U.S. patent application number 14/026900 was filed with the patent office on 2014-03-20 for systems, methods, and apparatus for facilitating chemical analyses.
This patent application is currently assigned to CambridgeSoft Corporation. The applicant listed for this patent is CambridgeSoft Corporation. Invention is credited to William B. Ballard, Scott Gregory Flicker, Shadrack Cgar Frazier, Sean Gerard Greenhow, Biying Huang, Robin Young Smith.
Application Number | 20140082015 14/026900 |
Document ID | / |
Family ID | 45871665 |
Filed Date | 2014-03-20 |
United States Patent
Application |
20140082015 |
Kind Code |
A1 |
Huang; Biying ; et
al. |
March 20, 2014 |
SYSTEMS, METHODS, AND APPARATUS FOR FACILITATING CHEMICAL
ANALYSES
Abstract
A knowledge management platform eliminates the trial and error
process for analytical chemists in, for example, identifying
appropriate methodologies for separating mixtures of chemical
compounds. The platform allows the analytical chemists to perform a
variety of searches on data existing from previous experiments,
procedures, and/or processes. The platform may be employed to make
faster decisions, and ultimately decreases the time taken in
selecting an appropriate separation methodology.
Inventors: |
Huang; Biying; (Apex,
NC) ; Flicker; Scott Gregory; (Raleigh, NC) ;
Ballard; William B.; (Raleigh, NC) ; Smith; Robin
Young; (San Jose, CA) ; Greenhow; Sean Gerard;
(Raleigh, NC) ; Frazier; Shadrack Cgar; (Durham,
NC) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
CambridgeSoft Corporation |
Waltham |
MA |
US |
|
|
Assignee: |
CambridgeSoft Corporation
Waltham
MA
|
Family ID: |
45871665 |
Appl. No.: |
14/026900 |
Filed: |
September 13, 2013 |
Related U.S. Patent Documents
|
|
|
|
|
|
Application
Number |
Filing Date |
Patent Number |
|
|
13239069 |
Sep 21, 2011 |
8538983 |
|
|
14026900 |
|
|
|
|
61384822 |
Sep 21, 2010 |
|
|
|
Current U.S.
Class: |
707/769 |
Current CPC
Class: |
G06F 16/245 20190101;
G16C 20/20 20190201; G16C 20/90 20190201 |
Class at
Publication: |
707/769 |
International
Class: |
G06F 17/30 20060101
G06F017/30 |
Claims
1-14. (canceled)
15. An apparatus for electronically identifying a separation method
for separating one or more chemical compounds in a sample, the
apparatus comprising: a processor; and a memory having a set of
instructions stored thereon, wherein the instructions, when
executed by the processor, cause the processor to: (i) receive a
user query comprising one or more criteria comprising at least one
of a chemical structure, a chemical sub-structure, a separation
method property, and a separation run property; (ii) access a
relational database, wherein the relational database comprises:
substance data corresponding to a plurality of substances, wherein
each substance of the plurality of substances comprises a
respective set of chemical substance properties, and each substance
of the plurality of substances identifies one or more of a
molecule, a biologic, an enzyme, and a protein; and experimental
run data from a plurality of completed separation experiments,
wherein the experimental run data comprises a set of separation
method properties and a set of separation run properties, wherein
each separation method property of the set of separation method
properties and each separation run property of the set of
separation run properties is linked in the relational database to
at least one respective chemical structure object of a plurality of
chemical structure objects, wherein each chemical structure object
of the plurality of chemical structure objects corresponds to one
or more compounds separated in a respective separation experiment
of the plurality of completed separation experiments, and wherein
each chemical structure object of the plurality of chemical
structure objects is linked in the relational database to a
respective set of chemical structure properties associated with a
particular substance of the plurality of substances; (iii)
identify, within the relational database, responsive to the user
query, query results, wherein the query results comprises at least
one of: (a) one or more separation method properties corresponding
to the one or more criteria, and (b) one or more separation run
properties corresponding to the one or more criteria; and (iv)
cause the presentation of the query results.
Description
CROSS-REFERENCE TO RELATED APPLICATION
[0001] This application claims priority to and the benefit of, and
incorporates herein by reference in its entirety, U.S. Provisional
Patent Application No. 61/384,822, which was filed on Sep. 21,
2010.
TECHNICAL FIELD
[0002] In various embodiments, the present invention relates to
systems, methods, and apparatus for facilitating chemical analyses.
More specifically, described herein are exemplary systems, methods,
and apparatus for determining methodologies, and the parameters
thereof, to separate substances.
BACKGROUND
[0003] A typical day for an analytical chemist often includes
performing a variety of chemical analyses, including the
development of methodologies and procedures to separate mixtures of
compounds in reaction batches, the deconvolution of degradation
products, and/or the validation of product specifications. The
methodologies used to analyze and separate mixtures of chemical
compounds generally involve various machine settings, detector
settings, and materials suitable to perform the separation.
