JP2004226068A - Cartridge for biochip - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a cartridge for a biochip capable of performing pretreatment and cleaning in the cartridge, and detecting a hybridized biopolymer by using a general purpose reading device. <P>SOLUTION: This cartridge for the biochip for measuring the biopolymer is equipped with a cartridge base body formed from an elastic material. The cartridge base body has a pretreatment mechanism which is capable of performing pretreatment for changing a biosample into a measurable biopolymer, and a slide glass type biopolymer microarray mounted so that the treated biopolymer can be immobilized on the array part of the microarray. <P>COPYRIGHT: (C)2004,JPO&NCIPI

Description

[0001]
TECHNICAL FIELD OF THE INVENTION
The present invention relates to a biochip cartridge for testing biopolymers such as DNA and RNA (mRNA and cDNA) and proteins, and a biochip cartridge that can be combined with a general-purpose slide glass type DNA microarray. It is about.
[0002]
[Prior art]
Conventionally, an inspection method for inspecting a biopolymer such as DNA using a biochip is well known. FIG. 5 shows an example of a conventional biochip (see Patent Document 1). In this biochip, the biopolymer solution is injected into the collection section 43 in the sealed bag, and the solution is sent to the back by crushing the bag from the entrance. On the way, the pretreatment is carried out by mixing the pretreatment liquid extruded from the bags 48 and 49 in the pretreatment unit 44 into the solution.
[0003]
The pretreated solution is sent to the binding section 45, where hybridization with the biopolymer fixed on the substrate 46 is performed. The biopolymer in the bag after hybridization is read using a fluorescence reader.
[0004]
Such a biochip has the advantage that the pretreatment and the hybridization are performed in the bag, so that the danger of virus or the like leaking out during the processing can be prevented beforehand, but a general-purpose slide glass type DNA microarray is used. There is a problem that is not available.
[0005]
On the other hand, there is a cassette that can be hybridized using a general-purpose slide glass type DNA microarray (see Non-Patent Document 1).
[0006]
[Patent Document 1]
JP-A-2002-365299 (pages 3 to 5, FIG. 1)
[0007]
[Non-patent document 1]
Takara Hybridization Chamber, [online], [searched on December 18, 2002], Internet <URL:
http: // bio. Takara. co. jp / catalog / catalog_d. asp? C_ID = C1443>
[0008]
[Problems to be solved by the invention]
However, in such a cassette, although a general-purpose DNA microarray can be used, cDNA or labeling (for example, fluorescent labeling) is required in a laboratory or the like, and washing after hybridization is also required. There is a problem that requires a place and special skills.
On the other hand, the dedicated chip as shown in FIG. 5 requires a dedicated reader suitable for the chip, and there is a problem that a general-purpose reader cannot be used.
[0009]
An object of the present invention is to solve the above problems, and to provide a biochip cartridge that can perform pretreatment and washing in a cartridge and that can detect a hybridized biopolymer using a general-purpose reader. It is in.
[0010]
[Means for Solving the Problems]
In order to achieve such an object, the invention of claim 1
A biochip cartridge for measuring biopolymers,
A slide glass-type biopolymer microarray comprising a cartridge base formed of an elastic material, a pretreatment mechanism for performing pretreatment for converting a biological sample into a measurable biopolymer on the cartridge base. Is attached so that the biopolymer after the treatment can be immobilized on the array portion of the microarray.
[0011]
According to such a configuration, the biological sample can be pre-processed in the cartridge and immediately sent to the array portion of the general-purpose microarray to immobilize the biopolymer.
The biopolymer immobilized on the microarray can be easily measured using a general-purpose reader after removing the microarray from the cartridge.
[0012]
In this case, as the slide glass-type biopolymer microarray, one having a short side and a long side within 25 ± 1 mm and 75 ± 1 mm, respectively, is usually used.
[0013]
Further, the pretreatment mechanism includes a collection unit for storing a biological sample, a pretreatment liquid storage unit for storing a pretreatment liquid to be applied to the biological sample, and a biopolymer after the pretreatment. A washing solution storage unit for storing a washing solution for washing, a coupling unit for performing hybridization on the general-purpose microarray, a waste liquid storage unit for storing waste liquid, and a flow path connecting these components, and a coupling unit is connected from the collection unit side. It is configured such that the biological sample can be moved to the part side.
[0014]
The movement of the biological sample is realized by crushing the cartridge base from the collection unit side to the coupling unit side with a roller as described in claim 4.
[0015]
Also, the microarray is hermetically mounted at a position where the coupling portion and the array portion face each other. Thus, the sample solution is appropriately sent to the array portion of the microarray, and the hybridization can be reliably performed. Further, since the microarray is hermetically attached to the cartridge substrate, the sample solution does not flow out of the gap between the cartridge substrate and the microarray.
[0016]
Further, a cover formed of a hard material is joined to the cartridge base, a gap is provided between the cartridge base and the cover, and the general-purpose microarray is inserted into the gap. You can also. Also in this case, the same effect as in the case of the fifth aspect is exhibited.
[0017]
Further, the pre-processing mechanism may include a mechanism for extracting DNA or RNA as described in claim 7.
[0018]
BEST MODE FOR CARRYING OUT THE INVENTION
Hereinafter, the present invention will be described in detail with reference to the drawings. FIG. 1 is a configuration diagram showing one embodiment of a biochip cartridge according to the present invention. FIG. 1A is a plan view, and FIGS. 1B and 1C are side views.
[0019]
The biochip cartridge 100 includes a cartridge base 110 and a cover 120. According to the present invention, the pretreatment and the hybridization of the biological sample can be integrally performed with the general-purpose slide glass type biopolymer microarray 140 attached to the cartridge 100.
[0020]
The cartridge base 110 is formed of an elastic body such as rubber that is airtight and elastic, and has a pretreatment mechanism formed therein for performing pretreatment for a solution containing a biopolymer (also simply referred to as a biological sample). ing.
[0021]
