JP3667216B2 - Synthetic DNA set generation system and control method thereof - Google Patents

Description

[0001]
BACKGROUND OF THE INVENTION
  The present invention generates a synthetic DNA set using a network.systemAnd a control method thereof.
[0002]
[Prior art]
With the development of a DNA synthesizer, DNA can be synthesized relatively easily, and it becomes possible to synthesize DNA having an arbitrary sequence. However, in order to synthesize DNA having various sequences, various synthesis reagents are required.
[0003]
Although these reagents are expensive, in order to synthesize DNA having various sequences, it is necessary to use a variety of different reagents in small quantities. Therefore, it may be possible to synthesize DNA cheaper if you purchase a reagent for DNA synthesis and order the necessary DNA from a specialized company that manufactures and sells DNA rather than chemically synthesizing the required amount of DNA yourself. is there.
[0004]
In recent years, with the movement of worldwide projects to decode the entire human gene sequence, the DNA array method has attracted attention, and various methods have been developed as its production method.
[0005]
The DNA array is used to determine the base sequence of nucleic acids, to detect target nucleic acids in samples, and to identify various bacteria quickly and accurately on the same glass substrate. Developed for the purpose of determination, a variety of DNA probes are bonded at high density on the glass substrate of the DNA array. This DNA probe is a substance that specifically binds to a target nucleic acid, and the base sequence of the gene is identified by DNA hybridization using this DNA array.
[0006]
There are roughly two types of DNA array manufacturing methods.
[0007]
In the first production method, DNA is synthesized on a glass substrate. First, Southern et al. Developed a method for producing probes having different sequences by one base at a time on the same glass substrate (Nucleic Acids Research, Vol. 22). 1368 (1994)). Next, Affymetrix applied a photolithographic method to synthesize nucleotides of 15 bases by repeating the reaction of linking nucleotides on a glass substrate, and 400,000 DNA probes on a 1/2 inch square substrate. (Science, 274, 610 (1996)).
[0008]
The second production method is a method of preparing a DNA array by supplying pre-synthesized DNA as a spot (one drop) on a glass substrate and fixing it. As an example of this method, there is a method of arranging relatively long cDNAs in an array by micropipetting (Science, 270, p467 (1995)), and a method using a synthetic oligonucleotide as a probe ( JP-A-11-187900) is also attracting attention as a simple method.
[0009]
When DNA is prepared using an automatic DNA synthesizer, in the case of DNA synthesis reaction using nucleotides, the unreacted product always remains because the synthesis reaction does not proceed with 100% efficiency. Therefore, in the DNA after the synthesis reaction, there is a DNA shorter than the desired length of DNA. This means that in the case of the first production method in which separation of unreacted substances is difficult because DNA is synthesized on a glass substrate, the probe concentration on the DNA array has non-uniformity and affects quantitativeness. means.
[0010]
However, in the case of the second production method in which DNA is immobilized on glass after pre-synthesis with an automatic synthesizer, it is possible to purify the unreacted material after synthesizing the DNA. The probes having the same concentration can be placed on the DNA array.
[0011]
For this reason, the accuracy of the hybridization reaction of the DNA array produced by the second production method is improved as compared with the DNA array produced by the first production method. Examples of a method for supplying a chemically synthesized DNA probe to a DNA array include a micro spotting method using a pin or the like, an ink jet method, and the like.
[0012]
In addition, the second production method of immobilizing DNA on a glass substrate after DNA synthesis is flexible in that a probe having an arbitrary base sequence can be arranged at an arbitrary position on the DNA array, and a photolithography method is also available. The number of manufacturing steps is smaller than that of the method, which is simple and the manufacturing cost can be kept low. However, when DNA is actually immobilized by the above-described immobilization method, it is necessary to purchase many kinds of expensive synthetic raw materials in order to synthesize DNA, and the synthesis cost increases, and further, from synthesis to purification of DNA. The problem is that it takes a considerable amount of work time.
[0013]
The inventor has paid attention to the fact that the amount of DNA necessary for DNA array production is enormous, but the amount of each DNA used is insignificant. For example, in the DNA array preparation method by the inkjet method developed by the inventor (Japanese Patent Laid-Open No. 11-187900), the amount of liquid required to constitute one spot is on the order of picoliter (pl) (1 pl is 10^-12l). For example, even if 1 million DNA solutions of 8 μM concentration are prepared in 50 pl, the amount of probe DNA required is only 50 μl (40 pmol) for each sequence.
[0014]
Even in the case of a DNA array production method by a microspotting method using pins or the like, the amount of DNA used is a nanoliter order droplet, so if there is 10 microliters of DNA, 10,000 arrays are produced. It will be.
[0015]
However, in order to synthesize DNA necessary for the above-mentioned use, it is necessary to synthesize DNA at least 100 times the amount used. Further, the synthesized DNA needs to be purified, and it is necessary to analyze the synthesized DNA by high performance liquid chromatography in order to confirm that the synthesized DNA is purified as prescribed.
[0016]
Therefore, the amount of purified DNA that can be detected by high performance liquid chromatography is the minimum necessary unit of DNA, and the concentration that can be quantified by absorption or the like is the minimum unit that can be handled. In other words, the amount of DNA required for DNA array production is not the amount of DNA used by the above-mentioned micro spotting method, but the amount necessary for analysis to confirm that the synthesized DNA is purified as prescribed. For this reason, much more DNA must be synthesized than the amount used.
[0017]
On the other hand, as a method for producing a DNA array in which a DNA probe is fixed on a glass substrate, Japanese Patent Application Laid-Open No. 11-187900 discloses a method using a maleimide group on a substrate and a thiol group at a DNA terminal. The reaction using these functional groups is known as a method suitable for the ink jet method because of extremely short reaction time and good reaction efficiency. In addition, as a composition of a DNA solution suitable for the reaction, there is a disclosure of a solution containing glycerin 7.5%, urea-7.5%, thiodiglycol 7, 5%, and acetylenol EHl%.