Unfortunately, to determine an appropriate methodology to be
utilized in separating one or more chemical compounds from a
sample, the analytical chemist typically has to employ a
time-consuming and costly trial and error process utilizing his or
her own experience and training.
[0004] The results of the analytical chemist's method runs may be
stored in, for example, a scientific data management system (SDMS),
a laboratory information management system (LIMS), or in any of a
variety of other databases or digital library systems. However,
using existing systems, the analytical data is often stored in such
a way that very few other analytical chemists, even within the same
laboratory, are able to thereafter effectively reuse the
methodologies from those historical experiments, procedures, and/or
processes.
[0005] For example, when wanting to separate a molecule that an
analytical chemist in a laboratory worked with several months
prior, another analytical chemist within that laboratory will
typically undertake another time-consuming and costly trial and
error process to determine the appropriate machine settings,
detector settings, and materials to perform the separation.
Complicating matters is the fact that data from previous separation
runs are normally stored on a variety of different machines used in
the laboratory, making it more difficult to determine what
separation methodologies were successfully employed in the
past.
[0006] As such, needs exist for improved procedures for
facilitating chemical analyses, such as the development of
separation methodologies, the deconvolution of degradation
products, and the validation of product specifications.
SUMMARY OF THE INVENTION
[0007] Described herein are various embodiments of systems,
methods, and apparatus that eliminate the trial and error process
for analytical chemists in, for example, identifying appropriate
methodologies for separating mixtures of compounds, deconvolving
degradation products, and/or validating product specifications. In
one embodiment, a knowledge management platform is provided that
allows scientists, such as analytical chemists, to perform a
variety of searches on data existing from previous experiments,
procedures, and/or processes that may have been stored in a
disorganized manner in order to find the best methodology to
separate molecules. Advantageously, the platform connects
methodologies, structures, and parameters that may be scattered
across disparate, and physically separate, information stores, and
may present to the user thereof (e.g., the analytical chemist) a
single, searchable repository. As such, the platform may be
employed to make faster decisions, and ultimately decreases the
time taken in selecting an appropriate methodology.
[0008] In general, in one aspect, embodiments of the invention
feature an apparatus for electronically identifying a separation
method for separating one or more chemical compounds in a sample.
The apparatus includes a memory for storing a relational database,
a memory for storing a code defining a set of instructions, and a
processor for executing the set of instructions. The code may
include a search module. The memory for storing the relational
database may be the same or a different memory from that which is
used for storing the code.
[0009] The relational database includes data harvested from one or
more other databases (e.g., a laboratory information management
system (LIMS), a scientific data management system (SDMS), an
electronic laboratory notebook, another relational database, a web
page, and/or a searchable text file) that contain(s) experimental
run data from completed separation experiments. The data in the
relational database may be actively accessed from the one or more
other databases, or the data may be copied from the one or more
other databases into a consolidated database (i.e., the relational
database). A set of separation method properties and a set of
separation run properties from the harvested data are linked in the
relational database to each of a plurality of chemical structure
objects corresponding to one or more compounds separated in the
completed separation experiments, and each of the one or more
chemical structure objects is associated with a corresponding set
of chemical structure properties in the relational database. The
correlated separation method properties, separation run properties,
and chemical structure properties are indexed and stored in the
relational database.
[0010] For its part, the search module is configured to identify
and display one or more chemical structures and corresponding
separation method properties, separation run properties, and,
optionally, chemical structure properties, in response to a user
query of the relational database.
[0011] In various embodiments, the user query comprises two or more
chemical structures or substructures as input, and the search
module is configured to identify and display separation method
properties and separation run properties common to all of the two
or more chemical structures or substructures.
[0012] In one embodiment, the separation method properties include
one or more text-based, numeric, and/or alphanumeric strings and/or
ranges, such as a method name, a mobile phase indicator, a
temperature, a temperature range, a flow rate, a flow rate range, a
gradient method indicator, a wavelength, a wavelength range, an
instrument name, a column name, a column particle size, a column
length, and a column internal diameter. The separation run
properties may include one or more text-based, numeric, and/or
alphanumeric strings and/or ranges, such as a sample name, a vial
number, a run date, a run date range, a process date, a process
date range, a scientist name, a run time, a run time range, an
injection number, an injection number range, an injection volume,
and an injection volume range. For their part, the chemical
structure properties may include one or more text-based, numeric,
and/or alphanumeric strings and/or ranges, such as a compound
number, a compound name, an IUPAC name, a molecular weight, a
molecular weight range, a CLogP, a CLogP range, a molar volume, and
a molar volume range.
