JP3877296B2 - Microchip substrate - Google Patents

Description

[0001]
BACKGROUND OF THE INVENTION
The present invention relates to a microchip substrate. For example, the present invention relates to a microchip substrate which is a device in which nucleic acids, proteins, enzymes, other physiological substances, etc. are arranged and fixed on the surface of a solid phase substrate.
[0002]
[Prior art]
For analysis of DNA chips, a dedicated device called a scanner that applies the principle of confocal fluorescence microscopy is often used, but confocal microscopy detects signals within a few μm from the focal point, so accurate measurement over the entire surface of the substrate In order to perform this, it is necessary to maintain the flatness of the substrate surface on the order of several μm. However, as a general property of plastic, it is less rigid than glass and easily deforms by external force. Therefore, the surface of the substrate is distorted and warped by the force applied from the substrate fixing jig of the scanner. May occur.
For example, in a method of applying a force to the lower surface of the substrate with a plate spring and pressing and fixing it to a jig on the upper portion of the substrate, if the force of the plate spring is excessive, the plastic substrate is deformed. When the substrate is deformed, the entire measurement surface cannot be focused, and the signal amount varies depending on the position on the substrate, making it impossible to perform accurate evaluation.
[0003]
[Problems to be solved by the invention]
An object of the present invention is to provide a microchip substrate in which deformation of a sample fixing surface due to non-uniform force application from a substrate fixing jig of a measuring apparatus does not occur.
[0004]
[Means for Solving the Problems]
The present invention
(1) A microchip substrate , characterized in that means for limiting the contact surface with the substrate fixing jig of the measuring apparatus is provided on the back surface of the sample fixing surface, and the means for limiting the contact surface is the sample Providing a convex part on a part of the back surface of the fixing surface, the convex part is an outer edge part thicker than the thickness of the sample fixing surface, and the substrate material for the microchip is a saturated cyclic polyolefin;
It is.
[0005]
DETAILED DESCRIPTION OF THE INVENTION
The present invention will be described in more detail. When the evaluation is performed using a scanner whose detection system is confocal, if deformation such as distortion or warpage occurs on the sample fixing surface of the DNA chip substrate, it becomes difficult to focus and accurate data cannot be obtained. The cause of substrate deformation is often due to the force received from the substrate fixing jig in the scanner. In order to avoid deformation based on the force from the jig, (A) the rigidity of the substrate is increased, (B) the specimen fixing surface and the jig are not in direct contact, and the force is transmitted to the specimen fixing surface. A method such as minimization can be mentioned.
[0006]
Specific methods of (A) include increasing the thickness of the substrate and increasing the strength of the material itself by kneading the filler. However, increasing the thickness of the substrate may cause a serious adverse effect that makes it impossible to use conventional devices and instruments. Further, the method of kneading the filler has problems such as accelerated wear of the molding die and changes in surface treatment properties, which is not preferable in practice. On the other hand, the above problem does not occur in the method (B). That is, since the thickness of the entire substrate is the same as that of the conventional product, it is not necessary to switch between devices and instruments, and the substrate material itself does not change, so that there is no problem in manufacturing.
[0007]
(Board shape)
The shape of the substrate fixing jig of the scanner varies depending on the model, but the most widely used method is to push up the lower surface of the substrate with a leaf spring and press the upper jig to fix it. In this method, when the force of pushing up the leaf spring is too large, the center portion of the substrate is pushed up, and the measurement surface may be distorted. Therefore, an area protruding from the sample fixing surface is provided on the outer edge of the substrate, and contact with the jig is limited to only the protruding portion, thereby eliminating uneven stress on the sample fixing surface and avoiding deformation. be able to. As the shape of the protruding portion, it is preferable to provide a frame-like region on the outer edge of the back surface of the sample fixing portion as shown in FIGS. 1 to 4 and to make the thickness of this portion thicker than the sample fixing surface. By increasing the thickness of the outer edge, the rigidity of this area increases and the majority of the force from the substrate fixing jig is borne, so stress applied to the sample fixing surface is reduced and deformation can be avoided. Become.
[0008]