[0018]
Furthermore, the base sequence of a DNA array used for gene diagnosis can be any set of genes such as oncogenes. Recently, the base sequence of a major histocompatibility complex (MHC) has been revealed. (Nature vol 401, p921-923, 1999).
[0019]
This sequence is a region in which the genes of the immune system are most concentrated in the human genome, and can be used to determine a constitution or allergic constitution that is likely to cause illness.
[0020]
[Problems to be solved by the invention]
Various experiments using DNA, not limited to DNA arrays, have a tendency to further reduce the amount of DNA necessary for the experiments because the experimental scale is becoming smaller year by year. However, although the amount of DNA required for each experiment is decreasing, it is necessary to synthesize a large amount of DNA as described above in order to obtain high-purity DNA with a high synthesis yield. In the present situation, the cost of purchasing reagents as raw materials cannot be reduced, and experiments using DNA require wasteful costs and synthesis time for synthesizing extra DNA.
[0021]
Moreover, since various experiments using DNA tend to increase in the future, individual researchers all over the world who want to conduct research using DNA of the same sequence synthesize a large amount of DNA of the same sequence that is required. Currently, most of the DNA that was not used in the experiment was disposed of.
[0022]
One way to solve this problem is to reduce the amount of DNA synthesized. To this end, individual researchers can reduce the amount of DNA synthesized in accordance with the experimental scale in which DNA is used. As described above (for example, a very large amount of DNA compared to the amount of DNA actually used is synthesized to confirm the purity of the synthesized DNA).
[0023]
On the other hand, in general, chemical synthesis is performed on a large scale, and the yield of synthesis is high and loss due to purification is reduced. Therefore, it is better to synthesize DNA together than to synthesize the DNA required by each researcher. The synthesis yield is good, the loss due to purification is reduced, and the production cost can be reduced.
[0024]
  The present invention has been made in order to solve the above-mentioned problems, and its purpose is to provide each researcher who needs it with the necessary types and amounts quickly and inexpensively. Synthetic DNA set generation forsystemAnd a control method thereof.
[0025]
[Means for Solving the Problems]
  Synthetic DNA set generation that is one embodiment of the present invention to achieve the above objectsystemHas the following configuration. That is, from the orderer side device via the networkOrder dataReceiveServer device to be held in advanceSynthetic DNA selected from multiple types of synthetic DNAA DNA injection apparatus for producing a synthetic DNA set by injecting a plurality of wells into a well of a container partitioned into a plurality of wells, managing the types and storage addresses of the plurality of types of synthetic DNA, and receiving the order data received by the server apparatus A DNA injection control device for controlling the DNA injection device so as to produce synthetic DNA under the conditions in accordance withSynthetic DNA set generationsystemBecauseThe server deviceIn the orderer side device,For instructing the orderer of the number of types of the base sequence of the synthetic DNA set, the type of end modification of the synthetic DNA set, the amount of DNA, and the well in which the synthetic DNA is arranged among the plurality of wellsInterfaceSendDoAnd means for receiving the selection instruction data input via the interface in the orderer side device as the order data and storing and storing it in a storage unit, wherein the DNA injection device is stored in the server device The selection instruction data stored in the storage unit is received via the DNA injection control device, and the selection instruction dataBased onBeforeSelect at least one of the multiple types of synthetic DNAAs well as, Each of the selected synthetic DNAs,Specified by the selection instruction data among the plurality of wellsThe synthetic DNA set is injected into the wellMeans to makeIt is characterized by providing.
[0046]
  To achieve the above object, a synthetic DNA set according to an embodiment of the present inventionGeneration systemThis control method has the following configuration. That is, from the orderer side device via the networkOrder dataReceiveServer device to be held in advanceSynthetic DNA selected from multiple types of synthetic DNAA DNA injection apparatus for producing a synthetic DNA set by injecting a plurality of wells into a well of a container partitioned into a plurality of wells, managing the types and storage addresses of the plurality of types of synthetic DNA, and receiving the order data received by the server apparatus A DNA injection control device for controlling the DNA injection device so as to produce synthetic DNA under the conditions in accordance withSynthetic DNA set generationsystemControl method,The server device isIn the orderer side device,For instructing the orderer of the number of types of the base sequence of the synthetic DNA set, the type of end modification of the synthetic DNA set, the amount of DNA, and the well in which the synthetic DNA is arranged among the plurality of wellsInterfaceSendDoIn addition, the selection instruction data input via the interface in the orderer side apparatus is received as the order data and stored in the storage unit.Process,The DNA injection device receives the selection instruction data stored in the storage unit of the server device via the DNA injection control device, and the selection instruction dataBased onBeforeSelect at least one of the multiple types of synthetic DNAAs well as, Each of the selected synthetic DNAs,Specified by the selection instruction data among the plurality of wellsThe synthetic DNA set is injected into the wellProductionAnd a step of performing.
[0049]
DETAILED DESCRIPTION OF THE INVENTION
An embodiment according to the present invention will be described below with reference to the drawings. However, although the present embodiment has been described as a synthetic DNA sales system, it is not intended to limit the scope of the present invention to the description examples.
[0050]
[Synthetic DNA sales system]
FIG. 1 is a block diagram showing components used in a synthetic DNA sales system, where 100 is a system on the orderer side, 200 is a system on the order side, and both systems are connected to the network 10. Connected with internet protocol.