[0013] In one embodiment, the search module is configured to
identify and display via a graphical user interface, in response to
the user query, a plurality of graphical representations of
chemical structures from the relational database corresponding to
one or more of: (A) a user-identified structure, (B) one or more
substructures within the user-identified structure, (C) one or more
structures containing the user-identified structure as a
substructure therein, (D) one or more structures that are
chemically similar to the user-identified structure, and/or (E) one
or more structures corresponding to chemical compounds separated
using separation method properties, separation run properties,
and/or chemical structure properties identified in the user query.
In addition, the search module may be further configured to, upon
selection by the user of one of the chemical structures that are
graphically represented on the graphical user interface, identify
and display the separation method properties, separation run
properties, and, optionally, chemical structure properties from the
relational database corresponding to the user-selected chemical
structure.
[0014] In another embodiment, the search module is further
configured to archive data corresponding to the user query and
query results in the relational database, thereby facilitating
later data retrieval in response to a future user query.
[0015] In general, in another aspect, embodiments of the invention
feature a procedure for electronically identifying a separation
method for separating one or more chemical compounds in a sample.
The procedure includes harvesting data from one or more databases
(e.g., a laboratory information management system (LIMS), a
scientific data management system (SDMS), an electronic laboratory
notebook, a relational database, a web page, and/or a searchable
text file) that contain(s) experimental run data from completed
separation experiments. The procedure also includes correlating a
set of separation method properties and a set of separation run
properties from the harvested data with one or more chemical
structure objects corresponding to one or more compounds separated
in the completed separation experiments. Each of the one or more
chemical structure objects is associated with a corresponding set
of chemical structure properties. In addition, the procedure
includes indexing and storing the correlated separation method
properties, separation run properties, and chemical structure
properties in a relational database, and displaying one or more
chemical structures and corresponding separation method properties,
separation run properties, and, optionally, chemical structure
properties, in response to a user query of the relational
database.
[0016] In various embodiments, the user query includes two or more
chemical structures or substructures as input, and the separation
method properties and separation run properties common to all of
the two or more chemical structures or substructures are displayed
in response to the user query.
[0017] In one embodiment, the separation method properties include
one or more text-based, numeric, and/or alphanumeric strings and/or
ranges, such as a method name, a mobile phase indicator, a
temperature, a temperature range, a flow rate, a flow rate range, a
gradient method indicator, a wavelength, a wavelength range, an
instrument name, a column name, a column particle size, a column
length, and a column internal diameter. The separation run
properties may include one or more text-based, numeric, and/or
alphanumeric strings and/or ranges, such as a sample name, a vial
number, a run date, a run date range, a process date, a process
date range, a scientist name, a run time, a run time range, an
injection number, an injection number range, an injection volume,
and an injection volume range. For their part, the chemical
structure properties may include one or more text-based, numeric,
and/or alphanumeric strings and/or ranges, such as a compound
number, a compound name, an IUPAC name, a molecular weight, a
molecular weight range, a CLogP, a CLogP range, a molar volume, and
a molar volume range.
[0018] In one embodiment, displaying the one or more chemical
structures and corresponding separation method properties,
separation run properties, and, optionally, chemical structure
properties, in response to the user query of the relational
database, includes displaying via a graphical user interface a
plurality of graphical representations of chemical structures from
the relational database corresponding to one or more of (i) a
user-identified structure, (ii) one or more substructures within
the user-identified structure, (iii) one or more structures
containing the user-identified structure as a substructure therein,
(iv) one or more structures that are chemically similar to the
user-identified structure, and/or (v) one or more structures
corresponding to chemical compounds separated using separation
method properties, separation run properties, and/or chemical
structure properties identified in the user query. Upon selection
by the user of one of the chemical structures that are graphically
represented on the graphical user interface, the separation method
properties, separation run properties, and, optionally, chemical
structure properties from the relational database corresponding to
the user-selected chemical structure may be displayed.
[0019] In another embodiment, data corresponding to the user query
and the query results is archived in the relational database,
thereby facilitating later data retrieval in response to a future
user query.
[0020] Elements of embodiments described with respect to a given
aspect of the invention may be used in various embodiments of
another aspect of the invention. For example, it is contemplated
that features of dependent claims depending from one independent
claim can be used in apparatus, systems, and/or methods of any of
the other independent claims.