Since the deformation due to the force from the substrate fixing jig is about 20 to 100 μm, the difference in thickness between the sample fixing portion and the outer edge portion is preferably 20 to 500 μm, more preferably 20 to 200 μm. Most preferably, it is 100 μm.
[0009]
Furthermore, by setting it as said shape, the effect which prevents a sample fixing surface from being damaged when handling a board | substrate is acquired. That is, in the case of a substrate having a flat entire surface, a fine scratch may be attached to the sample fixing surface or the back surface when the substrate is placed on a work table or the like, and may be detected as noise during measurement. Since this substrate is not in direct contact, the possibility of scratches is reduced, and high-accuracy measurement is possible.
[0010]
(Substrate material)
The plastic substrate having the above shape can be inexpensively and mass-produced by thermoforming. A thermoplastic resin or a thermosetting resin can be used as the synthetic resin used as the material of the substrate, but a thermoplastic resin is preferable from the viewpoint of manufacturing efficiency. As the low-fluorescence thermoplastic resin, it is preferable to use, for example, linear polyolefins such as polyethylene and polypropylene, cyclic polyolefins, fluorine-containing resins, and the like, and cyclic that is particularly excellent in heat resistance, chemical resistance, low fluorescence, and moldability. More preferably, polyolefin is used. Here, the cyclic polyolefin refers to a saturated polymer obtained by hydrogenating a polymer having a cyclic olefin structure or a copolymer of a cyclic olefin and an α-olefin.
[0011]
Examples of the former are produced by hydrogenating norbornene monomers represented by, for example, norbornene, dicyclopentadiene, and tetracyclododecene, and polymers obtained by ring-opening polymerization of these alkyl-substituted products. It is a saturated polymer.
[0012]
The latter copolymer is composed of α-olefin such as ethylene, propylene, isopropylene, 1-butene, 3-methyl-1-butene, 1-pentene, 3-methyl-1-pentene, 1-hexene and 1-octene. It is a saturated polymer produced by hydrogenating a random copolymer of cyclic olefin monomers. As the copolymer, a copolymer with ethylene is most preferable. These resins may be used alone, or two or more copolymers or a mixture may be used.
[0013]
【Example】
The present invention will be specifically described by the following examples.
Example 1
A substrate shown in FIG. 1 having a length of 76 mm, a width of 26 mm, a sample fixing portion thickness of 0.9 mm, and an outer edge portion thickness of 1 mm was injection molded using a norbornene-based polyolefin resin. The surface roughness of the molded product was 0.002 to 0.003 μm, and no distortion or warping was observed over the entire substrate. This substrate was scanned using a microarray scanner 'ScanArray LITE' manufactured by Packard BioChip Technologies. Scanning conditions were laser output 90% and PMT sensitivity 90%. As shown in the histogram of FIG. 5, the background fluorescence amount was less uneven, warped on the substrate surface, and was not deformed such as distortion.
[0014]
(Comparative Example 1)
A 76 × 26 × 1 mm slide glass substrate was injection molded using the same resin as in Example 1. The surface roughness of the molded product was 0.002 to 0.003 μm, and no distortion or warpage was observed over the entire substrate. As a result of scanning under the same conditions as in the examples, as shown in the histogram of FIG. This is because the substrate surface is deformed by the stress from the fixing jig.
[0015]
【The invention's effect】
According to the present invention, it is possible to produce a microchip substrate in which the sample fixing surface does not deform due to stress from the substrate fixing jig of the measuring apparatus. Although the deformation of the sample fixing surface hinders the focus adjustment of the detector and causes variations in signal amount, the present invention makes it possible to produce a substrate that can be accurately evaluated.
[Brief description of the drawings]
FIG. 1 is a conceptual diagram showing an example of a substrate shape of the present invention. FIG. 2 is a conceptual diagram showing another example of a substrate shape of the present invention. FIG. 4 is a conceptual diagram showing another embodiment of the substrate shape of the present invention. FIG. 5 is a histogram showing the distribution of background fluorescence in the examples and comparative examples.
[Explanation of symbols]
1: Back surface of sample fixing surface 2: Thick part

Claims (1)

A microchip substrate characterized in that means for limiting the contact surface with the substrate fixing jig of the measuring apparatus is provided on the back surface of the sample fixing surface, and the means for limiting the contact surface is provided on the sample fixing surface. A microchip substrate in which a convex portion is provided on a part of the back surface, the convex portion is an outer edge portion thicker than the thickness of the sample fixing surface, and the substrate material is a saturated cyclic polyolefin .

Images