, have attracted attention as means for achieving high throughput in drug discovery research and clinical tests. Typical examples of the physiologically active substance to be immobilized include nucleic acids, proteins, antibodies, sugar chains, glycoproteins, aptamers, etc. Nucleic acid microarrays, which are biochips on which nucleic acids are immobilized, are already available in many products. It is on the market. The form of the chip is a form in which various physiologically active substances are spotted and immobilized on a flat substrate, and are mainly used for research analysis in research institutions.

  In recent years, research on miniaturization of chemical reaction, separation, and analysis system using microfabrication technology called micro analysis chip, μTAS (micro total analytical system), or lab-on-chip has become active. Various chemical reactions, particularly physiological reactions, can be performed on the (fine channel). In this system, since a very small amount of sample can be analyzed quickly, it is expected to be commercialized as a next-generation biochip that takes advantage of this feature, particularly as a diagnostic biochip in a medical institution ( Hereinafter, these systems are referred to as micro-analysis chips). The microreactor chip, which also has a microchannel, is different from the microanalysis chip and is not intended for analysis but for the purpose of producing substances.

  Currently, the micro analysis chip and the microreactor chip are mainly made of glass, silicon or stainless steel. For example, when making a micro analysis chip with a glass substrate, the glass substrate surface is coated with chromium and a photoresist resin, and after exposing the resist to burn the microchannel pattern, the resist is developed and further with hydrofluoric acid. There is a method of performing an etching process. A considerable amount of work is required for processing. The same applies to silicon and stainless steel, which are not suitable for mass production. Therefore, attention has been focused on plastics that can be produced at low cost by molding and cutting.

  Plastic biochips and microanalysis chips can be manufactured by various molding methods such as injection molding and hot embossing using various plastics, and thus efficient and economical chip manufacturing is possible. Suitable for mass production. On the other hand, however, the molding process is not suitable for small-scale production, and when plastic products are manufactured in a small quantity and in a large variety, cutting rather than molding is preferably used. By these processes, it is possible to produce a plastic microanalysis chip or microreactor chip with relatively good performance. However, there are still problems with plastic chips and their practical application is insufficient. There are various problems, but one example is lack of transparency. In order to detect a chemical substance to be analyzed or produced, usually an optical detection device, for example, confirmation of fluorescence intensity, detection by a thermal lens microscope, detection by IR spectrum or UV spectrum, etc. is suitably performed. In many cases, light is incident on the chip and the intensity of light is confirmed from the opposite surface or the incident surface. Therefore, regardless of whether it is made of plastic or non-plastic, the micro analysis chip and the microreactor chip, particularly the micro analysis chip, are required to have high transparency (Patent Document 1).

  However, until now, since it was mainly made of glass with high transparency, the numerical value of transparency was not particularly limited. However, in the case of a plastic microanalysis chip, the transparency of the plastic itself tends to be inferior to that of glass, and depending on the processing method of the fine channel, the transparency of the fine channel part, that is, the light transmittance may be significantly inferior. Yes, the detection sensitivity of chemical substances to be analyzed or produced tends to decrease significantly. Therefore, it was judged that it was extremely important to limit the transparency of the microchannels numerically for these microanalysis chips and microreactor chips.

Patent Publication 2004-340752

  It is an object of the present invention to provide a plastic product having a channel with good transparency, particularly a plastic micro-analysis chip and a microreactor chip with good optical analysis accuracy and sensitivity because the channel portion has good transparency. And even provide a biochip.

  As a result of intensive studies to achieve the above-mentioned problems, the present inventors have found that in a plastic product having a fine channel, particularly a plastic microanalysis chip and a microreactor chip, the light transmittance in the fine channel is an important factor. And found out that the present invention.

That is, the present invention
(1) A plastic product made of plastic has a fine flow channel having a width of 1 mm or less and a depth of 1 mm or less inside or on the surface, and the light transmittance of the fine flow channel part is 70% or more. Plastic products, characterized by
(2) The plastic product according to (1) 1, wherein a surface roughness (Ra) of the fine channel portion is 0.2 μm or less,
(3) The plastic product according to (1) or (2), wherein the transmittance of light under the crossed Nicols of the polarizing microscope in the fine channel portion is 30% or less,
(4) The plastic product according to any one of (1) to (3), wherein the formation of the fine flow path is by cutting, hot embossing, or injection molding.
(5) A microreactor chip composed of the plastic product according to any one of (1) to (4),
(6) A biochip or a micro analysis chip composed of the plastic product according to any one of (1) to (4),
(7) The plastic biochip according to (6), which is at least one selected from a nucleic acid chip, a protein chip, an antibody chip, an aptamer chip, and a glycoprotein chip,
It is.