BRIEF DESCRIPTION OF THE DRAWINGS
[0021] The foregoing and other objects, aspects, features, and
advantages of the invention will become more apparent and may be
better understood by referring to the following description taken
in conjunction with the accompanying drawings, in which:
[0022] FIG. 1 is a block diagram of a system for facilitating
chemical analyses in accordance with an illustrative embodiment of
the invention;
[0023] FIG. 2 is an image of a method search screen for inputting
method properties and run details, in accordance with an
illustrative embodiment of the invention;
[0024] FIG. 3 is an image of a structure search screen for
inputting one or more chemical structures and/or structure
properties, in accordance with an illustrative embodiment of the
invention;
[0025] FIG. 4 is an image of a search results screen displaying
chemical structures, structure properties, method properties, and
run details, in accordance with an illustrative embodiment of the
invention;
[0026] FIG. 5 is an image of a method properties screen displaying
information associated with a particular method, in accordance with
an illustrative embodiment of the invention;
[0027] FIG. 6 is an image of a structure details screen displaying
information associated with a particular chemical structure, in
accordance with an illustrative embodiment of the invention;
[0028] FIG. 7 is an image of a run details screen displaying
information associated with a particular run, in accordance with an
illustrative embodiment of the invention;
[0029] FIG. 8 is an image of a structure search screen displaying
two chemical structures, in accordance with an illustrative
embodiment of the invention; and
[0030] FIG. 9 is an image of a search results screen displaying the
results for a search to find separation methods for two structures,
in accordance with an illustrative embodiment of the invention.
DESCRIPTION
[0031] In general, in various embodiments, the present invention
pertains to systems, methods, and apparatus for facilitating
chemical analyses. In broad overview, in accordance with one
embodiment of the invention, a user (e.g., an analytical chemist)
employs a computing system to rapidly identify one or more
methodologies appropriate for separating mixtures of compounds,
deconvolving degradation products, and/or validating product
specifications. In particular, in one embodiment, the computing
system employs algorithms to connect together the discrete
methodologies, structures, and parameters that may be scattered
across otherwise unconnected databases, instruments, etc., and then
suggests to the user the best method(s) to utilize in performing
the separation and analytical analysis.
[0032] FIG. 1 depicts a system 100, according to an illustrative
embodiment of the invention, for facilitating chemical analyses.
The system 100 includes a client node 104, a server node 108, a
relational database 110, multiple additional databases
112.sup.1-112.sup.N (which, in one embodiment, are disparate and
physically separate from one another), and, for enabling
communications therebetween, a network 116. As illustrated, the
server node 108 may include a search module 120 and a display
module 124.
[0033] The network 116 may be, for example, a local-area network
(LAN), such as a company or laboratory Intranet, a metropolitan
area network (MAN), or a wide area network (WAN), such as the
Internet. Each of the client node 104, server node 108, relational
database 110, and additional databases 112.sup.1-112.sup.N may be
connected to the network 116 through a variety of connections
including, but not limited to, standard telephone lines, LAN or WAN
links (e.g., T1, T3, 56 kb, X.25), broadband connections (e.g.,
ISDN, Frame Relay, ATM), or wireless connections. The connections,
moreover, may be established using a variety of communication
protocols (e.g., HTTP, TCP/IP, IPX, SPX, NetBIOS, NetBEUI, SMB,
Ethernet, ARCNET, Fiber Distributed Data Interface (FDDI), RS232,
IEEE 802.11, IEEE 802.11a, IEEE 802.11b, IEEE 802.11g, and direct
asynchronous connections).
[0034] The client node 104 may be any type of personal computer,
Windows-based terminal, network computer, wireless device,
information appliance, RISC Power PC, X-device, workstation, mini
computer, main frame computer, personal digital assistant, set top
box, handheld device, or other computing device that is capable of
both presenting information/data to, and receiving commands from, a
user of the client node 104 (e.g., an analytical chemist). The
client node 104 may include, for example, a visual display device
(e.g., a computer monitor), a data entry device (e.g., a keyboard),
persistent and/or volatile storage (e.g., computer memory), a
processor, and a mouse. In one embodiment, the client node 104
includes a web browser, such as, for example, the INTERNET EXPLORER
program developed by Microsoft Corporation of Redmond, Wash., to
connect to the World Wide Web.
[0035] For its part, the server node 108 may be any computing
device that is capable of receiving information/data from and
delivering information/data to the client node 104, for example
over the network 116, and that is capable of querying, receiving
information/data from, and delivering information/data to the
relational database 110 and/or additional databases
112.sup.1-112.sup.N. For example, as further explained below, the
server node 108 may receive a search query from a user of the
client node 104, query the relational database 110 and receive
search results therefrom, and present the search results to the
user at the client node 104. The server node 108 may include a
processor and persistent and/or volatile storage, such as computer
memory.
[0036] Each database 112.sup.1-112.sup.N may be any computing
device that is capable of storing and managing collections of data,
such as data relating to methodologies that may be used in
separating mixtures of compounds. For example, each database
112.sup.1-112.sup.N may store experimental run data from completed
separation experiments, such as appropriate machine settings,
detector settings, and materials to perform the work. Each database
112.sup.1-112.sup.N may communicate using SQL or another language,
or may use other techniques to store, receive, and transmit
data.