The pretreatment mechanism includes an injection port 111 for injecting a biological sample, a collection unit 112 for storing the injected solution, and a pretreatment liquid storage unit for storing a pretreatment solution for labeling biopolymers and the like. 113, a coupling portion 115 for performing a hybridization process, a washing solution storage portion 114 for storing a washing solution for washing away (washing) an extra biological sample after hybridization, and collecting the washed extra biological sample (waste solution). It consists of a plurality of hollow chambers of a waste liquid storage section 116, an insertion hole 117 for inserting the slide 130, and a flow path 118 connecting these, and moves the biological sample from the collection section to the connection section. It has a function of performing pretreatment for converting a biological sample into a measurable biopolymer.
[0022]
A rubber-like stopper (not shown) is hermetically attached to the injection port 111, and a syringe needle is inserted into the stopper when the solution is injected. When the needle is pulled out, the needle hole of the stopper naturally closes.
[0023]
The cover 120 is formed of a hard material, and is hermetically joined to the back surface of the cartridge base 110 by a detachable adhesive or the like as shown in FIG. 1B.
A general-purpose slide glass-type biopolymer microarray (hereinafter, simply referred to as a slide) 130 has an array section 131 in which a plurality of biopolymers are fixed at the center. The array section 131 is located immediately below the connecting section 115 when the array section 131 is inserted into the insertion hole 117 of the cartridge base 110 or the cover 120 is once peeled off and mounted.
[0024]
The size of the general-purpose slide 130 is standardized: 26 × 76 (mm) in Japan, 1 × 3 (inch) in the United States, and 25 × 75 (mm) in Europe. The insertion hole of the cartridge base 110 is formed to have a size suitable for a slide to be used. In Japan, it is specified in Japanese Industrial Standard JIS R3703.
[0025]
As shown in FIG. 1C, a packing 140 made of an elastic material such as rubber is attached to the bottom surface of the cartridge base 110, and the surface of the slide 130 and the bottom surface of the cartridge base 110 are sealed and connected. The structure is such that external leakage of the solution in the portion 115 can be prevented.
[0026]
Next, a method of operating the biochip having such a configuration will be described. After attaching the slide 130 to the insertion hole 117 of the cartridge base 110, the solution is injected from the injection port 111, and the solution is stored in the collection unit 112.
It is assumed that a pretreatment liquid and a cleaning liquid are stored in the pretreatment liquid storage unit 113 and the cleaning liquid storage unit 114, respectively.
[0027]
After the solution accumulates in the collection unit 112, as shown in FIG. 1C, the roller 200 is pressed from above the cartridge base 110, and is rotated from the injection port 111 toward the coupling unit 115 (to the left). . The solution in the collecting section 112 is sent out to the connecting section 115 through the flow path 118.
[0028]
Next, when the pretreatment liquid storage unit 113 is crushed by the roller 200, the pretreatment liquid is sent out to the coupling unit 115 through the flow path 118 and mixed with the solution to perform labeling.
The labeled solution hybridizes with the biopolymer of the array section 131 of the slide 130.
[0029]
After the hybridization, the roller 200 is moved to crush the cleaning liquid storage unit 114 to send out the cleaning liquid to the coupling unit 115, and to wash (wash) the non-hybridized biopolymer together with the solution, and to discharge the waste liquid into the waste liquid storage unit 116. Send to
[0030]
After the washing, the slide 130 is removed from the cartridge base 110, and the array section 131 is measured with a general-purpose reader (not shown) to detect the hybridized biopolymer.
[0031]
According to such a biochip cartridge, pretreatment and washing of a biopolymer sample can be performed in the cartridge. For detection of a biopolymer on a slide after hybridization, a general-purpose reader can be used instead of a dedicated reader.
[0032]
The present invention is not limited to the above-described embodiment, but includes many more changes and modifications without departing from the essence thereof.
For example, the solution may be delivered by a method such as liquid expansion using a piezoelectric element or a heater instead of a roller as in the embodiment.
[0033]
The slide 130 may be entirely contained in the cartridge base 110 as shown in FIG. Alternatively, on the contrary, as shown in FIG. 3A, the whole cartridge base 110 may be placed on the slide 130. However, in this case, the cover 120 is not used, and the peripheral portion 150 of the cartridge base 110 is detachably adhered to the upper surface of the slide 130 with an adhesive as shown in FIGS. 3B and 3C.
[0034]
In addition, the cartridge base 110 is provided with not only the coupling part 115 for hybridization but also an extraction part 119 for extracting DNA and RNA such as blood as shown in FIG. You may make it detectable.
The labeling may be not only a fluorescent label but also an attachment of a light absorbing dye or a luminescent dye.
[0035]
Further, as shown in FIG. 5, a pre-processing unit may be provided at a stage preceding the coupling unit, and the pre-processing unit may mix a pre-treatment liquid into a biological sample to perform labeling of a biopolymer. .
【The invention's effect】
As described above, the present invention has the following effects.
(1) The biopolymer can be subjected to pretreatment such as labeling in the cartridge. In this case, since the processing is performed in a sealed cartridge, there is no danger that a virus or the like leaks outside during the processing.
[0036]
(2) A general-purpose slide can be used for the cartridge, and the biopolymer immobilized (for example, hybridized) in the array portion of the slide can be used as a general-purpose reader without requiring a dedicated reader. Can be easily measured.
[Brief description of the drawings]
FIG. 1 is a configuration diagram showing one embodiment of a biochip chip cartridge according to the present invention.
FIG. 2 is a diagram showing another embodiment of the present invention.
FIG. 3 is a diagram showing still another embodiment of the present invention.
FIG. 4 is a diagram showing still another embodiment of the present invention.
FIG. 5 is a configuration diagram showing an example of a conventional biochip.
[Explanation of symbols]
100 Biochip cartridge 111 Injection port 112 Sampling unit 113 Pretreatment liquid storage unit 114 Washing liquid storage unit 115 Joining unit 116 Waste liquid storage unit 117 Slide insertion hole 118 Channel 119 Extraction unit 120 Cover 130 Slide 131 Array unit 140 Packing 150 Peripheral part 200 rollers