[0051]
First, an outline of a synthetic DNA production and delivery system will be described with reference to FIG. The orderer transmits an order for the desired synthetic DNA from the orderer's system 100 to the orderer's system 200, which is the orderer, via the network 10. When the ordering party receives the ordering signal from the orderer's system 100 by the orderer's system 200, the contractor creates a DNA array of the sequence ordered according to the orderer's order, and creates the orderer by courier service. Send the DNA array.
[0052]
Here, the contractor is, for example, a DNA synthesis company or a pharmaceutical company, and the ordering party is, for example, a researcher who uses synthetic DNA, a medical / professional company that manufactures and sells DNA arrays using synthetic DNA probes. These include physical equipment sales companies, pharmaceutical companies, and pharmaceutical companies.
[0053]
Next, the orderer side system 100 and the orderer side system 200 will be described in detail. The system 100 on the orderer side includes a WWW browser device 20. As the WWW browser device 20, a general-purpose system in which WWW browser software is installed on a commercially available general-purpose personal computer can be used as it is, and this general-purpose system can be used as an orderer computer.
[0054]
Therefore, it is not necessary to prepare special dedicated hardware or software for the system 100 on the orderer side in carrying out the present invention, and a general-purpose system that can be connected to the network 10 and browse a homepage with a WWW browser is used as it is. Use it.
[0055]
On the other hand, the system 200 on the side of the orderer includes an order receiving system including a WWW server device 70, a first storage unit 40, a second storage unit 80, a DNA injection device 50, and a DNA injection control unit 30 via the network 10. Is configured.
[0056]
The first storage unit 40 includes a list of data relating to the base sequence, length, and modification type of DNA held by the contractor (owned DNA list), and an address representing the location and container in which each DNA is stored. (Retained DNA address), and the type, shape, and position information of each well that can be used in a commercially available DNA array production apparatus are stored.
[0057]
The first storage unit 40 is external to the DNA injection control unit 30 for controlling the DNA injection device 50 that injects a necessary amount of a stored DNA solution into a specified well of a specified microplate. It is a storage unit and also has a control program for realizing the function of controlling the DNA injection device 50, and is composed of a hard disk, an MO drive, or the like.
[0058]
The WWW server device 70 provides home page data stored in the second storage unit 80 to the WWW browser device 20 via the network 10. Any system in which the WWW server software is installed in the server computer can be used. The second storage device 80 is an external storage device of the WWW server device 70, and includes a hard disk device, an MO drive device, and the like.
[0059]
The DNA injection control unit 30 manages the type and storage address of each stored synthetic DNA, and controls the DNA injection device 50 so as to produce synthetic DNA under the conditions selected and instructed by the WWW server device 70.
[0060]
The DNA injection device 50 injects each stored synthetic DNA into a well in a designated microplate in accordance with a predetermined condition in accordance with an instruction from the DNA control unit 30 to produce a synthetic DNA set 60 ordered by the orderer. To do.
[0061]
The produced synthetic DNA set 60 is sent to the orderer by various methods.
It should be noted that the system 200 on the contractor side can anticipate the widespread use of DNA array production apparatuses, and can sell synthetic DNA in a shape suitable for each DNA array production apparatus. Therefore, the orderer can save the trouble of dispensing the obtained synthetic DNA into the storage portion of the DNA solution of the DNA array production apparatus, and can also prevent the loss of DNA accompanying the dispensing.
[0062]
That is, a lot of synthetic DNA is held in the system 200 on the contractor side. For example, if the DNA is 10 bases long, the type is 10⁶Yes, if it is 18 bases long, 6.8X10^TenThere are species, but they are retained.
[0063]
In the system 200 on the contractor side, the base sequence of the synthetic DNA ordered by the orderer is selected from the stored synthetic DNA list, and the required amount is taken out from the storage solution by associating it with the storage address. Is used to inject into the wells of a container partitioned into a plurality of wells having a shape designated by the orderer.
[0064]
As a result, the synthetic DNA ordered by the orderer is filled in the required amount of the well designated by the orderer and sent to the orderer. Synthetic DNA is sent in a dry state in a container or as a designated solution.
[0065]
In the following description, as an example of selling synthetic DNA, a case where it is necessary for the production of a DNA microarray will be described. However, selling synthetic DNA is not limited to this application, but for any application that requires synthetic DNA. It can also be sold.
[0066]
[Ordering and obtaining synthetic DNA]
Next, referring to FIGS. 3 to 16 using the flowcharts of FIGS. 2A and 2B, the orderer orders the synthetic DNA having the desired base sequence by the synthetic DNA sales system shown in FIG. The process until obtaining the synthesized DNA will be described.
[0067]
However, in the following description, the orderer is the DNA of 64 kinds of base sequences numbered from 1 to 64, in which the 5 ′ ends of the DNA shown in FIG. 5 are all chemically modified with SH groups. The case of placing an order as a set will be described. It is assumed that the DNAs of these 64 kinds of base sequences can be supplied by the contractor.
[0068]
Further, in the present embodiment, the orderer numbers 64 wells in the designated area (8 × 8) on the desired microplate shown in FIG. 3 as shown in FIG. In addition, each well was filled with 0.075 OD (1 OD is a unit in which the absorption intensity at 260 nm indicates 1 OD when DNA is dissolved in 1 ml), and the DNA of the same number numbered in FIG. Shall order a set of synthetic DNAs prepared in a dry state.
[0069]
As another example, as shown in FIG. 16, a thiol-modified DNA probe in which a thiol group is chemically modified at the end of DNA is glycerin 7.5 wt%, urea 7.5 wt%, thiodiglycol 7.5 wt%. An order was made for a DNA array in which probes were covalently immobilized by dissolving them in an aqueous solution containing 1 wt% of acetylenol EH (Kawamura Fine Chemicals) and supplying them on a glass substrate having maleimide groups previously inserted on the surface by an inkjet method. The case where a person places an order will also be described.