[0037] As used herein, the term "database" is broadly used to refer
to any repository of information. For example, a database
112.sup.1-112.sup.N may be a scientific data management system
(SDMS), a laboratory information management system (LIMS), a
relational database, an electronic laboratory notebook, or a
computing device or any information store storing a web page, a
searchable text file, PowerPoint slides, an Excel spreadsheet, etc.
In addition, a database 112.sup.1-112.sup.N can be any information
store storing the files output by an instrument used in chemical
analyses, whether that be a computer memory onboard the instrument
itself or a separate information store to which the output files of
the instrument have been transferred. Exemplary instruments that
may be used in chemical analyses include, but are not limited to,
the Agilent 1100 instrument manufactured by Agilent Technologies of
Santa Clara, Calif.; the Acquity UPLC, the Trizaic UPLC, and the
Method Station X5 SFC manufactured by Waters Corporation of
Milford, Mass.; the UltiMate 3000 HPLC manufactured by Dionex
Corporation of Sunnyvale, Calif.; and the Flexar FX-15 UHPLC
manufactured by Perkin Elmer of Waltham, Mass.
[0038] For its part, the relational database 110 is, in one
embodiment, any computing device that is capable of receiving
commands/queries and information/data from, and of delivering
information/data to, the server node 108 and/or the client node
104. In one embodiment, the databases 112.sup.1-112.sup.N are
disparate and physically separate databases, and the relational
database 110 is a centralized database that stores and manages
collections of data harvested from one or more of the databases
112.sup.1-112.sup.N. Again, the relational database 110 may
communicate using SQL or another language, or may use other
techniques to store, receive, and transmit data.
[0039] The data stored within the relational database 110 may be
harvested from the additional databases 112.sup.1-112.sup.N in any
manner. For example, the data may be actively accessed from the
additional databases 112.sup.1-112.sup.N or copied therefrom. In
one embodiment, the harvesting is performed utilizing indexing and
structure recognition algorithms, and the harvested data is
connected together by examining and correlating the disjointed
information that is found. For example, a set of separation method
properties and a set of separation run properties (which are
further described below) obtained from the harvested data may be
linked in the relational database 110 to each of a plurality of
chemical structure objects corresponding to one or more compounds
that were separated in the completed separation experiments. The
chemical structure objects may be, for example, of the type
described in co-pending U.S. patent application Ser. No. 13/100,217
(e.g., computerized representations identifying various atoms,
bonds, etc.), and each such chemical structure object may be
associated with a corresponding set of chemical structure
properties in the relational database 110. The entire content of
co-pending U.S. patent application Ser. No. 13/100,217 is hereby
incorporated herein by reference. Once the separation method
properties, the separation run properties, and the chemical
structure properties are correlated, they may then be indexed and
stored in the relational database 110.
[0040] The search module 120 and the display module 124 of the
server node 108 may each be implemented as any software program
and/or hardware device, for example an application specific
integrated circuit (ASIC) or a field programmable gate array
(FPGA), that is capable of providing the functionality described
below. It will be understood by one having ordinary skill in the
art, however, that the illustrated modules 120 and 124, and the
organization of the server node 108, are conceptual, rather than
explicit, requirements. For example, the two illustrated modules
120 and 124 may be combined into a single module, such that the
functions performed by the two modules 120 and 124, as described
below, are in fact performed by the single module. In addition, it
should be understood that any single one of the illustrated modules
120 and 124 may in fact be implemented as multiple modules, such
that the functions performed by the single module, as described
below, are in fact performed by the multiple modules.
[0041] Although not shown in FIG. 1, each of the client node 104,
the server node 108, the relational database 110, and the
additional databases 112.sup.1-112.sup.N may also include its own
transceiver (or separate receiver and transmitter) that is capable
of receiving and transmitting communications, including requests,
responses, and commands, such as, for example, inter-processor
communications and networked communications. The transceivers (or
separate receivers and transmitters) may each be implemented as a
hardware device, or as a software module with a hardware
interface.
[0042] It will also be understood by those skilled in the art that
FIG. 1 is a simplified illustration of the system 100 and that it
is depicted as such to facilitate the explanation of the present
invention's embodiments. Moreover, the system 100 may be modified
in a variety of manners without departing from the spirit and scope
of the invention. For example, rather than both being implemented
on a single server node 108, the illustrated modules 120 and 124
may instead each be implemented on a different computing device
(not shown) and such computing devices may communicate with one
another directly, over the network 116, or over another additional
network (not shown). In yet another example, the functionality of
the relational database 110 may in fact be resident on the server
node 108 (e.g., be implemented in the computer memory thereof).
Additional options are for the server node 108 and/or the
relational database 110 to be local to the client node 104 (such
that they may all communicate directly without using the network
116), or for the functionality of the server node 108 and/or the
relational database 110 to be implemented on the client node 104
(e.g., for the search module 120, the display module 124, and/or
the relational database 110 to reside on the client node 104). As
such, the depiction of the system 100 in FIG. 1 is
non-limiting.