Claims (7)

A biochip cartridge for measuring biopolymers,
A slide glass-type biopolymer microarray comprising a cartridge base formed of an elastic material, a pretreatment mechanism for performing pretreatment for converting a biological sample into a measurable biopolymer on the cartridge base. Wherein the biopolymer after the treatment is immobilized on the array portion of the microarray. 2. The biochip cartridge according to claim 1, wherein the slide glass-type biopolymer microarray has a short side and a long side within 25 ± 1 mm and 75 ± 1 mm, respectively. The pretreatment mechanism includes a collection unit that stores a biological sample, a pretreatment solution storage unit that stores a pretreatment solution to be applied to the biological sample, and a cleaning solution that stores a cleaning solution that cleans the pretreated biopolymer. A storage unit, a coupling unit for performing hybridization on the general-purpose microarray, a waste liquid storage unit that stores waste liquid, and a flow path that connects these units,
The biochip cartridge according to claim 1, wherein the biological sample is configured to be able to move a biological sample from the collection unit side to the coupling unit side. 4. The method according to claim 1, wherein the movement of the biological sample is performed by squeezing the cartridge base from the sampling unit side to the coupling unit side with a rigid roller. The biochip cartridge according to any one of the above. 5. The method according to claim 1, wherein when a general-purpose microarray is mounted on the cartridge base, the microarray array portion is hermetically mounted so as to face the coupling portion. Biochip cartridge. A cover made of a hard material is joined to the cartridge base, a gap is provided between the cartridge base and the cover, and when the general-purpose microarray is inserted into the gap, the array part of the microarray faces the coupling part. The biochip cartridge according to any one of claims 1 to 5, wherein the cartridge is formed so as to be hermetically mounted. The biochip cartridge according to any one of claims 1 to 6, wherein the pretreatment mechanism includes a mechanism for extracting DNA or RNA.

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