  In plastic products with fine flow paths, especially plastic microanalysis chips and microreactor chips, by limiting the light transmittance of the fine flow path parts, chips with good performance for various optical detections Can be obtained.

Hereinafter, embodiments of the present invention will be described in detail.
The present invention relates to a plastic product having a fine flow path, and particularly to a plastic microanalysis chip and a microreactor chip. As their definition, micro-channel processing is performed on the premise that liquid, gas, supercritical fluid, and mixtures thereof, or a mixture of them and solid components flow on the surface or inside of plastic. Show things. The fine flow path in the present invention refers to a groove having a width of 1 mm or less and a depth of 1 mm or less. The cross-sectional shape of the groove (flow path) is not particularly limited, and there is no problem even if it is rectangular, trapezoidal, triangular, semicircular, or a composite shape thereof. However, a shape having a bottom surface parallel to the plastic surface, such as a rectangle or a trapezoid, is most preferably used, and it is determined that it is also suitable for optical measurement. There are no particular restrictions on the overall shape and shape of the fine channel, for example, whether it is linear, Y-shaped or bent, or the length of the entire channel, and it is free according to the purpose. There are no restrictions on the use of various forms. The overall shape of the plastic product may be any shape such as a plate shape, a cube shape, a rectangular parallelepiped shape, a spherical shape, or any other shape without any problem, but the plate shape is preferably used because it is the easiest to use.

  Examples of the plastic used in the present invention include high-density polyethylene, low-density polyethylene, polypropylene, polystyrene, various cyclic polyolefins, polymethyl methacrylate, polynorbornene, polyphenylene oxide, polycarbonate, polyamide, polyester, polytetrafluoroethylene, and various silicones. Resin, semi-cured or fully cured phenolic resin, semi-cured or fully cured epoxy resin, and other various thermoplastic or thermosetting plastics in general. It does not specifically limit regarding physical properties, such as a kind of plastic, a polymerization degree, melting | fusing point, Tg, an elasticity modulus, and gas barrier property. Furthermore, there is no problem with a composite of a plurality of plastics. Further, there is no problem even if a metal, metal oxide, various inorganic substances, physiologically active substances, and various oily substances are mixed / applied / adhered / embedded on the surface or inside of the plastic. Regarding the light transmittance, it is preferable to select a plastic material having a high transmittance. However, the light transmittance limitation in the present invention is not a limitation regarding the plastic material, but the light transmittance in the fine channel portion of the plastic product. Therefore, it can be said that there is no restriction on the light transmittance of the plastic material used.

  The processing method of the fine flow path used in the present invention is not particularly limited, but it is desirable that the processing is performed by cutting processing at the time of small-scale production, injection molding at the time of mass production, hot emboss molding, RIM molding, transfer molding, or the like. . In particular, cutting by various end mills, injection molding, or hot embossing is most preferably used.

As an important technical element in the present invention, in a plastic product having a fine channel, the light transmittance of the fine channel part is 70% or more. In the micro analysis chip and the microreactor chip, when measuring the liquid flowing in the fine flow path, since the measurement is performed exclusively by the optical method as described above, the light transmittance in the portion becomes extremely important. It is. As a method for measuring the light transmittance, when the amount of light incident on the plastic product is A and the amount of light transmitted through the fine channel portion in the plastic product is B, the light transmittance T1 in the fine channel portion. (%) Is represented by the following formula (1).
T1 (%) = B / A × 100 Formula (1)
The measuring method of the light quantity A and the light quantity B is not particularly limited, but it is desirable to measure the light quantity by image analysis of a transmission type optical microscope. The light used for measuring the light transmittance T1 (%) of the flow path portion is most preferably light having the same wavelength as the light used for measuring internal information in the micro analysis chip or microreactor chip. There is no problem to measure using visible light. When the light transmittance in the fine channel portion is less than 70%, the sensitivity of optical measurement from the outside of the plastic product, especially the plastic microanalysis chip or microreactor chip is reduced, and the microchip The performance of will deteriorate. The measurement of transmitted light in the fine channel section is performed in a state where water, various organic solvents, various gases, a mixed fluid thereof, a mixture of them and a solid component, etc. are not flowing in the channel, that is, air is present in the channel. It is assumed that the measurement is in the state where it is in. In the fine flow path in the plastic product of the present invention, it is not necessary that all the transmittances are 70% or more throughout the entire flow path, and the transmittance of only a part, for example, a portion where optical measurement is performed is 70% or more. If so, no problem.

