# Patent

## Title
Systems and methods for ordering oligonucleotides

## Abstract

A system is described for ordering oligonucleotides through a network, such as the Internet. The system provides a mechanism for validating the data provided by a customer, and then displaying graphical images to represent any data that has errors. The system can also pool multiple oligonucleotide samples together by providing graphical images representing oligonucleotide containers, and allowing the customer to select the proper containers to pool.

## Background
CROSS REFERENCE TO RELATED APPLICATIONS
This application is a continuation of U.S. patent application Ser. No. 11/184,215, filed Jul. 15, 2005, which claims the benefit of U.S. Provisional Application Ser. No. 60/634,164 filed Dec. 7, 2004 and entitled “Oligonucleotide Ordering System” the entirety of which is hereby incorporated by reference.


SEQUENCE LISTING
The Sequence Listing in electronic format is provided as a file entitled ILLINC.050C1.TXT, created May 25, 2010, which is 19.4 KB in size. The information in the electronic format of the Sequence Listing is incorporated herein by reference in its entirety.
FIELD OF THE INVENTION
This invention relates to a system for ordering oligonucleotides. More specifically, the invention relates to an on-line ordering system for ordering oligonucleotides through a computer network.
BACKGROUND OF THE INVENTION
Description of the Related Art
Many product ordering systems are available on the Internet. Companies such as Amazon®, Dell®, Microsoft® and many others sell a variety of products through the Internet. However, the process of ordering biological reagents that are used for specific experimental procedures can be daunting. For example, many biological products require specific customization that has been difficult to implement through an Internet ordering system.
One such biological product is an oligonucleotide, essentially a fragment of DNA that is used in a variety of experimental procedures. Although some companies provide systems for ordering oligonucleotides on-line, the ability to customize such orders and the efficiency of the ordering systems is limited. Thus, what is needed in the art is an efficient mechanism for ordering custom oligonucleotides through the Internet.
SUMMARY OF THE INVENTION
One embodiment of the invention is a system for ordering oligonucleotides, that includes: a database configured to receive a parameter defining a type of container for storing the oligonucleotides; a server comprising a storage configured to receive a customer data file comprising oligonucleotide sequence data; a first module configured to check the parameter and the oligonucleotide sequence data for errors; and a second module configured to display a graphic representing the type of container, wherein the graphic indicates whether the oligonucleotide sequence data has at least one error.
Another embodiment of the invention is an online system for creating an order for a mixture of different oligonucleotides. This embodiment includes: a first module configured to present graphics representing a first container and a second container for holding oligonucleotides, where the graphics are selectable by a customer; a storage for storing the identity of graphics that are selected by the customer; and a second module configured to identify the containers corresponding to the graphics selected by the customer and creating an order for a container comprising a mixture of oligonucleotides from the selected containers.
Still another embodiment of the invention is a method in a computer for ordering oligonucleotides online that includes: receiving a parameter defining a type of container for storing oligonucleotides; storing a customer data file comprising oligonucleotide sequence data; verifying the parameter and the oligonucleotide sequence data for errors; and displaying a graphic representing the type of container, wherein the graphic indicates whether the oligonucleotide sequence data has at least one error.
One other embodiment of the invention is a method for creating an order for a mixture of different oligonucleotides. This embodiment includes: presenting graphics representing a first container and a second container for holding oligonucleotides, where the graphics are selectable by a customer; storing the identity of graphics that are selected by the customer; identifying the containers corresponding to the graphics selected by the customer; and creating an order for a container comprising a mixture of oligonucleotides from the selected containers.
Yet another embodiment is a system for placing an electronic order of oligonucleotides. This system includes a storage configured to receive a customer data file comprising data corresponding to oligonucleotides to be ordered; a first module configured to check the data file for errors; and a second module configured to display a graphic, wherein the graphic indicates whether any data in the data file has at least one error.



BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a schematic drawing of one embodiment of an oligonucleotide ordering system.
FIG. 2 is a schematic drawing of one embodiment of an ordering server within an oligonucleotide ordering system.
FIG. 3 is a process flow diagram illustrating an overview of one embodiment of a method for ordering oligonucleotides.
FIG. 4 is a process flow diagram illustrating one embodiment of a process for validating an oligonucleotide order.
FIG. 5A is a screenshot of container graphics illustrating an invalid oligonucleotide order. FIG. 5B is an expanded view of one container graphic from FIG. 5A that indicates invalid entries.
FIG. 6 is a screenshot of container graphics illustrating a valid oligonucleotide order.
FIG. 7 is a process flow diagram illustrating one embodiment of a method for pooling multiple oligonucleotide containers.
FIG. 8 is a screenshot of an interface to a method of pooling multiple oligonucleotide containers.