[0070]
In addition, when the orderer wants to know whether the synthetic DNA for ordering can be supplied by the contractor as described above, it can be known by the following procedure. That is, the orderer's storage device 80 stores the DNA base sequence, length of the DNA base sequence, presence / absence of chemical modification in the DNA base sequence, and the DNA base sequence as the data for the homepage. A list of data related to the type of the product.
[0071]
The above DNA base sequence can be searched in alphabetical order, or by the name of the protein encoded by each gene, or by the name of a base sequence set established as a probe for gene diagnosis, etc. Yes, the orderer accesses the contractor's WWW server 70 via the network 10 so that the website can be searched from various points of view.
For example, when it is desired to know whether or not the desired DNA set can be supplied by the contractor, as shown in FIG. 17, in accordance with the instructions on the homepage provided by the contractor's storage device 80 shown in FIG. Enter the base sequence of the desired DNA set.
[0072]
If the base sequence name of the desired DNA set is known in advance, it can be input by selecting the desired selection method from 172 to 174. For example, if you want to enter the base sequence alphabetically, select 172, if you want to enter the name of the protein encoded by the gene, select 173, and enter the name of the base sequence set established as a probe for gene diagnosis. If it is desired to input, 173 may be selected.
[0073]
In addition, if the base sequence name of the desired DNA set is unknown, or if it is desired to display a list of DNA sets that are held, 175 may be selected.
[0074]
FIG. 18 shows a screen when the list display of the DNA set 175 held in FIG. 17 is selected. That is, a protein name list is displayed at 181, a base sequence list for gene diagnosis is displayed at 182, and a base sequence list is displayed at 183. Therefore, the orderer can obtain the base sequence list shown in FIG. 5, for example, by inputting the desired DNA set in accordance with the instruction of 184.
[0075]
In addition, the storage device 80 of the contractor stores information on the types of microplates suitable for various types of DNA array production apparatuses as a container partitioned into a plurality of wells. For example, when an orderer selects a microplate suitable for a pin-type DNA array production device from the homepage, it is possible to specify which well is to be injected with DNA having a base sequence selected from the list of the storage device 80 of the contractor. It is set so that. FIG. 3 shows a 128-hole microplate manufactured by B company as an example of the microplate. For the probe set for gene diagnosis, several patterns to be arranged on the microplate are stored and set so that the orderer can select.
[0076]
Similarly, when the orderer selects a microplate suitable for the inkjet DNA array production apparatus from the homepage, the orderer's storage device 80 stores information on the type of ink cartridge, the type of head with cartridge, and each Data relating to the coordinates of the ink cartridge is stored, and is set so that the orderer can select it.
[0077]
First, in step S100, when the orderer accesses the homepage of the contractor from the WWW browser device 20, the synthetic DNA ordering screen shown in FIG. 6 or FIG. 14 is displayed. The orderer inputs the base sequence of the DNA to be ordered, the type of terminal modification, the form of DNA, the amount of DNA, and the method of the DNA array production apparatus.
[0078]
FIG. 6 shows an example of contents ordered by the orderer. That is, 64 types are selected as the type of DNA to order shown in 51, SH and 5 ′ end are selected as the types of end modification shown in 52, and dryness is selected as the form of DNA shown in 53, The case where 0.075 OD is selected as the amount of DNA shown in FIG. In addition, as a method of the DNA array production apparatus shown in 55, the case where the pin method is selected is shown.
[0079]
FIG. 14 shows an example of the contents ordered by the orderer as in FIG. 6, and the type of DNA, the type of end modification, and the amount of DNA are the same as those in FIG. However, the form of DNA shown in 53 shows a solution, and the case where the inkjet system is selected as the system of the DNA array production apparatus shown in 55 is shown.
[0080]
Next, in step S100, when the orderer orders synthetic DNA under either of the conditions in FIG. 6 or FIG. 14, the process proceeds to step S110. In step S110, the method of the ordered DNA array manufacturing apparatus is checked. If the pin method shown in FIG. 6 is selected, the process proceeds to step S120. If the ink jet method shown in FIG. Proceed to step S250 shown in 2B.
[0081]
Next, in step S120, the screen shown in FIG. 7 is displayed. FIG. 7 displays an order condition selected by the orderer and a microplate selection screen.
[0082]
That is, 61 in the screen of FIG. 7 shows that the selected order conditions are 64 types of DNA, types of terminal modification are SH and 5 ′ end, DNA is dried up, and the amount of each DNA is 0. 075 OD indicates that the pin method is selected as the method of the DNA array production apparatus. Next, the orderer selects the type of the microplate used for the pin method on the screen 62 in FIG. In the example of FIG. 7, a case where 128 wells of company B are selected is shown.
[0083]
Next, in step S130, the screen shown in FIG. 8 or FIG. 11 is displayed. Reference numeral 71 in FIG. 8 or FIG. 11 displays the microplate selected by the orderer, and displays an input screen for selecting and arranging areas for arranging 64 types of DNA.
[0084]
Next, the orderer designates an area for arranging 64 types of DNA in accordance with the instructions on the screen 71 shown in FIG. 8 or FIG. For example, 64 wells (8 × 8) indicated by 72 in FIG. 8 or FIG. 11 are designated. If it is desired to arrange DNA different from 64 types (for example, 80), a necessary well area (for example, 8 × 10) may be designated.
Next, an arrangement input method 73 is selected. In the example of FIG. 8, a case where individual input is selected as the arrangement input method 73 is shown. In the example of FIG. 11, a case where format input is selected as the arrangement input method 73 is shown.
[0085]
Next, in step S140, the selected input method is checked. If the individual input shown in FIG. 8 is selected as the selected input method, the process proceeds to step S150, and if the format input shown in FIG. 11 is selected as the selected input method, the process proceeds to step S200.