  In the present invention, it is desirable that the surface roughness (Ra) in the fine channel portion is 0.2 μm or less. This is because if the surface roughness of the flow path is rough, light scattering tends to occur, and as a result, the light transmittance in the flow path tends to decrease. Measurement of the surface roughness of the flow path is not particularly limited, but measurement with a contact-type surface roughness meter, a laser-type non-contact type surface roughness meter, an ultra-deep microscope, or the like is desirable. When the surface roughness Ra exceeds 0.2 μm, measurement by light may be difficult.

In the present invention, it is desirable that the light transmittance in the fine channel portion under the crossed Nicols of the polarizing microscope is 30% or less. In the micro analysis chip and the microreactor chip, when measuring the liquid flowing in the fine flow path, the measurement is performed exclusively by the optical method as described above. This is because it is greatly influenced by the light deflectability of the light. As a measuring method, in a polarizing microscope, the amount of transmitted light when the deflector and the plastic product are not inserted is C, the amount of transmitted light when the deflector in the direct Nicole state is inserted and the plastic product is not inserted is D, Then, when the amount of transmitted light when a deflector in a straight Nicole state is inserted and a plastic product is inserted to focus on the fine flow path portion is E, the light transmittance T2 when the polarization microscope is crossed Nicol (%) Is shown by Formula (2).
T2 (%) = (ED) / (CD) × 100 Formula (2)
Although there is no particular limitation on the measurement method of the light amounts C, D, and E, it is desirable to measure the light amount by image analysis with a polarizing microscope. The light used for measuring the light amounts C, D, and E is most preferably the same as the wavelength of light used for measuring internal information in the micro analysis chip or microreactor chip, but visible light is used. There is no problem to measure. When the light transmittance of the microchannel portion under the crossed Nicols of the polarizing microscope exceeds 30%, the analysis sensitivity of the plastic product, especially the plastic microanalysis chip or microreactor chip, is reduced. As a result, the performance deteriorates. The measurement of transmitted light in the fine channel section is performed in a state where water, various organic solvents, various gases, a mixed fluid thereof, a mixture of them and a solid component, etc. are not flowing in the channel, that is, air is present in the channel. It is assumed that the measurement is in the state where it is in. In the fine flow path in this plastic product, it is not necessary that all T2 is 30% or less throughout the entire flow path, and if T2 is 30% or less only in a small part, for example, a portion where optical measurement is performed, there is a problem. Absent.

  The plastic product in the present invention is not limited at all in terms of its intended use and usage. However, examples of suitable applications include microanalysis chips and microreactor chips, in particular, plastic biochips such as nucleic acid chips, protein chips, antibody chips, aptamer chips, and glycoprotein chips.

  EXAMPLES The present invention will be specifically described below with reference to examples, but the present invention is not limited to these examples.

Example 1
A 3 mm square, 1 mm thick cyclic polyolefin sheet was cut by a 0.2 mm diameter end mill, and a microchannel (width 0.2 mm, length 18 mm, depth 0.1 mm) as shown in FIG. ) Was processed. As processing conditions, the end mill rotational speed was 30,000 (rpm), the feed speed was 0.1 mm / second, the cutting depth pitch was cut every 50 μm, and the final flow path depth was 100 μm. The channel cross section is rectangular. Further, through holes (inner diameter 1 mm) as shown in FIG. 1 were provided by a 1 mmφ drill. This was covered with a 3 mm square and 1 mm thick cyclic polyolefin sheet (no flow path processing), and sealed by thermocompression to obtain a microanalysis chip.

(Example 2)
A microanalysis chip was obtained by processing under the same conditions as in Example 1 except that a sheet of polymethyl methacrylate having a size of 3 cm square and a thickness of 1 mm was used as a material for the flow path portion and the lid portion.

(Example 3)
A channel portion of FIG. 1 (width 0.2 mm, length 18 mm, depth) by hot embossing using a micro mold obtained by silicon wet etching on a 3 cm square polymethyl methacrylate sheet 1 mm thick 1 mm), and the through hole (inner diameter 1 mm) of FIG. 1 was provided by a 1 mmφ drill. The channel cross-sectional shape is a trapezoid. This was covered with a sheet of polymethylmethacrylate (3 cm square and 1 mm thick) (no flow path processing), and sealed by thermocompression to obtain a microanalysis chip.