DETAILED DESCRIPTION
Embodiments of the invention relate to an on-line ordering system that allows a customer to order oligonucleotides through a computer network such as the Internet. In one embodiment, the system provides an enhanced validation engine which thoroughly scans a customer's order for errors. In this embodiment, a customer uploads a customer data file, such as a text file or an XML file, containing a list of oligonucleotides to a server. Once the file is uploaded, it can be scanned for a variety of errors. Errors can be identified according to configurable business rules and manufacturing parameters stored within the ordering system.
In order to provide a simplistic mechanism for the customer to know whether an error has occurred or not, embodiment of the system display graphical indicia of oligonucleotide containers which are color coded to indicate whether an error has occurred or not. For example, if the customer has ordered his oligonucleotides to arrive in three 96-well plates, then graphical indicia of these three containers will appear after the customer data file has been uploaded. In one embodiment, these container graphics will be color coded to indicate whether or not an error has occurred with any of the oligonucleotides that correspond to the container.
For example, if an error has occurred in one oligonucleotide of the second plate, then that plate may be colored red whereas the other two plates for which errors have not been identified may be colored green. Of course, the invention is not limited to any particular graphical indicia or, if color is the indicia used, any particular coloring scheme.
In one embodiment, if the customer selects the container graphic indicating an error by, for example, using a mouse or other input device, then an enhanced container graphic will be displayed. For example, if the container is a 96 well plate then each of the 96 wells of the microtiter plate can be shown as a dot. Within this enhanced container graphic, each individual well can be displayed as a dot. Each of the wells can be coded with error or pass indicia such as a color code that indicates which well contains an oligonucleotide with an error, and which well does not, respectively. For example, in one embodiment, the wells with oligonucleotides having an error will be indicated in red whereas the other dots will be indicated in green. If desired, an error or pass indicia or both can be associated with a text message that is displayed to the customer. A text error message can be useful to indicate the presence of an error as well as to advise a customer of possible solutions that will remove the error.
Additionally, the system may provide that when a customer moves the mouse cursor over any particular dot of a container graphic indicating an error, then a text or graphical display can appear in order to identify the type of error associated with the oligonucleotide at that position. Of course it should be realized that the invention is not limited to any particular shape of the containers or color schemes. For example, the container graphics might indicate a 384-well microtiter plate, an eppendorf tube, a falcon tube or any other well-known container designed to hold molecules such as oligonucleotides. Furthermore, error indicia can be accessed or selected by methods other than a mouse click such as a combination of keystrokes (often referred to in the art as a short-cut) or other methods known in the art for manipulating an image in a presentation layer or graphical customer interface.
An additional embodiment of the invention provides a system for conveniently ordering pools of oligonucleotides such that multiple different oligonucleotides are combined within a single container as part of the order. As will be explained more completely below, one embodiment of the invention provides a system wherein a container graphic indicating each container that has been ordered is displayed to the customer. The customer then selects a particular container from the container graphic to indicate the first container that holds one or more oligonucleotides to be part of the pooled mixture. In this embodiment, the customer then selects a second container graphic that holds the second oligonucleotide(s) that are to be admixed with the oligonucleotide(s) from the first selected container. The system then generates a list of the containers that are to be mixed together to create the proper pooled container of oligonucleotide mixtures. It should be realized that the system may display a variety of container graphics that allow the customer to choose which containers to mix into one or more pools. The system can further display parameters by which the containers should be mixed.
DEFINITIONS
Container
Container refers to any vessel or substrate designed to hold, store or transfer biologically active molecules such as oligonucleotides. Examples of containers include multiwell plates, eppendorf tubes and falcon tubes. A multiwell plate can include, for example, 8, 16, 96, 384, or 1536 wells.
Further examples of containers include a substrate having a surface to which one or more biologically active molecule is attached such as a bead or array. Arrays are populations of different molecules that are attached to one or more substrates such that the different molecules can be differentiated from each other according to relative location. Useful arrays include, without limitation, an array synthesized by photolithography-based polymer synthesis, such as an Affymetrix® GeneChip® and others known in the art (see, for example, U.S. patent application Ser. No. 09/536,841, International Publication No. WO 00/58516; U.S. Pat. Nos. 5,143,854, 5,242,974, 5,252,743, 5,324,633, 5,445,934, 5,744,305, 5,384,261, 5,405,783, 5,424,186, 5,451,683, 5,482,867, 5,491,074, 5,527,681, 5,550,215, 5,571,639, 5,578,832, 5,593,839, 5,599,695, 5,624,711, 5,631,734, 5,795,716, 5,831,070, 5,837,832, 5,856,101, 5,858,659, 5,936,324, 5,968,740, 5,974,164, 5,981,185, 5,981,956, 6,025,601, 6,033,860, 6,040,193, 6,090,555, 6,136,269, 6,269,846, 6,022,963, 6,083,697, 6,291,183, 6,309,831 and 6,428,752; and in PCT Application Nos. PCT/U.S.99/00730 (International Publication No. WO 99/36760) and PCT/U.S.01/04285); a spotted array such as a CodeLinkTM Array (Amersham Biosciences), an array manufactured using inkjet printing, such as a SurePrintTM array (Agilent Technologies); or a BeadChipTM Array (Illumina Inc.) or other bead based array such as those described in U.S. Pat. Nos. 6,023,540, 6,200,737, 6,327,410, 6,355,431 and 6,429,027; U.S. patent application publication No. U.S. 2002/0102578 and PCT Publication Nos. WO 00/63437, WO 98/40726, and WO 98/50782.
Container Graphics
Container graphics refer to any pictorial representation of a container. The representation can be generated for display on a monitor, printout or a report. In one example, the representation can be rectangular and appear as an image of a microtiter plate or be circular and represent an eppendorf tube. Of course, the term container graphic is not limited to any particular shape. If desired a container graphic can include text or other characters. Alternatively, a container graphic can exclude such characters. Accordingly, a container graphic can include at least one pictorial representation that is not a text character.
Input Devices
The input device can be, for example, a keyboard, rollerball, mouse, voice recognition system or other device capable of transmitting information from a customer to a computer. The input device can also be a touch screen associated with the display, in which case the customer responds to prompts on the display by touching the screen. The customer may enter textual information through the input device such as the keyboard or the touch-screen. An input device can also be detector used to identify an item such as a bar code reader, RF tag reader or other tag reader.
Instructions
Instructions refer to computer-implemented steps for processing information in the system. Instructions can be implemented in software, firmware or hardware and include any type of programmed step undertaken by components of the system.
LAN
One example of the Local Area Network may be a corporate computing network, including access to the Internet, to which computers and computing devices comprising the system are connected. In one embodiment, the LAN conforms to the Transmission Control Protocol/Internet Protocol (TCP/IP) industry standard. In alternative embodiments, the LAN may conform to other network standards, including, but not limited to, the International Standards Organization's Open Systems Interconnection, IBM's SNA, Novell's Netware, and Banyan VINES.
Media
Media refers to images, sounds, video or any other multimedia type data that is entered into a system described herein. For example, media can include a document that is entered into the system by a document scanner or transmitted over a network connection.
Microprocessor
The microprocessor may be any conventional general purpose single- or multi-chip microprocessor such as a Pentium® processor, a Pentium® Pro processor, a 8051 processor, a MIPS® processor, a Power PC® processor, or an ALPHA® processor. In addition, the microprocessor may be any conventional special purpose microprocessor such as a digital signal processor or a graphics processor. The microprocessor typically has conventional address lines, conventional data lines, and one or more conventional control lines.