[0086]
Next, in step S150, the screen shown in FIG. 9 is displayed. 9 in FIG. 9 displays the area set in step S130 for placing the 64 types of DNA selected by the orderer, and 92 in FIG. 9 indicates how to number the 64 wells in the area. A screen for selecting whether to place is displayed.
[0087]
Next, the orderer selects from among the arrangements 1 to 3 how to arrange the numbers to the 64 wells according to the instruction on the selection screen 92 in FIG.
[0088]
In arrangement 1, 64 wells (8 rows × 8 columns) are numbered in the order shown in the figure. That is, the eight wells in the first row are numbered from 1 to 8 from left to right, and the eight wells in the second row are similarly numbered from left to right. Numbers 9 to 16 are assigned. In the same manner, 64 wells are given 64 numbers as shown in the figure.
[0089]
Similarly, in arrangement 2, arrangement 1 is numbered in the order shown in the figure in 64 wells (8 rows × 8 columns). That is, the four wells from the left in the first row are numbered from 1 to 4 from the left to the right, and in the same manner, the four wells from the left in the eighth row are Numbers 29 to 32 are assigned from left to right.
[0090]
In addition, 5 to 8 wells from the left in the first row are numbered from 33 to 36 from the left to the right, and in the same manner, 5 to 8 wells from the left in the eighth row. The wells are numbered from 61 to 64 from left to right.
[0091]
Similarly, arrangement 3 is numbered in the order as shown in the figure for 64 wells (8 rows × 8 columns). That is, the eight wells in the first row are numbered 1 to 8 from top to bottom, and the eight wells in the second row are 9 to 16 from top to bottom. In the same manner, 64 wells are numbered 64 as shown in the figure.
[0092]
The above arrangement shows an example in the case of 64. However, when different DNA types (for example, 10 rows × 8 columns in the area of FIG. 8) are set by the orderer, Depending on the selected area, the number of wells in the arrangements 1 to 3 and their numbers may be changed and displayed. (For example, when 10 rows × 8 columns are selected in the area of FIG. 8, the number of the first row of arrangement 1 is changed to 1 to 10)
In the example of FIG. 9, the arrangement 2 is selected by the orderer.
[0093]
Next, in step S160, the arrangement selected by the orderer is examined. If arrangement 2 is selected from arrangements 1 to 3 in FIG. 9, the process proceeds to step S180. If arrangement 1 is selected, the arrangement 1 is selected. Proceeding to step S170, if arrangement 3 is selected, the process proceeds to step S190.
[0094]
Next, in step S180, the screen shown in FIG. 10 is displayed. 101 of FIG. 10 displays an example of the arrangement of wells in which 1 to 64 are numbered in the selected arrangement 1, and 102 indicates the type (base sequence) of DNA to be filled in each well of 1 to 64. Screens requesting input in order are displayed.
[0095]
The orderer sequentially inputs the 64 types of base sequences shown in FIG. 5 into the numbers “1” to “64” of 102, and designates the DNA to be filled in each well of the arrangement 1.
[0096]
For example, the first "SH-GATGGGACTCAAGTTCAT" in FIG. 5 is input to the "1" position shown in 102, the second "SH-GATGGGACTACTAGGTTTCAT" in FIG. 5 is input to the "2" position, and so on. By inputting, 64 kinds of DNAs to be filled in each well of arrangement 1 are designated.
[0097]
However, the input method is not limited to the above-described method. For example, when the number “1” of the first base sequence in FIG. “SH-GATGGGACTCAAGTTCAT” which is the first base sequence in FIG. 5 may be displayed. When all 64 types of DNA have been input, the process proceeds to step S220.
[0098]
If arrangement 1 is selected in step S160, the process proceeds to step S170. In step S170, although not shown, wells in which the numbers 1 to 64 are assigned to the arrangement 2 selected in FIG. 9 are displayed in the same manner as 101 in FIG. Further, a screen for requesting input of DNA types (base sequences) 1 to 64 to be filled in each well shown in 102 of FIG. 10 is displayed.
[0099]
The orderer sequentially inputs 64 kinds of base sequences shown in FIG. 5 to numbers 1 to 64 shown in 102 as in FIG. 10, designates DNA to be filled in each well of arrangement 1, and inputs all When is finished, the process proceeds to step S220.
[0100]
Furthermore, when arrangement 3 is selected in step S160, the process proceeds to step S190. In step S190, although not shown, wells in which the numbers 1 to 64 are assigned to the arrangement 2 selected in FIG. 9 are displayed in the same manner as 101 in FIG. Further, a screen for requesting input of DNA types (base sequences) 1 to 64 to be filled in each well shown in 102 of FIG. 10 is displayed.
[0101]
The orderer, for example, sequentially inputs 64 types of base sequences shown in FIG. 5 to the numbers 1 to 64 shown in 102 as in FIG. When the input is completed, the process proceeds to step S220.
[0102]
On the other hand, if the format input shown in FIG. 11 is selected in step S140, the process proceeds to step S200, and the screen shown in FIG. 12 is displayed. Reference numeral 111 in FIG. 12 denotes a screen for prompting the orderer to input the 64 types of DNAs shown in FIG. 5 selected by the orderer in the format.
[0103]
The orderer, for example, puts 64 types of DNA into “GATGGG” in 111 of FIG.N ₁ CTCN ₂ N _Three By inputting in the format format “GTTTCAT”, the arrangement of the 64 types of DNA is expressed in the format format, and the process proceeds to step S210.
[0104]
A method for determining the arrangement of 64 types of DNA in this format will be described below.