(Comparative Example 1)
In Example 1, a microanalysis chip was obtained in exactly the same manner as in Example 1 except that the processing conditions of the flow path were 5000 rpm (end mill) and the feed rate was 0.5 mm / sec.

(Evaluation method 1) Measurement of light transmittance of flow path portion:
A transmission type optical microscope is used. A digital camera is connected to the eyepiece so that images can be stored. The light source was white light from a light bulb. First, a photograph of the transmitted light is taken without placing a sample of the microanalysis chip. Next, the sample of the microanalysis chip obtained in Examples 1 to 3 and Comparative Example 1 is set in a microscope, and a photograph is taken in a state where the channel portion is focused. Here, measurement is performed in a state where water or solvent does not flow through the microchannel and air is contained in the channel. The amount of light A was calculated by image analysis of a photograph taken without a sample. The amount of transmitted light B was calculated by image analysis of a photograph taken with the sample placed and focused on the flow path portion. Based on the result, the light transmittance T1 of the flow path surface was calculated and obtained according to Equation 3.
T1 (%) = B / A × 100 Formula (3)

(Evaluation Method 2) Measurement of Surface Roughness of Channel Portion The surface roughness of the microchannel obtained in Examples 1 to 3 and Comparative Example 1 was measured using a laser-type non-contact surface shape measuring instrument.

(Evaluation method 3) Measurement of deflection of flow path portion A polarizing microscope is used for measurement. A digital camera is connected to the eyepiece so that images can be stored. The light source was white light from a light bulb. First, a photograph of the transmitted light is taken with no sample of the microanalysis chip and no deflector inserted. Next, a deflector in a crossed Nicols state is inserted to take a picture. Furthermore, after setting the sample of the microanalysis chip obtained in Examples 1 to 3 and Comparative Example 1 in a microscope and selecting a sample arrangement that can obtain the brightest image by turning the sample, focus on the channel portion. Take a photo in contact. Here, measurement is performed in a state where water or solvent does not flow through the microchannel and air is contained in the channel. The amount of light C was calculated by image analysis of a photograph taken without a deflector and a sample. The light quantity D was calculated by image analysis of a photograph taken with a deflector inserted and no sample. The amount of transmitted light E was calculated by image analysis of a photograph taken with the deflector and sample inserted and focused on the flow path portion. Based on the result, the light transmittance T2 of the flow path surface was calculated according to Equation 4 and obtained.
T2 (%) = (ED) / (CD) × 100 Formula (4)

(Evaluation Method 4) Measurement of Flow Channel Part with Thermal Lens Microscope The micro flow channel part of the microanalysis chip obtained in Examples 1 to 3 and Comparative Example 1 is filled with water, and in this state, a thermal lens microscope is used. I tried to measure.

(Evaluation results)
Table 1 shows the result of light transmittance of the channel part, the measurement result of the surface roughness of the channel part, the measurement result of the deflection of the channel part, and the measurement result of the channel part by the thermal lens microscope. In the comparative example, the transparency of the flow path is poor and the light transmittance is low, and as a result, it is difficult to measure with a thermal lens microscope.

実施例１〜３、及び比較例１の評価結果

Evaluation results of Examples 1 to 3 and Comparative Example 1

It is the schematic diagram and the schematic diagram of a cross section which show the shape of the microanalysis chip | tip in an Example and a comparative example.

Explanation of symbols

DESCRIPTION OF SYMBOLS 1 Sheet | seat of cyclic polyolefin or polymethylmethacrylate 2 Micro flow path processed by cutting or hot embossing shaping | molding 3 Through-hole obtained by cutting

Claims (7)

A plastic product made of plastic has a fine flow path having a width of 1 mm or less and a depth of 1 mm or less inside or on the surface thereof, and the light transmittance of the fine flow path portion is 70% or more. Plastic products. The plastic product according to claim 1, wherein a surface roughness (Ra) of the fine channel portion is 0.2 μm or less. The plastic product according to claim 1 or 2, wherein a light transmittance under a crossed Nicol of a polarizing microscope in the fine channel portion is 30% or less. The plastic product according to any one of claims 1 to 3, wherein the fine channel is formed by cutting, hot embossing, or injection molding. The microreactor chip comprised from the plastic product in any one of Claims 1-4. A biochip or microanalysis chip comprising the plastic product according to claim 1. The plastic biochip according to claim 6, which is at least one selected from a nucleic acid chip, a protein chip, an antibody chip, an aptamer chip, and a glycoprotein chip.

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