Modules
The system is comprised of various modules as discussed in detail below. As can be appreciated by one of ordinary skill in the art, each of the modules can include various sub-routines, procedures, definitional statements or macros, or a combination thereof. Each of the modules are typically separately compiled and linked into a single executable program. Therefore, the following description of each of the modules is used for convenience to describe the functionality of a particular system. Thus, the processes that are undergone by each of the modules may be arbitrarily redistributed to one of the other modules, combined together in a single module, or made available in, for example, a shareable dynamic link library.
Networks
The system may include any type of electronically connected group of computers including, for instance, the following networks: Internet, Intranet, Local Area Networks (LAN) or Wide Area Networks (WAN). In addition, the connectivity to the network may be, for example, remote modem, Ethernet (IEEE 802.3), Token Ring (IEEE 802.5), Fiber Distributed Datalink Interface (FDDI) or Asynchronous Transfer Mode (ATM). Note that computing devices may be desktop, server, portable, hand-held, set-top, or any other desired type of configuration. As used herein, an Internet includes network variations such as public internet, a private internet, a secure internet, a private network, a public network, a value-added network, an intranet, and the like.
Operating Systems
The system may be used in connection with various operating systems such as: UNIX, Disk Operating System (DOS), OS/2, or a Windows system such as Windows 3.X, Windows 95, Windows 98, Windows 2000, Windows 2003, Windows XP, and Windows NT.
Oligonucleotide
As used here, “Oligonucleotide” means a DNA fragment. The fragment may be any length having more than two nucleotides such as at least about 7, 10, 15, 25, 50, 75 or more nucleotides. Useful ranges include, without limitation from about 2-500 nucleotides, or from about 10-100 nucleotides or from 5-25 nucleotides or from about 20-70 nucleotides in length.
Programming Languages
The system may be written in any programming language such as C, C++, C# (C sharp), BASIC, Pascal, Java, Visual Basic and FORTRAN and ran under the well-known operating system. C, C++, BASIC, Pascal, Java, Visual Basic and FORTRAN are industry standard programming languages for which many commercial compilers can be used to create executable code.
Exemplary embodiments of useful systems and methods are set forth in further detail below. It should be understood that various modifications can be made without departing from the invention.
System Overview
FIG. 1 provides an overview of an oligonucleotide ordering system 10. The system includes an ordering server 15 that communicates with a network 18. The ordering server 15 may communicate with the network 18 through any well-known means, including high-speed digital data lines or wireless communication systems.
Communicating with the ordering server 15 is an integration server 20. The integration server 20 integrates data from a variety of sources to provide an enhanced oligonucleotide ordering system 10. As illustrated, the integration server 20 communicates with a financial system 30, and a laboratory information management system (LIMS) 35. As shown, the LIMS 35 communicates with a synthesis system 40. The financial system 30 may be any well-known financial system for managing a corporation, such as that provided by SAP®, Oracle®, PeopleSoft®, JD Edwards® or other well-known vendors. The laboratory information management system (LIMS) 35 may be any well-known system such as those offered by WildType® or PerkinElmer®. The synthesis system 40 can be a manufacturing environment for producing oligonucleotides. Many such systems exist, such as those housed at oligonucleotide synthesis companies such as Illumina Inc.®, or InVitrogen® or those housed at array manufacturers such as those described previously herein.
As shown in FIG. 1, a series of customers 25A, 25B and 25C communicate with a network 18 in order to access the ordering server 15 and place an oligonucleotide order. The customer computers 25A-C can be any well-known computer system that communicates through a network, such as the Internet. It will be understood that customers can be individuals or entities that access a system externally, for example, through the Internet or can be internal customers that access the system from a local network such as an Intranet.
Referring now to FIG. 2, the ordering server 15 is explained in more detail. As shown, the ordering system 15 includes a processor 80 that connects to a memory 85. The ordering server 15 can include any well-known type of processor 80, such as those designed by Intel, AMD or Motorola. In addition, the memory 85 can be any type of conventional random access memory or read-only memory which interacts with the processor 80. Also within the ordering server 15 and linked to the processor 80 is an oligonucleotide ordering module 100 which manages the interface presented to the customer. The ordering module 100 includes a database 105, a validation module 110 and a pricing module 112. As will be explained below, the database 105 and validation module 110 are used to validate the oligonucleotide customer data file provided by each of the customers 25A-C. Also within the oligonucleotide ordering module 100 is a presentation layer 63 that is used to generate the container graphics that will be explained in more detail below.
Process Overview
FIG. 3 provides one embodiment of a process 300 for ordering oligonucleotides through an on-line ordering system. The process 300 begins at a start state 302 and then moves to a state 305 where initial parameters regarding the order are received from the customer and stored to a database. The database for storing the parameters can be the database 105 or any other database within the system 10. These parameters might be, for example, the type of container desired by the customer, such as a microtiter plate or eppendorf tube. Other parameters might be whether the oligonucleotides should be delivered in solution, or dried. Other parameters include a synthesis scale, buffer type, normalization, volume and concentration. For example, validation can be carried out to determine that the normalized volume of solution and concentration of each oligonucleotide does not exceed predetermined levels for a selected optical density at 260 nm.
Once the initial parameters are obtained by the system from the customer at state 305, the process 300 moves to a state 310 wherein the parameters are validated to ensure that the order can proceed properly. For example, the system may ensure that the volume of solution ordered by the customer will fit into the type of containers also selected by the customer. Other types of validation include ensuring that the normalized volume of solution is sufficient to achieve the required concentration of each oligonucleotide and ensuring that the resulting concentration of oligonucleotide is sufficient to achieve a predetermined optical density at 260 nm which indicates the yield of DNA in the solution.
If the process 300 does not pass validation at the decision state 315, the process 300 moves to an error state 320 wherein the customer is provided with a message indicating the errors and the parameters being validated. The message can be, for example, an on-screen text message, new window, printout or e-mail message. The process 300 then returns to the state 305 in order to obtain corrected parameters.
Once the parameters have been validated at the state 310, the process 300 moves to a decision state 315 wherein a determination is made whether the initial parameters have passed the validation test. If the initial parameters pass the validation test, then the process 300 moves to a decision state 318 to determine whether the required parameters have been entered, and thus the order can be completed. If additional parameters are required, then the process 300 returns to the state 305 to obtain the additional parameters. If there are no more parameters required, the process 300 moves to state 325 wherein a customer data file containing the oligonucleotides is imported to the ordering server.
This importation process is normally achieved by uploading the customer data file to a storage in the server 15, through the network 18. The storage can include random access memory or a hard disk. The customer data file may include the list of oligonucleotides being ordered, including their DNA sequences, plus a variety of other useful parameters. As used herein, the term “oligonucleotide sequence data” refers to the nucleotide sequence of an oligonucleotide being ordered. These parameters might be, for example, the name, location, sequence, modification or comments associated with each oligonucleotide. One example of the format of a customer data file for a 96 well microtiter plate is shown below in Table 1.