[0105]
"GATGGGN ₁ CTCN ₂ N _Three In the format format of “GTTTCAT”,N ₁ ,N ₂ ,N _Three Are variables indicating the same change, and indicate a mutated portion of the base sequence, and other portions indicate a common portion of the base sequence that does not change. That is,N ₁ ,N ₂ ,N _Three Each variable of A changes from A → G → C → T.
[0106]
Also, “GATGGGN ₁ CTCN ₂ N _Three Three variables in one expression, such as “GTTTCAT”N ₁ ,N ₂ ,N _Three Is the last (third) variable if appears simultaneouslyN _Three To A → G → C → T. At this time, the other (first, second)N 1,N 2Does not change, the last (third) variableN ThreeChanges sequentially from A → G → C → T. The above description will be described in detail with reference to FIG.
[0107]
For example, the first to fourth base sequences in FIG. 5 are the last (third) variables.N _Three Changes from A → G → C → T,N ₁ ,N ₂ Shows an example in which A remains unchanged.
[0108]
Next, the secondN 2Changes from A → G → C → T. That is, the secondN 2First changes from A to G, and the thirdN ThreeHowever, A → G → C → T changes. For example, the fifth to eighth base sequences in FIG.N 2Changes from A to G,N ThreeShows an example in which A → G → C → T.
[0109]
Then the secondN ₂ Changes from G to C, the thirdN _Three However, A → G → C → T changes. For example, the 9th to 12th base sequences in FIG.N ₂ Changes from G to C,N _Three Shows an example in which A → G → C → T. Then, the secondN ₂ Changes from C to T, the thirdN _Three However, A → G → C → T changes. For example, the 13th to 16th base sequences in FIG.N ₂ Changes from C to T,N _Three Shows an example in which A → G → C → T.
[0110]
In the same manner, “GATGGG”N ₁ CTCN ₂ N _Three By using the “GTTTCAT” format, 64 types of DNA that can be expressed in the order shown in FIG. 5 can be expressed in the format.
[0111]
In the above example, “GATGGGN ₁ CTCN ₂ N _Three Three variables in one expression, such as “GTTTCAT”N ₁ ,N ₂ ,N _Three Is the last (third) variable if appears simultaneouslyN _Three To A → G → C → T in this order, and the other (first, second)N ₁ ,N ₂ Does not change, the last (third) variableN _Three An example has been described in which changes sequentially from A → G → C → T.
[0112]
However, the order of change is not limited to the above, for example, the first (first) variable.N ₁ To A → G → C → T in this order, and the other (second and third)N ₁ ,N ₂ It is also possible to change by various methods such as not changing.
[0113]
In the above example, the case of three variables has been described as an example. However, the number of variables is not limited to three, and an arbitrary number can be taken. The variable changing method in this case may be changed based on the concept described above.
[0114]
In addition, as described above, by designating the common part of the base sequence of the input DNA, displaying the mutated part as a variable, and assuming that this variable represents A, G, T, C, If there are three such variables in the base sequence as in the above example, 64 types of DNA base sequences can be designated. In addition, if this variable has one location in the base sequence, 4 types can be specified, and if there are 2 locations in the base sequence, 16 types of DNA base sequences can be specified. It is also possible to select an array.
[0115]
Next, in step S210, the screen shown in FIG. 13 is displayed. 131 in FIG. 13 displays the arrangement of 64 kinds of DNAs arranged in 64 wells, and 122 is a display requesting the orderer to input arrangement confirmation (YES, NO). FIG. 13 shows that the arrangement shown in 131 has been confirmed (YES) by the orderer. When the confirmation of the arrangement is completed, the process proceeds to step S220.
[0116]
On the other hand, if step S250 is selected in step S110, the process proceeds to step S250, and the screen shown in FIG. 15 is displayed. FIG. 15 shows a screen for selecting an order condition, an ink jet method, and an ink cartridge selected by the orderer.
[0117]
That is, 151 in FIG. 15 shows 64 types of DNA, SH and 5 ′ end as types of end modification, solution state as DNA form, 100 μl at a concentration of 8 μM for each DNA amount, DNA array production system method Indicates that the inkjet method was selected.
[0118]
Next, the orderer selects the ink jet method and the type of ink cartridge on the screen 152 in FIG. The example of FIG. 15 shows a case where only an ink cartridge is selected as the ink jet method, and 96 types of ink cartridges of BC62 are selected as the type of ink cartridge.
[0119]
Next, in step S260, the screen shown in FIG. 16 is displayed. 161 of FIG. 16 displays 96 types of ink cartridges of BC62 by the head of company A selected by the orderer, and displays an input screen for selecting and arranging areas for arranging 64 types of DNA.
[0120]
Next, the orderer first designates, for example, 64 wells (8 × 8) indicated by 162 in FIG. 16 as an area in which 64 types of DNA are arranged in accordance with the instruction of 163 on the screen of FIG. Next, an arrangement input method is selected. The example of FIG. 16 shows a case where individual input is selected.
[0121]
Next, in step S270, the selected input method is checked. If the individual input shown in FIG. 16 is selected, the process proceeds to step S280, and if the format input is selected, the process proceeds to step S330.
[0122]
Next, in step S280, a screen similar to that shown in FIG. The left side of this figure is the same as 161 in FIG. 16 and displays an area 162 in which 64 types of DNA selected by the orderer are placed, and the right side of the figure is the same as 92 in FIG. A selection screen for how to arrange DNA is displayed.
[0123]
Next, the orderer selects from the arrangements 1 to 3 how to arrange 64 types of DNA in the designated area in accordance with this figure, similarly to 92 on the screen of FIG. That is, when arrangement 1 is selected, the process proceeds to step S300. When arrangement 2 is selected, the process proceeds to step S310. When arrangement 3 is selected, the process proceeds to step S320. The operations performed in step S300, step S310, and step S320 are the same as the operations in step S170, step S180, and step S190 that have already been described, and thus description thereof is omitted here.