[0043] In certain embodiments, the system 100 accelerates the
process of developing a method to separate chemical compounds by
mining and utilizing existing data sets to suggest methods and
procedures that work against new molecules requiring testing. For
example, when a user executes a search for a desired chemical
structure, the system 100 may display one or more separation
methods that have been used previously to separate that structure.
When the user selects one of these methods, the system 100 may then
display one or more runs (e.g., tests, experiments, or
measurements) that have been performed using that method. Each
displayed structure, method, and/or run may include a link to one
or more screens that display the details of the corresponding
selection. The details may be viewed simultaneously so that a user
can compare and contrast the differences between the individual
runs, molecules, or methods from the plurality of choices resulting
from the query. As previously described, the relational database
110 is obtained by harvesting information from a plurality of data
sources. In general, the harvesting process occurs before
correlation of the data, which may take place prior to populating
the relational database 110. User querying, selection, and
comparison activities generally occur after the relational database
110 has been populated.
[0044] In certain embodiments, the system 100 correlates individual
substances (e.g., molecules, biologics, enzymes, and proteins) that
were separated in a run (e.g., a test or measurement) to
information contained in other systems that capture and track
method and run data, but not substance data. While the substance
data may be missing key components, the system 100 back-fills those
missing components by crawling or searching ancillary systems that
may not be related to method development or run execution, and by
associating the information found in an amalgamated system that
makes correlation of the run/method/substance information possible.
A query engine is then layered upon the data so that users can
query against this highly dimensional information in an easy to use
manner. As further described below, the system 100 returns the
results as a combination of visual images and tables that are
combined and that interact with one another so that large volumes
of this information can be filtered and visualized quickly.
[0045] A person or organization may use the system 100 to
rationalize data and information from legacy systems. A user of the
system 100 is able to query this data and information, run
simulations, and/or develop hypotheses before any actual work
commences.
[0046] While the system 100 may be used to target methods for
separating substances, the general process and algorithms used by
the system 100 for harvesting, indexing, and storing data, coupled
with the advanced query and display technologies, can be applied to
other methods. For the example, the system 100 may be used to
search for food science methods, engineering methodologies,
business process methodologies, and other business practices that
follow a repetitive and complex workflow with many dimensions of
data that are stored.
[0047] In certain embodiments, the system 100 produces a suggested
method for use by the querying user. This method can then be
applied to the real world process in a more efficient manner. The
method can then be stored as an electronic record for future use or
for use in a validated and/or controlled environment.
[0048] In certain embodiments, the systems, procedures, and
apparatus described herein allow a user to search for the best
method (e.g., a method of separating a chemical compound from a
mixture) by querying the system 100 using a single search parameter
or a combination of parameters. For example, referring to FIGS. 2
and 3, the system 100 allows the user to search by method
properties, run details, and/or structure properties.
[0049] FIG. 2 is an image of a method search screen 200 for
inputting method properties and run details, according to an
embodiment of the invention. As depicted, method properties may
include method name, temperature, mobile phase, flow rate,
wavelength, gradient methods, column name, and/or instrument name.
Additional method properties may include a column particle size, a
column length, and/or a column internal diameter. Examples of
method names include metabolite quantification, quality control of
Guizhi Fuling capsules, multi-inlet TOF-MS, and KMD methylated.
Temperatures, flow rates, and wavelengths (e.g., in mm) may be
searched as numerical ranges. Gradient methods are typically
searched as a yes or no choice. Instrument names are typically
trade names or brand names of the instruments, such as A1100 (for
the AGILENT 1100 instrument), ACQUITY UPLC, TRIZAIC UPLC, METHOD
STATION X5 SFC, ULTIMATE 3000 UHPLC, and FLEXAR FX-15 UHPLC. Column
names are typically trade names, such as CHIRALPAK ID, KINETEX PFP,
KINETEX PHENYL-HEXYL, C8, C18, and STANDARD WIDEPORE C5. Sometimes
a dimension will be included, such as LUNA 3 .mu.m C18(2) 100
.ANG.150.times.4.6 mm and GEMINI-NX 5 .mu.m C18 110
.ANG.150.times.4.6 mm. Run details may include sample name
(typically a text string), vial (typically an alpha numeric
string), run date, process date, scientist(s), run time, injection
number, and/or injection volume.