TABLE 1







Example Customer Data File
















SEQ



Label
Row
Col
Long Description
ID NO.
Sequence















Ill_040422_01_F
A
1
013379_F_IRAV01-03_A02_I117rc
1
TGTGTCCGTGTGGTGGTC


Ill_040422_01_F
A
2
010310_F_IRAV01-03_B11_Oprs1
2
ATGAGGAGCTGCAGTGGG


Ill_040422_01_F
A
3
013459_F_IRAV01-03_C02_Nr4a1
3
TCCCTGGACGTTATCCGA


Ill_040422_01_F
A
4
013434_F_IRAV01-03_C14_BC003323
4
CGTGTGTGGCTTCGTCTG


Ill_040422_01_F
A
5
012154_F_IRAV01-03_C21_Slc29a1
5
CCCAGAATGTGTCCTCGG


Ill_040422_01_F
A
6
010320_F_IRAV01-03_D17_Scgf
6
CCCACCAGACTGGGACAC


Ill_040422_01_F
A
7
013079_F_IRAV01-03_E09_Slc25a11
7
AAGTTCCTGTTTGGGGGC


Ill_040422_01_F
A
8
013099_F_IRAV01-03_E19_D19Ertd675e
8
CTGACTGCGACGGCTACA


Ill_040422_01_F
A
9
010996_F_IRAV01-03_H15_Fcgrt
9
CATCTACGGGGCTTCCCT


Ill_040422_01_F
A
10 
013209_F_IRAV01-03_I19_Tcf11
10
AAGCGCAGAGTCGTCACC


Ill_040422_01_F
A
11 
010170_F_IRAV01-03_I22_Irak1
11
TTCCTTGCTTGCCCTTTG


Ill_040422_01_F
A
12 
010315_F_IRAV01-03_J15_I113ra2
12
TTGCAATGGAAACCTCCTG


Ill_040422_01_F
B
1
013549_F_IRAV01-03_K06_Slc25a10
13
CTGCGCATGACTGGAATG


Ill_040422_01_F
B
2
011086_F_IRAV01-03_K08_E2f5
14
TCCTGGATCTCAAAGCGG


Ill_040422_01_F
B
3
010215_F_IRAV01-03_K24_Crlf3
15
TCCTTGGAGTGTTCCCCA


Ill_040422_01_F
B
4
013554_F_IRAV01-03_M10_Cklfsf3
16
GGACTTCCTGCGCTGTGT


Ill_040422_01_F
B
5
011729_F_IRAV01-03_M17_Pla2g6
17
AAGCCAGCGTTCATCCTG


Ill_040422_01_F
B
6
013559_F_IRAV01-03_M18_Abtb1
18
CCTGGAGGCTAAGTGCGA


Ill_040422_01_F
B
7
013564_F_IRAV01-03_M22_Tnfaip1
19
ACCCCTCGAGTCCCTGAC


Ill_040422_01_F
B
8
012554_F_IRAV01-03_N03_Bcap31
20
TCCCATCCCTCTGTTGGA


Ill_040422_01_F
B
9
013369_F_IRAV01-03_O03_Araf
21
AGCAACGTGACCAGGAGC


Ill_040422_01_F
B
10 
013364_F_IRAV01-03_O05_Nrbp
22
GGGGCACCAACACATGAT


Ill_040422_01_F
B
11 
013744_F_IRAV01-03_P13_Lass4
23
TTGTGGTCGCCATCATTG


Ill_040422_01_F
B
12 
022456_F_IRAV55-58_A09_1500001K17Rik
24
ACAAGGCTAGGATGGGGC


Ill_040422_01_F
C
1
023186_F_IRAV55-58_A17_2410002K23Rik
25
CCCGCTTCACTTTGCACT


Ill_040422_01_F
C
2
023710_F_IRAV55-58_A21_Slc6a13
26
CATGGTCGTTCTCCTGGG


Ill_040422_01_F
C
3
024532_F_IRAV55-58_B04_5031409J19Rik
27
CCACTGTGGACCCCTCTG


Ill_040422_01_F
C
4
024027_F_IRAV55-58_B05_Slc11a2
28
GCATCGCGCTCTTTGTTT


Ill_040422_01_F
C
5
024542_F_IRAV55-58_B10_C430015I23Rik
29
AGTCAACAGCGCAGCCTT


Ill_040422_01_F
C
6
024072_F_IRAV55-58_B22_Fgf15
30
GCCCAGAGAACAGCTCCA


Ill_040422_01_F
C
7
020650_F_IRAV55-58_C12_Gnat1
31
TTCTGTAGCCCTGCAGCC


Ill_040422_01_F
C
8
039408_F_IRAV55-58_C18_Gng1
32
AGCTTGTTCATGAGAGCTGG


Ill_040422_01_F
C
9
023511_F_IRAV55-58_C20_Opn1sw
33
TAAGCAGTTCCGGGCTTG


Ill_040422_01_F
C
10 
024207_F_IRAV55-58_D10_Slc6a12
34
AGAAGGGCCAGCTGGAGT


Ill_040422_01_F
C
11 
022751_F_IRAV55-58_E13_Foxj2
35
AACTGCACAGGGAGACGC


Ill_040422_01_F
C
12 
023321_F_IRAV55-58_E14_Apob48r
36
AAGGAACTCCTGGGCCAC


Ill_040422_01_F
D
1
023406_F_IRAV55-58_E16_Slco4a1
37
CTCCCAGCGCTACGTTGT


Ill_040422_01_F
D
2
022861_F_IRAV55-58_E23_Fbs1
38
ACACGAACCCTGAGCTGC


Ill_040422_01_F
D
3
023992_F_IRAV55-58_F13_Stc1
39
ATCAAACGCACCTCCCAA


Ill_040422_01_F
D
4
024667_F_IRAV55-58_F15_1110019O13Rik
40
ACCAAGGTGCAGAGTGGC


Ill_040422_01_F
D
5
024147_F_IRAV55-58_F16_Ldlr
41
GGTTGCCCTCCTTGTCCT


Ill_040422_01_F
D
6
023136_F_IRAV55-58_G05_Slc13a3
42
AGTTTGCTGAACAGGCCG


Ill_040422_01_F
D
7
023056_F_IRAV55-58_G13_Kcnj16
43
TGCTCCACAAAGATGGCA


Ill_040422_01_F
D
8
024937_F_IRAV55-58_G24_4930429H24Rik
44
TGCTGCACGAAGCAAGAC


Ill_040422_01_F
D
9
024352_F_IRAV55-58_H01_Tmprss4
45
CAGTGCTGCTGAGCCTGA


Ill_040422_01_F
D
10 
024807_F_IRAV55-58_H04_Slc26a1
46
AGAATGTGGGACAGGCCA


Ill_040422_01_F
D
11 
035729_F_IRAV55-58_I14_Arf1
47
TGAACCAGACCCCTCCCT


Ill_040422_01_F
D
12 
024287_F_IRAV55-58_I24_Ovoll
48
CACCTCAAGGAACGCCAC


Ill_040422_01_F
E
1
024442_F_IRAV55-58_J04_Slc16a4
49
GGGGCTGCTACCTGGTTT


Ill_040422_01_F
E
2
024232_F_IRAV55-58_J17_Trip4
50
TCCTGCTTCCTGGTCGTC


Ill_040422_01_F
E
3
024457_F_IRAV55-58_J24_AI648912
51
ACAGCCTTCGTGTCCAGC


Ill_040422_01_F
E
4
022596_F_IRAV55-58_K05_Slc27a4
52
ATGCGGCCTGATGACATT


Ill_040422_01_F
E
5
024292_F_IRAV55-58_K24_F2rll
53
GCCTCCTCCTTTGCATGA


Ill_040422_01_F
E
6
024412_F_IRAV55-58_L09_Syap1
54
CAGTCGGCCCAACTCACT


Ill_040422_01_F
E
7