[0124]
On the other hand, if format input is selected in step S270, the process proceeds to step S330, and the screen shown in FIG. 12 is displayed. Reference numeral 111 in FIG. 12 prompts input of 64 types of DNAs shown in FIG. 5 selected by the orderer in a format format. Therefore, in the same method described in step S200, the orderer, for example, adds 64 types of DNA to “GATGGG” in 111 of FIG.N ₁ CTCN ₂ N _Three By inputting in the format format “GTTTCAT”, the arrangement of the 64 types of DNA is expressed in the format format, and the process proceeds to step S350.
[0125]
Next, in step S350, the arrangement 4 of 64 types of DNA arranged in the 64 wells shown in FIG. 13 is displayed. Furthermore, a screen for requesting input of the arrangement confirmation (YES, NO) shown at 132 is displayed. FIG. 13 shows that the displayed arrangement may be selected (YES). When the DNA to be filled in each well of the arrangement 4 is designated and all inputs are completed, the process proceeds to step S220.
[0126]
Next, in step S220, the order content of the synthetic DNA determined by the orderer is transmitted to the WWW server 70 of the contractor side system.
[0127]
  Next, in step S230, based on an instruction from the WWW server 70, the order content determined by the orderer is output to the DNA injection device 50.As a result, the DNA injection device 50For example, a specified set of synthetic DNA is injected into a well of a microplate in a specified order and in a specified order.
[0128]
Next, in step S240, the synthetic DNA produced based on the ordering contents of the orderer is sent to the orderer.
In this way, the orderer can obtain the synthetic DNA produced by the designated method.
[0129]
As described above, according to the present embodiment, there is a method in which an orderer accesses a contractor computer using a network and orders and obtains a very small amount of synthetic DNA by inputting the sequence of the synthetic DNA. Provided. Due to recent developments in overseas distribution methods, ordered synthetic DNA is delivered to the orderer within a few days, and it is not only cheaper than the methods that each researcher orders and synthesizes, but also obtains it early. The point that can be mentioned as a feature.
[0130]
In addition, according to the present embodiment, the amount required by each researcher can be obtained by synthesizing a large amount of DNAs having various sequences that were conventionally performed individually by many researchers as needed. A synthetic DNA sales system that synthesizes DNA with high synthesis yield and high purification yield, and quickly provides only the necessary types and amounts of DNA to each researcher who needs the synthesized DNA with various sequences. Can be provided.
[0131]
As a result, many researchers can purchase only the required amount of DNA they need, so each researcher has conventionally purchased expensive synthetic raw materials and inevitably synthesizes and uses more than the necessary amount of DNA. It is possible to effectively utilize DNA that has been discarded too much by providing it to many researchers. In addition, each researcher can reduce the work time for synthesizing a large amount of DNA more than necessary.
[0132]
That is, in a system that supplies synthetic DNA of a predetermined sequence in accordance with an order given from the orderer to the contractor, the contractor computer and the orderer computer are connected via a network to the contractor computer. Provides information such as the base sequence of synthetic DNA that can be supplied, the presence / absence of chemical modification at the end, and the type of information, and the computer on the ordering side corresponds to the ordering side's synthetic DNA list via the network. A function to select and select synthetic DNA is provided, and the computer on the contractor side takes this selection instruction via the network and sends a set of synthetic DNAs having the base sequence specified by the selection instruction to the orderer. can do.
[0133]
In addition, when the orderer does not instruct to select DNA from the DNA list of the contractor, but enters information on the base sequence of the desired DNA and chemical modification, the computer on the contractor's side automatically It is also possible to add a function of selecting and displaying a corresponding synthetic DNA from the synthetic DNA list held in
[0134]
In addition, as a container partitioned into a plurality of wells, a microplate, an ink cartridge, a head for an ink jet printer with an ink cartridge are applied, and the synthetic DNA solution is in a dry state or a solution composition instructed by the orderer. The solution can be sold in a form in which the liquid amount specified by the orderer is filled at the concentration indicated by the orderer in the solution.
[0135]
In addition, it is possible to link to the address of the selected synthetic DNA stock solution and add a function of inhaling the ordered amount from the stock solution by a micropipette or the like and injecting it into the wells of a container partitioned into a plurality of predetermined wells. it can.
[0136]
In addition, by registering as a synthetic DNA set having a base sequence necessary for a specific genetic diagnosis, when the orderer orders this synthetic DNA set described in the contractor's computer via the network, the orderer's It is also possible to fill and send a solution of a synthetic DNA set to a designated area on a container partitioned into a plurality of designated wells. In addition, the synthetic DNA set includes a gene set relating to a major histocompatibility complex as a set of base sequences necessary for specific gene diagnosis.
[0137]
Further, in the present embodiment, the DNA solution in the state where the DNA is filled in the ink jet cartridge suitable for the DNA array preparation method or the DNA solution is filled in the ink jet head integrated with the ink jet cartridge. Can also be sold.
[0138]
[Other Embodiments]
Note that the present invention can be applied to a system including a plurality of devices (for example, a host computer, an interface device, a reader, and a printer), and a device (for example, a copying machine and a facsimile device) including a single device. You may apply to.
[0139]
Another object of the present invention is to supply a storage medium (or recording medium) in which a program code of software that realizes the functions of the above-described embodiments is recorded to a system or apparatus, and the computer (or CPU or CPU) of the system or apparatus. Needless to say, this can also be achieved by the MPU) reading and executing the program code stored in the storage medium. In this case, the program code itself read from the storage medium realizes the functions of the above-described embodiments, and the storage medium storing the program code constitutes the present invention. Further, by executing the program code read by the computer, not only the functions of the above-described embodiments are realized, but also an operating system (OS) running on the computer based on the instruction of the program code. It goes without saying that a case where the function of the above-described embodiment is realized by performing part or all of the actual processing and the processing is included.