[0050] In certain embodiments, the mobile phase may be any text
based string. Examples of mobile phases that may be queried or
utilized include HPLC grade water with 0.1% formic acid, and
acetonitrile with 0.1% formic acid. These two examples include a
solvent plus a buffer (i.e., formate as formic acid). Other
possible buffers include phosphate, citrate, formate, acetate,
tris(hydorxymethyl) aminomethane, ammonia, borate, and/or
diethylamine. Any combination of the following exemplary mobile
phase solvents may also be used: cyclohexane, n-hexane,
1-chlorobutane, carbon tetrachloride, i-propyl ether, toluene,
diethyl ether, tetrahydrofuran, chloroform, ethanol, ethyl acetate,
dioxane, methanol, acetonitrile, nitromethane, ethylene glycol, and
water.
[0051] As depicted in FIG. 2, in certain embodiments, the method
search screen 200 includes one or more dropdown menus, buttons,
and/or cells or fields that the user may access to select or input
search criteria using an input device, such as a mouse or keyboard.
As depicted, the method search screen 200 includes a search button
202 that the user may select to begin a search. The method search
screen 200 also includes a reset button 204 that the user may
select to reset or clear the displayed search criteria.
[0052] FIG. 3 is an image of a structure search screen 300 for
inputting one or more chemical structures and/or structure
properties, according to an embodiment of the invention. As
depicted, structure properties may include structure name (e.g., IU
PAC name, or compound name), weight, cLogP, and molar volume.
Additional structure properties may include LogD, melting point,
boiling point, # of H donors or acceptors, pKa, and/or refraction
index. In one embodiment, any combination of the method properties,
run details, and structure properties may be entered by the user
and searched by the system 100.
[0053] In certain embodiments, the structure search screen 300
includes structure buttons 302 and element buttons 304 that the
user may select to build and display one or more chemical
structures to be searched. For example, the user may add a benzene
ring to a chemical structure by selecting a benzene ring button.
Similarly, the user may add a nitrogen atom to a structure by
selecting an "N" button. In another embodiment, structures may be
copied or imported from other sources, such as CHEMDRAW, available
from Perkin Elmer of Waltham, Mass. As depicted, the structure
search screen 300 may include a search button 306 and a reset
button 308 for initiating a search and resetting input data,
respectively.
[0054] In certain embodiments, once the desired structure(s) has
been created or obtained by the user, the system 100 allows the
user to search (i) by substructure (i.e., the user can find methods
through a substructure search), (ii) by similarity (i.e., the user
can find methods through a similarity search of a drawn structure),
or (iii) for separation methods for two or more structures (i.e.,
the user can request the system 100 to find the best methods for
separating two or more drawn structures). Any of these searches may
be performed with additional search criteria, such as one or more
method properties and/or run details. Radio buttons may be selected
by the user to identify the desired type of search. For example, in
the embodiment depicted in FIG. 3, the user may select a first
radio button 310 to search by substructure. In this case, the
system 100 finds methods that have been used to separate structures
having a desired substructure. Similarly, a second radio 312 button
may be selected to search by similarity to find methods that have
been used to separate similar structures. When evaluating the
similarity of structures, the search module 120 may use, for
example, a Tanimoto score and/or a Jaccard index. For example, the
results may be ranked with a Tanimoto score indicating the
similarity between the desired structure and the structures in the
search results. A third radio button 314 may be selected to search
for separation methods for two or more desired structures. With the
third radio button 314 selected, the search module 120 will scan
the relational database 110 to find methods for separating both of
the drawn structures.
[0055] After the user has input the desired search criteria (i.e.,
method properties, run details, and/or structure properties), the
user directs the system 100 to perform the search by selecting one
of the search buttons 202, 306. The search module 120 then accesses
the relational database 110 or the databases 112 and identifies
search results that satisfy the search criteria. The display module
124 then displays the search results for the user. For example, the
user may search for methods having a method name of "KMD
Methylated." To perform this search, the user enters "KMD
Methylated" in the method name cell of the method search screen
200. The user then selects the search button 202 and the system 100
returns all methods containing the name "KMD Methylated."
Similarly, the user may search for runs (e.g., tests or
measurements) associated with a particular injection number. After
the user enters the desired injection number in the method search
screen 200, the system 100 returns all runs associated with that
injection number. As another example, the user may request a search
for structures having a weight less than 300 daltons and cLogP less
than 3.0, and the system 100 will identity structures that satisfy
these criteria. In certain embodiments, any combination of method
properties, run properties, and/or structure properties may be
searched.
[0056] FIG. 4 is an image of a search results screen 400 depicting
the results of a search for method names that include the term
"halo," in accordance with one embodiment of the invention. As
depicted, the search results include two methods 402 having "halo"
in the method name. In addition to identifying these two methods,
the system 100 returned run properties 404, structures 406, and
structure properties 408 associated with the two methods. For
example, the search results include images or graphical
representations of structures 406 associated with the two methods.
The search results also include details about the structure
properties 408, the methods 402, and the run properties 404,
associated with the two methods. In another embodiment, the user
may sort the tabulated results by selecting a column header.