024917_F_IRAV55-58_M08_Mef2a
55
AGAGCCCTGATGCTGACG


Ill_040422_01_F
E
8
023151_F_IRAV55-58_M11_Slc18a1
56
TTGGGACTTCTGGTGGGA


Ill_040422_01_F
E
9
023977_F_IRAV55-58_M12_Mtvr2
57
TCTACAGCCAACGGAGCC


Ill_040422_01_F
E
10 
024707_F_IRAV55-58_N03_P2ry12
58
TCCTGTTCTTTGCTGGGC


Ill_040422_01_F
E
11 
024907_F_IRAV55-58_N10_Hoxd9
59
CCCCCAGTTTAGCGGACT


Ill_040422_01_F
E
12 
024057_F_IRAV55-58_N13_Tnfrsf11a
60
CCCTGGGCAGAAGTCAGA


Ill_040422_01_F
F
1
024367_F_IRAV55-58_N15_Hmmr
61
ATATTGCTGCTCACGCCC


Ill_040422_01_F
F
2
024377_F_IRAV55-58_N17_Asb6
62
CATCAACAGGAGGGACCG


Ill_040422_01_F
F
3
039682_F_IRAV55-58_N20_Taf13
63
CCGTTCGTACTTCCCGAG


Ill_040422_01_F
F
4
023965_F_IRAV55-58_P04_Scnn1g
64
CACTGGAGCCAAGGTGCT


Ill_040422_01_F
F
5
025092_F_IRAV59-62_A02_Gcgr
65
GGCTGCTGAAGACACGGT


Ill_040422_01_F
F
6
024557_F_IRAV59-62_A05_AA691260
66
AGCTGGGCCTGCTTTTCT


Ill_040422_01_F
F
7
026618_F_IRAV59-62_B06_Slc9a8
67
CTCACAGGCCCTTGGCTA


Ill_040422_01_F
F
8
026628_F_IRAV59-62_B10_Agtrl1
68
AAAGGGATGGAGCCTTGC


Ill_040422_01_F
F
9
034194_F_IRAV59-62_C04_Kcnip1
69
GACACTCCCAGGCAGCAT


Ill_040422_01_F
F
10 
026753_F_IRAV59-62_D04_Pdgfd
70
ACTGCTGATGCCCTGGAC


Ill_040422_01_F
F
11 
026828_F_IRAV59-62_D08_A930021G21Rik
71
CTGGCCCTCTGCTGTGAT


Ill_040422_01_F
F
12 
026371_F_IRAV59-62_D13_Gpnmb
72
AGGGGCAGATGATGGTGA


Ill_040422_01_F
G
1
026356_F_IRAV59-62_D17_Wnt2
73
GTACAATGGGGCCATCCA


Ill_040422_01_F
G
2
026898_F_IRAV59-62_D20_Nfkbie
74
GGATGGAGACACGCTGCT


Ill_040422_01_F
G
3
026893_F_IRAV59-62_D22_Synpr
75
AATCTGGGGCCAACTTCC


Ill_040422_01_F
G
4
026001_F_IRAV59-62_E05_Gpr84
76
TCCTCATTGCCCACCCTA


Ill_040422_01_F
G
5
026768_F_IRAV59-62_F08_Cacnb4
77
CTGGAGGCATACTGGCGT


Ill_040422_01_F
G
6
026808_F_IRAV59-62_F16_Syt13
78
GCCTCAAGAGGCAGGTCA


Ill_040422_01_F
G
7
025626_F_IRAV59-62_G02_Chx10
79
CGGTGTGGCGAGTTCTCT


Ill_040422_01_F
G
8
026206_F_IRAV59-62_H07_Bmp4
80
CCTGCAGCGATCCAGTCT


Ill_040422_01_F
G
9
025601_F_IRAV59-62_I02_Cklfsf4
81
CCTCGAGCACCTCCATGA


Ill_040422_01_F
G
10 
026573_F_IRAV59-62_J13_Hnf4
82
CACAGCCATCACCACCAA


Ill_040422_01_F
G
11 
026903_F_IRAV59-62_J14_Slc12a8
83
TGCTTGGTGCCGTCTGTA


Ill_040422_01_F
G
12 
026888_F_IRAV59-62_J16_Slc2a3
84
AAGGAGACCCCTGGCAAC


Ill_040422_01_F
H
1
038057_F_IRAV59-62_J21_Retnlb
85
GCAGCTGTTGCTTATCAAGG


Ill_040422_01_F
H
2
025401_F_IRAV59-62_K22_Fgfr4
86
TCCACGGGGAGAATCGTA


Ill_040422_01_F
H
3
026503_F_IRAV59-62_L01_AW538212
87
TAAGGCTGGCCCAGAATG


Ill_040422_01_F
H
4
026813_F_IRAV59-62_L20_Gng7
88
CGCCCCTAGACCCTTGTT


Ill_040422_01_F
H
5
026433_F_IRAV59-62_L21_Rai3
89
TCTTGCCCGAGTTTCGAC


Ill_040422_01_F
H
6
038172_F_IRAV59-62_L22_Sra1
90
AGCTGTACGTGAAGCCCG


Ill_040422_01_F
H
7
025811_F_IRAV59-62_M11_Siglecl1
91
GAAAGAAGGATGCGGGGT


Ill_040422_01_F
H
8
026673_F_IRAV59-62_N20_Kcne2
92
TCGGCATGTTCTCGTTCA


Ill_040422_01_F
H
9
025581_F_IRAV59-62_O15_Six1
93
CTCGGTCCTTCTGCTCCA


Ill_040422_01_F
H
10 
026081_F_IRAV59-62_O21_Slc26a7
94
GTTTTGATCATTGCCGCC


Ill_040422_01_F
H
11 
026386_F_IRAV59-62_P11_Syt13
95
TCCCGACCCTGTTTTGAA


Ill_040422_01_F
H
12 
026663_F_IRAV59-62_P24_Slc4a10
96
CTCAGGGAAAGGCGTTGA









Once the customer data file has been imported into the system, the process 300 moves to a process state 330 wherein the customer data file is validated using values in database 105 (FIG. 2) and the business rules validation module 110 to determine whether the format of the customer data file is proper for continued processing within the system. This will be explained more completely with reference to FIG. 4 below.
Once a comparison has been achieved at the process state 330, the process 300 moves to a decision state 335 wherein a determination is made whether the customer wishes to pool individual oligonucleotide samples together to create a mixture of oligonucleotides. If the customer does wish to create a pool of oligonucleotides, the process 300 moves to a process state 340 wherein the customer can manage which pools are created from the individual oligonucleotide samples. This process of managing pools, and mixing individual oligonucleotide samples together, is explained more completely with reference to FIG. 7 below.