[0140]
Furthermore, after the program code read from the storage medium is written into a memory provided in a function expansion card inserted into the computer or a function expansion unit connected to the computer, the function is determined based on the instruction of the program code. It goes without saying that the CPU or the like provided in the expansion card or the function expansion unit performs part or all of the actual processing and the functions of the above-described embodiments are realized by the processing.
[0141]
When the present invention is applied to the above-described storage medium, the storage medium stores program codes corresponding to the flowcharts described above (shown in FIGS. 2A and 2B).
[0142]
【The invention's effect】
As described above, according to the present invention, a synthetic DNA sales system that provides each researcher who needs a DNA having various synthesized sequences, only the necessary types and amounts, quickly and inexpensively, and a control method therefor It is possible to provide a contractor side device and a control method thereof.
[Brief description of the drawings]
FIG. 1 is a diagram showing a synthetic DNA sales system using a network according to an embodiment of the present invention.
FIG. 2A is a flowchart showing the process from ordering to obtaining synthetic DNA.
FIG. 2B is a flowchart showing the process from ordering to obtaining synthetic DNA.
FIG. 3 is a diagram illustrating an example of a designated area of a microplate.
FIG. 4 is a diagram showing an example of arrangement of 64 kinds of DNA.
FIG. 5 is a diagram showing examples of 64 DNA base sequences.
FIG. 6 is a diagram showing a homepage where an orderer orders synthetic DNA.
FIG. 7 is a diagram showing a homepage where an orderer orders synthetic DNA.
FIG. 8 is a diagram showing a homepage where an orderer orders synthetic DNA.
FIG. 9 is a diagram showing a homepage where an orderer orders synthetic DNA.
FIG. 10 is a diagram showing a homepage where an orderer orders synthetic DNA.
FIG. 11 is a diagram showing a homepage where an orderer orders synthetic DNA.
FIG. 12 is a diagram showing a homepage where an orderer orders synthetic DNA.
FIG. 13 is a diagram showing a homepage where an orderer orders synthetic DNA.
FIG. 14 is a diagram showing a homepage where an orderer orders synthetic DNA.
FIG. 15 is a diagram showing a homepage where an orderer orders synthetic DNA.
FIG. 16 is a diagram showing a homepage where an orderer orders synthetic DNA.
FIG. 17 is a diagram showing a homepage where an orderer orders synthetic DNA.
FIG. 18 is a diagram showing a homepage where an orderer orders synthetic DNA.
[Explanation of symbols]
10 network
20 Ordering side computer
30 DNA injection controller
40 First storage device
50 DNA injection device
60 synthetic DNA sets
70 Contractor's server
80 Second storage device
100 Ordering system
200 Contractor's system

Claims (4)

A server device that receives order data from the orderer side device via the network, and a synthetic DNA selected from a plurality of types of synthetic DNA possessed in advance is injected into the wells of a container partitioned into a plurality of wells and synthesized. A DNA injection device for producing a DNA set, and the types and storage addresses of the plurality of synthetic DNAs are managed, and the DNA injection device is controlled so as to produce synthetic DNA under conditions according to the order data received by the server device. A synthetic DNA set generation system including a DNA injection control device ,
The server device places the number of types of base sequences of the synthetic DNA set, the type of end modification of the synthetic DNA set, the amount of DNA, and the synthetic DNA among the plurality of wells in the orderer side device. Means for transmitting an interface for instructing an orderer to the well, and receiving selection instruction data input via the interface in the orderer side device as the ordering data, and storing and storing it in the storage unit With
The DNA injection device, the selection instruction data stored and held in the storage unit of the server device received via the DNA injection control device of the prior SL plural kinds of synthetic DNA based on the selection instruction data characterized in that it comprises with selecting at least one, the means of generating the synthesized DNA set by injecting the selected synthetic DNA to each, the wells being designated by said selection instruction data of the plurality of wells A synthetic DNA set generation system . State as providing the form of the interface further, synthetic DNA, state solution of the synthesized DNA is is dryness injected into each well on the container, or synthetic DNA is filled with a predetermined concentration in a solution of a given solution composition The synthetic DNA set generation system according to claim 1 , wherein the orderer is designated by any of the above. 2. The synthetic DNA set generation system according to claim 1 , wherein the container is any one of an ink cartridge used in a DNA array production apparatus, an ink jet printer head with an ink cartridge, or a microplate. A server device that receives order data from the orderer side device via the network, and a synthetic DNA selected from a plurality of types of synthetic DNA possessed in advance is injected into the wells of a container partitioned into a plurality of wells and synthesized. A DNA injection device for producing a DNA set, and the types and storage addresses of the plurality of synthetic DNAs are managed, and the DNA injection device is controlled so as to produce synthetic DNA under conditions according to the order data received by the server device. A method for controlling a synthetic DNA set generation system , including a DNA injection control device ,
The server device arranges the number of types of base sequences of the synthetic DNA set, the type of end modification of the synthetic DNA set, the amount of DNA, and the synthetic DNA among the plurality of wells in the orderer side device. A step of transmitting an interface for instructing an orderer of a well, and receiving selection instruction data input via the interface in the orderer side device as the ordering data, and storing and storing it in a storage unit When,
The DNA injection device, the selection instruction data stored and held in the storage unit of the server device received via the DNA injection control device of the prior SL plural kinds of synthetic DNA based on the selection instruction data thereby selecting at least one, and the step of producing the synthetic DNA set by injecting the selected synthetic DNA to each, the wells being designated by said selection instruction data of the plurality of wells,
A method for controlling a synthetic DNA set generation system , comprising:

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