[0057] In certain embodiments, the images of the structures 406
provided in the search results screen 400 may correspond to (A) a
user-identified structure (e.g., a structure drawn by the user),
(B) a substructure within the user-identified structure, (C) a
structure containing the user-identified structure as a
substructure therein, and/or (D) a structure that is chemically
similar to the user-identified structure. In one embodiment, upon
selecting an image of a structure 406, the system 100 displays
additional information about the structure 406, such as separation
method properties, separation run properties, and/or chemical
structure properties, corresponding to the user-selected
structure.
[0058] As depicted, in certain embodiments, the search results
screen 400 includes information buttons 410 that the user may
select to obtain additional, detailed information about the methods
402, run properties 404, or structures properties 408. In one
embodiment, each information button 410 is associated with a row in
the tabulated search results. For example, referring to FIG. 5, by
selecting an information button 410 associated with a method in a
row, the system 100 displays a method details screen 500 that
includes detailed information about the method, such as the
temperature and flow rate. Likewise, referring to FIG. 6, when an
information button 410 associated with a structure is selected, the
system 100 displays a structure details screen 600 that includes
detailed information about the structure, including the name,
weight, and molar volume. Further, referring to FIG. 7, when the
user selects an information button 410 associated with a run, the
system 100 displays a run details screen 700 that includes
information about the run, including the sample name, date, and
injection volume. In certain embodiments, the information displayed
in FIGS. 5-7 can be viewed simultaneously so that the user can
compare and contrast the differences of the individual runs,
molecules, and/or methods from the plurality of choices resultant
from the query.
[0059] FIGS. 8 and 9 depict a structure search screen 800 and a
search results screen 900, respectively, associated with a search
for methods that separate two or more structures, in accordance
with one embodiment of the present invention. As depicted in FIG.
8, the user has drawn a first chemical structure 802 and a second
chemical structure 804, using the structure buttons 302 and element
buttons 304. The user has also selected the third radio button 314
to indicate that a search for methods that separate the two
structures 802, 804 is desired. The results from the search are
displayed in the search results screen 900 of FIG. 9. As depicted,
the search results include methods 902 that may be used to separate
the two structures. The search results also indicate method
properties, run details 904, and structure properties 906,
associated with the two structures 802, 804.
[0060] In certain embodiments, the system 100 identifies methods
that separate two or more structures by identifying methods that
were previously successful for separating each structure on its
own. The system 100 then compares the method properties and run
details for these previous methods and identifies a preferred
method that includes method properties and run details that are
common to each of the previous methods. For example, if a previous
method for separating a first structure included a temperature
range of 100.degree. C. to 200.degree. C., and a previous method
for separating a second structure included a temperature range of
150.degree. C. to 250.degree. C., then the preferred method may
include a temperature range of 150.degree. C. to 200.degree. C.
(i.e., the region of overlap between the two previous temperature
ranges).
[0061] In another embodiment, the system 100 archives search
criteria and search results for later access by one or more users.
For example, the system 100 may store, in the relational database
110, the method properties, run details, structure properties, and
search results associated with a particular search. When a user
wants to perform the same or similar search at a later date, the
search parameters and/or search results may be retrieved before the
additional search is conducted.
[0062] Accordingly, it can readily be seen that embodiments of the
present invention provide a robust and powerful search application
that, for example, facilitates the identification of appropriate
methodologies for separating mixtures of compounds, deconvolving
degradation products, and/or validating product specifications.
[0063] It should also be noted that embodiments of the present
invention may be provided as one or more computer-readable programs
embodied on or in one or more articles of manufacture. The article
of manufacture may be any suitable hardware apparatus, such as, for
example, a floppy disk, a hard disk, a CD ROM, a CD-RW, a CD-R, a
DVD ROM, a DVD-RW, a DVD-R, a flash memory card, a PROM, a RAM, a
ROM, or a magnetic tape. In general, the computer-readable programs
may be implemented in any programming language. Some examples of
languages that may be used include C, C++, or JAVA. The software
programs may be further translated into machine language or virtual
machine instructions and stored in a program file in that form. The
program file may then be stored on or in one or more of the
articles of manufacture.
[0064] Certain embodiments of the present invention were described
above. It is, however, expressly noted that the present invention
is not limited to those embodiments, but rather the intention is
that additions and modifications to what was expressly described
herein are also included within the scope of the invention.
Moreover, it is to be understood that the features of the various
embodiments described herein were not mutually exclusive and can
exist in various combinations and permutations, even if such
combinations or permutations were not made express herein, without
departing from the spirit and scope of the invention. In fact,
variations, modifications, and other implementations of what was
described herein will occur to those of ordinary skill in the art
without departing from the spirit and the scope of the invention.
As such, the invention is not to be defined only by the preceding
illustrative description.
* * * * *