Once the process of managing pools has been completed at the process state 340, the process 300 moves to a process state 345 wherein the oligonucleotide pricing is managed by the system.
However, if a determination is made at the decision state 335 that the customer does not wish to pool any of the samples, the process 300 moves directly to the process state 345 in order to manage the pricing of the order. Pricing can be determined by a pricing engine that generates values based on, for example, specific components of the present order, customer order history such as earned discounts or rates pertaining to a particular customer or group of customers.
Once the process of managing pricing has been completed at the process state 345, the process 300 moves to a state 347 wherein the customer can checkout of the ordering process. At the state 347, an online shopping cart, for example, may be used to assist the customer in processing the order. This also allows the customer to store their order for a particular time period and then come back to complete the order at a later time.
Once the customer has initiated the checkout procedure, the process 300 moves to a payment state 348 wherein the system requests input as to the type of payment being made. Once payment has been arranged, the process 300 displays an online confirmation to the customer at a state 349. The process 300 then moves to a state 350 wherein a confirmation e-mail can be sent to the customer. The process then terminates at an end state 355.
Referring now to FIG. 4, an exemplary process 330 of comparing the imported customer data file to the business rules is explained more completely. The process 330 begins at a start state 405 and then moves to a state 415 wherein the customer data file is parsed into individual records wherein each record corresponds to a single oligonucleotide. This allows the process 330 to individually analyze each oligonucleotide that is being ordered from within the imported customer data file.
The process 330 then moves to a state 420 wherein the first record within the imported customer data file is identified. At state 425, the process 330 validates the first record of the imported customer data file using values in the rules database. During this validation, a number of checks are made concerning the oligonucleotide identified in the record, the parameters previously obtained at state 305 (FIG. 3), and the values stored within the rules database. Examples of such rules can be seen in Table 2 below.







TABLE 2





Examples of Rules in a Rules Database
















1
Accepted oligo lengths are 15 to 80 bases.


2
For unmodified oligos, the length difference between the longest



and shortest oligo in a plate must be 30 bases or less.


3
An order containing oligos greater than 50 bases in length must



select a starting synthesis scale of 50 nmol or higher.


4
Orders must contain a minimum average of 48 oligos per plate



across the entire order.


5
Plate names must be unique for all plates within an order.


6
Plate names must be 15 characters or less in length.


7
Valid sequences can contain A, C, G, or T only.


8
Row and column designations within a plate must be unique.


9
Accepted row and column designations for a 96-well plate are A1



through H12.


10
Accepted row and column designations for a 384-well plate are A1



through P24.


11
Normalized volume must not exceed the working volume for the



selected plate.


12
Normalized volume must be 10 μl or greater.


13
Normalized concentration must be greater than 1 and less than



200 uM.


14
Normalized volume and concentration must not exceed the



guaranteed minimum ending OD yield at the selected synthesis



scale.


15
Plate pooling is only available when concentration and volume



normalization are selected.


16
Aliquoting is only available when concentration or volume



normalization is selected.


17
Volume per aliquot must be 10 μl or greater.


18
Combined aliquot volume and concentration must not exceed the



guaranteed minimum ending OD yield at the selected synthesis



scale.


19
Pooled plate name must be 15 characters or less in length.


20
Pooled plate must contain 10 μl or greater volume from each



source plate.


21
Each source plate can only be used in a single pooled plate.









As demonstrated by the example of Table 2, a rule can require that the length of an oligonucleotide that is ordered be within a particular range. Thus, a rule can require a minimum length or maximum length for an oligo being ordered. A rule can specify the average length or range of lengths for a set of oligos. For example, a maximum length difference between the longest and shortest oligos in an order can be established by a rule. A rule can also require that particular synthesis conditions are used for oligonucleotides of a particular length. For example, a minimum synthesis scale can be required based on the length of one or more oligos being at or above a particular threshold value. The number of oligos ordered, in total or in one or more containers, can be specified by a rule. For example, a rule can specify that each plate in an order have a minimum number of oligonucleotides, or a minimum average number of oligonucleotides per plate can be specified across all or part of an order.
One or more rules can require that naming conventions are maintained such as the syntax of a container name, non-redundancy for the names of separate containers, location of wells in a container, or the like. General storage or synthesis conditions can be required to occur within particular limits according to rules. For example, one or more rules can specify minimum or maximum volume for a container, concentration of an oligo in a container, consistency between requested yield and requested reaction conditions (such as concentration and volume).
One or more rule can specify that particular criteria are satisfied for pooling such as the volume of sample to be transferred to a pooled container (i.e. the recipient container into which samples from donor plates are combined) is within a predefined range, the volume capacity for a pooled container is not exceeded, or the oligo mixture in a pooled late has a final yield in a particular range. One or more rules can specify naming conventions for a pooled plate as exemplified above for other containers.
Of course, it should be realized that Table 2 only provides exemplary rules, and that the system is flexible enough to validate the customer data file for a wide variety of errors. In addition, new rules can be added to the algorithm or new values can be added to the rules database at any time in order to enhance the validation process.
Once a comparison has been completed at the state 425, the process 330 moves to a decision state 430 to determine whether an oligonucleotide error was found within the first record. Examples of such errors include: an incorrect nucleotide within the sequence, invalid length, invalid name or invalid location.
If a determination is made that there were no oligonucleotide errors at the decision state 430, the process 330 moves to a decision state 435 to determine whether any plate errors occurred as a result of the identified record within the customer data file. Examples of plate errors include invalid well location, invalid oligonucleotide quantity or invalid combination of modifications.
However, if a determination is made that there was an oligonucleotide error at the decision state 430, then the process 330 updates an error report log at a state 440 in order to track the particular error within this record of the customer data file. The process 330 then returns to decision state 435 to determine whether a plate error has occurred.
If no plate error has occurred at the decision state 435, then a decision is made whether an order error has occurred at the decision state 445. An order error is an error regarding a complete order, which results in the process 330 generating an error report at a state 450 and then terminating at an end state 455. Examples of such order errors include invalid optical density (yield), invalid file format or invalid average oligonucleotide length.
However, it should be realized that if there was a plate error at the decision state 435, then the error report log is updated at a state 458 to identify the particular error on the identified record of the customer data file. The process then returns to state 445 to determine whether any order errors had been made.
If a determination is made at the decision state 445 that no order errors have occurred, then the process 330 moves to a state 446 wherein the selected record is sent to the memory 85 so that a cached set of records is built. Once the current record is stored to memory, a determination is made at a decision state 460 whether more records exist within the customer data file to analyze. If additional records do exist, then the system moves to the next record at a state 470 and then returns to the state 425 to compare the newly obtained record to the rules database.
If a determination is made that more records do not exist in the customer data file, then the process 330 determines whether any errors had been found during processing at a decision state 465. If a determination is made that any errors occurred, for example at decision states 430 or 435, then the process moves to a state 475 wherein a series of container graphics indicating an error are displayed to the customer. One example of such display can be found in FIG. 5. Once the container graphics indicating an error have been displayed to the customer, the process 330 terminates at an end state 455.
If however no errors were found during processing at the decision state 465, then the process 330 displays a series of container graphics showing that the imported customer data file was validated at a state 480. An example of such a display can be found in FIG. 6. After the container graphics indicating validated entry of the customer data file have been displayed at the state 480, the process 330 terminates at the end state 455.
Accordingly, process 330 provides a module configured to check the parameters entered by the customer, and also check the oligonucleotide sequence data for errors. Process 330 also provides a module that is configured to display a graphic representing the type of container indicated by the customer. As explained above, the graphic is displayed to the customer in a way that indicates whether the oligonucleotide sequence data within the customer data file had at least one error.
FIG. 5A shows a screen shot of a display screen showing container graphics which indicate both valid and invalid entries from the customer data file. As indicated, the screen shows microtiter plate graphics, which are one type of container graphic, having reference numerals 505A, B, C, D, E, F, G, H. As indicated, graphics 505A and B are shaded to indicate that an error has occurred within those plates, whereas graphics 505C, D, E, F, G and H are shown as white to indicate that no errors occurred within the oligonucleotides corresponding to those microtiter plates.
FIG. 5B shows a separate screen shot of microtiter plate 505B in a magnified view to indicate the display to the customer if that graphic is selected by a mouse click on the designated container. If the customer selects graphic 505B, then a graphic 508 is presented to the customer. As shown, the graphic 508 includes a series of rows and columns mimicking the look of a 96-well microtiter plate. Each well of the microtiter plate is indicated by a colored dot. However, it should be noted that a first well 510 and a second well 512 are represented to have errors by showing them in a different color than the other dots. This indicates to the customer that the oligonucleotide data corresponding to those positions of the microtiter plate have an error. Thus, the graphic 508 can be configured to display a first color if the oligonucleotide sequence data has no errors and a second color if the oligonucleotide sequence data has at least one error.
In one embodiment, if the customer moves the mouse pointer over the top of either indicia 510 or 512, then text will appear over the indicia indicating the error found with the oligonucleotide data associated with that position of the microtiter plate. Alternatively or additionally, a window can pop up with information indicating the error. This display mechanism, of showing the customer a graphical indicia of the container being ordered, such as a microtiter plate, and color coding that container to easily identify where errors have occurred, provides a convenient means for reporting errors to the customer. Furthermore, presentation of a text message provides the customer with guidance for correcting an error.
In one embodiment, the system is configured to allow a customer to send an error message to a printer or an e-mail message. Such a “send error message” option provides an advantage for communication regarding defects in a customer data file. This is particularly helpful for customers from larger organizations, in which an individual placing the order may not have sufficient technical knowledge to correct an error at the point of ordering and may wish to inform an appropriate individual of what errors have occurred.
Of course it should be realized that the graphical indicia shown on screen 500 can be in any format of a container for holding the oligonucleotides. It is not required that the containers be any particular graphic shape or color. In this embodiment of the invention, the container graphics are in the shape of a 96-well microtiter plate. However, container graphics of other types of microtiter plates and containers are within the scope of the invention. For example, the container graphics could be circular and represent tubes, where, for example, each circular graphic represents one eppendorf tube.
Referring to FIG. 6, a screenshot 600 of a valid oligonucleotide order is presented. In the screenshot 600 a series of container graphics 605A-F in the shape of a microtiter plate are shown. As indicated, each of the container graphics has the same color indicating that no errors occurred during processing of the customer data file. The customer is now assured that the oligonucleotide order can proceed from this state without any errors having been found in the order thus far.
Referring now to FIG. 7, an exemplary process 340 (FIG. 3) of managing pools of oligonucleotides is explained more completely. It should be realized that a pool of oligonucleotides is a mixture of different oligonucleotides taken from containers that have been ordered by the customer. As explained below, the system 10 is configured to present graphics representing a first container and a second container for holding oligonucleotides to the customer. The customer can then select the graphics which correspond to the containers he wishes to mix.
The process begins at a start state 705 and then moves to a state 710 wherein the pooling interface is displayed to the customer. One example of such an interface is provided in FIG. 8. A determination is then made at a decision state 715 whether or not to use a predefined template to aid in pooling samples. Such predefined templates can include, for example, automatic pooling of every other container in an order. Another type of predefined template would be automatic pooling of the first half of containers of an order with the second half of containers in an order. If a determination is made at state 715 that no template pooling will be done, the process 340 moves to a state 720 wherein input on the first pool set is gathered from the customer. As shown in FIG. 8, a series of graphics depicting the various containers that have already been ordered is presented to the customer. The customer then selects a first graphic that corresponds to the first container to be pooled. The customer then selects the second graphic that corresponds to a second container. After at least two containers have been selected in this manner, the customer indicates a choice by an input device such as a button or menu item to request for a pool to be made from the containers that have been selected through their corresponding graphics. Accordingly, the system is configured to present graphics representing a first selectable container and a second selectable container to the customer.
If a determination is made to use a template in order to pool samples together, then the process 340 moves to a state 725 wherein the template pool is created. After the template pool has been created by selecting the appropriate graphics, the process 340 moves to a state 730 where a description of the template pool is displayed to the customer.
A determination is then made at state 733 whether the correct template pools have been created. If a determination is made that the template pools were correct, then the process 340 terminates at state 750. However, if a determination is made that the pools were not created properly, the process 340 moves to a state 734 wherein the improper oligonucleotide pools are removed from the pool list. The process 340 then moves to a decision state 735 wherein a determination is made whether all of the plates that are being pooled have been removed from the list of possible pooled plates. If all of the plates have been removed, then the process 340 returns to the decision state 715 to begin the pooling process again.
If however, it is determined that not all plates have been removed, the process 340 moves to state 720 where input on the first pool set is gathered from the customer. Then the process 340 moves to a state 738 wherein a pool entry is created in memory from the input gathered at state 720. The process 340 then moves to a state 740 where a description of the pool entry is displayed to the customer. After displaying the pool entry description, a determination is made at state 745 whether more pools are desired. If it is determined at state 745 that more pools are desired, the process 340 moves to a state 755 where input on the next pool set is gathered. The process 340 then returns to state 735 where a pool entry is created from the input gathered at state 755. This pool entry is essentially a new order for a container that has a mixture of oligonucleotides from the selected containers. Accordingly, the system is configured to identify the containers corresponding to the graphics that were selected by the customer and thereafter create an order for a container comprising a mixture of oligonucleotides from the selected containers. If however, it is determined at state 745 that no further pools are desired, the process terminates at an end state 750.
Referring to FIG. 8, an exemplary screenshot 800 of the pooling interface is presented. Window 805 displays oligonucleotide containers 815A-D which a customer can select for pooling with a mouse click. Window 810 shows the description 740 (FIG. 7) of each pool entry 820A and 820B. Of course, it should be realized that the pool interface is not limited to what is shown in 800 but could be in any format for selecting oligonucleotide containers for pooling. Also, It is not required that the containers or descriptions be any particular graphic shape, or color.
INCORPORATION BY REFERENCE
All references cited herein, including patents, patent applications, papers, text books, and the like, and the references cited therein, to the extent that they are not already, are hereby incorporated herein by reference in their entirety.
EQUIVALENTS
The foregoing written specification is considered to be sufficient to enable one skilled in the art to practice the invention. The foregoing description and Examples detail certain preferred embodiments of the invention and describes the best mode contemplated by the inventors. It will be appreciated, however, that no matter how detailed the foregoing may appear in text, the invention may be practiced in many ways and the invention should be construed in accordance with the appended claims and any equivalents thereof.

## Claims

1. A system for placing an electronic order of oligonucleotides, comprising:
a non-transient storage configured to receive a customer data file, wherein the data file comprises data corresponding to oligonucleotides to be ordered;
a first module configured to check said data file for errors; and
a second module configured to display a graphic, wherein the graphic indicates whether data in the data file has at least one error.

2. The system of claim 1, wherein said graphic comprises a plurality of dots.

3. The system of claim 1, wherein the graphic comprises a plurality of indicia that are aligned in the shape of wells of a microtiter plate.

4. The system of claim 3, wherein the plurality of indicia are aligned in the shape of wells of a 96-well microtiter plate.

5. The system of claim 3, wherein the plurality of indicia are aligned in the shape of wells of a 384-well microtiter plate.

6. The system of claim 1, wherein the graphic comprises indicia that indicate the location of oligonucleotide data having at least one error.

7. The system of claim 6, wherein the indicia indicating the at least one error are colored red.

8. The system of claim 6, wherein the indicia indicating the at least one error are selectable by a mouse click.

9. The system of claim 8, wherein selection of the indicia results in display of a window showing the data corresponding to an oligonucleotide.

10. The system of claim 1, wherein said system is an Internet-based oligonucleotide ordering system.

11. The system of claim 1, wherein the data in the data file comprises at least one nucleotide sequence for the oligonucleotides to be ordered.